US20080027348A1 - Minimally Invasive Monitoring Systems for Monitoring a Patient's Propensity for a Neurological Event - Google Patents
Minimally Invasive Monitoring Systems for Monitoring a Patient's Propensity for a Neurological Event Download PDFInfo
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- US20080027348A1 US20080027348A1 US11/766,761 US76676107A US2008027348A1 US 20080027348 A1 US20080027348 A1 US 20080027348A1 US 76676107 A US76676107 A US 76676107A US 2008027348 A1 US2008027348 A1 US 2008027348A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/372—Arrangements in connection with the implantation of stimulators
- A61N1/37211—Means for communicating with stimulators
- A61N1/37217—Means for communicating with stimulators characterised by the communication link, e.g. acoustic or tactile
- A61N1/37223—Circuits for electromagnetic coupling
- A61N1/37229—Shape or location of the implanted or external antenna
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0002—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network
- A61B5/0031—Implanted circuitry
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
- A61B5/316—Modalities, i.e. specific diagnostic methods
- A61B5/369—Electroencephalography [EEG]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
- A61B5/316—Modalities, i.e. specific diagnostic methods
- A61B5/369—Electroencephalography [EEG]
- A61B5/372—Analysis of electroencephalograms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
- A61B5/316—Modalities, i.e. specific diagnostic methods
- A61B5/369—Electroencephalography [EEG]
- A61B5/386—Accessories or supplementary instruments therefor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/40—Detecting, measuring or recording for evaluating the nervous system
- A61B5/4076—Diagnosing or monitoring particular conditions of the nervous system
- A61B5/4094—Diagnosing or monitoring seizure diseases, e.g. epilepsy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
- A61N1/36064—Epilepsy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2560/00—Constructional details of operational features of apparatus; Accessories for medical measuring apparatus
- A61B2560/02—Operational features
- A61B2560/0204—Operational features of power management
- A61B2560/0214—Operational features of power management of power generation or supply
Definitions
- the present invention relates generally to systems and methods for sampling one or more physiological signals from a patient. More specifically, the present invention relates to long term, ambulatory monitoring and analysis of one or more neurological signals from a patient using a minimally invasive system to estimate the patient's propensity for a seizure.
- Epilepsy is a disorder of the brain characterized by chronic, recurring seizures. Seizures are a result of uncontrolled discharges of electrical activity in the brain. A seizure typically manifests itself as sudden, involuntary, disruptive, and often destructive sensory, motor, and cognitive phenomena. Seizures are frequently associated with physical harm to the body (e.g., tongue biting, limb breakage, and burns), a complete loss of consciousness, and incontinence. A typical seizure, for example, might begin as spontaneous shaking of an arm or leg and progress over seconds or minutes to rhythmic movement of the entire body, loss of consciousness, and voiding of urine or stool.
- a typical seizure for example, might begin as spontaneous shaking of an arm or leg and progress over seconds or minutes to rhythmic movement of the entire body, loss of consciousness, and voiding of urine or stool.
- a single seizure most often does not cause significant morbidity or mortality, but severe or recurring seizures (epilepsy) results in major medical, social, and economic consequences.
- Epilepsy is most often diagnosed in children and young adults, making the long-term medical and societal burden severe for this population of patients. People with uncontrolled epilepsy are often significantly limited in their ability to work in many industries and usually cannot legally drive an automobile.
- An uncommon, but potentially lethal form of seizure is called status epilepticus, in which a seizure continues for more than 30 minutes. This continuous seizure activity may lead to permanent brain damage, and can be lethal if untreated.
- epilepsy can result from head trauma (such as from a car accident or a fall), infection (such as meningitis), or from neoplastic, vascular or developmental abnormalities of the brain.
- head trauma such as from a car accident or a fall
- infection such as meningitis
- neoplastic, vascular or developmental abnormalities of the brain Most epilepsy, especially most forms that are resistant to treatment (i.e., refractory), are idiopathic or of unknown causes, and is generally presumed to be an inherited genetic disorder.
- an “average” subject with focal epilepsy has between 3 and 4 seizures per month, in which each of the seizures last for several seconds or minutes, the cumulative time the subject would be seizing is only about one hour per year. The other 99.98% of the year, the epileptic subject is free from seizures.
- the debilitating aspect of epilepsy is not necessarily the seizures themselves, but rather the fear and uncertainly of when the next seizure is going to occur.
- the risk of social embarrassment resulting from unforewarned seizures causes epileptic subjects to remove themselves from society.
- the danger posed by unforewarned seizures often prevents epileptic subjects from performing activities that most non-epileptic subjects take for granted.
- the present invention provides methods and systems for monitoring one or more physiological signals from the patient.
- the present invention provides minimally-invasive systems that provide for the long-term, ambulatory monitoring of patient's brain activity to facilitate the estimation of the patients propensity for a neurological event (e.g., seizure, migraine headache, episode of depression, etc.).
- the systems of the present invention will typically include one or more implantable devices that are capable of sampling and transmitting a signal that is indicative of the patient's brain activity to a data collection device that is external to the patient's body.
- the ambulatory systems of the present invention provide for substantially continuous sampling of brain wave electrical signals (e.g., electroencephalography or “EEG” and electrocorticogram “ECoG”, which are hereinafter referred to collectively as “EEG”).
- EEG electroencephalography
- ECG electrocorticogram
- a patient could wear their external data collection device at all times of the day (except while showering, etc.).
- the data from the external data collection device could be uploaded into a physician's computer, which could then automatically analyze the stored EEG data and calculate certain metrics that would provide insight into the patient's condition.
- such metrics may allow the epileptologist to assess seizure frequency, monitor for sub-clinical seizures, determine the efficacy of treatment, determine the effect of adjustments of the dosage of the AED, determine the effects of adjustments of the type of AED, adjust parameters of electrical stimulation, or the like.
- the output from the external device may be a control signal to an implanted therapy device—such as the implanted devices or to an independent therapy device (such as a vagus nerve stimulator, spinal cord stimulator, cortical stimulator, deep brain stimulator, cranial nerve stimulator, implanted drug pump, etc.).
- an implanted therapy device such as the implanted devices or to an independent therapy device (such as a vagus nerve stimulator, spinal cord stimulator, cortical stimulator, deep brain stimulator, cranial nerve stimulator, implanted drug pump, etc.).
- an independent therapy device such as a vagus nerve stimulator, spinal cord stimulator, cortical stimulator, deep brain stimulator, cranial nerve stimulator, implanted drug pump, etc.
- the output from the external device may be delivered to a user interface so as to provide an output communication to the patient that indicates the patient's propensity for the neurological event.
- the neurological event includes, but is not limited to, a seizure, a migraine headache, an episode of depression, a tremor, or the like.
- the one or more implanted devices are leadless. Some of the devices are passive or semi-passive and are at least partly energized by an externally generated signal field.
- the external field is generated by a generator in the external device.
- the generator is typically a radiofrequency generator, but other types of wireless signals may be used to generate a signal that energizes and interrogates the implanted devices.
- the external device may be configured to provide an output communication when the data signal from the one or more implanted devices are not being received by the external device.
- the sampling of the brain activity signals is typically performed on a substantially continuous basis so as to provide substantially continuous monitoring of the patient's neurological condition.
- the external device comprises a memory that is used to store at least some of the substantially continuous brain activity signals.
- the brain activity signals may be encrypted prior to transmission to maintain patient confidentiality and stored either encrypted or in a unencrypted format.
- the present invention provides a minimally invasive method of monitoring a patient's propensity for a neurological event.
- the method comprises transmitting a signal from an external device that is configured to interrogate and provide power to one or more implanted devices that are positioned in between one or more layers of the patient's scalp and skull.
- the external device receives a wireless data signal from the one or more implanted leadless devices that are encoded with data indicative of sampled brain activity signals.
- the received data signal is derived from the transmitted signal from the external device.
- the data signal is processed in a processing assembly of the external device to estimate the patient's propensity for the neurological event and an output communication is provided to the patient that provides a real time indication of the patient's propensity for the neurological event.
- the output communication to the patient that indicates the patient's propensity for the neurological event is typically performed on a substantially continuous basis so as to provide substantially continuous communication to the patient regarding their propensity for the neurological condition.
- the neurological event includes, but is not limited to, a seizure, a migraine headache, an episode of depression, a tremor, or the like.
- the one or more implanted devices are leadless. Some of the devices are passive or semi-passive and are at least partly energized by an externally generated signal field.
- the external field is generated by a generator in the external device.
- the generator is typically a radiofrequency generator, but other types of wireless signals may be used to generate a signal that energizes and interrogates the implanted devices.
- the external device may be configured to provide an output communication when the data signal from the one or more implanted devices are not being received by the external device.
- the external device comprises a memory that is used to store at least some of the substantially continuous brain activity signals.
- the brain activity signals may be encrypted prior to transmission to maintain patient confidentiality and stored either encrypted or in a unencrypted format.
- the present invention provides a minimally invasive method of monitoring a patient's EEG signals for use in monitoring a patient's propensity for a neurological event.
- the method comprises receiving a substantially continuous interrogation signal in an implanted device that is positioned between at least one layer of the patient's scalp and skull from a device external to the patient's body.
- the implanted device substantially continuously samples an EEG signal from the patient.
- a wireless data signal encoded with data that is indicative of the sampled EEG signal is transmitted from the patient to the device external to the patient's body, wherein the sampled EEG signal is processed in the external device to provide a real-time of estimate the patient's propensity for a neurological event.
- FIG. 1A illustrates a simplified system embodied by the present invention which comprises one or more implantable devices in communication with an external device.
- FIG. 1B illustrates simplified methods of operating the system of the present invention.
- FIG. 2A illustrates a bottom view of one embodiment of an active implantable device that is encompassed by the present invention.
- FIG. 2B illustrates a cross-sectional view of the active implantable device of FIG. 2A along lines B-B.
- FIG. 2C is a linear implantable device that comprises a plurality of electrode contacts in which at least one electrode contact comprises the active implantable device of FIG. 2A .
- FIG. 2D is a cross sectional view of the implantable device of FIG. 2C along lines D-D.
- FIG. 2E is a 4 ⁇ 4 electrode array that comprises a plurality of electrode contacts in which at least one electrode contact comprises the active implantable contact of FIG. 2A .
- FIG. 3A is a cross-sectional view of another embodiment of an implantable device that is encompassed by the present invention.
- FIG. 3B is a cross-sectional view of another embodiment of the implantable device in which a conductive can forms a housing around the electronic components and acts as an electrode.
- FIG. 3C illustrates a simplified plan view of an embodiment that comprises four electrodes disposed on the implanted device.
- FIG. 4 illustrates one embodiment of the electronic components that may be disposed within the implantable device.
- FIG. 5 is a block diagram illustrating one embodiment of electronic components that may be in the external device.
- FIG. 6 illustrates a simplified trocar or needle-like device that may be used to implant the implantable device beneath the patient's skin.
- FIG. 7 illustrates a method of inserting an implantable device in the patient and wirelessly sampling EEG signals from a patient.
- FIG. 8 illustrates a method of lateralizing a seizure focus.
- FIG. 9 illustrates a method of measuring seizure activity data for clinical and/or sub-clinical seizures.
- FIG. 10 illustrates a method of evaluating efficacy of a therapy.
- FIG. 11 illustrates a method of titrating an efficacious therapy.
- FIG. 12 illustrates a simplified method of performing a clinical trial.
- FIG. 13 illustrates a more detailed method of performing a clinical trial.
- FIG. 14 is a kit that is encompassed by the present invention.
- condition is used herein to generally refer to the patient's underlying disease or disorder—such as epilepsy, depression, Parkinson's disease, headache disorder, etc.
- state is used herein to generally refer to calculation results or indices that are reflective a categorical approximation of a point (or group of points) along a single or multi-variable state space continuum of the patient's condition. The estimation of the patient's state does not necessarily constitute a complete or comprehensive accounting of the patient's total situation. As used in the context of the present invention, state typically refers to the patient's state within their neurological condition.
- the patient may be in a different states along the continuum, such as an ictal state (a state in which a neurological event, such as a seizure, is occurring), a pre-ictal state (which is a neurological state that immediately precedes the ictal state), a pro-ictal state (a state in which the patient has an increased risk of transitioning to the ictal state), an inter-ictal state (a state in between ictal states), a contra-ictal state (a protected state in which the patient has a low risk of transitioning to the ictal state within a calculated or predetermined time period), or the like.
- a pro-ictal state may transition to either an ictal or inter-ictal state.
- a pro-ictal state that transitions to an ictal state may also be referred to herein as a “pre-ictal state.”
- the estimation and characterization of “state” may be based on one or more patient dependent parameters from the a portion of the patient's body, such as electrical signals from the brain, including but not limited to electroencephalogram signals and electrocorticogram signals “ECoG” or intracranial EEG (referred to herein collectively as EEG“), brain temperature, blood flow in the brain, concentration of AEDs in the brain or blood, changes thereof, etc.). While parameters that are extracted from brain-based signals are preferred, the present invention may also extract parameters from other portions of the body, such as the heart rate, respiratory rate, blood pressure, chemical concentrations, etc.
- An “event” is used herein to refer to a specific event in the patient's condition. Examples of such events include transition from one state to another state, e.g., an electrographic onset of seizure, end of seizure, or the like. For conditions other than epilepsy, the event could be an onset of a migraine headache, onset of a depressive episode, a tremor, or the like.
- the occurrence of a seizure may be referred to as a number of different things.
- the patient is considered to have exited a “pre-ictal state” or “pro-ictal state” and has transitioned into the “ictal state”.
- the electrographic onset of the seizure (one event) and/or the clinical onset of the seizure (another event) have also occurred during the transition of states.
- a patient's “propensity” for a seizure is a measure of the likelihood of transitioning into the ictal state.
- the patient's propensity for seizure may be estimated by determining which “state” the patient is currently in. As noted above, the patient is deemed to have an increased propensity for transitioning into the ictal state (e.g., have a seizure) when the patient is determined to be in a pro-ictal state. Likewise, the patient may be deemed to have a low propensity for transitioning into the ictal state when it is determined that the patient is in a contra-ictal state.
- the methods, devices and systems of the present invention are useful for long-term, ambulatory sampling and analysis of one or more physiological signals, such as a patient's brain activity.
- the system of the present invention may be used to monitor and store one or more substantially continuously sampled EEG signals from the patient, while providing a minimal inconvenience to the patient.
- Attempts at developing ambulatory monitoring systems in the past have relied on an array of electrodes being placed on the patient's head and scalp with adhesive. Unfortunately, such systems are poorly tolerated by patients and are impractical for the duration of time needed for the accurate evaluation of the patient's EEG and evaluation of the efficacy of the treatment the patients are undergoing.
- the ambulatory monitoring systems of the present invention typically include one or more devices that are implanted in a minimally invasive fashion in the patient and will be largely unnoticed by a patient as they go about their day-to-day activities.
- the implantable devices may be in wireless communication with an external device that may be carried by the patient or kept in close proximity to the patient. Consequently, the ambulatory monitoring systems of the present invention are conducive to longer, more effective monitoring of the patient (e.g., one week or longer, one month or longer, two months or longer, three months or longer, six months or longer, one year or longer, etc.).
- the methods, devices and systems of the present invention may also find use in an emergency room or neurological intensive care units (ICU).
- ICU neurological intensive care units
- the systems may be used to monitor patients who have complex, potentially life-threatening neurological illnesses or brain injuries.
- Neuro ICUs may monitor patients who have suffered (or thought to have suffered) a stroke (e.g., cerebral infarction, transient ischemic attacks, intracerebral hemorrhage, aneurismal subarachnoid hemorrhage, arteriovenous malformations, dural sinus thrombosis, etc.), head trauma, spinal cord injury, tumors (e.g., spinal cord metastases, paraneoplastic syndromes), infections (e.g., encephalitis, meningitis, brain abscess), neuromuscular weakness (e.g., Guillain-barre syndrome, myasthenia gravis), eclampsia, neuropleptic malignant syndrome, CNS vasculitis, migraine headaches, or the
- the neuro-ICUs require the ability to monitor the patient's neurological condition for a long period of time to identify issues and diagnose the patient before permanent neurological damage occurs. Because the systems of the present invention are able to provide real-time monitoring of a patient's EEG and many embodiments have the ability to detect or predict neurological events, such systems will be beneficial to patients and the staff of the ICU to allow the neurologist and support staff to detect and/or prevent complications that may arise from the patient's neurological condition, before the patient's condition deteriorates.
- a patient who is suffering from head trauma may be outfitted with a system of the present invention and because the implantable portions are MRI safe, the patient's may still undergo MRI sessions.
- the systems of the present invention may also be used to continuously monitor a patient's response to a drug therapy while the patient is in the neuro-ICU and when the patient leaves the neuro-ICU.
- the monitoring systems of the present invention may be used in conjunction with, or as an alternative to, the in-patient video-EEG monitoring that occurs in the EMU.
- in-patient video-EEG monitoring in some embodiments it may be desirable to provide one or more video recorders in the patient's home to provide time-synced video recording of the patient as they live with their ambulatory monitoring system.
- Such a video system may or may not be in communication with the ambulatory monitoring system of the present invention; but both the video and the monitored EEG signals should be time-synced and analyzed together by the physician to assess the patient's condition and/or efficacy of any therapy that the patient may be undergoing.
- the systems and methods of the present invention may incorporate EEG analysis software to estimate and monitor the patient's brain state substantially in real-time.
- the EEG analysis software may include a safety algorithm, a seizure prediction algorithm and/or a seizure detection algorithm that uses one or more extracted features from the EEG signals (and/or other physiological signals) to estimate the patient's brain state (e.g., predict or detect the onset of a seizure). Additionally, some systems of the present invention may be used to facilitate delivery of a therapy to the patient to prevent the onset of a predicted seizure and/or abort or mitigate a seizure after it has started.
- Facilitation of the delivery of the therapy may be carried out by outputting a warning or instructions to the patient or automatically delivering a therapy to the patient (e.g., pharmacological, electrical stimulation, etc.).
- the therapy may be delivered to the patient using the implanted devices that are used to collect the ambulatory signals, or it may be delivered to the patient through a different implanted device.
- a description of some systems that may be used to delivery a therapy to the patient are described in commonly owned U.S. Pat. Nos. 6,366,813 and 6,819,956, U.S. Patent Application Publication Nos. 2005/0021103 (published Jan. 27, 2005), 2005/0119703 (published Jun. 2, 2005), 2005/0021104 (published Jan. 27, 2005), 2005/0240242 (published Oct.
- the systems of the present invention may be used to provide data and other metrics to the patients and physicians that heretofore have not been accurately measurable.
- the data may be analyzed to (1) determine whether or not the patient has epilepsy, (2) determine the type of epilepsy, (3) determine the types of seizures, (4) localize or lateralize one or more seizure foci, (5) assess baseline seizure statistics and/or change from the baseline seizure statistics (e.g., seizure count, frequency, duration, seizure pattern, etc.) (6) monitor for sub-clinical seizures, assess a baseline frequency of occurrence, and/or change from the baseline occurrence, (7) measure the efficacy of AED treatments, (8) assess the effect of adjustments of the dosage of the AED, (9) determine the effects of adjustments of the type of AED, (10) determine the effect of, and the adjustment to parameters of, electrical stimulation (e.g., vagus nerve stimulation (VNS), deep brain stimulation (DBS), cortical stimulation, etc.
- VNS vagus nerve stimulation
- the systems of the present invention typically include one or more implantable devices that are in wireless communication with an external data collection device, typically with a high frequency communication link.
- the implantable devices of the present invention are typically implanted in a minimally invasive fashion beneath at least one layer of the scalp, above the patient's skull/calvarium, and over one or more target area of the patient's brain.
- the implantable devices are typically injected underneath the skin/scalp using an introducer, trocar or syringe-like device using local anesthesia. It is contemplated that such a procedure could be completed in 20 to 30 minutes by a physician or neurologist in an out-patient procedure.
- the implantable devices are typically used to continuously sample the physiological signals for a desired time period so as to be able to monitor fluctuations of the physiological signal over substantially the entire time period.
- the implantable devices may be used to periodically sample the patient's physiological signals or selectively/aperiodically monitor the patient's physiological signals.
- the implantable devices may be permanently or temporarily implanted in the patient. If permanently implanted, the devices may be used for as long as the monitoring is desired, and once the monitoring is completed, because the implanted devices are biocompatible they may remain permanently implanted in the patient without any long term detrimental effects for the patient. However, if it is desired to remove the implanted devices, the devices may be explanted from the patient under local anesthesia. For ease of removal, it may be desirable to tether or otherwise attach a plurality of the implantable devices together (e.g., with a suture or leash) so that a minimal number of incisions are needed to explant the implantable devices.
- a plurality of the implantable devices e.g., with a suture or leash
- Exact positioning of the implanted devices will usually depend on the desired type of monitoring. For patients who are being monitored for epilepsy diagnosis, the suspected type of epilepsy may affect the positioning of the implantable devices. For example, if the patient is thought to have temporal lobe epilepsy, a majority of the implantable devices will likely be located over the patient's temporal lobe. Additionally, if the focus of the seizure is known, it may be desirable to place a plurality of implantable devices directly over the focus. However, if the focus has not been localized, a plurality of implantable devices may be spaced over and around the target area of the patient's brain (and one or more implantable devices contralateral to the target area) in an attempt to locate or lateralize the seizure focus.
- the number of implantable devices that are implanted in the patient will depend on the number of channels that the physician wants to concurrently monitor in the patient. Typically however, the physician will implant 32 or less, and preferably between about 2 and about 16 implantable devices, and most preferably between about 4 and about 8 implantable devices. Of course, in some instances, it may be desirable to implant more or less, and the present invention is not limited to the aforementioned number of implanted devices.
- the implanted devices may be implanted under the skin of the patient's face, within the muscle of the patient's face, within the skull, above the jaw (e.g., sphenoidal implant that is placed under the skin just above the jaw to monitor the brain activity in the temporal lobes), or any other desired place on the patient's body.
- the system of the present invention may be used to monitor one or more of a blood pressure, blood oxygenation, temperature of the brain or other portion of the patient, blood flow measurements in the brain or other parts of the body, ECG/EKG, heart rate signals and/or change in heart rate signals, respiratory rate signals and/or change in respiratory rate signals, chemical concentrations of medications, pH in the blood or other portions of the body, other vital signs, other physiological or biochemical parameters of the patient's body, or the like.
- the systems of the present invention may be useful for monitoring and assisting in the analysis of treatments for a variety of other neurological conditions, psychiatric conditions, episodic and non-episodic neurological phenomenon, or other non-neurological and non-psychiatric maladies.
- the present invention may be useful for patients suffering from sleep apnea and other sleep disorders, migraine headaches, depression, Alzheimer's, Parkinson's Disease, eating disorders, dementia, attention deficit disorder, stroke, cardiac disease, diabetes, cancer, or the like.
- the present invention may also be used to assess the symptoms, efficacy of pharmacological and electrical therapy on such disorders.
- FIG. 1A illustrates a simplified system 10 embodied by the present invention.
- System 10 includes one or more implantable devices 12 that are configured to sample electrical activity from the patient's brain (e.g., EEG signals).
- the implantable devices may be active (with internal power source), passive (no internal power source), or semi-passive (internal power source to power components, but not to transmit data signal).
- the implantable devices 12 may be implanted anywhere in the patient, but typically one or more of the devices 12 may be implanted adjacent a previously identified epileptic focus or a portion of the brain where the focus is believed to be located. Alternatively, the devices 12 themselves may be used to help determine the location of the epileptic focus.
- the physician may implant any desired number of devices in the patient.
- one or more additional implanted devices 12 may be implanted to measure other physiological signals from the patient.
- Implantable devices 12 While it may be possible to implant the implantable devices 12 under the skull and in or on the brain, it is preferred to implant the implantable devices 12 in a minimally invasive fashion under at least one layer of the patient's scalp and above the skull. Implantable devices 12 may be implanted between any of the layers of the scalp (sometimes referred to herein as “sub-galeal”).
- the implantable devices may be positioned between the skin and the connective tissue, between the connective tissue and the epicranial aponeurosis/galea aponeurotica, between the epicranial aponeurosis/galea aponeurotica and the loose aerolar tissue, between the loose aerolar tissue and the pericranium, and/or between the pericranium and the calvarium.
- Implantable devices 12 will typically be configured to substantially continuously sample the brain activity of the groups of neurons in the immediate vicinity of the implanted device.
- the electrodes may be sized to be able to sample activity of a single neuron in the immediate vicinity of the electrode (e.g., a microelectrode).
- the implantable device 12 will be interrogated and powered by a signal from the external device to facilitate the substantially continuous sampling of the brain activity signals.
- Sampling of the brain activity is typically carried out at a rate above about 200 Hz, and preferably between about 200 Hz and about 1000 Hz, and most preferably at about 400 Hz, but it could be higher or lower, depending on the specific condition being monitored, the patient, and other factors.
- Each sample of the patient's brain activity will typically contain between about 8 bits per sample and about 32 bits per sample, and preferably between about 12 bits per sample and about 16 bits per sample.
- the data transfer rate from the implantable devices 12 to the external device 14 is at least about 6.4 Kbits/second.
- the total data transfer rate for the system 10 would be about 205 Kbits/second.
- the implantable devices 12 may be configured to sample the brain activity signals periodically (e.g., once every 10 seconds) or aperiodically.
- Implantable device 12 may comprise a separate memory module for storing the recorded brain activity signals, a unique identification code for the device, algorithms, other programming, or the like.
- a patient instrumented with the implanted devices 12 will typically carry a data collection device 14 that is external to the patient's body.
- the external device 14 would receive and store the signal from the implanted device 12 with the encoded EEG data (or other physiological signals).
- the external device is typically of a size so as to be portable and carried by the patient in a pocket or bag that is maintained in close proximity to the patient.
- the device may be configured to be used in a hospital setting and placed alongside a patient's bed.
- Communication between the data collection device 14 and the implantable device 12 typically takes place through wireless communication.
- the wireless communication link between implantable device 12 and external device 14 may provide a communication link for transmitting data and/or power.
- External device 14 may include a control module 16 that communicates with the implanted device through an antenna 18 .
- antenna 18 is in the form of a necklace that is in communication range with the implantable devices 12 .
- control module 16 may be attached around an arm or belt of the patient, integrated into a hat, integrated into a chair or pillow, and/or the antenna may be integrated into control module 16 .
- the antenna of the external device and the implantable devices must be in communication range of each other.
- the frequency used for the wireless communication link has a direct bearing on the communication range.
- the communication range is between at least one foot, preferably between about one foot and about twenty feet, and more preferably between about six feet and sixteen feet.
- the present invention is not limited to such communication ranges, and larger or smaller communication ranges may be used. For example, if an inductive communication link is used, the communication range will be smaller than the aforementioned range.
- the interface may take the form of a magnetically attached transducer, as with cochlear implants. This could enable power to be continuously delivered to the implanted devices 12 and provide for higher rates of data transmission.
- system 10 may include one or more intermediate transponder (not shown) that facilitates data transmission and power transmission between implantable device 12 and external device 14 .
- the intermediate transponder may be implanted in the patient or it may be external to the patient. If implanted, the intermediate transponder will typically be implanted between the implantable device 12 and the expected position of the external device 14 (e.g., in the neck, chest, or head). If external, the transponder may be attached to the patient's skin, positioned on the patient's clothing or other body-worn assembly (e.g., eyeglasses, cellular phone, belt, hat, etc.) or in a device that is positioned adjacent the patient (e.g., a pillow, chair headrest, etc.).
- body-worn assembly e.g., eyeglasses, cellular phone, belt, hat, etc.
- the intermediate transponder may be configured to only transmit power, only transmit data, or it may be configured to transmit both data and power.
- the external device 14 may be placed outside of its normal communication range from the implanted devices 12 (e.g., on a patient's belt or in a patient's bag), and still be able to substantially continuously receive data from the implantable device 12 and/or transmit power to the implantable device 12 .
- Radiofrequency link Transmission of data and power between implantable device 12 and external device 14 is typically carried out through a radiofrequency link, but may also be carried out through magnetic induction, electromagnetic link, Bluetooth® link, Zigbee link, sonic link, optical link, other types of wireless links, or combinations thereof.
- One preferred method 11 of wirelessly transmitting data and power is carried out with a radiofrequency link, similar to the link used with radiofrequency identification (RFID) tags.
- RFID radiofrequency identification
- one or more radio frequency signals are emitted from the external device 14 through antenna 18 (step 13 ). If the external device 14 is in communication range of the implantable devices, at step 15 the radiofrequency (RF) energy signal illuminates the passive, implantable devices 12 .
- the same RF signal interrogates the energized implantable device 12 to allow the implantable device to sample the desired physiological signal from the patient (such as an EEG signal).
- the implantable device samples the instantaneous EEG signal (or other physiological signal) from the patient.
- the implantable device 12 then communicates a return RF signal to the external device 14 that is encoded with data that is indicative of the sampled EEG signal.
- the return RF signal is a based on the RF signal generated by the external device and includes detectable modifications which indicate the sampled EEG signal.
- the return signal is typically a backscattering of the RF signal from the external device with the detectable modifications that indicate the sampled EEG signal.
- backscattering does not require generation of a separate radiating signal and would not require an internal power source.
- the return RF signals may also include the identification code of the implanted device so as to identify which device the data is coming from.
- the return RF signal emitted by the internal device 12 is received by the antenna 18 , and the RF signal is decoded to extract the sampled EEG signal.
- the sampled EEG signal may thereafter be stored in a memory of the external device 14 .
- data will be stored until accessed by the patient.
- data will be analyzed on a separate device (e.g., physician's computer workstation).
- the received RF signal with the sampled EEG may be analyzed by the EEG analysis algorithms to estimate the patient's brain state which is typically indicative of the patient's propensity for a neurological event (step 25 ).
- the neurological event may be a seizure, migraine headache, episode of depression, tremor, or the like.
- the estimation of the patient's brain state may cause generation of an output (step 27 ).
- the output may be in the form of a control signal to activate a therapeutic device (e.g., implanted in the patient, such as a vagus nerve stimulator, deep brain or cortical stimulator, implanted drug pump, etc.).
- the output may be used to activate a user interface on the external device to produce an output communication to the patient.
- the external device may be used to provide a substantially continuous output or periodic output communication to the patient that indicates their brain state and/or propensity for the neurological event.
- Such a communication could allow the patient to manually initiate therapy (e.g., wave wand over implanted vagus nerve stimulator, cortical, or deep brain stimulator, take a fast acting AED, etc.) or to make themselves safe.
- the return RF signal is transmitted (e.g., backscattered) immediately after sampling of the EEG signal to allow for substantially real-time transfer (and analysis) of the patient's EEG signals.
- the return RF signal may be buffered in an internal memory and the communication transmission to the external device 14 may be delayed by any desired time period and may include the buffered EEG signal and/or a real-time sampled EEG signal.
- the return RF signal may use the same frequency as the illumination RF signal or it may be a different frequency as the illumination RF signal.
- some embodiment of the methods and devices of the present invention substantially continuously sample physiological signals from the patient and communicate in real-time small amounts of data during each return RF signal communication. Because only small amounts of data (one or a small number of sampled EEG signals from each implantable device 12 ) are transmitted during each communication, a lower amount of power is consumed and the illumination of the implanted device from the incoming high-frequency RF signal will be sufficient to power the implantable device 12 for a time that is sufficient to allow for sampling of the patient's EEG signal. Consequently, in most embodiments no internal power source, such as a battery, is needed in the implantable device 12 —which further reduces the package size of the implantable device 12 .
- the implantable devices 12 and the external devices 14 of the present invention typically use an electromagnetic field/high frequency communication link to both illuminate the implantable device and enable the high data transfer rates of the present invention.
- Conventional devices typically have an internally powered implantable device and use a slower communication link (e.g., that is designed for long link access delays) and transmit data out on a non-continuous basis.
- some embodiments of the present invention uses a fast access communication link that transmits a smaller bursts of data (e.g., single or small number of EEG sample at a time) on a substantially continuous basis.
- the frequencies used to illuminate and transfer data between the implantable devices 12 and external device are typically between 13.56 MHz and 10 GHz, preferably between 402 MHz and 2.4 GHz, more preferably between 900 MHz and 2.4 GHz. While it is possible to use frequencies above 2.4 GHz, Applicants have found that it is preferred to use a frequency below 2.4 GHz in order to limit attenuation effects caused by tissue. As can be appreciated, while the aforementioned frequencies are the preferred frequencies, the present invention is not limited to such frequencies and other frequencies that are higher and lower may also be used. For example, it may be desirable us use the MICS (Medical Implant Communication Service band) that is between 402-405 MHz to facilitate the communication link. In Europe, it may be desirable to use ETSI RFID allocation 869.4-869.65 MHz.
- MICS Medical Implant Communication Service band
- the system 10 of the present invention may also make use of conventional or proprietary forward error correction (“FEC”) methods to control errors and ensure the integrity of the data transmitted from the implantable device 12 to the external device 14 .
- FEC forward error correction
- Such forward error correction methods may include such conventional implementations such as cyclic redundancy check (“CRC”), checksums, or the like.
- the data signals that are wirelessly transmitted from implantable device 12 may be encrypted prior to transmission to the control module 16 .
- the data signals may be transmitted to the control module 16 as unencrypted data, and at some point prior to the storage of the data signals in the control module 16 or prior to transfer of the data signals to the physician's office, the EEG data may be encrypted so as to help ensure the privacy of the patient data.
- FIGS. 3A and 3B illustrate two embodiments of the externally powered leadless, implantable device 12 that may be used with the system 10 of the present invention.
- the implantable devices 12 of the present invention are preferably passive or semi-passive and are “slaves” to the “master” external device 14 .
- the implantable devices will typically remain dormant until they are interrogated and possibly energized by an appropriate RF signal from the external device 14 .
- the implantable device 14 may have minimal electronic components and computing power, so as to enable a small package size for the implantable device.
- the embodiment illustrated in FIGS. 3A and 3B are minimally invasive and may be implanted with an introducer, trocar or syringe-like device under local anesthesia by a physician or potentially even a physician's assistant.
- the implanted device of FIG. 3A may have a longitudinal dimension 20 of less than about 3 cm, and preferably between about 1 cm and about 10 cm, and a lateral dimension 22 of less than about 2 mm, and preferably between about 0.5 mm and about 10 mm.
- such dimensions are merely illustrative, and other embodiments of implanted device may have larger or smaller dimensions.
- FIG. 3A illustrates an embodiment that comprises a first electrode 24 and a second electrode 26 that are disposed on opposing ends of housing 28 .
- the first and second electrodes 24 , 26 may be composed of platinum, platinum-iridium alloy, stainless steel, or any other conventional material.
- the electrodes may include a coating or surface treatment such as platinum-iridium or platinum-black in order to reduce electrical impedance.
- the first and second electrodes 24 , 26 will typically have a smooth or rounded shape in order to reduce tissue erosion and may have a surface area of about 3 mm 2 , but other embodiments may be smaller or larger. Since electrodes 24 , 26 are typically adapted to only sense physiological signals and are not used to deliver stimulation, the surface area of the electrodes may be smaller than conventional implantable devices. The smaller electrodes have the advantage of reducing the overall device size which can be beneficial for improving patient comfort and reducing the risk of tissue erosion.
- Housing 28 is typically in the form of a radially symmetrical, substantially cylindrical body that hermetically seals electronic components 30 disposed within a cavity 32 .
- Housing 28 may be composed of a biocompatible material, such as glass, ceramic, liquid crystal polymer, or other materials that are inert and biocompatible to the human body and able to hermetically seal electronic components.
- Housing 28 may have embedded within or disposed thereon one or more x-ray visible markers 33 that allow for x-ray localization of the implantable device. Alternatively, one or more x-ray visible markers may be disposed within the cavity 32 .
- Cavity 32 may be filled with an inert gas or liquid, such as an inert helium nitrogen mixture which may also be used to facilitate package leakage testing.
- the liquid encapsulant may comprise silicone, urethane, or other similar materials.
- housing 28 is illustrated as a substantially cylindrical body with the electrodes 24 , 26 on opposing ends, housing may take any desired shape and the electrodes may be positioned at any position/orientation on the housing 28 .
- housing 28 may taper in one direction, be substantially spherical, substantially oval, substantially flat, or the like. Additionally or alternatively, the body may have one or more substantially planar surfaces so as to enhance the conformity to the patient's skull and to prevent rotation of the implantable device 12 .
- housing 28 may optionally include a conductive electromagnetic interference shield (EMI) that is configured to shield the electronic components 30 in housing 28 .
- the EMI shield may be disposed on an inner surface of the housing, outer surface of the housing, or impregnated within the housing.
- housing 28 may optionally comprise an anchoring assembly (not shown) that improves the anchoring of the implantable device 12 to the skull or the layers within the scalp.
- anchoring may be carried out with adhesive, spikes, barbs, protuberances, suture holes, sutures, screws or the like.
- first electrode 24 is disposed on a first end of housing 28 and is in electrical communication with the electronic components 30 through a hermetic feedthrough 34 .
- Feedthrough 34 may be the same material as the first electrode 24 or it may be composed of a material that has a similar coefficient of thermal expansion as the housing 28 and/or the first electrode 24 .
- Feedthrough 34 may make direct contact with a pad (not shown) on a printed circuit board 36 , or any other type of conventional connection may be used (e.g., solder ball, bond wire, wire lead, or the like) to make an electrical connection to the printed circuit board 36 .
- Second electrode 26 may be spaced from a second, opposing end of the housing 28 via an elongated coil member 38 .
- the second electrode 26 typically comprises a protuberance 39 that is disposed within and attached to a distal end of the coil member 38 .
- Coil member 38 acts as an electrical connection between second electrode and the electronic components 30 disposed within housing 28 .
- Coil member 38 will typically be composed of stainless steel, a high strength alloy such as MP35N, or a combination of materials such as a MP35N outer layer with silver core.
- coil member 38 has a largest lateral dimension (e.g., diameter) that is less than the largest lateral dimension (e.g., diameter) of housing 28 , but in other embodiments, the coil may have the same lateral dimension or larger lateral dimension from housing 28 .
- Coil member 38 may also be used as an antenna to facilitate the wireless transmission of power and data between the implantable device 12 and the external device 14 (or other device).
- coil member 38 may be used to receive and transmit radiofrequency signals.
- coil member 38 may be inductively coupled to an external coil to receive energy from a modulating, alternating magnetic field.
- the RF antenna is disposed outside of the housing 28 and extends from one end of housing 28 . It should be appreciated however, that the present invention is not limited to a substantially cylindrical antenna extending from an end of the housing 28 and various other configurations are possible. For example, it may be desirable to wind the antenna around or within the housing 28 . Furthermore, it may be desirable to use a substantially flat antenna (similar to RFID tags) to facilitate the transmission of power and data. To facilitate implantation, such antennas may be rolled into a cylindrical shape and biased to take the flat shape upon release from the introducer.
- the second antenna may be used for power and downlink using a first frequency, e.g., 13.56 MHz, while the first antenna may be used for uplink using a second frequency, e.g., 902-928 MHz.
- the implantable devices would need to have an internal timebase (e.g., oscillator and a frequency synthesizer).
- an internal timebase or frequency synthesizer is not needed—and the timebase established by the master (e.g., external device 14 ) can be used.
- Coil member 38 may be in electrical communication with the electronic components 30 with a hermetic feedthrough 42 that extends through a via 44 in housing 28 .
- Feedthrough 42 is typically composed of a material that has a coefficient of thermal expansion that is substantially similar to the material of housing 40 . Because the coil member 38 is outside of the housing 28 the length of the implantable device 12 will be increased, but the flexible coil will be better exposed to the RF signals and will be allowed to conform to the shape of the patient's skull.
- Coil member 38 is typically disposed outside of the housing 28 and disposed within an elongate, substantially flexible housing 40 .
- the flexible housing 40 is better able to conform to the shape of an outer surface of the patient's skull, more comfortable for the patient and reduces the chance of tissue erosion.
- Flexible housing 40 may comprise silicone, polyurethane, or the like In the illustrated embodiment, flexible housing 40 extends along the entire length of coil member 38 , but in other embodiments, flexible housing 40 may extend less than or longer than the longitudinal length of coil member 38 .
- Flexible housing 40 will typically have a substantially cylindrical shape, but if desired a proximal end 46 of the cylindrical housing may be enlarged or otherwise shaped to substantially conform to a shape of the housing 28 .
- the shaped proximal end 46 may be adhered or otherwise attached to the end of the housing 40 to improve the hermetic seal of the housing and may reduce any potential sharp edge or transition between the housings 28 , 40 . While FIG. 3A only illustrates a single layered flexible housing, if desired, the flexible housing 40 may comprise a plurality of layers, and the different layers may comprise different types of materials, have embedded x-ray markers, or the like.
- a longitudinal length of flexible housing 40 and the longitudinal length of the rigid housing 28 may vary depending on the specific embodiment, but a ratio of the longitudinal length of the flexible housing 40 : the longitudinal length of the more rigid housing 28 is typically between about 0.5:1 and about 3:1, and preferably between about 1:1 and about 2:1.
- a ratio of the longitudinal length of the flexible housing 40 : the longitudinal length of the more rigid housing 28 is typically between about 0.5:1 and about 3:1, and preferably between about 1:1 and about 2:1.
- the implantable devices 12 of the present invention consume a minimal amount of energy and use a high frequency RF coupling to power the device and communicate the EEG signals to the external device, unlike other conventional devices, some of the implantable devices 12 of the present invention will not need a ferrite core to store energy, and the electronic components 30 of the present invention will typically include aluminum or other MRI-safe material. Consequently, the patient's implanted with the implantable device 12 may safely undergo MRI imaging.
- FIG. 3B illustrates another embodiment of implantable device 12 that is encompassed by the present invention.
- the embodiment of FIG. 3B shares many of the same components as the embodiment of FIG. 3A , and such components are noted with the same reference numbers as FIG. 3A . There are, however, a few notable exceptions.
- the embodiment of FIG. 3B provides a conductive body 48 that acts as both the housing for the electronic components 30 and as the second electrode.
- Conductive body 48 may be composed of a metallized polymer, one or more metal or metal alloys, or other conductive material. Because body 48 is conductive, it may act as an electromagnetic interference (EMI) shield to the electronic components disposed within the cavity 32 .
- Electrical connections to the printed circuit board 36 may be carried out with one or more conductive spring conductors 50 or other conventional lead connectors.
- EMI electromagnetic interference
- Feedthrough 42 that is connected to the coil member 38 extends from the end of coil member 38 and makes an electrical connection with a lead on the printed circuit board 36 .
- the feedthrough 42 works in conjunction with one or more dielectric seals or spacers 52 to hermetically seal the cavity 32 . Similar to above, the cavity 32 may be filled with an inert gas or an encapsulant.
- the proximal end 46 of flexible body 40 may be coupled to the seals 52 and/or coupled to the conductive body 48 .
- the surface area of conductive body 48 (e.g., the first electrode) may be larger than the surface area of the second electrode 26 . In other embodiments, however, the surface area of the second electrode 26 may have the substantially same surface area and/or shape as the conductive body 48 .
- the implantable devices shown in FIGS. 3A and 3B function completely independent of the other implantable devices 12 and there is no physical connection or communication between the various devices. If desired, however, the implantable devices 12 may be physically coupled to each other with a connecting wire or tether and/or in communication with each other. If the plurality of implanted devices 12 are in communication with one another, it may be desired to use a communication frequency between the implanted devices 12 that is different from the frequency to communicate between the implanted devices and the external device 14 . Of course, the communication frequency between the implanted devices 12 may also be the same frequency as the communication frequency with the external device 14 .
- FIGS. 3A and 3B illustrate a first and second electrode 24 , 26
- the implantable devices 12 of the present invention are not limited to only two electrodes. Any number of electrodes may be coupled to the implantable device in any orientation.
- the electrodes do not have to extend from ends of the housing, but may be positioned anywhere along a portion of the housings 28 , 40 .
- a plurality of electrodes and their leads may be disposed along the length of the flexible housing 40 and/or rigid housing 28 so as to provide more than two electrodes per implantable device.
- FIG. 3C illustrates a simplified embodiment in which there are two additional electrode 24 ′, 26 ′ positioned on the rigid housing 28 and flexible housing 40 , respectively.
- the spacing between the various contacts 24 , 24 ′, 26 , 26 ′ may vary or be the same distance between each other.
- the spacing between electrodes will likely depend on the overall length of the implantable device, but will typically be between about 2 mm and about 20 mm and preferably be between about 5 mm and about 10 mm.
- FIGS. 3A-3B illustrate some currently preferred embodiments of the implantable device 12
- the present invention further encompasses other types of minimally invasive implantable devices 12 that can monitor the brain activity and other physiological signals from the patient.
- a plurality of electrodes might reside on a single lead that could be tunneled under the scalp from a single point of entry. Examples of such embodiments are shown in FIGS. 2A-2E .
- Such implantable devices 12 include an active electrode contact 400 that is in communication with one or more passive electrode contacts 401 .
- the active electrode contact 400 may be used to facilitate monitoring of the physiological signals using the array of active and passive electrode contacts.
- the arrays of electrode contacts may be arranged in a linear orientation ( FIG. 2C ) or in a grid pattern ( FIG. 2E ), or any other desired pattern (e.g., circular, star pattern, customized asymmetric pattern, etc.)
- the implantable device comprises two electrode contacts (e.g., one active contact and one passive contact)
- such an embodiment would have a similar configuration as the embodiment of FIG. 3A .
- the implantable device were to have four substantially linearly positioned electrode contacts (e.g., one active contact and three passive contacts)
- such an embodiment would be substantially similar to the configuration shown in FIG. 3C .
- FIG. 2A illustrates a bottom view of an active electrode contact 400 that may be part of the implantable device 12 of the present invention.
- the active electrode contact comprises a base 402 that is coupled to a contact portion 404 .
- the base 402 and contact portion may be composed of any number of different types of materials, such as platinum, platinum-iridium alloy, stainless steel, or any other conventional material. In preferred embodiments, both the base 402 and contact portion 404 are formed to their desired shape.
- the base 402 may comprise a plurality of hermetic feedthroughs 413 that is implemented using conventional glass metal seal technology (e.g., pins 408 , glass seal 414 , and vias 406 ).
- the hermetic feedthroughs 413 may be used to connect to an antenna (not shown) for communication with the external device 14 or to make an electrical connection with an adjacent passive electrode contact 401 in the implanted device 12 .
- base 402 comprises four hermetic feedthroughs 413 . But as can be appreciated the base 402 may comprise any desired number of feedthroughs 413 (e.g., anywhere between two and sixty four feedthroughs).
- FIG. 2B illustrates a cross-sectional view of the active electrode contact 400 along lines B-B in FIG. 2A .
- the contact portion 404 is shaped to as to align the base 402 along a bottom surface defined by flanges 409 .
- Base 402 may be coupled to the contact portion 404 with a laser weld, glass metal seal, or other conventional connector 410 along an outer perimeter of the base 402 to hermetically seal components of the active electrode contact within a cavity 412 defined by the base 402 and contact portion 404 .
- the cavity 412 may be backfilled with nitrogen and/or helium to facilitate package leak testing.
- a thin or thick filmed microcircuit or a printed circuit board (“PCB”) 416 may be mounted onto an inner surface of the base 402 .
- PCB 416 may have active components 418 (e.g., integrated circuits, ASIC, memory, etc.) and passive components 420 (e.g., resistors, capacitors, etc.) mounted thereto.
- Leads or bond wires 422 from the active and passive components may be electrically attached to pads on the PCB (not shown) which make electrical connections to leads or bond wires 424 that are attached to the hermetic feedthroughs 413 .
- the active electrode contact 400 may comprise a rechargeable or non-rechargeable power supply (e.g., batteries), and/or x-ray visible markers (not shown).
- FIGS. 2C and 2D illustrate an embodiment of the implantable device 12 in which one active contact 400 is housed in a body 426 along with a plurality of passive contacts 401 to form a multiple contact implantable device 12 .
- the contact portion of the active contact 400 is exposed through an opening in the body 426 to allow for sampling of the physiological signals (e.g., EEG) from the patient.
- the body 426 may be substantially flexible or rigid and may have similar dimensions and/or shapes as the embodiments shown in FIGS. 3A-3C .
- Body 426 may be composed of a biocompatible material such as silicone, polyurethane, or other materials that are inert and biocompatible to the human body. Body 426 may also be composed of a rigid material such as polycarbonate. The implantable device may be injected into the patient using the introducer assembly shown in FIG. 6 and methods shown in FIG. 7 .
- wire leads 427 may extend from the passive contacts 401 and be electrically and physically coupled to one of the hermetic feedthroughs 413 of the active contact 400 to facilitate sampling of the physiological signals using all four electrode contacts.
- one of the feedthroughs may be coupled to an antenna 428 that is configured to wirelessly communicate with the external device.
- FIGS. 2C-2E may have any of the components or variations as described above in relation to FIGS. 3A-3B .
- FIG. 2E illustrates an alternative embodiment of the implantable device 12 in which the implantable device 12 is in the form of a 4 ⁇ 4 grid array of active and passive contacts.
- At least one of the electrode contacts may be an active contact 400 so as to facilitate monitoring of the patient's physiological signals with the array.
- the contacts in the leftmost column are active electrode contacts 400
- the contacts in remaining column are electrically connected to one of the active contacts 400 .
- any number of active contacts 400 and passive contacts 401 may be in the grid array and the active contact(s) 400 may be positioned anywhere desired. For example, if the active electrode contact 400 has sixteen or more hermetic feedthroughs, only one of the contacts in the array needs to be active and the remaining fifteen contacts could be passive contacts.
- FIG. 4 illustrates one simplified embodiment of the electronic components 30 (e.g., active components 418 and passive components 420 in FIG. 2B ) that may be disposed in the implantable devices 12 as shown in FIGS. 2A-3C .
- the electronic components 30 of the implantable device 12 may include any combination of conventional hardware, software and/or firmware to carry out the functionality described herein.
- the electronic components 30 may include many of the components that are used in passive RF integrated circuits.
- the first and second electrodes will be used to sample a physiological signal from the patient—typically an EEG signal 53 , and transmit the sampled signal to the electronic components 30 . While it may be possible to record and transmit the analog EEG signal to the external device, the analog EEG signal will typically undergo processing before transmission to the external device 14 .
- the electronic components typically include a printed circuit board that has, among others, an amplifier 54 , one or more filters 56 (e.g., bandpass, notch, lowpass, and/or highpass) and an analog-to-digital converter 58 .
- the processed EEG signals may be sent to a transmit/receive sub-system 60 for wireless transmission to the external device via an antenna (e.g., coil member 38 ). Additional electronic components that might be useful in implantable device 12 may be found in U.S. Pat. Nos. 5,193,539, 5,193,540, 5,312,439, 5,324,316, 5,405,367 and 6,051,017.
- the electronic components 30 may include a memory 64 (e.g., RAM, EEPROM, Flash, etc.) for permanently or temporarily storing or buffering the processed EEG signal.
- memory 64 may be used as a buffer to temporarily store the processed EEG signal if there are problems with transmitting the data to the external device. For example, if the external device's power supply is low, the memory in the external device is removed, or if the external device is out of communication range with the implantable device, the EEG signals may be temporarily buffered in memory 64 and the buffered EEG signals and the current sampled EEG signals may be transmitted to the external device when the problem has been corrected.
- the external device may be configured to provide a warning or other output signal to the patient to inform them to correct the problem.
- the implantable device may automatically continue the transfer the temporarily buffered data and the real-time EEG data to the memory in the external device.
- the electronic components 30 may optionally comprise dedicated circuitry and/or a microprocessor 62 (referred to herein collectively as “microprocessor”) for further processing of the EEG signals prior to transmission to the external device.
- the microprocessor 62 may execute EEG analysis software, such as a seizure prediction algorithm, a seizure detection algorithm, safety algorithm, or portions of such algorithms, or portions thereof.
- the microprocessor may run one or more feature extractors that extract features from the EEG signal that are relevant to the purpose of monitoring.
- the extracted features may be indicative or predictive of a seizure.
- the microprocessor 62 may send the extracted feature(s) to the transmit/receive sub-system 60 for the wireless transmission to the external device and/or store the extracted feature(s) in memory 64 . Because the transmission of the extracted features is likely to include less data than the EEG signal itself, such a configuration will likely reduce the bandwidth requirements for the communication link between the implantable device and the external device. Since the extracted features do not add a large amount of data to the data signal, in some embodiments, it may also be desirable to concurrently transmit both the extracted feature and the EEG signal. A detailed discussion of various embodiments of the internal/external placement of such algorithms are described in commonly owned U.S. patent application Ser. No. 11/322,150, filed Dec. 28, 2005 to Bland et al., the complete disclosure of which is incorporated herein by reference.
- the electronic components 30 may include a rechargeable or non-rechargeable power supply 66 and an internal clock (not shown).
- the rechargeable or non-rechargeable power supply may be a battery, a capacitor, or the like.
- the rechargeable power supply 66 may also be in communication with the transmit/receive sub-system 60 so as to receive power from outside the body by inductive coupling, radiofrequency (RF) coupling, etc. Power supply 66 will generally be used to provide power to the other components of the implantable device.
- the implanted device may generate and transmit its own signal with the sampled EEG signal for transmission back to the external device. Consequently, as used herein “transmit” includes both passive transmission of a signal back to the external device (e.g., backscattering of the RF signal) and internal generation of a separate signal for transmission back to the external device.
- FIG. 5 is a simplified illustration of some of the components that may be included in external device 14 .
- Antenna 18 and a transmit/receive subsystem 70 will receive a data signal that is encoded with the EEG data (or other physiological data) from the antenna 38 of the implantable device 12 ( FIG. 4 ).
- EEG data may include a raw EEG signal, a processed EEG signal, extracted features from the EEG signal, an answer from an implanted EEG analysis software (e.g., safety, prediction and/or detection algorithm), or any combination thereof.
- the EEG data may thereafter be stored in memory 72 , such as a hard drive, RAM, permanent or removable Flash Memory, or the like and/or processed by a microprocessor 74 or other dedicated circuitry.
- Microprocessor 74 may be configured to request that the implantable device perform an impedance check between the first and second electrodes and/or other calibrations prior to EEG recording and/or during predetermined times during the recording period to ensure the proper function of the system.
- the EEG data may be transmitted from memory 72 to microprocessor 74 where the data may optionally undergo additional processing. For example, if the EEG data is encrypted, it may be decrypted.
- the microprocessor 74 may also comprise one or more filters that filter out high-frequency artifacts (e.g., muscle movement artifacts, eye-blink artifacts, chewing, etc.) so as to prevent contamination of the high frequency components of the sampled EEG signals.
- the microprocessor may process the EEG data to measure the patient's brain state, detect seizures, predict the onset of a future seizure, generate metrics/measurements of seizure activity, or the like.
- the computing power of the system of the present invention may be performed in a computer system or workstation 76 that is separate from the system 10 , and the external device 14 may simply be used as a data collection device.
- the personal computer 76 may be located at the physician's office or at the patient's home and the EEG data stored in memory 72 may be uploaded to the personal computer 76 via a USB interface 78 , removal of the memory (e.g., Flash Memory stick), or other conventional communication protocols, and minimal processing may be performed in the external device 14 .
- the personal computer 76 may contain the filters, decryption algorithm, EEG analysis software, such as a prediction algorithm and/or detection algorithm, report generation software, or the like.
- EEG analysis software such as a prediction algorithm and/or detection algorithm, report generation software, or the like.
- External device 14 may also comprise an RF signal generator 75 that is configured to generate the RF field for interrogating and optionally powering the implanted devices 12 .
- RF generator 75 will be under control of the microprocessor 74 and generate the appropriate RF field to facilitate monitoring and transmission of the sampled EEG signals to the external device.
- External device 14 will typically include a user interface 80 for displaying outputs to the patient and for receiving inputs from the patient.
- the user interface typically comprise outputs such as auditory devices (e.g., speakers) visual devices (e.g., LCD display, LEDs to indicate brain state or propensity to seizure), tactile devices (e.g., vibratory mechanisms), or the like, and inputs, such as a plurality of buttons, a touch screen, and/or a scroll wheel.
- auditory devices e.g., speakers
- visual devices e.g., LCD display, LEDs to indicate brain state or propensity to seizure
- tactile devices e.g., vibratory mechanisms
- the user interface may be adapted to allow the patient to indicate and record certain events.
- the patient may indicate that medication has been taken, the dosage, the type of medication, meal intake, sleep, drowsiness, occurrence of an aura, occurrence of a seizure, or the like.
- Such inputs may be used in conjunction with the recorded EEG data to improve the analysis of the patient's condition and determine the efficacy of the medications taken by the patient.
- the LCD display of the user interface 80 may be used to output a variety of different communications to the patient including, status of the device (e.g., memory capacity remaining), battery state of one or more components of system, whether or not the external device 14 is within communication range of the implantable devices 12 , brain state indicators (e.g., a warning (e.g., seizure warning), a prediction (e.g., seizure prediction), unknown brain state, safety indication, a recommendation (e.g., “take drugs”), or the like).
- a warning e.g., seizure warning
- a prediction e.g., seizure prediction
- unknown brain state e.g., safety indication
- a recommendation e.g., “take drugs”
- the brain state indicators may be separate from the LCD display to as to provide a clear separation between the device status outputs and the brain state indicators.
- the external device may comprise different colored LEDs to indicate different brain states. For example, a green LED may indicate a safe brain state, a yellow light may indicate an unknown brain state, and a red light may indicate either a seizure detection or seizure prediction.
- External device may also include a medical grade power source 82 or other conventional power supply that is in communication with at least one other component of external device 14 .
- the power source 82 may be rechargeable. If the power source 80 is rechargeable, the power source may optionally have an interface for communication with a charger 84 .
- external device 14 will typically comprise a clock circuit (e.g., oscillator and frequency synthesizer) to provide the time base for synchronizing external device 14 and the internal device(s) 12 .
- a clock circuit e.g., oscillator and frequency synthesizer
- the internal device(s) 12 are slaves to the external device and the implantable devices 12 will not have to have an individual oscillator and a frequency synthesizer, and the implantable device(s) 12 will use the “master” clock as its time base. Consequently, it may be possible to further reduce the size of the implantable devices.
- one or more of the implantable devices are implanted in the patient.
- the implanted device is interrogated and powered so that the EEG signals are sampled from the patient's brain.
- the EEG signals are processed by the implanted device and the processed EEG signals are wirelessly transmitted from the implanted device(s) to an external device.
- the EEG signals are stored for future or substantially real-time analysis.
- the implantable devices are implanted in a minimally invasive fashion under the patient's scalp and above an outer surface of the skull.
- FIG. 6 illustrates a simplified introducer assembly 90 that may be used to introduce the implantable devices into the patient.
- the introducer assembly 90 is typically in the form of a cannula and stylet or a syringe-like device that can access the target area and inject the implanted device under the skin of the patient.
- the implantable devices 12 are preferably implanted beneath at least one layer of the patient's scalp and above the patient's skull. Because of the small size of the implantable devices 12 , the devices may be injected into the patient under local anesthesia in an out-patient procedure by the physician or neurologist.
- implantable devices are implanted entirely beneath the skin infection risk would be reduced and there would be minimal cosmetic implications. Due to the small size of the implantable devices 12 , it may be desirable to have a plurality of implantable devices pre-loaded into a sterile introducer assembly 90 or into a sterile cartridge (not shown) so as to minimize the risk of contamination of the implantable devices 12 prior to implantation.
- FIG. 7 schematically illustrates one example of a minimally invasive method 100 of implanting the implantable devices for ambulatory monitoring of a patient's EEG signals.
- an incision is made in the patient's scalp.
- an introducer assembly is inserted into the incision and a distal tip of the introducer assembly is positioned at or near the target site.
- the introducer assembly itself may be used to create the incision.
- the syringe tip may be made to create the incision and steps 102 and 104 may be consolidated into a single step.
- the introducer assembly is actuated to inject the implantable device 12 to the target site.
- the introducer may be repositioned to additional target sites underneath the patient's skin and above the skull. If needed, additional incisions may be created in the patient's skin to allow for injection of the implantable device 12 at the additional target sites.
- the introducer assembly is removed from the target site.
- the implantable devices are activated and used to perform long term monitoring of the patient's EEG signals from each of the target sites.
- the sampled EEG signals are then wirelessly transmitted to an external device.
- the sampled EEG signals may then be stored in a memory in the external device or in another device (e.g., personal computer). If desired, the EEG signals may then be processed in the external device or in a personal computer of the physician.
- anchoring may be performed with tissue adhesive, barbs or other protrusions, sutures, or the like.
- the implantable devices are able to monitor EEG signals from the patient without the use of burr holes in the skull or implantation within the brain—which significantly reduces the risk of infection for the patient and makes the implantation process easier. While there is some attenuation of the EEG signals and movement artifacts in the signals, because the implantable devices are below the skin, it is believed that there will be much lower impedance than scalp electrodes. Furthermore, having a compact implantable device 14 below the skin reduces common-mode interference signals which can cause a differential signal to appear due to any imbalance in electrode impedance and the skin provides some protection from interference caused by stray electric charges (static).
- FIG. 7 illustrates one preferred method of implanting the implantable devices in the patient and using the implantable devices to monitor the patient's EEG
- the present invention is not limited to such a method, and a variety of other non-invasive and invasive implantation and monitoring methods may be used.
- minimally invasive monitoring is the preferred method
- the systems and devices of the present invention are equally applicable to more invasive monitoring.
- intracranial EEG signals e.g., ECoG
- it may be possible to implant one or more of the implantable devices inside the patient's skull e.g., in the brain, above or below the dura mater, or a combination thereof
- ECoG intracranial EEG signals
- the monitoring systems 10 of the present invention may be used for a variety of different uses.
- the systems of the present invention may be used to diagnose whether or not the patient has epilepsy.
- Patients are often admitted to video-EEG monitoring sessions in an EMU to determine if the patient is having seizures, pseudo-seizures, or is suffering from vaso-vagal syncope, and the like.
- the patient has infrequent “seizures,” it is unlikely that the short term stay in the EMU will record a patient's seizure and the patient's diagnose will still be unclear.
- the patient may undergo an ambulatory, long term monitoring of the patient's EEG using the system of the present invention for a desired time period.
- the time period may be one day or more, a week or more, one month or more, two months or more, three months or more, six months or more, one year or more, or any other desired time period in between.
- the patient may be implanted with the system 10 using the method described above, and after a predetermined time period, the patient may return to the physician's office where the EEG data will be uploaded to the physician's personal computer for analysis.
- a conventional or proprietary seizure detection algorithm may be applied to the EEG data to determine whether or not a seizure occurred in the monitoring time period. If it is determined that one or more seizures occurred during the monitoring period, the seizure detection algorithm may be used to provide an output to the physician (and/or generate a report for the patient) indicating the occurrence of one or more seizures, and various seizure activity metrics, such as spike count over a period of time, seizure count over a period of time, average seizure duration over a period of time, the pattern of seizure occurrence over time, and other seizure and seizure related metrics.
- the software may be used to display the actual EEG signals from specific events or selected events for physician confirmation of seizure activity. Such data may be used as a “baseline” for the patient when used in assessing efficacy of AEDs or other therapies that the patient will undergo.
- the present invention may also be used to determine the epilepsy classification and/or seizure type.
- a desired number of implantable devices may be implanted in the patient for the long term monitoring of the patient's pattern of electrical activity in the different portions of the patient's brain. Such monitoring will be able to provide insight on whether or not the patient has partial/focal seizures or generalized seizures.
- the classification may determine the desired placement for the implantable devices in the patient.
- the implantable devices will likely be focused over the temporal lobe and adjacent and/or over the regions of epileptiform activity.
- some or all of the implantable devices will be positioned over the parietal lobe and adjacent and/or over the regions of epileptiform activity.
- the seizure focus or foci are known, at least some of the implantable devices may be positioned over the seizure focus or foci and some may be positioned contralateral to the known seizure focus or foci.
- FIG. 8 illustrates one method 120 of lateralizing a seizure focus in a patient.
- a set of implantable devices are implanted beneath at least one layer of the patient's scalp and above the patient's skull (or below the skull, if desired).
- the implantable devices will comprise more than two electrodes to improve the ability to localize the seizure focus. For embodiments that only include two electrodes, a very large number of implantable devices may be required to actually localize the seizure focus.
- implantation may be carried out using the method steps 102 - 108 illustrated in FIG. 7 .
- the set of implantable devices are used to sample the patient's EEG signals.
- each of the EEG signals from the implantable devices are analyzed over a period of time (e.g., with EEG analysis software, such as a seizure detection algorithm) to monitor the patient's seizure activity and once a seizure has occurred try to lateralize the seizure focus.
- EEG analysis software such as a seizure detection algorithm
- the seizure focus is lateralized, a subset of the implantable devices that are lateralized to the seizure focus are identified.
- the EEG signals from the subset of implantable may continue to be sampled, and such EEG signals may thereafter be stored and processed to analyze the patient's brain activity.
- the implantable devices that are not lateralized to the focus may be removed from the patient, disabled, or the EEG signals from such implantable devices may be ignored or not captured/stored. However, if desired, such EEG signals may continue to be stored and processed.
- the location and/or lateralization o the seizure focus may thereafter be used by the physicians to determine whether or not the patient is a candidate for resective surgery or other procedures.
- the present invention may be used to quantify seizure activity statistics for the patient.
- the most common method of quantifying a patient's seizure activity is through patient self reporting using a seizure diary. Unfortunately, it has been estimated that up to 63% of all seizures are missed by patients. Patient's missing the seizures are usually caused by the patients being amnesic to the seizures, unaware of the seizures, mentally incapacitated, the seizures occur during sleep, or the like.
- FIG. 9 illustrates a simplified method 140 of measuring and reporting a patient's seizure activity statistics.
- one or more implantable devices are implanted in a patient, typically in a minimally invasive fashion as shown in FIG. 7 .
- the implantable devices are used to substantially continuously sample EEG signals from the patient.
- the sampled EEG signals are wirelessly transmitted from the implantable device to an external device.
- the sampled EEG signals are stored in a memory.
- the stored EEG signals are analyzed with EEG analysis software, typically using a seizure prediction and/or detection algorithm, to derive statistics for the clinical seizures and/or the sub-clinical seizures for the patient based on the long-term, ambulatory EEG data. For example, the following statistics may be quantified using the present invention:
- report generation software may be used to generate a report based on the statistics for the seizure activity.
- the report may include some or all of the statistics described above, an epilepsy/no epilepsy diagnosis, identification of a seizure focus, and may also include the EEG signal(s) associated with one or more of the seizures.
- the report may include text, graphs, charts, images, or a combination thereof so as to present the information to the physician and/or patient in an actionable format.
- the systems may be used to generate a baseline report for the patient, and the system may be continuously used to record data over a long period of time and provide a quantification of the patient's change in their condition and/or the efficacy of any therapy that the patient is undergoing (described in more detail below).
- the present invention enables the documentation and long term monitoring of sub-clinical seizures in a patient. Because the patient is unaware of the occurrence of sub-clinical seizures, heretofore the long term monitoring of sub-clinical seizures was not possible. Documentation of the sub-clinical seizures may further provide insight into the relationship between sub-clinical seizures and clinical seizures, may provide important additional information relevant to the effectiveness of patient therapy, and may further enhance the development of additional treatments for epilepsy.
- FIG. 10 illustrates one exemplary method of how the seizure activity data may be used to evaluate the efficacy or clinical benefit of a current or potential therapy and allow for the intelligent selection of an appropriate therapy for an individual patient and/or stopping the usage of ineffective therapies.
- effectiveness of the AED therapy is based on self-reporting of the patient, in which the patient makes entries in a diary regarding the occurrence of their seizure(s). If the entries in the patient diary indicate a reduction in seizure frequency, the AED is deemed to be effective and the patient continues with some form of the current regimen of AEDs.
- the AEDs are deemed to be ineffective, and typically another AED is prescribed—and most often in addition to the AED that was deemed to be ineffective. Because AEDs are typically powerful neural suppressants and are associated with undesirable side-effects, the current methodology of assessing the efficacy of the AEDs often keeps the patient on ineffective AEDs and exposes the patient to unnecessary side-effects.
- a medically refractory patient coming to an epilepsy center for the first time might first have the system of the present invention implanted and then asked to collect data for a prescribed time period, e.g., 30 days.
- the initial 30 days could be used to establish a baseline measurement for future reference.
- the physician could then prescribe an adjustment to the patient's medications and have the patient collect data for another time period, e.g., an additional 30 day period.
- Metrics from this analysis could then be compared to the previous analysis to see if the adjustment to the medications resulted in an improvement. If the improvement was not satisfactory, the patient can be taken off of the unsatisfactory medication, and a new medication could be tried. This process could continue until a satisfactory level of seizure control was achieved.
- the present invention provides a metric that allows physicians and patients to make informed decisions on the effectiveness and non-effectiveness of the medications.
- FIG. 10 schematically illustrates one example of such a method.
- one or more implantable devices are implanted in the patient, typically in a minimally-invasive fashion.
- the one or more implantable devices are used to monitor the patient's EEG to obtain a baseline measurement for the patient.
- the baseline measurement is typically seizure activity statistics for a specific time period (e.g., number of seizures, seizure duration, seizure pattern, seizure frequency, etc.).
- the baseline measurement may include any number of types of metrics.
- the baseline metric may include univariate, bivariate, or multivariate features that are extracted from the EEG, or the like.
- the baseline measurement is performed while the patient is not taking any AEDs or using any other therapy. In other embodiments, however, the patient may be taking one or more AEDs and the baseline measurement will be used to evaluate adjustments to dosage or efficacy of other add-on therapies.
- the therapy that is to be evaluated is commenced.
- the therapy will typically be an AED and the patient will typically have instructions from the neurologist, epileptologist, or drug-manufacturer regarding the treatment regimen for the AED.
- the treatment regimen may be constant (e.g., one pill a day) throughout the evaluation period, or the treatment regimen may call for varying of some parameter of the therapy (e.g., three pills a day for the first week, two pills a day for the second week, one pill a day for the third week, etc.) during the evaluation period.
- the implantable device(s) will be used to substantially continuously sample the patient's EEG and assess the effect that the AED has on the patient's EEG.
- the sampled EEG may thereafter be processed to obtain a follow-up measurement for the patient (Step 168 ). If the baseline measurement was seizure statistics for the baseline time period, then the follow-up measurement will be the corresponding seizure statistics for the evaluation period. At step 170 , the baseline measurement is compared to the follow-up measurement to evaluate the therapy. If the comparison indicates that the therapy did not significantly change the patient's baseline, the therapy may be stopped, and other therapies may be tried.
- the primary metric in evaluating the efficacy of an AED is whether or not the AED reduces the patient's seizure count.
- the systems of the present invention would be able to track any reduction in seizure duration, modification in seizure patterns, reduction in seizure frequency, or the like. While seizure count is important, because the present invention is able to provide much greater detail than just seizure count, efficacy of an AED may be measured using a combination of additional metrics, if desired.
- the systems of the present invention would be able to provide metrics for such a situation.
- the patient and physician would not be aware of such a reduction, and such an AED would be determined to be non-efficacious for the patient.
- the present invention is able to provide metrics for the sub-clinical seizures, the efficacious medication could be continued, if desired.
- the epileptologist or neurologist may decide to change one or more parameters of the therapy. For example, they may change a dosage, frequency of dosage, form of the therapy or the like, and thereafter repeat the follow-up analysis for the therapy with the changed parameter.
- the second follow up data may be obtained and thereafter compared to the “first” follow up measurements and/or the baseline measurements.
- the method may also comprise generating a report that details the patient's metrics, change in metrics, recommendations, etc.
- the metrics that are provided by the present invention also enable an intelligent titration of a patient's medications.
- the present invention may be used to reduce/titrate a dosage or frequency of intake of the AED or AEDs, or other pharmacological agents.
- one or more implantable devices are minimally invasively implanted in the patient.
- the patient will already be on a treatment regimen of the efficacious therapy, but if not, the efficacious therapy is commenced with the prescribed parameters, e.g., “standard” dosage (Step 184 ).
- the patient's EEG (and/or other physiological signal) is monitored for a desired time period to obtain a first patient data measurement for the patient (e.g., the baseline measurement).
- the first patient data measurement may be any desired metrics, but will typically be clinical seizure frequency, clinical seizure duration, sub-clinical seizure frequency, sub-clinical seizure duration, medication side effects.
- the first efficacious therapy is stopped and a therapy with at least one changed parameter is started (referred to as “therapy with second parameters” in FIG. 11 ).
- the changed parameter will be a reduction in dosage, but it could be changing a frequency of the same dosage, a change in formulation or form of the same AED, or the like.
- the patient's EEG is monitored and processed to obtain a second patient data measurement for the patient (e.g., follow-up data measurement). If the neurologist or epileptologist is satisfied with the results, the titration may end. But in many embodiments, the titration process will require more than one modification of parameters of the therapy.
- the second therapy is stopped (step 192 ), and a therapy with N th parameters (e.g., third, fourth, fifth . . . ) is commenced (step 194 ).
- Monitoring and processing of the patient's EEG signals are repeated (step 196 ), and the process is repeated a desired number of times (as illustrated by arrow 197 ).
- the various patient data measurements may be analyzed (e.g., compared to each other) to determine the most desirous parameters for the therapy (step 198 ).
- seizure activity statistics e.g., clinical seizure frequency, sub-clinical seizure frequency, seizure rate per time period, seizure duration, seizure patterns, etc.
- seizure activity statistics may be used to assess the efficacy and differences between the therapies.
- the process of selecting appropriate AEDs and the titration of dosages of such AEDs could occur much faster and with much greater insight than ever before. Further, the chance of a patient remaining on an incremental AED that was providing little incremental benefit would be minimized. Once a patient was under control, the patient could cease the use of the system, but the implantable device could remain in the patient. In the future, the patient might be asked to use the system again should their condition change or if the efficacy of the AED wane due to tolerance effects, etc.
- FIGS. 10 and 11 are primarily directed toward assessing the efficacy of a pharmacological agent (e.g., AED), such methods are equally applicable to assessing the efficacy and optimizing patient-specific parameters of non-pharmacological therapies.
- the present invention may also be used to evaluate and optimize parameters for the electrical stimulation provided by the Vagus Nerve Stimulator (sold by Cyberonics Corporation), Responsive Neurostimulator (RNS) (manufactured by NeuroPace Corporation), Deep Brain Stimulators (manufactured by Medtronic), and other commercial and experimental neural and spinal cord stimulators.
- the systems of the present invention will also be able to provide metrics for the effectiveness of changes to various electrical parameters (e.g., frequency, pulse amplitude, pulse width, pulses per burst, burst frequency, burst/no-burst, duty cycle, etc.) for the electrical stimulation treatments.
- metrics will provide a reliable indication regarding the effectiveness of such parameter changes, and could lead to optimization of stimulation for parameters for individual patients or the patient population as a whole.
- the present invention may have beneficial use in the clinical trials for the development of experimental AEDs and other therapies for the epileptic patient population (and other neurological conditions).
- One of the greatest barriers to developing new AEDs (and other pharmacological agents) is the costs and difficulties associated with the clinical trials.
- the standard metric for such clinical trials is patient seizure count. Because this metric is self-reported and presently so unreliable, to power the study appropriately clinical trials for AEDs must involve very large patient populations, in which the patient's must have a high seizure count. At an estimated cost of $20,000 per patient for pharmacological trials, the cost of developing a new drug for epilepsy is exceedingly high and may deter drug companies from developing AEDs.
- the minimally invasive systems of the present invention may be used to facilitate these clinical trials. Such systems could result in significantly more reliable data, which would result in much smaller sample patient populations, and could include a broader types of patients (e.g., patient's who don't have frequent seizures) for appropriately powering the study. Improved certainty in efficacy would also reduce risk to the company, as it moved from safety studies to efficacy studies. Significantly reducing risk and improving the economics of these studies by reducing the required number of study subjects could lead to an increase in the development of new therapies for this patient population, and other patient populations.
- the present invention is not limited to clinical trials for epilepsy therapies, and the present invention has equal applicability to other clinical trials (e.g., cancer therapy, cardiac therapy, therapy for other neurological disorders, therapy for psychiatric disorders, or the like.)
- FIGS. 12-13 illustrate some methods of performing clinical trials that are encompassed by the present invention.
- the present invention is applicable to any type of clinical trial, including but not limited to a randomized clinical trial, e.g., an open clinical trial, a single-blinded study, a double-blinded study, a triple-blinded study, or the like.
- FIG. 12 illustrates a simplified method 200 of performing a clinical trial according to the present invention.
- participants are enrolled in the clinical trial.
- selected participants in the clinical trial are implanted with one or more leadless, implantable devices (such as those described above) in order to sample one or more physiological signal from the patient.
- the physiological signal is an EEG signal.
- the EEG signal is sampled substantially continuously for the entire baseline period for each of the participants in the clinical trial. In alternative embodiments, it may be desirable to sample the EEG signals in a non-continuous basis.
- a “second” evaluation period (and a second follow-up measurement) in which at least one parameter of the experimental therapy is changed and the changed experimental therapy is administered to the patient. Similar to the method of FIG. 11 , such a method may provide guidance to finding the appropriate dosing, formulation, and/or form of delivery of the experimental therapy.
- the baseline period and the evaluation period are typically the same time length.
- the time length may be any desired time, but is typically at least one week, and preferably between at least one month and at least three months.
- Evaluation of the experimental therapy may be to evaluate dosing requirements, evaluate toxicity of the experimental therapy, evaluate long-term adverse effects of the experimental therapy or to determine efficacy of the experimental therapy.
- the comparison may simply determine whether there was a statistically significant change in a seizure count between the baseline period and the evaluation period.
- the baseline data measurement and follow-up data measurement may include any metric that is extracted from the EEG signals.
- FIG. 13 illustrates a more detailed method of performing a clinical trial according to the present invention.
- participants are enrolled in the clinical trial.
- the participants in the clinical trial are implanted with one or more leadless, implantable devices (such as those described above) in order to sample one or more physiological signal from the patient.
- the physiological signal is an EEG signal.
- the EEG signal is sampled substantially continuously for the entire baseline period for each of the participants in the clinical trial.
- the sampled EEG signals are processed to obtain a first patient data measurement, e.g., a baseline data measurement, for each of the participants in the clinical trial. If the patient's do not have any seizures during the baseline period, then the patient's will most likely be excluded from the remainder of the clinical trial. The remaining participants in the clinical trial are then broken into an intervention group and a control group. The experimental therapy is commenced in the intervention group of the patient population (step 228 ), and a placebo therapy is commenced in the control group of the patient population (step 230 ).
- a first patient data measurement e.g., a baseline data measurement
- the implantable devices are used to substantially continuously sample the EEG signals of both the intervention group and the control group during an evaluation period.
- the EEG signals are processed to obtain follow-up seizure activity data (or some other metric) for both groups (step 232 , 234 ).
- the baseline data and the follow up data for both the intervention group and the control group are analyzed, (e.g., compared with each other) to evaluate the efficacy of the experimental therapy for the patient population (step 236 ).
- the method may further include changing one or more parameters of the experimental therapy and comparing the “second” follow up data to the baseline data and/or other follow up data.
- the present invention is equally applicable to clinical trials for other experimental pharmacological agents, biologics, devices, and other non-pharmacological therapies.
- the present invention may also be used to evaluate the Vagus Nerve Stimulator (sold by Cyberonics Corporation), Responsive Neurostimulator (RNS) (manufactured by NeuroPace Corporation), Deep Brain Stimulators manufactured by Medtronic, and other commercial and experimental neural and spinal cord stimulators.
- the minimally invasive systems of the present invention may be implanted in patients who are equipped with any of the above stimulators to provide metrics regarding the efficacy of the electrical stimulation treatments.
- FIG. 14 illustrates a packaged system or kit 300 that is encompassed by the present invention.
- the packaged system 300 may include a package 302 that has one or more compartments for receiving an introducer assembly 304 and one or more implantable devices 12 .
- the introducer 304 is typically in the form of a syringe-like device or a cannula and stylet.
- the implantable device 12 may include any of the embodiments described herein.
- One or more of the implantable devices 12 may be pre-loaded within the introducer 304 .
- the implantable devices 12 may be loaded in its separate sterile packaging (shown in dotted lines) for easy loading into the introducer 304 .
- the packaged system 300 may include instructions for use (“IFU”) 306 that describe any of the methods described herein.
- Alternative embodiments of the implantable device of the present invention may require a neurosurgeon to create a more invasive incision in the patient's scalp.
- a neurosurgeon may be desirable to use a low profile device that is not substantially cylindrical, but instead is substantially planar or concave so as to conform to the curvature of the patient's skull.
- Such embodiments would likely not be able to be implanted without general anesthesia and may require a surgeon to implant the device.
- Such embodiments include “implantable” devices 12 that are not actually implanted, but instead are “wearable” and may be attached to the outer surface of the skin with adhesive or a bandage so as to maintain contact with the patient's skin. For example, it may be possible to surface mount the device 12 behind the ears, in the scalp, on the forehead, along the jaw, or the like. Because the electrodes are wireless and are such a small size, unlike conventional electrodes, the visual appearance of the electrodes will be minimal.
- the implantable device 12 will include a pulse generator and associated hardware and software for delivering stimulation to the patient through the first and second electrodes 24 , 26 (or other electrodes coupled to the device.
- the external device 14 will include the hardware and software to generate the control signals for delivering the electrical stimulation to the patient.
- power to the implanted devices may be derived wirelessly from an external device and/or from a battery in the implanted device
- the internal devices may derive or otherwise “scavenge” power from other types of conventional or proprietary assemblies.
- Such scavenging methods may be used in conjunction with the external power source and/or the internal power source, or it may be used by itself to provide the necessary power for the implanted devices.
- the implanted devices may include circuitry and other assemblies (e.g., a microgenerator) that derive and store power from patient-based energy sources such as kinetic movement/vibrations (e.g., gross body movements), movement of organs or other bodily fluids (e.g., heart, lungs, blood flow), and thermal sources in the body (e.g., temperature differences and variations across tissue).
- patient-based energy sources such as kinetic movement/vibrations (e.g., gross body movements), movement of organs or other bodily fluids (e.g., heart, lungs, blood flow), and thermal sources in the body (e.g., temperature differences and variations across tissue).
- kinetic movement/vibrations e.g., gross body movements
- organs or other bodily fluids e.g., heart, lungs, blood flow
- thermal sources in the body e.g., temperature differences and variations across tissue.
- the monitoring system may include an integral patient diary functionality.
- the patient diary may be a module in the external device and inputs by the patient may be used to provide secondary inputs to provide background information for the sampled EEG signals. For example, if a seizure is recorded, the seizure diary may provide insight regarding a trigger to the seizure, or the like.
- the diary may automatically record the time and date of the entry by the patient. Entries by the patient may be a voice recording, or through activation of user inputs on the external device.
- the diary may be used to indicate the occurrence of an aura, occurrence of a seizure, the consumption of a meal, missed meal, delayed meal, activities being performed, consumption of alcohol, the patient's sleep state (drowsy, going to sleep, waking up, etc.), mental state (e.g., depressed, excited, stressed), intake of their AEDs, medication changes, missed dosage of medication, menstrual cycle, illness, or the like.
- the patient inputs recorded in the diary may also be used by the physician in assessing the patient's epilepsy state and/or determine the efficacy of the current treatment.
- the physician may be able to compare the number of seizures logged by the patient to the number of seizures detected by the seizure detection algorithm.
Abstract
Description
- The present application claims benefit of U.S. Provisional Patent Application Ser. No. 60/805,710, filed Jun. 23, 2006, to Harris et al., entitled “Implantable Ambulatory Brain Monitoring System,” the complete disclosure of which is incorporated herein by reference.
- The present invention relates generally to systems and methods for sampling one or more physiological signals from a patient. More specifically, the present invention relates to long term, ambulatory monitoring and analysis of one or more neurological signals from a patient using a minimally invasive system to estimate the patient's propensity for a seizure.
- Epilepsy is a disorder of the brain characterized by chronic, recurring seizures. Seizures are a result of uncontrolled discharges of electrical activity in the brain. A seizure typically manifests itself as sudden, involuntary, disruptive, and often destructive sensory, motor, and cognitive phenomena. Seizures are frequently associated with physical harm to the body (e.g., tongue biting, limb breakage, and burns), a complete loss of consciousness, and incontinence. A typical seizure, for example, might begin as spontaneous shaking of an arm or leg and progress over seconds or minutes to rhythmic movement of the entire body, loss of consciousness, and voiding of urine or stool.
- A single seizure most often does not cause significant morbidity or mortality, but severe or recurring seizures (epilepsy) results in major medical, social, and economic consequences. Epilepsy is most often diagnosed in children and young adults, making the long-term medical and societal burden severe for this population of patients. People with uncontrolled epilepsy are often significantly limited in their ability to work in many industries and usually cannot legally drive an automobile. An uncommon, but potentially lethal form of seizure is called status epilepticus, in which a seizure continues for more than 30 minutes. This continuous seizure activity may lead to permanent brain damage, and can be lethal if untreated.
- While the exact cause of epilepsy is often uncertain, epilepsy can result from head trauma (such as from a car accident or a fall), infection (such as meningitis), or from neoplastic, vascular or developmental abnormalities of the brain. Most epilepsy, especially most forms that are resistant to treatment (i.e., refractory), are idiopathic or of unknown causes, and is generally presumed to be an inherited genetic disorder.
- If it is assumed that an “average” subject with focal epilepsy has between 3 and 4 seizures per month, in which each of the seizures last for several seconds or minutes, the cumulative time the subject would be seizing is only about one hour per year. The other 99.98% of the year, the epileptic subject is free from seizures. The debilitating aspect of epilepsy is not necessarily the seizures themselves, but rather the fear and uncertainly of when the next seizure is going to occur. The risk of social embarrassment resulting from unforewarned seizures causes epileptic subjects to remove themselves from society. The danger posed by unforewarned seizures often prevents epileptic subjects from performing activities that most non-epileptic subjects take for granted.
- To that end, there have been a number of proposals from groups around the world for predicting seizures and warning the subject of the impending seizure. Most of such proposals attempt to analyze the subject's electroencephalogram or electrocorticograms (referred to collectively as “EEGs”), detect or predict the onset of the seizure. Unfortunately, many of the proposed systems are highly invasive and such invasiveness could reduce the number of patients that would take advantage of such technology.
- It would be particularly advantageous if such systems could provide for substantially continuous monitoring of the patient and be implemented in a minimally invasive manner. Consequently, what are needed are methods and systems that are capable of long-term, out-patient monitoring of epileptic patients. It would further be desirable if the long-term monitoring would facilitate real time estimation and communication to the patient of the patient's propensity for a seizure. It would also be desirable to have system that could record seizure activity, to enable the meaningful study of the patient's condition by the physician.
- The present invention provides methods and systems for monitoring one or more physiological signals from the patient. In preferred embodiments, the present invention provides minimally-invasive systems that provide for the long-term, ambulatory monitoring of patient's brain activity to facilitate the estimation of the patients propensity for a neurological event (e.g., seizure, migraine headache, episode of depression, etc.). The systems of the present invention will typically include one or more implantable devices that are capable of sampling and transmitting a signal that is indicative of the patient's brain activity to a data collection device that is external to the patient's body.
- The ambulatory systems of the present invention provide for substantially continuous sampling of brain wave electrical signals (e.g., electroencephalography or “EEG” and electrocorticogram “ECoG”, which are hereinafter referred to collectively as “EEG”). A patient could wear their external data collection device at all times of the day (except while showering, etc.). At the physicians' office, the data from the external data collection device could be uploaded into a physician's computer, which could then automatically analyze the stored EEG data and calculate certain metrics that would provide insight into the patient's condition. For example, such metrics may allow the epileptologist to assess seizure frequency, monitor for sub-clinical seizures, determine the efficacy of treatment, determine the effect of adjustments of the dosage of the AED, determine the effects of adjustments of the type of AED, adjust parameters of electrical stimulation, or the like.
- The systems of the present invention typically include one or more low power implantable devices for sampling the patient's EEG signal. The implantable devices are in communication with a device that is external to the patient's body which comprises algorithms that estimate the patient's propensity for a neurological event. The external device is typically configured to transmit power into the implantable device and to store the EEG signal that is sampled by the implantable device. The implantable device and the external device will be in communication with each other through a wireless communication link. While any number of different wireless communication links may be used, in preferred embodiments the systems of the present invention uses a high-frequency communication link. Such a communication link enables transmission of power into the implantable device and facilitates data transfer to and from the implantable device.
- In one aspect, the present invention provides a minimally invasive method for monitoring a patient who has neurological condition. The method comprises sampling brain activity signals with the one or more implanted devices that are positioned between at least one layer of scalp and the skull of the patient and wirelessly transmitting a data signal that is encoded with data indicative of the sampled brain activity signals from the one or more implanted devices to an external device. The data signal is processed in a processing assembly of the external device to estimate the patient's propensity for a neurological event and an output is generated in response to the processing of the data signal.
- The output from the external device may be a control signal to an implanted therapy device—such as the implanted devices or to an independent therapy device (such as a vagus nerve stimulator, spinal cord stimulator, cortical stimulator, deep brain stimulator, cranial nerve stimulator, implanted drug pump, etc.). In other embodiments, the output from the external device may be delivered to a user interface so as to provide an output communication to the patient that indicates the patient's propensity for the neurological event.
- The neurological event includes, but is not limited to, a seizure, a migraine headache, an episode of depression, a tremor, or the like.
- In some embodiments, the one or more implanted devices are leadless. Some of the devices are passive or semi-passive and are at least partly energized by an externally generated signal field. In one configuration, the external field is generated by a generator in the external device. The generator is typically a radiofrequency generator, but other types of wireless signals may be used to generate a signal that energizes and interrogates the implanted devices. The external device may be configured to provide an output communication when the data signal from the one or more implanted devices are not being received by the external device.
- The sampling of the brain activity signals is typically performed on a substantially continuous basis so as to provide substantially continuous monitoring of the patient's neurological condition. In preferred embodiments, the external device comprises a memory that is used to store at least some of the substantially continuous brain activity signals. The brain activity signals may be encrypted prior to transmission to maintain patient confidentiality and stored either encrypted or in a unencrypted format.
- In another aspect, the present invention provides a minimally invasive method of monitoring a patient's propensity for a neurological event. The method comprises transmitting a signal from an external device that is configured to interrogate and provide power to one or more implanted devices that are positioned in between one or more layers of the patient's scalp and skull. The external device receives a wireless data signal from the one or more implanted leadless devices that are encoded with data indicative of sampled brain activity signals. The received data signal is derived from the transmitted signal from the external device. The data signal is processed in a processing assembly of the external device to estimate the patient's propensity for the neurological event and an output communication is provided to the patient that provides a real time indication of the patient's propensity for the neurological event.
- The output communication to the patient that indicates the patient's propensity for the neurological event is typically performed on a substantially continuous basis so as to provide substantially continuous communication to the patient regarding their propensity for the neurological condition.
- The neurological event includes, but is not limited to, a seizure, a migraine headache, an episode of depression, a tremor, or the like.
- In some embodiments, the one or more implanted devices are leadless. Some of the devices are passive or semi-passive and are at least partly energized by an externally generated signal field. In one configuration, the external field is generated by a generator in the external device. The generator is typically a radiofrequency generator, but other types of wireless signals may be used to generate a signal that energizes and interrogates the implanted devices. The external device may be configured to provide an output communication when the data signal from the one or more implanted devices are not being received by the external device.
- In preferred embodiments, the external device comprises a memory that is used to store at least some of the substantially continuous brain activity signals. The brain activity signals may be encrypted prior to transmission to maintain patient confidentiality and stored either encrypted or in a unencrypted format.
- In yet another aspect, the present invention provides a minimally invasive method of monitoring a patient's EEG signals for use in monitoring a patient's propensity for a neurological event. The method comprises receiving a substantially continuous interrogation signal in an implanted device that is positioned between at least one layer of the patient's scalp and skull from a device external to the patient's body. In response to the interrogation signal the implanted device substantially continuously samples an EEG signal from the patient. A wireless data signal encoded with data that is indicative of the sampled EEG signal is transmitted from the patient to the device external to the patient's body, wherein the sampled EEG signal is processed in the external device to provide a real-time of estimate the patient's propensity for a neurological event.
- The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:
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FIG. 1A illustrates a simplified system embodied by the present invention which comprises one or more implantable devices in communication with an external device. -
FIG. 1B illustrates simplified methods of operating the system of the present invention. -
FIG. 2A illustrates a bottom view of one embodiment of an active implantable device that is encompassed by the present invention. -
FIG. 2B illustrates a cross-sectional view of the active implantable device ofFIG. 2A along lines B-B. -
FIG. 2C is a linear implantable device that comprises a plurality of electrode contacts in which at least one electrode contact comprises the active implantable device ofFIG. 2A . -
FIG. 2D is a cross sectional view of the implantable device ofFIG. 2C along lines D-D. -
FIG. 2E is a 4×4 electrode array that comprises a plurality of electrode contacts in which at least one electrode contact comprises the active implantable contact ofFIG. 2A . -
FIG. 3A is a cross-sectional view of another embodiment of an implantable device that is encompassed by the present invention. -
FIG. 3B is a cross-sectional view of another embodiment of the implantable device in which a conductive can forms a housing around the electronic components and acts as an electrode. -
FIG. 3C illustrates a simplified plan view of an embodiment that comprises four electrodes disposed on the implanted device. -
FIG. 4 illustrates one embodiment of the electronic components that may be disposed within the implantable device. -
FIG. 5 is a block diagram illustrating one embodiment of electronic components that may be in the external device. -
FIG. 6 illustrates a simplified trocar or needle-like device that may be used to implant the implantable device beneath the patient's skin. -
FIG. 7 illustrates a method of inserting an implantable device in the patient and wirelessly sampling EEG signals from a patient. -
FIG. 8 illustrates a method of lateralizing a seizure focus. -
FIG. 9 illustrates a method of measuring seizure activity data for clinical and/or sub-clinical seizures. -
FIG. 10 illustrates a method of evaluating efficacy of a therapy. -
FIG. 11 illustrates a method of titrating an efficacious therapy. -
FIG. 12 illustrates a simplified method of performing a clinical trial. -
FIG. 13 illustrates a more detailed method of performing a clinical trial. -
FIG. 14 is a kit that is encompassed by the present invention. - Certain specific details are set forth in the following description and figures to provide an understanding of various embodiments of the invention. Certain well-known details, associated electronics and devices are not set forth in the following disclosure to avoid unnecessarily obscuring the various embodiments of the invention. Further, those of ordinary skill in the relevant art will understand that they can practice other embodiments of the invention without one or more of the details described below. Finally, while various processes are described with reference to steps and sequences in the following disclosure, the description is for providing a clear implementation of particular embodiments of the invention, and the steps and sequences of steps should not be taken as required to practice this invention.
- The term “condition” is used herein to generally refer to the patient's underlying disease or disorder—such as epilepsy, depression, Parkinson's disease, headache disorder, etc. The term “state” is used herein to generally refer to calculation results or indices that are reflective a categorical approximation of a point (or group of points) along a single or multi-variable state space continuum of the patient's condition. The estimation of the patient's state does not necessarily constitute a complete or comprehensive accounting of the patient's total situation. As used in the context of the present invention, state typically refers to the patient's state within their neurological condition. For example, for a patient suffering from an epilepsy condition, at any point in time the patient may be in a different states along the continuum, such as an ictal state (a state in which a neurological event, such as a seizure, is occurring), a pre-ictal state (which is a neurological state that immediately precedes the ictal state), a pro-ictal state (a state in which the patient has an increased risk of transitioning to the ictal state), an inter-ictal state (a state in between ictal states), a contra-ictal state (a protected state in which the patient has a low risk of transitioning to the ictal state within a calculated or predetermined time period), or the like. A pro-ictal state may transition to either an ictal or inter-ictal state. A pro-ictal state that transitions to an ictal state may also be referred to herein as a “pre-ictal state.”
- The estimation and characterization of “state” may be based on one or more patient dependent parameters from the a portion of the patient's body, such as electrical signals from the brain, including but not limited to electroencephalogram signals and electrocorticogram signals “ECoG” or intracranial EEG (referred to herein collectively as EEG“), brain temperature, blood flow in the brain, concentration of AEDs in the brain or blood, changes thereof, etc.). While parameters that are extracted from brain-based signals are preferred, the present invention may also extract parameters from other portions of the body, such as the heart rate, respiratory rate, blood pressure, chemical concentrations, etc.
- An “event” is used herein to refer to a specific event in the patient's condition. Examples of such events include transition from one state to another state, e.g., an electrographic onset of seizure, end of seizure, or the like. For conditions other than epilepsy, the event could be an onset of a migraine headache, onset of a depressive episode, a tremor, or the like.
- The occurrence of a seizure may be referred to as a number of different things. For example, when a seizure occurs, the patient is considered to have exited a “pre-ictal state” or “pro-ictal state” and has transitioned into the “ictal state”. However, the electrographic onset of the seizure (one event) and/or the clinical onset of the seizure (another event) have also occurred during the transition of states.
- A patient's “propensity” for a seizure is a measure of the likelihood of transitioning into the ictal state. The patient's propensity for seizure may be estimated by determining which “state” the patient is currently in. As noted above, the patient is deemed to have an increased propensity for transitioning into the ictal state (e.g., have a seizure) when the patient is determined to be in a pro-ictal state. Likewise, the patient may be deemed to have a low propensity for transitioning into the ictal state when it is determined that the patient is in a contra-ictal state.
- The methods, devices and systems of the present invention are useful for long-term, ambulatory sampling and analysis of one or more physiological signals, such as a patient's brain activity. In one preferred embodiment, the system of the present invention may be used to monitor and store one or more substantially continuously sampled EEG signals from the patient, while providing a minimal inconvenience to the patient. Attempts at developing ambulatory monitoring systems in the past have relied on an array of electrodes being placed on the patient's head and scalp with adhesive. Unfortunately, such systems are poorly tolerated by patients and are impractical for the duration of time needed for the accurate evaluation of the patient's EEG and evaluation of the efficacy of the treatment the patients are undergoing. Unlike conventional ambulatory EEG systems, the ambulatory monitoring systems of the present invention typically include one or more devices that are implanted in a minimally invasive fashion in the patient and will be largely unnoticed by a patient as they go about their day-to-day activities. The implantable devices may be in wireless communication with an external device that may be carried by the patient or kept in close proximity to the patient. Consequently, the ambulatory monitoring systems of the present invention are conducive to longer, more effective monitoring of the patient (e.g., one week or longer, one month or longer, two months or longer, three months or longer, six months or longer, one year or longer, etc.).
- The methods, devices and systems of the present invention may also find use in an emergency room or neurological intensive care units (ICU). For example, the systems may be used to monitor patients who have complex, potentially life-threatening neurological illnesses or brain injuries. Neuro ICUs may monitor patients who have suffered (or thought to have suffered) a stroke (e.g., cerebral infarction, transient ischemic attacks, intracerebral hemorrhage, aneurismal subarachnoid hemorrhage, arteriovenous malformations, dural sinus thrombosis, etc.), head trauma, spinal cord injury, tumors (e.g., spinal cord metastases, paraneoplastic syndromes), infections (e.g., encephalitis, meningitis, brain abscess), neuromuscular weakness (e.g., Guillain-barre syndrome, myasthenia gravis), eclampsia, neuropleptic malignant syndrome, CNS vasculitis, migraine headaches, or the like.
- The neuro-ICUs require the ability to monitor the patient's neurological condition for a long period of time to identify issues and diagnose the patient before permanent neurological damage occurs. Because the systems of the present invention are able to provide real-time monitoring of a patient's EEG and many embodiments have the ability to detect or predict neurological events, such systems will be beneficial to patients and the staff of the ICU to allow the neurologist and support staff to detect and/or prevent complications that may arise from the patient's neurological condition, before the patient's condition deteriorates.
- For example, a patient who is suffering from head trauma may be outfitted with a system of the present invention and because the implantable portions are MRI safe, the patient's may still undergo MRI sessions. Furthermore, the systems of the present invention may also be used to continuously monitor a patient's response to a drug therapy while the patient is in the neuro-ICU and when the patient leaves the neuro-ICU.
- For epilepsy patients in particular, the monitoring systems of the present invention may be used in conjunction with, or as an alternative to, the in-patient video-EEG monitoring that occurs in the EMU. If used as an alternative to in-patient video-EEG monitoring, in some embodiments it may be desirable to provide one or more video recorders in the patient's home to provide time-synced video recording of the patient as they live with their ambulatory monitoring system. In some embodiments, it may be desirable to provide a patient-mounted video system so as to allow video-monitoring of the patient outside of their home. Such a video system may or may not be in communication with the ambulatory monitoring system of the present invention; but both the video and the monitored EEG signals should be time-synced and analyzed together by the physician to assess the patient's condition and/or efficacy of any therapy that the patient may be undergoing.
- The systems and methods of the present invention may incorporate EEG analysis software to estimate and monitor the patient's brain state substantially in real-time. The EEG analysis software may include a safety algorithm, a seizure prediction algorithm and/or a seizure detection algorithm that uses one or more extracted features from the EEG signals (and/or other physiological signals) to estimate the patient's brain state (e.g., predict or detect the onset of a seizure). Additionally, some systems of the present invention may be used to facilitate delivery of a therapy to the patient to prevent the onset of a predicted seizure and/or abort or mitigate a seizure after it has started. Facilitation of the delivery of the therapy may be carried out by outputting a warning or instructions to the patient or automatically delivering a therapy to the patient (e.g., pharmacological, electrical stimulation, etc.). The therapy may be delivered to the patient using the implanted devices that are used to collect the ambulatory signals, or it may be delivered to the patient through a different implanted device. A description of some systems that may be used to delivery a therapy to the patient are described in commonly owned U.S. Pat. Nos. 6,366,813 and 6,819,956, U.S. Patent Application Publication Nos. 2005/0021103 (published Jan. 27, 2005), 2005/0119703 (published Jun. 2, 2005), 2005/0021104 (published Jan. 27, 2005), 2005/0240242 (published Oct. 27, 2005), 2005/0222626 (published Oct. 6, 2005), and U.S. patent application Ser. No. 11/282,317 (filed Nov. 17, 2005), Ser. Nos. 11/321,897, 11/321,898, and 11/322,150 (all filed Dec. 28, 2005), the complete disclosures of which are incorporated herein by reference.
- For patients suspected or known to have epilepsy, the systems of the present invention may be used to provide data and other metrics to the patients and physicians that heretofore have not been accurately measurable. For example, the data may be analyzed to (1) determine whether or not the patient has epilepsy, (2) determine the type of epilepsy, (3) determine the types of seizures, (4) localize or lateralize one or more seizure foci, (5) assess baseline seizure statistics and/or change from the baseline seizure statistics (e.g., seizure count, frequency, duration, seizure pattern, etc.) (6) monitor for sub-clinical seizures, assess a baseline frequency of occurrence, and/or change from the baseline occurrence, (7) measure the efficacy of AED treatments, (8) assess the effect of adjustments of the dosage of the AED, (9) determine the effects of adjustments of the type of AED, (10) determine the effect of, and the adjustment to parameters of, electrical stimulation (e.g., vagus nerve stimulation (VNS), deep brain stimulation (DBS), cortical stimulation, etc.), (11) determine “triggers” for the patient's seizures, (12) assess outcomes from surgical procedures, (13) provide immediate biofeedback to the patient, (14) screen patients for determining if they are an appropriate candidate for a seizure advisory system or other neurological monitoring or therapy system, or the like.
- The systems of the present invention typically include one or more implantable devices that are in wireless communication with an external data collection device, typically with a high frequency communication link. The implantable devices of the present invention are typically implanted in a minimally invasive fashion beneath at least one layer of the scalp, above the patient's skull/calvarium, and over one or more target area of the patient's brain. As will be described in more detail below, the implantable devices are typically injected underneath the skin/scalp using an introducer, trocar or syringe-like device using local anesthesia. It is contemplated that such a procedure could be completed in 20 to 30 minutes by a physician or neurologist in an out-patient procedure.
- The implantable devices are typically used to continuously sample the physiological signals for a desired time period so as to be able to monitor fluctuations of the physiological signal over substantially the entire time period. In alternative embodiments, however, the implantable devices may be used to periodically sample the patient's physiological signals or selectively/aperiodically monitor the patient's physiological signals.
- The implantable devices may be permanently or temporarily implanted in the patient. If permanently implanted, the devices may be used for as long as the monitoring is desired, and once the monitoring is completed, because the implanted devices are biocompatible they may remain permanently implanted in the patient without any long term detrimental effects for the patient. However, if it is desired to remove the implanted devices, the devices may be explanted from the patient under local anesthesia. For ease of removal, it may be desirable to tether or otherwise attach a plurality of the implantable devices together (e.g., with a suture or leash) so that a minimal number of incisions are needed to explant the implantable devices.
- Exact positioning of the implanted devices will usually depend on the desired type of monitoring. For patients who are being monitored for epilepsy diagnosis, the suspected type of epilepsy may affect the positioning of the implantable devices. For example, if the patient is thought to have temporal lobe epilepsy, a majority of the implantable devices will likely be located over the patient's temporal lobe. Additionally, if the focus of the seizure is known, it may be desirable to place a plurality of implantable devices directly over the focus. However, if the focus has not been localized, a plurality of implantable devices may be spaced over and around the target area of the patient's brain (and one or more implantable devices contralateral to the target area) in an attempt to locate or lateralize the seizure focus.
- The number of implantable devices that are implanted in the patient will depend on the number of channels that the physician wants to concurrently monitor in the patient. Typically however, the physician will implant 32 or less, and preferably between about 2 and about 16 implantable devices, and most preferably between about 4 and about 8 implantable devices. Of course, in some instances, it may be desirable to implant more or less, and the present invention is not limited to the aforementioned number of implanted devices.
- While the remaining discussion focuses on methods of using the systems and devices of the present invention for ambulatory monitoring of EEG signals of patients and patient populations for the diagnosis of epilepsy and/or evaluation of the efficacy and dosing of the patient's AEDs, it should be appreciated that the present invention is not limited to sampling EEG signals for epilepsy or for monitoring the efficacy of AEDs. For example, the implanted devices may be implanted under the skin of the patient's face, within the muscle of the patient's face, within the skull, above the jaw (e.g., sphenoidal implant that is placed under the skin just above the jaw to monitor the brain activity in the temporal lobes), or any other desired place on the patient's body. Furthermore, in addition to or as an alternative to monitoring EEG signals from the patient, it may be desired to monitor other physiological signals from a patient. For example, the system of the present invention may be used to monitor one or more of a blood pressure, blood oxygenation, temperature of the brain or other portion of the patient, blood flow measurements in the brain or other parts of the body, ECG/EKG, heart rate signals and/or change in heart rate signals, respiratory rate signals and/or change in respiratory rate signals, chemical concentrations of medications, pH in the blood or other portions of the body, other vital signs, other physiological or biochemical parameters of the patient's body, or the like.
- Furthermore, the systems of the present invention may be useful for monitoring and assisting in the analysis of treatments for a variety of other neurological conditions, psychiatric conditions, episodic and non-episodic neurological phenomenon, or other non-neurological and non-psychiatric maladies. For example, the present invention may be useful for patients suffering from sleep apnea and other sleep disorders, migraine headaches, depression, Alzheimer's, Parkinson's Disease, eating disorders, dementia, attention deficit disorder, stroke, cardiac disease, diabetes, cancer, or the like. Likewise, the present invention may also be used to assess the symptoms, efficacy of pharmacological and electrical therapy on such disorders.
- Referring now to the Figures,
FIG. 1A illustrates asimplified system 10 embodied by the present invention.System 10 includes one or moreimplantable devices 12 that are configured to sample electrical activity from the patient's brain (e.g., EEG signals). The implantable devices may be active (with internal power source), passive (no internal power source), or semi-passive (internal power source to power components, but not to transmit data signal). Theimplantable devices 12 may be implanted anywhere in the patient, but typically one or more of thedevices 12 may be implanted adjacent a previously identified epileptic focus or a portion of the brain where the focus is believed to be located. Alternatively, thedevices 12 themselves may be used to help determine the location of the epileptic focus. - The physician may implant any desired number of devices in the patient. As noted above, in addition to monitoring brain signals, one or more additional implanted
devices 12 may be implanted to measure other physiological signals from the patient. - While it may be possible to implant the
implantable devices 12 under the skull and in or on the brain, it is preferred to implant theimplantable devices 12 in a minimally invasive fashion under at least one layer of the patient's scalp and above the skull.Implantable devices 12 may be implanted between any of the layers of the scalp (sometimes referred to herein as “sub-galeal”). For example, the implantable devices may be positioned between the skin and the connective tissue, between the connective tissue and the epicranial aponeurosis/galea aponeurotica, between the epicranial aponeurosis/galea aponeurotica and the loose aerolar tissue, between the loose aerolar tissue and the pericranium, and/or between the pericranium and the calvarium. In some configurations, it may be useful to implant differentimplantable devices 12 between different layers of the scalp. -
Implantable devices 12 will typically be configured to substantially continuously sample the brain activity of the groups of neurons in the immediate vicinity of the implanted device. In some embodiments, if placed below the skull and in contact with the cortical surface of the brain, the electrodes may be sized to be able to sample activity of a single neuron in the immediate vicinity of the electrode (e.g., a microelectrode). Typically, theimplantable device 12 will be interrogated and powered by a signal from the external device to facilitate the substantially continuous sampling of the brain activity signals. Sampling of the brain activity is typically carried out at a rate above about 200 Hz, and preferably between about 200 Hz and about 1000 Hz, and most preferably at about 400 Hz, but it could be higher or lower, depending on the specific condition being monitored, the patient, and other factors. Each sample of the patient's brain activity will typically contain between about 8 bits per sample and about 32 bits per sample, and preferably between about 12 bits per sample and about 16 bits per sample. Thus, if each return communication transmission to the external device includes one EEG sample per transmission, and the sample rate is 400 Hz and there are 16 bits/sample, the data transfer rate from theimplantable devices 12 to theexternal device 14 is at least about 6.4 Kbits/second. If there are 32 implantable devices, the total data transfer rate for thesystem 10 would be about 205 Kbits/second. In alternative embodiments, it may be desirable to have the implantable devices sample the brain activity of the patient in a non-continuous basis. In such embodiments, theimplantable devices 12 may be configured to sample the brain activity signals periodically (e.g., once every 10 seconds) or aperiodically. -
Implantable device 12 may comprise a separate memory module for storing the recorded brain activity signals, a unique identification code for the device, algorithms, other programming, or the like. - A patient instrumented with the implanted
devices 12 will typically carry adata collection device 14 that is external to the patient's body. Theexternal device 14 would receive and store the signal from the implanteddevice 12 with the encoded EEG data (or other physiological signals). The external device is typically of a size so as to be portable and carried by the patient in a pocket or bag that is maintained in close proximity to the patient. In alternative embodiments, the device may be configured to be used in a hospital setting and placed alongside a patient's bed. Communication between thedata collection device 14 and theimplantable device 12 typically takes place through wireless communication. The wireless communication link betweenimplantable device 12 andexternal device 14 may provide a communication link for transmitting data and/or power.External device 14 may include acontrol module 16 that communicates with the implanted device through anantenna 18. In the illustrated embodiment,antenna 18 is in the form of a necklace that is in communication range with theimplantable devices 12. It should be appreciated however, that the configuration ofantenna 18 andcontrol module 16 may be in a variety of other conventional or proprietary forms. For example, in anotherembodiment control module 16 may be attached around an arm or belt of the patient, integrated into a hat, integrated into a chair or pillow, and/or the antenna may be integrated intocontrol module 16. - In order to facilitate the transmission of power and data, the antenna of the external device and the implantable devices must be in communication range of each other. The frequency used for the wireless communication link has a direct bearing on the communication range. Typically, the communication range is between at least one foot, preferably between about one foot and about twenty feet, and more preferably between about six feet and sixteen feet. As can be appreciated, however, the present invention is not limited to such communication ranges, and larger or smaller communication ranges may be used. For example, if an inductive communication link is used, the communication range will be smaller than the aforementioned range.
- In some situations, it may be desirable, to have a wire running from the patient-worn
data collection device 14 to an interface (not shown) that could directly link up to the implanteddevices 12 that are positioned below the patient's skin. For example, the interface may take the form of a magnetically attached transducer, as with cochlear implants. This could enable power to be continuously delivered to the implanteddevices 12 and provide for higher rates of data transmission. - In some configurations,
system 10 may include one or more intermediate transponder (not shown) that facilitates data transmission and power transmission betweenimplantable device 12 andexternal device 14. The intermediate transponder may be implanted in the patient or it may be external to the patient. If implanted, the intermediate transponder will typically be implanted between theimplantable device 12 and the expected position of the external device 14 (e.g., in the neck, chest, or head). If external, the transponder may be attached to the patient's skin, positioned on the patient's clothing or other body-worn assembly (e.g., eyeglasses, cellular phone, belt, hat, etc.) or in a device that is positioned adjacent the patient (e.g., a pillow, chair headrest, etc.). The intermediate transponder may be configured to only transmit power, only transmit data, or it may be configured to transmit both data and power. By having such intermediate transponders, theexternal device 14 may be placed outside of its normal communication range from the implanted devices 12 (e.g., on a patient's belt or in a patient's bag), and still be able to substantially continuously receive data from theimplantable device 12 and/or transmit power to theimplantable device 12. - Transmission of data and power between
implantable device 12 andexternal device 14 is typically carried out through a radiofrequency link, but may also be carried out through magnetic induction, electromagnetic link, Bluetooth® link, Zigbee link, sonic link, optical link, other types of wireless links, or combinations thereof. - One
preferred method 11 of wirelessly transmitting data and power is carried out with a radiofrequency link, similar to the link used with radiofrequency identification (RFID) tags. As illustrated inFIGS. 1A and 1B , in such embodiments, one or more radio frequency signals are emitted from theexternal device 14 through antenna 18 (step 13). If theexternal device 14 is in communication range of the implantable devices, atstep 15 the radiofrequency (RF) energy signal illuminates the passive,implantable devices 12. - At step 17 the same RF signal interrogates the energized
implantable device 12 to allow the implantable device to sample the desired physiological signal from the patient (such as an EEG signal). Atstep 19, the implantable device samples the instantaneous EEG signal (or other physiological signal) from the patient. - At
step 21, theimplantable device 12 then communicates a return RF signal to theexternal device 14 that is encoded with data that is indicative of the sampled EEG signal. Typically, the return RF signal is a based on the RF signal generated by the external device and includes detectable modifications which indicate the sampled EEG signal. For example, the return signal is typically a backscattering of the RF signal from the external device with the detectable modifications that indicate the sampled EEG signal. Advantageously, such backscattering does not require generation of a separate radiating signal and would not require an internal power source. The return RF signals may also include the identification code of the implanted device so as to identify which device the data is coming from. Atstep 23, the return RF signal emitted by theinternal device 12 is received by theantenna 18, and the RF signal is decoded to extract the sampled EEG signal. The sampled EEG signal may thereafter be stored in a memory of theexternal device 14. For embodiments in which the method is used to collect data, such data will be stored until accessed by the patient. Typically, such data will be analyzed on a separate device (e.g., physician's computer workstation). - In alternative embodiments, however, in which the external device may comprise software to analyze the data in substantially real-time, the received RF signal with the sampled EEG may be analyzed by the EEG analysis algorithms to estimate the patient's brain state which is typically indicative of the patient's propensity for a neurological event (step 25). The neurological event may be a seizure, migraine headache, episode of depression, tremor, or the like. The estimation of the patient's brain state may cause generation of an output (step 27). The output may be in the form of a control signal to activate a therapeutic device (e.g., implanted in the patient, such as a vagus nerve stimulator, deep brain or cortical stimulator, implanted drug pump, etc.). In other embodiments, the output may be used to activate a user interface on the external device to produce an output communication to the patient. For example, the external device may be used to provide a substantially continuous output or periodic output communication to the patient that indicates their brain state and/or propensity for the neurological event. Such a communication could allow the patient to manually initiate therapy (e.g., wave wand over implanted vagus nerve stimulator, cortical, or deep brain stimulator, take a fast acting AED, etc.) or to make themselves safe.
- In preferred embodiments, the return RF signal is transmitted (e.g., backscattered) immediately after sampling of the EEG signal to allow for substantially real-time transfer (and analysis) of the patient's EEG signals. In alternate embodiments, however, the return RF signal may be buffered in an internal memory and the communication transmission to the
external device 14 may be delayed by any desired time period and may include the buffered EEG signal and/or a real-time sampled EEG signal. The return RF signal may use the same frequency as the illumination RF signal or it may be a different frequency as the illumination RF signal. - Unlike conventional digital implantable devices that send large packets of stored data with each return RF communication transmission, some embodiment of the methods and devices of the present invention substantially continuously sample physiological signals from the patient and communicate in real-time small amounts of data during each return RF signal communication. Because only small amounts of data (one or a small number of sampled EEG signals from each implantable device 12) are transmitted during each communication, a lower amount of power is consumed and the illumination of the implanted device from the incoming high-frequency RF signal will be sufficient to power the
implantable device 12 for a time that is sufficient to allow for sampling of the patient's EEG signal. Consequently, in most embodiments no internal power source, such as a battery, is needed in theimplantable device 12—which further reduces the package size of theimplantable device 12. - The
implantable devices 12 and theexternal devices 14 of the present invention typically use an electromagnetic field/high frequency communication link to both illuminate the implantable device and enable the high data transfer rates of the present invention. Conventional devices typically have an internally powered implantable device and use a slower communication link (e.g., that is designed for long link access delays) and transmit data out on a non-continuous basis. In contrast, some embodiments of the present invention uses a fast access communication link that transmits a smaller bursts of data (e.g., single or small number of EEG sample at a time) on a substantially continuous basis. - The frequencies used to illuminate and transfer data between the
implantable devices 12 and external device are typically between 13.56 MHz and 10 GHz, preferably between 402 MHz and 2.4 GHz, more preferably between 900 MHz and 2.4 GHz. While it is possible to use frequencies above 2.4 GHz, Applicants have found that it is preferred to use a frequency below 2.4 GHz in order to limit attenuation effects caused by tissue. As can be appreciated, while the aforementioned frequencies are the preferred frequencies, the present invention is not limited to such frequencies and other frequencies that are higher and lower may also be used. For example, it may be desirable us use the MICS (Medical Implant Communication Service band) that is between 402-405 MHz to facilitate the communication link. In Europe, it may be desirable to use ETSI RFID allocation 869.4-869.65 MHz. - While not illustrated in
FIG. 1B , thesystem 10 of the present invention may also make use of conventional or proprietary forward error correction (“FEC”) methods to control errors and ensure the integrity of the data transmitted from theimplantable device 12 to theexternal device 14. Such forward error correction methods may include such conventional implementations such as cyclic redundancy check (“CRC”), checksums, or the like. - If desired, the data signals that are wirelessly transmitted from
implantable device 12 may be encrypted prior to transmission to thecontrol module 16. Alternatively, the data signals may be transmitted to thecontrol module 16 as unencrypted data, and at some point prior to the storage of the data signals in thecontrol module 16 or prior to transfer of the data signals to the physician's office, the EEG data may be encrypted so as to help ensure the privacy of the patient data. -
FIGS. 3A and 3B illustrate two embodiments of the externally powered leadless,implantable device 12 that may be used with thesystem 10 of the present invention. Theimplantable devices 12 of the present invention are preferably passive or semi-passive and are “slaves” to the “master”external device 14. The implantable devices will typically remain dormant until they are interrogated and possibly energized by an appropriate RF signal from theexternal device 14. As will be described below, theimplantable device 14 may have minimal electronic components and computing power, so as to enable a small package size for the implantable device. - Advantageously, the embodiment illustrated in
FIGS. 3A and 3B are minimally invasive and may be implanted with an introducer, trocar or syringe-like device under local anesthesia by a physician or potentially even a physician's assistant. Typically, the implanted device ofFIG. 3A may have alongitudinal dimension 20 of less than about 3 cm, and preferably between about 1 cm and about 10 cm, and alateral dimension 22 of less than about 2 mm, and preferably between about 0.5 mm and about 10 mm. As can be appreciated, such dimensions are merely illustrative, and other embodiments of implanted device may have larger or smaller dimensions. -
FIG. 3A illustrates an embodiment that comprises afirst electrode 24 and asecond electrode 26 that are disposed on opposing ends ofhousing 28. The first andsecond electrodes second electrodes electrodes -
Housing 28 is typically in the form of a radially symmetrical, substantially cylindrical body that hermetically sealselectronic components 30 disposed within acavity 32.Housing 28 may be composed of a biocompatible material, such as glass, ceramic, liquid crystal polymer, or other materials that are inert and biocompatible to the human body and able to hermetically seal electronic components.Housing 28 may have embedded within or disposed thereon one or more x-ray visible markers 33 that allow for x-ray localization of the implantable device. Alternatively, one or more x-ray visible markers may be disposed within thecavity 32.Cavity 32 may be filled with an inert gas or liquid, such as an inert helium nitrogen mixture which may also be used to facilitate package leakage testing. Alternatively, it may be desirable to fill thecavity 32 with a liquid encapsulant (not shown) that hardens around the electronic components. The liquid encapsulant may comprise silicone, urethane, or other similar materials. - While
housing 28 is illustrated as a substantially cylindrical body with theelectrodes housing 28. For example,housing 28 may taper in one direction, be substantially spherical, substantially oval, substantially flat, or the like. Additionally or alternatively, the body may have one or more substantially planar surfaces so as to enhance the conformity to the patient's skull and to prevent rotation of theimplantable device 12. While not shown,housing 28 may optionally include a conductive electromagnetic interference shield (EMI) that is configured to shield theelectronic components 30 inhousing 28. The EMI shield may be disposed on an inner surface of the housing, outer surface of the housing, or impregnated within the housing. - If desired,
housing 28 may optionally comprise an anchoring assembly (not shown) that improves the anchoring of theimplantable device 12 to the skull or the layers within the scalp. Such anchoring may be carried out with adhesive, spikes, barbs, protuberances, suture holes, sutures, screws or the like. - In the illustrated embodiment,
first electrode 24 is disposed on a first end ofhousing 28 and is in electrical communication with theelectronic components 30 through ahermetic feedthrough 34.Feedthrough 34 may be the same material as thefirst electrode 24 or it may be composed of a material that has a similar coefficient of thermal expansion as thehousing 28 and/or thefirst electrode 24.Feedthrough 34 may make direct contact with a pad (not shown) on a printedcircuit board 36, or any other type of conventional connection may be used (e.g., solder ball, bond wire, wire lead, or the like) to make an electrical connection to the printedcircuit board 36. -
Second electrode 26 may be spaced from a second, opposing end of thehousing 28 via anelongated coil member 38. In the illustrated embodiment, thesecond electrode 26 typically comprises aprotuberance 39 that is disposed within and attached to a distal end of thecoil member 38.Coil member 38 acts as an electrical connection between second electrode and theelectronic components 30 disposed withinhousing 28. -
Coil member 38 will typically be composed of stainless steel, a high strength alloy such as MP35N, or a combination of materials such as a MP35N outer layer with silver core. - The illustrated embodiment shows that
coil member 38 has a largest lateral dimension (e.g., diameter) that is less than the largest lateral dimension (e.g., diameter) ofhousing 28, but in other embodiments, the coil may have the same lateral dimension or larger lateral dimension fromhousing 28. -
Coil member 38 may also be used as an antenna to facilitate the wireless transmission of power and data between theimplantable device 12 and the external device 14 (or other device). In preferred embodiments,coil member 38 may be used to receive and transmit radiofrequency signals. In alternative embodiments, however,coil member 38 may be inductively coupled to an external coil to receive energy from a modulating, alternating magnetic field. Unlike other conventional implantable devices, the RF antenna is disposed outside of thehousing 28 and extends from one end ofhousing 28. It should be appreciated however, that the present invention is not limited to a substantially cylindrical antenna extending from an end of thehousing 28 and various other configurations are possible. For example, it may be desirable to wind the antenna around or within thehousing 28. Furthermore, it may be desirable to use a substantially flat antenna (similar to RFID tags) to facilitate the transmission of power and data. To facilitate implantation, such antennas may be rolled into a cylindrical shape and biased to take the flat shape upon release from the introducer. - While not shown, it may also be desirable to provide a second antenna between the
first electrode 24 and thehousing 28. The second antenna may be used for power and downlink using a first frequency, e.g., 13.56 MHz, while the first antenna may be used for uplink using a second frequency, e.g., 902-928 MHz. In such embodiments, however, the implantable devices would need to have an internal timebase (e.g., oscillator and a frequency synthesizer). For the embodiments that use only a single frequency for the downlink and uplink, an internal timebase or frequency synthesizer is not needed—and the timebase established by the master (e.g., external device 14) can be used. -
Coil member 38 may be in electrical communication with theelectronic components 30 with ahermetic feedthrough 42 that extends through a via 44 inhousing 28.Feedthrough 42 is typically composed of a material that has a coefficient of thermal expansion that is substantially similar to the material ofhousing 40. Because thecoil member 38 is outside of thehousing 28 the length of theimplantable device 12 will be increased, but the flexible coil will be better exposed to the RF signals and will be allowed to conform to the shape of the patient's skull. -
Coil member 38 is typically disposed outside of thehousing 28 and disposed within an elongate, substantiallyflexible housing 40. Compared to the morerigid housing 28, theflexible housing 40 is better able to conform to the shape of an outer surface of the patient's skull, more comfortable for the patient and reduces the chance of tissue erosion.Flexible housing 40 may comprise silicone, polyurethane, or the like In the illustrated embodiment,flexible housing 40 extends along the entire length ofcoil member 38, but in other embodiments,flexible housing 40 may extend less than or longer than the longitudinal length ofcoil member 38.Flexible housing 40 will typically have a substantially cylindrical shape, but if desired aproximal end 46 of the cylindrical housing may be enlarged or otherwise shaped to substantially conform to a shape of thehousing 28. The shapedproximal end 46 may be adhered or otherwise attached to the end of thehousing 40 to improve the hermetic seal of the housing and may reduce any potential sharp edge or transition between thehousings FIG. 3A only illustrates a single layered flexible housing, if desired, theflexible housing 40 may comprise a plurality of layers, and the different layers may comprise different types of materials, have embedded x-ray markers, or the like. - A longitudinal length of
flexible housing 40 and the longitudinal length of therigid housing 28 may vary depending on the specific embodiment, but a ratio of the longitudinal length of the flexible housing 40: the longitudinal length of the morerigid housing 28 is typically between about 0.5:1 and about 3:1, and preferably between about 1:1 and about 2:1. By having the longitudinal length of the flexible housing longer than the longitudinal length of the rigid housing, advantageously the implantable device will be more comfortable and better able to conform to the outer surface of the patient's skull. In alternative embodiments, it may also be desirable to have a longitudinal length of therigid housing 28 be longer than the longitudinal length of theflexible housing 40, or in any other desired configuration. - Because the
implantable devices 12 of the present invention consume a minimal amount of energy and use a high frequency RF coupling to power the device and communicate the EEG signals to the external device, unlike other conventional devices, some of theimplantable devices 12 of the present invention will not need a ferrite core to store energy, and theelectronic components 30 of the present invention will typically include aluminum or other MRI-safe material. Consequently, the patient's implanted with theimplantable device 12 may safely undergo MRI imaging. -
FIG. 3B illustrates another embodiment ofimplantable device 12 that is encompassed by the present invention. The embodiment ofFIG. 3B shares many of the same components as the embodiment ofFIG. 3A , and such components are noted with the same reference numbers asFIG. 3A . There are, however, a few notable exceptions. Specifically, instead of having a hermetically sealed housing, the embodiment ofFIG. 3B provides aconductive body 48 that acts as both the housing for theelectronic components 30 and as the second electrode.Conductive body 48 may be composed of a metallized polymer, one or more metal or metal alloys, or other conductive material. Becausebody 48 is conductive, it may act as an electromagnetic interference (EMI) shield to the electronic components disposed within thecavity 32. Electrical connections to the printedcircuit board 36 may be carried out with one or moreconductive spring conductors 50 or other conventional lead connectors. -
Feedthrough 42 that is connected to thecoil member 38 extends from the end ofcoil member 38 and makes an electrical connection with a lead on the printedcircuit board 36. Thefeedthrough 42 works in conjunction with one or more dielectric seals orspacers 52 to hermetically seal thecavity 32. Similar to above, thecavity 32 may be filled with an inert gas or an encapsulant. Theproximal end 46 offlexible body 40 may be coupled to theseals 52 and/or coupled to theconductive body 48. - As shown in the embodiment of
FIG. 3B , the surface area of conductive body 48 (e.g., the first electrode) may be larger than the surface area of thesecond electrode 26. In other embodiments, however, the surface area of thesecond electrode 26 may have the substantially same surface area and/or shape as theconductive body 48. - In most embodiments, the implantable devices shown in
FIGS. 3A and 3B function completely independent of the otherimplantable devices 12 and there is no physical connection or communication between the various devices. If desired, however, theimplantable devices 12 may be physically coupled to each other with a connecting wire or tether and/or in communication with each other. If the plurality of implanteddevices 12 are in communication with one another, it may be desired to use a communication frequency between the implanteddevices 12 that is different from the frequency to communicate between the implanted devices and theexternal device 14. Of course, the communication frequency between the implanteddevices 12 may also be the same frequency as the communication frequency with theexternal device 14. - While
FIGS. 3A and 3B illustrate a first andsecond electrode implantable devices 12 of the present invention are not limited to only two electrodes. Any number of electrodes may be coupled to the implantable device in any orientation. For example, the electrodes do not have to extend from ends of the housing, but may be positioned anywhere along a portion of thehousings flexible housing 40 and/orrigid housing 28 so as to provide more than two electrodes per implantable device. For example,FIG. 3C illustrates a simplified embodiment in which there are twoadditional electrode 24′, 26′ positioned on therigid housing 28 andflexible housing 40, respectively. The spacing between thevarious contacts FIG. 3C , it may be desirable to have the additional electrodes only on theflexible housing 40 or only on therigid housing 28. While only four electrodes are shown on the implanted device, it should be appreciated that any desirable number of electrodes (e.g., anywhere between two electrodes and about sixteen electrodes) may coupled to the implanted device. - While
FIGS. 3A-3B illustrate some currently preferred embodiments of theimplantable device 12, the present invention further encompasses other types of minimally invasiveimplantable devices 12 that can monitor the brain activity and other physiological signals from the patient. For example, a plurality of electrodes might reside on a single lead that could be tunneled under the scalp from a single point of entry. Examples of such embodiments are shown inFIGS. 2A-2E . - Such
implantable devices 12 include anactive electrode contact 400 that is in communication with one or morepassive electrode contacts 401. Theactive electrode contact 400 may be used to facilitate monitoring of the physiological signals using the array of active and passive electrode contacts. The arrays of electrode contacts may be arranged in a linear orientation (FIG. 2C ) or in a grid pattern (FIG. 2E ), or any other desired pattern (e.g., circular, star pattern, customized asymmetric pattern, etc.) For example, if the implantable device comprises two electrode contacts (e.g., one active contact and one passive contact), such an embodiment would have a similar configuration as the embodiment ofFIG. 3A . Similarly, if the implantable device were to have four substantially linearly positioned electrode contacts (e.g., one active contact and three passive contacts), such an embodiment would be substantially similar to the configuration shown inFIG. 3C . -
FIG. 2A illustrates a bottom view of anactive electrode contact 400 that may be part of theimplantable device 12 of the present invention. The active electrode contact comprises a base 402 that is coupled to acontact portion 404. Thebase 402 and contact portion may be composed of any number of different types of materials, such as platinum, platinum-iridium alloy, stainless steel, or any other conventional material. In preferred embodiments, both thebase 402 andcontact portion 404 are formed to their desired shape. The base 402 may comprise a plurality ofhermetic feedthroughs 413 that is implemented using conventional glass metal seal technology (e.g., pins 408,glass seal 414, and vias 406). Thehermetic feedthroughs 413 may be used to connect to an antenna (not shown) for communication with theexternal device 14 or to make an electrical connection with an adjacentpassive electrode contact 401 in the implanteddevice 12. In the illustrated embodiment,base 402 comprises fourhermetic feedthroughs 413. But as can be appreciated the base 402 may comprise any desired number of feedthroughs 413 (e.g., anywhere between two and sixty four feedthroughs). -
FIG. 2B illustrates a cross-sectional view of theactive electrode contact 400 along lines B-B inFIG. 2A . As shown inFIG. 2B , thecontact portion 404 is shaped to as to align thebase 402 along a bottom surface defined byflanges 409.Base 402 may be coupled to thecontact portion 404 with a laser weld, glass metal seal, or otherconventional connector 410 along an outer perimeter of the base 402 to hermetically seal components of the active electrode contact within acavity 412 defined by thebase 402 andcontact portion 404. If desired, thecavity 412 may be backfilled with nitrogen and/or helium to facilitate package leak testing. - A thin or thick filmed microcircuit or a printed circuit board (“PCB”) 416 may be mounted onto an inner surface of the
base 402.PCB 416 may have active components 418 (e.g., integrated circuits, ASIC, memory, etc.) and passive components 420 (e.g., resistors, capacitors, etc.) mounted thereto. Leads orbond wires 422 from the active and passive components may be electrically attached to pads on the PCB (not shown) which make electrical connections to leads orbond wires 424 that are attached to thehermetic feedthroughs 413. While not shown inFIG. 2B , theactive electrode contact 400 may comprise a rechargeable or non-rechargeable power supply (e.g., batteries), and/or x-ray visible markers (not shown). - As noted above, the active contacts may be used in conjunction with one or more passive contacts to form an active
implantable device 12 to facilitate monitoring of the patient's physiological signals and to communicate with theexternal device 14.FIGS. 2C and 2D illustrate an embodiment of theimplantable device 12 in which oneactive contact 400 is housed in abody 426 along with a plurality ofpassive contacts 401 to form a multiple contactimplantable device 12. The contact portion of theactive contact 400 is exposed through an opening in thebody 426 to allow for sampling of the physiological signals (e.g., EEG) from the patient. Thebody 426 may be substantially flexible or rigid and may have similar dimensions and/or shapes as the embodiments shown inFIGS. 3A-3C .Body 426 may be composed of a biocompatible material such as silicone, polyurethane, or other materials that are inert and biocompatible to the human body.Body 426 may also be composed of a rigid material such as polycarbonate. The implantable device may be injected into the patient using the introducer assembly shown inFIG. 6 and methods shown inFIG. 7 . - As shown in
FIG. 2D wire leads 427 may extend from thepassive contacts 401 and be electrically and physically coupled to one of thehermetic feedthroughs 413 of theactive contact 400 to facilitate sampling of the physiological signals using all four electrode contacts. For embodiments which use a wireless link (e.g., RF) to wirelessly transmit data to theexternal device 14 and optionally to power the device, one of the feedthroughs may be coupled to anantenna 428 that is configured to wirelessly communicate with the external device. It should be appreciated, that while not described herein, the embodiments ofFIGS. 2C-2E may have any of the components or variations as described above in relation toFIGS. 3A-3B . -
FIG. 2E illustrates an alternative embodiment of theimplantable device 12 in which theimplantable device 12 is in the form of a 4×4 grid array of active and passive contacts. At least one of the electrode contacts may be anactive contact 400 so as to facilitate monitoring of the patient's physiological signals with the array. In the illustrated embodiment, the contacts in the leftmost column (highlighted with cross-hatching) areactive electrode contacts 400, and the contacts in remaining column are electrically connected to one of theactive contacts 400. Of course, any number ofactive contacts 400 andpassive contacts 401 may be in the grid array and the active contact(s) 400 may be positioned anywhere desired. For example, if theactive electrode contact 400 has sixteen or more hermetic feedthroughs, only one of the contacts in the array needs to be active and the remaining fifteen contacts could be passive contacts. -
FIG. 4 illustrates one simplified embodiment of the electronic components 30 (e.g.,active components 418 andpassive components 420 inFIG. 2B ) that may be disposed in theimplantable devices 12 as shown inFIGS. 2A-3C . It should be appreciated, however, that theelectronic components 30 of theimplantable device 12 may include any combination of conventional hardware, software and/or firmware to carry out the functionality described herein. For example, theelectronic components 30 may include many of the components that are used in passive RF integrated circuits. - The first and second electrodes will be used to sample a physiological signal from the patient—typically an
EEG signal 53, and transmit the sampled signal to theelectronic components 30. While it may be possible to record and transmit the analog EEG signal to the external device, the analog EEG signal will typically undergo processing before transmission to theexternal device 14. The electronic components typically include a printed circuit board that has, among others, anamplifier 54, one or more filters 56 (e.g., bandpass, notch, lowpass, and/or highpass) and an analog-to-digital converter 58. In some embodiments, the processed EEG signals may be sent to a transmit/receivesub-system 60 for wireless transmission to the external device via an antenna (e.g., coil member 38). Additional electronic components that might be useful inimplantable device 12 may be found in U.S. Pat. Nos. 5,193,539, 5,193,540, 5,312,439, 5,324,316, 5,405,367 and 6,051,017. - In some alternative embodiments of the present invention, the
electronic components 30 may include a memory 64 (e.g., RAM, EEPROM, Flash, etc.) for permanently or temporarily storing or buffering the processed EEG signal. For example,memory 64 may be used as a buffer to temporarily store the processed EEG signal if there are problems with transmitting the data to the external device. For example, if the external device's power supply is low, the memory in the external device is removed, or if the external device is out of communication range with the implantable device, the EEG signals may be temporarily buffered inmemory 64 and the buffered EEG signals and the current sampled EEG signals may be transmitted to the external device when the problem has been corrected. If there are problems with the transmission of the data from the implantable device, the external device may be configured to provide a warning or other output signal to the patient to inform them to correct the problem. Upon correction of the problems, the implantable device may automatically continue the transfer the temporarily buffered data and the real-time EEG data to the memory in the external device. - The
electronic components 30 may optionally comprise dedicated circuitry and/or a microprocessor 62 (referred to herein collectively as “microprocessor”) for further processing of the EEG signals prior to transmission to the external device. Themicroprocessor 62 may execute EEG analysis software, such as a seizure prediction algorithm, a seizure detection algorithm, safety algorithm, or portions of such algorithms, or portions thereof. For example, in some configurations, the microprocessor may run one or more feature extractors that extract features from the EEG signal that are relevant to the purpose of monitoring. Thus, if the system is being used for diagnosing or monitoring epileptic patients, the extracted features (either alone or in combination with other features) may be indicative or predictive of a seizure. Once the feature(s) are extracted, themicroprocessor 62 may send the extracted feature(s) to the transmit/receivesub-system 60 for the wireless transmission to the external device and/or store the extracted feature(s) inmemory 64. Because the transmission of the extracted features is likely to include less data than the EEG signal itself, such a configuration will likely reduce the bandwidth requirements for the communication link between the implantable device and the external device. Since the extracted features do not add a large amount of data to the data signal, in some embodiments, it may also be desirable to concurrently transmit both the extracted feature and the EEG signal. A detailed discussion of various embodiments of the internal/external placement of such algorithms are described in commonly owned U.S. patent application Ser. No. 11/322,150, filed Dec. 28, 2005 to Bland et al., the complete disclosure of which is incorporated herein by reference. - While most embodiments of the
implantable device 12 are passive and does not need an internal power source or internal clock, in some embodiments, theelectronic components 30 may include a rechargeable ornon-rechargeable power supply 66 and an internal clock (not shown). The rechargeable or non-rechargeable power supply may be a battery, a capacitor, or the like. Therechargeable power supply 66 may also be in communication with the transmit/receivesub-system 60 so as to receive power from outside the body by inductive coupling, radiofrequency (RF) coupling, etc.Power supply 66 will generally be used to provide power to the other components of the implantable device. In such embodiments, the implanted device may generate and transmit its own signal with the sampled EEG signal for transmission back to the external device. Consequently, as used herein “transmit” includes both passive transmission of a signal back to the external device (e.g., backscattering of the RF signal) and internal generation of a separate signal for transmission back to the external device. -
FIG. 5 is a simplified illustration of some of the components that may be included inexternal device 14.Antenna 18 and a transmit/receivesubsystem 70 will receive a data signal that is encoded with the EEG data (or other physiological data) from theantenna 38 of the implantable device 12 (FIG. 4 ). As used herein, “EEG data” may include a raw EEG signal, a processed EEG signal, extracted features from the EEG signal, an answer from an implanted EEG analysis software (e.g., safety, prediction and/or detection algorithm), or any combination thereof. - The EEG data may thereafter be stored in
memory 72, such as a hard drive, RAM, permanent or removable Flash Memory, or the like and/or processed by amicroprocessor 74 or other dedicated circuitry.Microprocessor 74 may be configured to request that the implantable device perform an impedance check between the first and second electrodes and/or other calibrations prior to EEG recording and/or during predetermined times during the recording period to ensure the proper function of the system. - The EEG data may be transmitted from
memory 72 tomicroprocessor 74 where the data may optionally undergo additional processing. For example, if the EEG data is encrypted, it may be decrypted. Themicroprocessor 74 may also comprise one or more filters that filter out high-frequency artifacts (e.g., muscle movement artifacts, eye-blink artifacts, chewing, etc.) so as to prevent contamination of the high frequency components of the sampled EEG signals. In some embodiments, the microprocessor may process the EEG data to measure the patient's brain state, detect seizures, predict the onset of a future seizure, generate metrics/measurements of seizure activity, or the like. A more complete description of seizure detection algorithms, seizure prediction algorithms, and related components that may be implemented in theexternal device 14 may be found in pending, commonly owned U.S. patent application Ser. Nos. 11/321,897 and 11/321,898, filed on Dec. 28, 2005, to Leyde et al. and DiLorenzo et al., and 60/897,551, filed on Jan. 25, 2007, to Leyde et al., the complete disclosures of which are incorporated herein by reference. - It should be appreciated, however, that in some embodiments some or all of the computing power of the system of the present invention may be performed in a computer system or
workstation 76 that is separate from thesystem 10, and theexternal device 14 may simply be used as a data collection device. In such embodiments, thepersonal computer 76 may be located at the physician's office or at the patient's home and the EEG data stored inmemory 72 may be uploaded to thepersonal computer 76 via aUSB interface 78, removal of the memory (e.g., Flash Memory stick), or other conventional communication protocols, and minimal processing may be performed in theexternal device 14. In such embodiments, thepersonal computer 76 may contain the filters, decryption algorithm, EEG analysis software, such as a prediction algorithm and/or detection algorithm, report generation software, or the like. Some embodiments of the present invention may take advantage of a web-based data monitoring/data transfer system, such as those described in U.S. Pat. Nos. 6,471,645 and 6,824,512, the complete disclosures of which are incorporated herein by reference. -
External device 14 may also comprise anRF signal generator 75 that is configured to generate the RF field for interrogating and optionally powering the implanteddevices 12.RF generator 75 will be under control of themicroprocessor 74 and generate the appropriate RF field to facilitate monitoring and transmission of the sampled EEG signals to the external device. -
External device 14 will typically include auser interface 80 for displaying outputs to the patient and for receiving inputs from the patient. The user interface typically comprise outputs such as auditory devices (e.g., speakers) visual devices (e.g., LCD display, LEDs to indicate brain state or propensity to seizure), tactile devices (e.g., vibratory mechanisms), or the like, and inputs, such as a plurality of buttons, a touch screen, and/or a scroll wheel. - The user interface may be adapted to allow the patient to indicate and record certain events. For example, the patient may indicate that medication has been taken, the dosage, the type of medication, meal intake, sleep, drowsiness, occurrence of an aura, occurrence of a seizure, or the like. Such inputs may be used in conjunction with the recorded EEG data to improve the analysis of the patient's condition and determine the efficacy of the medications taken by the patient.
- The LCD display of the
user interface 80 may be used to output a variety of different communications to the patient including, status of the device (e.g., memory capacity remaining), battery state of one or more components of system, whether or not theexternal device 14 is within communication range of theimplantable devices 12, brain state indicators (e.g., a warning (e.g., seizure warning), a prediction (e.g., seizure prediction), unknown brain state, safety indication, a recommendation (e.g., “take drugs”), or the like). Of course, it may be desirable to provide an audio output or vibratory output to the patient in addition to or as an alternative to the visual display on the LCD. In other embodiments, the brain state indicators may be separate from the LCD display to as to provide a clear separation between the device status outputs and the brain state indicators. In such embodiments, the external device may comprise different colored LEDs to indicate different brain states. For example, a green LED may indicate a safe brain state, a yellow light may indicate an unknown brain state, and a red light may indicate either a seizure detection or seizure prediction. - External device may also include a medical
grade power source 82 or other conventional power supply that is in communication with at least one other component ofexternal device 14. Thepower source 82 may be rechargeable. If thepower source 80 is rechargeable, the power source may optionally have an interface for communication with acharger 84. While not shown inFIG. 5 ,external device 14 will typically comprise a clock circuit (e.g., oscillator and frequency synthesizer) to provide the time base for synchronizingexternal device 14 and the internal device(s) 12. In preferred embodiments, the internal device(s) 12 are slaves to the external device and theimplantable devices 12 will not have to have an individual oscillator and a frequency synthesizer, and the implantable device(s) 12 will use the “master” clock as its time base. Consequently, it may be possible to further reduce the size of the implantable devices. - In use, one or more of the implantable devices are implanted in the patient. The implanted device is interrogated and powered so that the EEG signals are sampled from the patient's brain. The EEG signals are processed by the implanted device and the processed EEG signals are wirelessly transmitted from the implanted device(s) to an external device. The EEG signals are stored for future or substantially real-time analysis.
- As noted above, in preferred embodiments, the implantable devices are implanted in a minimally invasive fashion under the patient's scalp and above an outer surface of the skull.
FIG. 6 illustrates asimplified introducer assembly 90 that may be used to introduce the implantable devices into the patient. Theintroducer assembly 90 is typically in the form of a cannula and stylet or a syringe-like device that can access the target area and inject the implanted device under the skin of the patient. As noted above, theimplantable devices 12 are preferably implanted beneath at least one layer of the patient's scalp and above the patient's skull. Because of the small size of theimplantable devices 12, the devices may be injected into the patient under local anesthesia in an out-patient procedure by the physician or neurologist. Because the implantable devices are implanted entirely beneath the skin infection risk would be reduced and there would be minimal cosmetic implications. Due to the small size of theimplantable devices 12, it may be desirable to have a plurality of implantable devices pre-loaded into asterile introducer assembly 90 or into a sterile cartridge (not shown) so as to minimize the risk of contamination of theimplantable devices 12 prior to implantation. -
FIG. 7 schematically illustrates one example of a minimallyinvasive method 100 of implanting the implantable devices for ambulatory monitoring of a patient's EEG signals. Atstep 102, an incision is made in the patient's scalp. Atstep 104, an introducer assembly is inserted into the incision and a distal tip of the introducer assembly is positioned at or near the target site. Of course, the introducer assembly itself may be used to create the incision. For example, if the introducer assembly is in the form of a syringe, the syringe tip may be made to create the incision and steps 102 and 104 may be consolidated into a single step. Atstep 106, the introducer assembly is actuated to inject theimplantable device 12 to the target site. If desired, the introducer may be repositioned to additional target sites underneath the patient's skin and above the skull. If needed, additional incisions may be created in the patient's skin to allow for injection of theimplantable device 12 at the additional target sites. After a desired number of implantable devices are placed in the patient, atstep 108 the introducer assembly is removed from the target site. Atstep 110, the implantable devices are activated and used to perform long term monitoring of the patient's EEG signals from each of the target sites. Atstep 112, the sampled EEG signals are then wirelessly transmitted to an external device. Atstep 114, the sampled EEG signals may then be stored in a memory in the external device or in another device (e.g., personal computer). If desired, the EEG signals may then be processed in the external device or in a personal computer of the physician. - While not shown in
FIG. 7 , it may also be desirable to anchor the implantable devices to the patient to reduce the likelihood that the implantable devices are dislodged from their desired position. Anchoring may be performed with tissue adhesive, barbs or other protrusions, sutures, or the like. - Advantageously, the implantable devices are able to monitor EEG signals from the patient without the use of burr holes in the skull or implantation within the brain—which significantly reduces the risk of infection for the patient and makes the implantation process easier. While there is some attenuation of the EEG signals and movement artifacts in the signals, because the implantable devices are below the skin, it is believed that there will be much lower impedance than scalp electrodes. Furthermore, having a compact
implantable device 14 below the skin reduces common-mode interference signals which can cause a differential signal to appear due to any imbalance in electrode impedance and the skin provides some protection from interference caused by stray electric charges (static). - While
FIG. 7 illustrates one preferred method of implanting the implantable devices in the patient and using the implantable devices to monitor the patient's EEG, the present invention is not limited to such a method, and a variety of other non-invasive and invasive implantation and monitoring methods may be used. For example, while minimally invasive monitoring is the preferred method, the systems and devices of the present invention are equally applicable to more invasive monitoring. Thus, if it is desired to monitor and record intracranial EEG signals (e.g., ECoG), then it may be possible to implant one or more of the implantable devices inside the patient's skull (e.g., in the brain, above or below the dura mater, or a combination thereof) through a burr hole created in the patient's skull. - Once implanted in the patient, the
monitoring systems 10 of the present invention may be used for a variety of different uses. For example, in one usage the systems of the present invention may be used to diagnose whether or not the patient has epilepsy. Patients are often admitted to video-EEG monitoring sessions in an EMU to determine if the patient is having seizures, pseudo-seizures, or is suffering from vaso-vagal syncope, and the like. Unfortunately, if the patient has infrequent “seizures,” it is unlikely that the short term stay in the EMU will record a patient's seizure and the patient's diagnose will still be unclear. Consequently, in order to improve the patient's diagnosis, in addition to the in-hospital video-EEG monitoring or as an alternative to the in-hospital video-EEG monitoring, the patient may undergo an ambulatory, long term monitoring of the patient's EEG using the system of the present invention for a desired time period. The time period may be one day or more, a week or more, one month or more, two months or more, three months or more, six months or more, one year or more, or any other desired time period in between. The patient may be implanted with thesystem 10 using the method described above, and after a predetermined time period, the patient may return to the physician's office where the EEG data will be uploaded to the physician's personal computer for analysis. A conventional or proprietary seizure detection algorithm may be applied to the EEG data to determine whether or not a seizure occurred in the monitoring time period. If it is determined that one or more seizures occurred during the monitoring period, the seizure detection algorithm may be used to provide an output to the physician (and/or generate a report for the patient) indicating the occurrence of one or more seizures, and various seizure activity metrics, such as spike count over a period of time, seizure count over a period of time, average seizure duration over a period of time, the pattern of seizure occurrence over time, and other seizure and seizure related metrics. In addition, the software may be used to display the actual EEG signals from specific events or selected events for physician confirmation of seizure activity. Such data may be used as a “baseline” for the patient when used in assessing efficacy of AEDs or other therapies that the patient will undergo. - If the patient has been diagnosed with epilepsy (either using the system of the present invention or through conventional diagnosis methods), the present invention may also be used to determine the epilepsy classification and/or seizure type. To perform such methods, a desired number of implantable devices may be implanted in the patient for the long term monitoring of the patient's pattern of electrical activity in the different portions of the patient's brain. Such monitoring will be able to provide insight on whether or not the patient has partial/focal seizures or generalized seizures. In the event that the patient's epilepsy classification is already known, the classification may determine the desired placement for the implantable devices in the patient. For patients suspected or known to have temporal lobe epilepsy, the implantable devices will likely be focused over the temporal lobe and adjacent and/or over the regions of epileptiform activity. Likewise, for patient's suspected or known to have parietal lobe epilepsy, some or all of the implantable devices will be positioned over the parietal lobe and adjacent and/or over the regions of epileptiform activity. Furthermore, if the seizure focus or foci are known, at least some of the implantable devices may be positioned over the seizure focus or foci and some may be positioned contralateral to the known seizure focus or foci.
- If a seizure focus in the patient has not been lateralized, the present invention may be used to lateralize the seizure focus.
FIG. 8 illustrates onemethod 120 of lateralizing a seizure focus in a patient. Atstep 122, a set of implantable devices are implanted beneath at least one layer of the patient's scalp and above the patient's skull (or below the skull, if desired). Preferably, the implantable devices will comprise more than two electrodes to improve the ability to localize the seizure focus. For embodiments that only include two electrodes, a very large number of implantable devices may be required to actually localize the seizure focus. In one embodiment, implantation may be carried out using the method steps 102-108 illustrated inFIG. 7 . Atstep 124, the set of implantable devices are used to sample the patient's EEG signals. At step 126, each of the EEG signals from the implantable devices are analyzed over a period of time (e.g., with EEG analysis software, such as a seizure detection algorithm) to monitor the patient's seizure activity and once a seizure has occurred try to lateralize the seizure focus. At step 128, if the seizure focus is lateralized, a subset of the implantable devices that are lateralized to the seizure focus are identified. Atsteps - In another use, the present invention may be used to quantify seizure activity statistics for the patient. The most common method of quantifying a patient's seizure activity is through patient self reporting using a seizure diary. Unfortunately, it has been estimated that up to 63% of all seizures are missed by patients. Patient's missing the seizures are usually caused by the patients being amnesic to the seizures, unaware of the seizures, mentally incapacitated, the seizures occur during sleep, or the like.
FIG. 9 illustrates asimplified method 140 of measuring and reporting a patient's seizure activity statistics. Atstep 142, one or more implantable devices are implanted in a patient, typically in a minimally invasive fashion as shown inFIG. 7 . Atstep 144, the implantable devices are used to substantially continuously sample EEG signals from the patient. Atstep 146, the sampled EEG signals are wirelessly transmitted from the implantable device to an external device. Atstep 148, the sampled EEG signals are stored in a memory. Atstep 150, the stored EEG signals are analyzed with EEG analysis software, typically using a seizure prediction and/or detection algorithm, to derive statistics for the clinical seizures and/or the sub-clinical seizures for the patient based on the long-term, ambulatory EEG data. For example, the following statistics may be quantified using the present invention: -
- Seizure count over a time period—How many clinical and sub-clinical seizures does the patient have in a specific time period?
- Seizure frequency—How frequent does the patient have seizures? What is the seizure frequency without medication and with medication? Without electrical stimulation and with electrical stimulation?
- Seizure duration—How long do the seizures last? Without medication and with medication? Without electrical stimulation and with electrical stimulation?
- Seizure timing—When did the patient have the seizure? Do the seizures occur more frequently at certain times of the day?
- Seizure patterns—Is there a pattern to the patient's seizures? After certain activities are performed? What activities appear to trigger seizures for this particular patient?
- Finally, at
step 152, report generation software may be used to generate a report based on the statistics for the seizure activity. The report may include some or all of the statistics described above, an epilepsy/no epilepsy diagnosis, identification of a seizure focus, and may also include the EEG signal(s) associated with one or more of the seizures. The report may include text, graphs, charts, images, or a combination thereof so as to present the information to the physician and/or patient in an actionable format. Advantageously, the systems may be used to generate a baseline report for the patient, and the system may be continuously used to record data over a long period of time and provide a quantification of the patient's change in their condition and/or the efficacy of any therapy that the patient is undergoing (described in more detail below). - As noted above, the present invention enables the documentation and long term monitoring of sub-clinical seizures in a patient. Because the patient is unaware of the occurrence of sub-clinical seizures, heretofore the long term monitoring of sub-clinical seizures was not possible. Documentation of the sub-clinical seizures may further provide insight into the relationship between sub-clinical seizures and clinical seizures, may provide important additional information relevant to the effectiveness of patient therapy, and may further enhance the development of additional treatments for epilepsy.
-
FIG. 10 illustrates one exemplary method of how the seizure activity data may be used to evaluate the efficacy or clinical benefit of a current or potential therapy and allow for the intelligent selection of an appropriate therapy for an individual patient and/or stopping the usage of ineffective therapies. Currently, effectiveness of the AED therapy is based on self-reporting of the patient, in which the patient makes entries in a diary regarding the occurrence of their seizure(s). If the entries in the patient diary indicate a reduction in seizure frequency, the AED is deemed to be effective and the patient continues with some form of the current regimen of AEDs. If the patient entries in the patient diary do not indicate a change in seizure frequency, the AEDs are deemed to be ineffective, and typically another AED is prescribed—and most often in addition to the AED that was deemed to be ineffective. Because AEDs are typically powerful neural suppressants and are associated with undesirable side-effects, the current methodology of assessing the efficacy of the AEDs often keeps the patient on ineffective AEDs and exposes the patient to unnecessary side-effects. - By way of example, a medically refractory patient coming to an epilepsy center for the first time might first have the system of the present invention implanted and then asked to collect data for a prescribed time period, e.g., 30 days. The initial 30 days could be used to establish a baseline measurement for future reference. The physician could then prescribe an adjustment to the patient's medications and have the patient collect data for another time period, e.g., an additional 30 day period. Metrics from this analysis could then be compared to the previous analysis to see if the adjustment to the medications resulted in an improvement. If the improvement was not satisfactory, the patient can be taken off of the unsatisfactory medication, and a new medication could be tried. This process could continue until a satisfactory level of seizure control was achieved. The present invention provides a metric that allows physicians and patients to make informed decisions on the effectiveness and non-effectiveness of the medications.
-
FIG. 10 schematically illustrates one example of such a method. Atstep 162, one or more implantable devices are implanted in the patient, typically in a minimally-invasive fashion. At step 164, the one or more implantable devices are used to monitor the patient's EEG to obtain a baseline measurement for the patient. The baseline measurement is typically seizure activity statistics for a specific time period (e.g., number of seizures, seizure duration, seizure pattern, seizure frequency, etc.). It should be appreciated however, that the baseline measurement may include any number of types of metrics. For example, the baseline metric may include univariate, bivariate, or multivariate features that are extracted from the EEG, or the like. In one preferred embodiment, the baseline measurement is performed while the patient is not taking any AEDs or using any other therapy. In other embodiments, however, the patient may be taking one or more AEDs and the baseline measurement will be used to evaluate adjustments to dosage or efficacy of other add-on therapies. - At
step 166, the therapy that is to be evaluated is commenced. The therapy will typically be an AED and the patient will typically have instructions from the neurologist, epileptologist, or drug-manufacturer regarding the treatment regimen for the AED. The treatment regimen may be constant (e.g., one pill a day) throughout the evaluation period, or the treatment regimen may call for varying of some parameter of the therapy (e.g., three pills a day for the first week, two pills a day for the second week, one pill a day for the third week, etc.) during the evaluation period. During the evaluation period, the implantable device(s) will be used to substantially continuously sample the patient's EEG and assess the effect that the AED has on the patient's EEG. The sampled EEG may thereafter be processed to obtain a follow-up measurement for the patient (Step 168). If the baseline measurement was seizure statistics for the baseline time period, then the follow-up measurement will be the corresponding seizure statistics for the evaluation period. Atstep 170, the baseline measurement is compared to the follow-up measurement to evaluate the therapy. If the comparison indicates that the therapy did not significantly change the patient's baseline, the therapy may be stopped, and other therapies may be tried. - Currently, the primary metric in evaluating the efficacy of an AED is whether or not the AED reduces the patient's seizure count. In addition to seizure count, the systems of the present invention would be able to track any reduction in seizure duration, modification in seizure patterns, reduction in seizure frequency, or the like. While seizure count is important, because the present invention is able to provide much greater detail than just seizure count, efficacy of an AED may be measured using a combination of additional metrics, if desired. For example, if the patient was having a large number of sub-clinical seizures (which the patient was not aware of) and the AED was effective in reducing or stopping the sub-clinical seizures, the systems of the present invention would be able to provide metrics for such a situation. With conventional patient diary “metrics”, the patient and physician would not be aware of such a reduction, and such an AED would be determined to be non-efficacious for the patient. However, because the present invention is able to provide metrics for the sub-clinical seizures, the efficacious medication could be continued, if desired.
- At
step 172, the epileptologist or neurologist may decide to change one or more parameters of the therapy. For example, they may change a dosage, frequency of dosage, form of the therapy or the like, and thereafter repeat the follow-up analysis for the therapy with the changed parameter. After the “second” follow up measurement is complete, the second follow up data may be obtained and thereafter compared to the “first” follow up measurements and/or the baseline measurements. While not shown inFIG. 10 , the method may also comprise generating a report that details the patient's metrics, change in metrics, recommendations, etc. - In addition to evaluating an efficacy of a therapy for an individual patient, the metrics that are provided by the present invention also enable an intelligent titration of a patient's medications. As shown in
FIG. 11 , if the patient is on a treatment regimen of an efficacious therapy, the present invention may be used to reduce/titrate a dosage or frequency of intake of the AED or AEDs, or other pharmacological agents. Atstep 182, one or more implantable devices are minimally invasively implanted in the patient. Typically, the patient will already be on a treatment regimen of the efficacious therapy, but if not, the efficacious therapy is commenced with the prescribed parameters, e.g., “standard” dosage (Step 184). Atstep 186, the patient's EEG (and/or other physiological signal) is monitored for a desired time period to obtain a first patient data measurement for the patient (e.g., the baseline measurement). Similar to previous embodiments, the first patient data measurement may be any desired metrics, but will typically be clinical seizure frequency, clinical seizure duration, sub-clinical seizure frequency, sub-clinical seizure duration, medication side effects. At step 188, after the baseline measurement has been taken, the first efficacious therapy is stopped and a therapy with at least one changed parameter is started (referred to as “therapy with second parameters” inFIG. 11 ). Typically, the changed parameter will be a reduction in dosage, but it could be changing a frequency of the same dosage, a change in formulation or form of the same AED, or the like. - At
step 190, the patient's EEG is monitored and processed to obtain a second patient data measurement for the patient (e.g., follow-up data measurement). If the neurologist or epileptologist is satisfied with the results, the titration may end. But in many embodiments, the titration process will require more than one modification of parameters of the therapy. In such embodiments, the second therapy is stopped (step 192), and a therapy with Nth parameters (e.g., third, fourth, fifth . . . ) is commenced (step 194). Monitoring and processing of the patient's EEG signals are repeated (step 196), and the process is repeated a desired number of times (as illustrated by arrow 197). Once the desired numbers of modifications to the therapy have been made, the various patient data measurements may be analyzed (e.g., compared to each other) to determine the most desirous parameters for the therapy (step 198). As can be imagined, any number of different analyses or statistical methods may be performed. In one embodiment, seizure activity statistics (e.g., clinical seizure frequency, sub-clinical seizure frequency, seizure rate per time period, seizure duration, seizure patterns, etc.) may be used to assess the efficacy and differences between the therapies. - With the instrumentation provided by the present invention, the process of selecting appropriate AEDs and the titration of dosages of such AEDs could occur much faster and with much greater insight than ever before. Further, the chance of a patient remaining on an incremental AED that was providing little incremental benefit would be minimized. Once a patient was under control, the patient could cease the use of the system, but the implantable device could remain in the patient. In the future, the patient might be asked to use the system again should their condition change or if the efficacy of the AED wane due to tolerance effects, etc.
- While
FIGS. 10 and 11 are primarily directed toward assessing the efficacy of a pharmacological agent (e.g., AED), such methods are equally applicable to assessing the efficacy and optimizing patient-specific parameters of non-pharmacological therapies. For example, the present invention may also be used to evaluate and optimize parameters for the electrical stimulation provided by the Vagus Nerve Stimulator (sold by Cyberonics Corporation), Responsive Neurostimulator (RNS) (manufactured by NeuroPace Corporation), Deep Brain Stimulators (manufactured by Medtronic), and other commercial and experimental neural and spinal cord stimulators. - Furthermore, the systems of the present invention will also be able to provide metrics for the effectiveness of changes to various electrical parameters (e.g., frequency, pulse amplitude, pulse width, pulses per burst, burst frequency, burst/no-burst, duty cycle, etc.) for the electrical stimulation treatments. Such metrics will provide a reliable indication regarding the effectiveness of such parameter changes, and could lead to optimization of stimulation for parameters for individual patients or the patient population as a whole.
- In addition to facilitating the selection of appropriate AEDs and titration of dosages of the AEDs for an individual patient, the present invention may have beneficial use in the clinical trials for the development of experimental AEDs and other therapies for the epileptic patient population (and other neurological conditions). One of the greatest barriers to developing new AEDs (and other pharmacological agents) is the costs and difficulties associated with the clinical trials. Presently, the standard metric for such clinical trials is patient seizure count. Because this metric is self-reported and presently so unreliable, to power the study appropriately clinical trials for AEDs must involve very large patient populations, in which the patient's must have a high seizure count. At an estimated cost of $20,000 per patient for pharmacological trials, the cost of developing a new drug for epilepsy is exceedingly high and may deter drug companies from developing AEDs.
- The minimally invasive systems of the present invention may be used to facilitate these clinical trials. Such systems could result in significantly more reliable data, which would result in much smaller sample patient populations, and could include a broader types of patients (e.g., patient's who don't have frequent seizures) for appropriately powering the study. Improved certainty in efficacy would also reduce risk to the company, as it moved from safety studies to efficacy studies. Significantly reducing risk and improving the economics of these studies by reducing the required number of study subjects could lead to an increase in the development of new therapies for this patient population, and other patient populations.
- It should be appreciated however, that the present invention is not limited to clinical trials for epilepsy therapies, and the present invention has equal applicability to other clinical trials (e.g., cancer therapy, cardiac therapy, therapy for other neurological disorders, therapy for psychiatric disorders, or the like.)
-
FIGS. 12-13 illustrate some methods of performing clinical trials that are encompassed by the present invention. The present invention is applicable to any type of clinical trial, including but not limited to a randomized clinical trial, e.g., an open clinical trial, a single-blinded study, a double-blinded study, a triple-blinded study, or the like. -
FIG. 12 illustrates asimplified method 200 of performing a clinical trial according to the present invention. Atstep 201 participants are enrolled in the clinical trial. Atstep 202, selected participants in the clinical trial are implanted with one or more leadless, implantable devices (such as those described above) in order to sample one or more physiological signal from the patient. Typically, the physiological signal is an EEG signal. In preferred embodiments, the EEG signal is sampled substantially continuously for the entire baseline period for each of the participants in the clinical trial. In alternative embodiments, it may be desirable to sample the EEG signals in a non-continuous basis. - At step 204, the sampled EEG signals are processed for a desired time period to obtain a first patient data measurement, e.g., a baseline data measurement, for each of the participants in the clinical trial. After the participants have commenced the experimental therapy (typically by following a prescribed treatment regimen by the investigator or drug company), the same implantable devices are used to sample the EEG signals from the participant for an evaluation period, and the EEG signals are processed to provide a second patient data measurement, e.g., follow-up measurement (
Step 206, 208). Atstep 210, the baseline data measurement and the follow-up data measurement may be compared using conventional statistical methods in order to evaluate the experimental therapy on the patient population. - While not shown in
FIG. 12 , it may be desirable to have a “second” evaluation period (and a second follow-up measurement) in which at least one parameter of the experimental therapy is changed and the changed experimental therapy is administered to the patient. Similar to the method ofFIG. 11 , such a method may provide guidance to finding the appropriate dosing, formulation, and/or form of delivery of the experimental therapy. - The baseline period and the evaluation period are typically the same time length. The time length may be any desired time, but is typically at least one week, and preferably between at least one month and at least three months.
- Evaluation of the experimental therapy may be to evaluate dosing requirements, evaluate toxicity of the experimental therapy, evaluate long-term adverse effects of the experimental therapy or to determine efficacy of the experimental therapy. In one preferred embodiment, the comparison may simply determine whether there was a statistically significant change in a seizure count between the baseline period and the evaluation period. But as noted above, the baseline data measurement and follow-up data measurement may include any metric that is extracted from the EEG signals.
-
FIG. 13 illustrates a more detailed method of performing a clinical trial according to the present invention. Atstep 222 participants are enrolled in the clinical trial. Atstep 224, the participants in the clinical trial are implanted with one or more leadless, implantable devices (such as those described above) in order to sample one or more physiological signal from the patient. Typically, the physiological signal is an EEG signal. In preferred embodiments, the EEG signal is sampled substantially continuously for the entire baseline period for each of the participants in the clinical trial. - At step 226, the sampled EEG signals are processed to obtain a first patient data measurement, e.g., a baseline data measurement, for each of the participants in the clinical trial. If the patient's do not have any seizures during the baseline period, then the patient's will most likely be excluded from the remainder of the clinical trial. The remaining participants in the clinical trial are then broken into an intervention group and a control group. The experimental therapy is commenced in the intervention group of the patient population (step 228), and a placebo therapy is commenced in the control group of the patient population (step 230).
- The implantable devices are used to substantially continuously sample the EEG signals of both the intervention group and the control group during an evaluation period. The EEG signals are processed to obtain follow-up seizure activity data (or some other metric) for both groups (step 232, 234). Thereafter, the baseline data and the follow up data for both the intervention group and the control group are analyzed, (e.g., compared with each other) to evaluate the efficacy of the experimental therapy for the patient population (step 236). While not shown in
FIG. 13 , the method may further include changing one or more parameters of the experimental therapy and comparing the “second” follow up data to the baseline data and/or other follow up data. - While the preferred embodiments described above are directed toward evaluating experimental AEDs in the clinical trial, the present invention is equally applicable to clinical trials for other experimental pharmacological agents, biologics, devices, and other non-pharmacological therapies. For example, the present invention may also be used to evaluate the Vagus Nerve Stimulator (sold by Cyberonics Corporation), Responsive Neurostimulator (RNS) (manufactured by NeuroPace Corporation), Deep Brain Stimulators manufactured by Medtronic, and other commercial and experimental neural and spinal cord stimulators. The minimally invasive systems of the present invention may be implanted in patients who are equipped with any of the above stimulators to provide metrics regarding the efficacy of the electrical stimulation treatments.
- Furthermore, the systems of the present invention will also be able to provide metrics for the effectiveness of changes to various electrical parameters (e.g., frequency, pulse amplitude, pulse width, pulses per burst, burst frequency, burst/no-burst, etc.) for the electrical stimulation treatments. Such metrics will provide a reliable indication regarding the effectiveness of such parameter changes, and could lead to optimization of stimulation for parameters for individual patients or the patient population as a whole.
-
FIG. 14 illustrates a packaged system orkit 300 that is encompassed by the present invention. The packagedsystem 300 may include apackage 302 that has one or more compartments for receiving anintroducer assembly 304 and one or moreimplantable devices 12. Theintroducer 304 is typically in the form of a syringe-like device or a cannula and stylet. Theimplantable device 12 may include any of the embodiments described herein. One or more of theimplantable devices 12 may be pre-loaded within theintroducer 304. In other embodiments, theimplantable devices 12 may be loaded in its separate sterile packaging (shown in dotted lines) for easy loading into theintroducer 304. The packagedsystem 300 may include instructions for use (“IFU”) 306 that describe any of the methods described herein. - While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. For example, the present invention also encompasses other more invasive embodiments which may be used to monitor the patient's neurological system.
- Alternative embodiments of the implantable device of the present invention may require a neurosurgeon to create a more invasive incision in the patient's scalp. For example, it may be desirable to use a low profile device that is not substantially cylindrical, but instead is substantially planar or concave so as to conform to the curvature of the patient's skull. Such embodiments would likely not be able to be implanted without general anesthesia and may require a surgeon to implant the device.
- On the other hand, in some embodiments it may be desirable to be completely non-invasive. Such embodiments include “implantable”
devices 12 that are not actually implanted, but instead are “wearable” and may be attached to the outer surface of the skin with adhesive or a bandage so as to maintain contact with the patient's skin. For example, it may be possible to surface mount thedevice 12 behind the ears, in the scalp, on the forehead, along the jaw, or the like. Because the electrodes are wireless and are such a small size, unlike conventional electrodes, the visual appearance of the electrodes will be minimal. - Furthermore, in some embodiments, it may be desirable to modify the
implantable device 12 to provide stimulation to the patient. In such embodiments, theimplantable device 12 will include a pulse generator and associated hardware and software for delivering stimulation to the patient through the first andsecond electrodes 24, 26 (or other electrodes coupled to the device. In such embodiments, theexternal device 14 will include the hardware and software to generate the control signals for delivering the electrical stimulation to the patient. - While the above embodiments describe that power to the implanted devices may be derived wirelessly from an external device and/or from a battery in the implanted device, it should be appreciated that the internal devices may derive or otherwise “scavenge” power from other types of conventional or proprietary assemblies. Such scavenging methods may be used in conjunction with the external power source and/or the internal power source, or it may be used by itself to provide the necessary power for the implanted devices. For example, the implanted devices may include circuitry and other assemblies (e.g., a microgenerator) that derive and store power from patient-based energy sources such as kinetic movement/vibrations (e.g., gross body movements), movement of organs or other bodily fluids (e.g., heart, lungs, blood flow), and thermal sources in the body (e.g., temperature differences and variations across tissue). As can be imagined, such technology could reduce or eliminate the need for recharging of an implanted battery, replacement of a depleted battery, and/or the creation of an external RF field—and would improve the ease of use of the devices by the patients.
- Some embodiments of the monitoring system may include an integral patient diary functionality. The patient diary may be a module in the external device and inputs by the patient may be used to provide secondary inputs to provide background information for the sampled EEG signals. For example, if a seizure is recorded, the seizure diary may provide insight regarding a trigger to the seizure, or the like. The diary may automatically record the time and date of the entry by the patient. Entries by the patient may be a voice recording, or through activation of user inputs on the external device. The diary may be used to indicate the occurrence of an aura, occurrence of a seizure, the consumption of a meal, missed meal, delayed meal, activities being performed, consumption of alcohol, the patient's sleep state (drowsy, going to sleep, waking up, etc.), mental state (e.g., depressed, excited, stressed), intake of their AEDs, medication changes, missed dosage of medication, menstrual cycle, illness, or the like. Thereafter, the patient inputs recorded in the diary may also be used by the physician in assessing the patient's epilepsy state and/or determine the efficacy of the current treatment. Furthermore, the physician may be able to compare the number of seizures logged by the patient to the number of seizures detected by the seizure detection algorithm.
- It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.
Claims (26)
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Cited By (48)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060293720A1 (en) * | 1998-08-05 | 2006-12-28 | Dilorenzo Daniel J | Closed-loop feedback-driven neuromodulation |
US20070233193A1 (en) * | 2006-03-29 | 2007-10-04 | Catholic Healthcare West (D/B/A St. Joseph's Hospital And Medical Center) | Microburst electrical stimulation of cranial nerves for the treatment of medical conditions |
US20070255351A1 (en) * | 2006-04-28 | 2007-11-01 | Cyberonics, Inc. | Threshold optimization for tissue stimulation therapy |
US20080114417A1 (en) * | 2006-11-14 | 2008-05-15 | Leyde Kent W | Systems and methods of reducing artifact in neurological stimulation systems |
US20080208074A1 (en) * | 2007-02-21 | 2008-08-28 | David Snyder | Methods and Systems for Characterizing and Generating a Patient-Specific Seizure Advisory System |
US20080269839A1 (en) * | 2007-04-27 | 2008-10-30 | Armstrong Randolph K | Dosing Limitation for an Implantable Medical Device |
US20090171420A1 (en) * | 2007-12-28 | 2009-07-02 | David Brown | Housing for an Implantable Medical Device |
US20090171168A1 (en) * | 2007-12-28 | 2009-07-02 | Leyde Kent W | Systems and Method for Recording Clinical Manifestations of a Seizure |
US20090192564A1 (en) * | 2005-01-28 | 2009-07-30 | Armstrong Randolph K | Changeable electrode polarity stimulation by an implantable medical device |
US20100023089A1 (en) * | 1998-08-05 | 2010-01-28 | Dilorenzo Daniel John | Controlling a Subject's Susceptibility to a Seizure |
US20100125219A1 (en) * | 2006-06-23 | 2010-05-20 | Harris John F | Minimally invasive system for selecting patient-specific therapy parameters |
US20100168603A1 (en) * | 2008-12-23 | 2010-07-01 | Himes David M | Brain state analysis based on select seizure onset characteristics and clinical manifestations |
US20100179627A1 (en) * | 2009-01-09 | 2010-07-15 | Jared Floyd | Medical Lead Termination Sleeve for Implantable Medical Devices |
US20100217348A1 (en) * | 1998-08-05 | 2010-08-26 | Neurovista Corporation | Systems for Monitoring a Patient's Neurological Disease State |
US7869867B2 (en) | 2006-10-27 | 2011-01-11 | Cyberonics, Inc. | Implantable neurostimulator with refractory stimulation |
WO2011066852A1 (en) * | 2009-12-02 | 2011-06-09 | Widex A/S | Method and apparatus for alerting a person carrying an eeg assembly |
US7962220B2 (en) | 2006-04-28 | 2011-06-14 | Cyberonics, Inc. | Compensation reduction in tissue stimulation therapy |
US20110172554A1 (en) * | 2007-01-25 | 2011-07-14 | Leyde Kent W | Patient Entry Recording in an Epilepsy Monitoring System |
WO2011091856A1 (en) * | 2010-02-01 | 2011-08-04 | Widex A/S | Portable eeg monitor system with wireless communication |
US7996079B2 (en) | 2006-01-24 | 2011-08-09 | Cyberonics, Inc. | Input response override for an implantable medical device |
US20110218820A1 (en) * | 2010-03-02 | 2011-09-08 | Himes David M | Displaying and Manipulating Brain Function Data Including Filtering of Annotations |
US20110219325A1 (en) * | 2010-03-02 | 2011-09-08 | Himes David M | Displaying and Manipulating Brain Function Data Including Enhanced Data Scrolling Functionality |
US8036736B2 (en) | 2007-03-21 | 2011-10-11 | Neuro Vista Corporation | Implantable systems and methods for identifying a contra-ictal condition in a subject |
US8204603B2 (en) | 2008-04-25 | 2012-06-19 | Cyberonics, Inc. | Blocking exogenous action potentials by an implantable medical device |
US8260426B2 (en) | 2008-01-25 | 2012-09-04 | Cyberonics, Inc. | Method, apparatus and system for bipolar charge utilization during stimulation by an implantable medical device |
US8457747B2 (en) | 2008-10-20 | 2013-06-04 | Cyberonics, Inc. | Neurostimulation with signal duration determined by a cardiac cycle |
US8562523B2 (en) | 2011-03-04 | 2013-10-22 | Flint Hills Scientific, Llc | Detecting, assessing and managing extreme epileptic events |
US8562524B2 (en) | 2011-03-04 | 2013-10-22 | Flint Hills Scientific, Llc | Detecting, assessing and managing a risk of death in epilepsy |
US8684921B2 (en) | 2010-10-01 | 2014-04-01 | Flint Hills Scientific Llc | Detecting, assessing and managing epilepsy using a multi-variate, metric-based classification analysis |
US8786624B2 (en) | 2009-06-02 | 2014-07-22 | Cyberonics, Inc. | Processing for multi-channel signals |
US8849390B2 (en) | 2008-12-29 | 2014-09-30 | Cyberonics, Inc. | Processing for multi-channel signals |
US20150018705A1 (en) * | 2013-07-12 | 2015-01-15 | Innara Health | Neural analysis and treatment system |
US9044188B2 (en) | 2005-12-28 | 2015-06-02 | Cyberonics, Inc. | Methods and systems for managing epilepsy and other neurological disorders |
US9314633B2 (en) | 2008-01-25 | 2016-04-19 | Cyberonics, Inc. | Contingent cardio-protection for epilepsy patients |
US9415222B2 (en) | 1998-08-05 | 2016-08-16 | Cyberonics, Inc. | Monitoring an epilepsy disease state with a supervisory module |
US9504390B2 (en) | 2011-03-04 | 2016-11-29 | Globalfoundries Inc. | Detecting, assessing and managing a risk of death in epilepsy |
US9643019B2 (en) | 2010-02-12 | 2017-05-09 | Cyberonics, Inc. | Neurological monitoring and alerts |
EP3110323A4 (en) * | 2014-02-27 | 2017-08-09 | New York University | Minimally invasive subgaleal extra-cranial electroencephalography (eeg) monitoring device |
US9788744B2 (en) | 2007-07-27 | 2017-10-17 | Cyberonics, Inc. | Systems for monitoring brain activity and patient advisory device |
US9898656B2 (en) | 2007-01-25 | 2018-02-20 | Cyberonics, Inc. | Systems and methods for identifying a contra-ictal condition in a subject |
US10448839B2 (en) | 2012-04-23 | 2019-10-22 | Livanova Usa, Inc. | Methods, systems and apparatuses for detecting increased risk of sudden death |
US10653883B2 (en) | 2009-01-23 | 2020-05-19 | Livanova Usa, Inc. | Implantable medical device for providing chronic condition therapy and acute condition therapy using vagus nerve stimulation |
US11273283B2 (en) | 2017-12-31 | 2022-03-15 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement to enhance emotional response |
US11364361B2 (en) | 2018-04-20 | 2022-06-21 | Neuroenhancement Lab, LLC | System and method for inducing sleep by transplanting mental states |
US11452839B2 (en) | 2018-09-14 | 2022-09-27 | Neuroenhancement Lab, LLC | System and method of improving sleep |
US11717686B2 (en) | 2017-12-04 | 2023-08-08 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement to facilitate learning and performance |
US11723579B2 (en) | 2017-09-19 | 2023-08-15 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement |
US11786694B2 (en) | 2019-05-24 | 2023-10-17 | NeuroLight, Inc. | Device, method, and app for facilitating sleep |
Families Citing this family (166)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7209787B2 (en) | 1998-08-05 | 2007-04-24 | Bioneuronics Corporation | Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease |
US7044911B2 (en) * | 2001-06-29 | 2006-05-16 | Philometron, Inc. | Gateway platform for biological monitoring and delivery of therapeutic compounds |
US8447234B2 (en) * | 2006-01-18 | 2013-05-21 | Qualcomm Incorporated | Method and system for powering an electronic device via a wireless link |
US9130602B2 (en) | 2006-01-18 | 2015-09-08 | Qualcomm Incorporated | Method and apparatus for delivering energy to an electrical or electronic device via a wireless link |
JP2009529975A (en) * | 2006-03-17 | 2009-08-27 | ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー | Energy generation system for implantable medical devices |
US7747551B2 (en) * | 2007-02-21 | 2010-06-29 | Neurovista Corporation | Reduction of classification error rates and monitoring system using an artificial class |
US9774086B2 (en) * | 2007-03-02 | 2017-09-26 | Qualcomm Incorporated | Wireless power apparatus and methods |
US8214453B2 (en) * | 2007-03-14 | 2012-07-03 | Steven Charles Estes | Concept and associated device enabling multi-camera video and audio recording for synchronization with long term ambulatory electroencephalography (EEG) in the home, office, or hospital environment |
JP5309126B2 (en) | 2007-03-29 | 2013-10-09 | ニューロフォーカス・インコーポレーテッド | System, method, and apparatus for performing marketing and entertainment efficiency analysis |
WO2008137579A1 (en) | 2007-05-01 | 2008-11-13 | Neurofocus, Inc. | Neuro-informatics repository system |
US9886981B2 (en) | 2007-05-01 | 2018-02-06 | The Nielsen Company (Us), Llc | Neuro-feedback based stimulus compression device |
US8392253B2 (en) | 2007-05-16 | 2013-03-05 | The Nielsen Company (Us), Llc | Neuro-physiology and neuro-behavioral based stimulus targeting system |
US20090024449A1 (en) * | 2007-05-16 | 2009-01-22 | Neurofocus Inc. | Habituation analyzer device utilizing central nervous system, autonomic nervous system and effector system measurements |
US8494905B2 (en) | 2007-06-06 | 2013-07-23 | The Nielsen Company (Us), Llc | Audience response analysis using simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) |
US9124120B2 (en) * | 2007-06-11 | 2015-09-01 | Qualcomm Incorporated | Wireless power system and proximity effects |
CN101815467B (en) | 2007-07-30 | 2013-07-17 | 神经焦点公司 | Neuro-response stimulus and stimulus attribute resonance estimator |
CN101842962B (en) * | 2007-08-09 | 2014-10-08 | 高通股份有限公司 | Increasing the Q factor of a resonator |
KR20100047865A (en) * | 2007-08-28 | 2010-05-10 | 뉴로포커스, 인크. | Consumer experience assessment system |
US8635105B2 (en) | 2007-08-28 | 2014-01-21 | The Nielsen Company (Us), Llc | Consumer experience portrayal effectiveness assessment system |
US8386313B2 (en) | 2007-08-28 | 2013-02-26 | The Nielsen Company (Us), Llc | Stimulus placement system using subject neuro-response measurements |
US8392255B2 (en) | 2007-08-29 | 2013-03-05 | The Nielsen Company (Us), Llc | Content based selection and meta tagging of advertisement breaks |
US8014167B2 (en) * | 2007-09-07 | 2011-09-06 | Seagate Technology Llc | Liquid crystal material sealed housing |
EP2188863A1 (en) | 2007-09-13 | 2010-05-26 | QUALCOMM Incorporated | Maximizing power yield from wireless power magnetic resonators |
JP2010539857A (en) * | 2007-09-17 | 2010-12-16 | クゥアルコム・インコーポレイテッド | Transmitter and receiver for wireless energy transmission |
US20090083129A1 (en) | 2007-09-20 | 2009-03-26 | Neurofocus, Inc. | Personalized content delivery using neuro-response priming data |
US8494610B2 (en) | 2007-09-20 | 2013-07-23 | The Nielsen Company (Us), Llc | Analysis of marketing and entertainment effectiveness using magnetoencephalography |
WO2009049281A2 (en) * | 2007-10-11 | 2009-04-16 | Nigel Power, Llc | Wireless power transfer using magneto mechanical systems |
US8457757B2 (en) | 2007-11-26 | 2013-06-04 | Micro Transponder, Inc. | Implantable transponder systems and methods |
US9089707B2 (en) | 2008-07-02 | 2015-07-28 | The Board Of Regents, The University Of Texas System | Systems, methods and devices for paired plasticity |
GB0800615D0 (en) | 2008-01-14 | 2008-02-20 | Hypo Safe As | Implantable electronic device |
US8986253B2 (en) | 2008-01-25 | 2015-03-24 | Tandem Diabetes Care, Inc. | Two chamber pumps and related methods |
EP2092958B1 (en) * | 2008-02-22 | 2017-05-24 | Cochlear Limited | Interleaving power and data in a transcutaneous communications link |
US8629576B2 (en) | 2008-03-28 | 2014-01-14 | Qualcomm Incorporated | Tuning and gain control in electro-magnetic power systems |
EP2294524B1 (en) * | 2008-04-18 | 2017-06-07 | Medtronic, Inc. | Analyzing a washout period characteristic for psychiatric disorder therapy delivery |
US10493281B2 (en) * | 2008-04-18 | 2019-12-03 | Medtronic, Inc. | Timing therapy evaluation trials |
WO2009129480A2 (en) * | 2008-04-18 | 2009-10-22 | Medtronic, Inc. | Psychiatric disorder therapy control |
KR20100139144A (en) * | 2008-04-21 | 2010-12-31 | 카를 프레데릭 에드만 | Metabolic energy monitoring system |
US20110218605A1 (en) * | 2008-09-10 | 2011-09-08 | Adrian Cryer | Upgradeable implantable device |
US8408421B2 (en) | 2008-09-16 | 2013-04-02 | Tandem Diabetes Care, Inc. | Flow regulating stopcocks and related methods |
EP2334234A4 (en) | 2008-09-19 | 2013-03-20 | Tandem Diabetes Care Inc | Solute concentration measurement device and related methods |
CN102177519A (en) * | 2008-10-10 | 2011-09-07 | 皇家飞利浦电子股份有限公司 | Health-risk metric determination and/or presentation |
US20100114237A1 (en) * | 2008-10-31 | 2010-05-06 | Medtronic, Inc. | Mood circuit monitoring to control therapy delivery |
US8204574B2 (en) * | 2008-11-21 | 2012-06-19 | Medtronic, Inc. | Stylet for use with image guided systems |
US8792973B2 (en) * | 2008-11-21 | 2014-07-29 | Washington University | Bipolar sieve electrode and method of assembly |
WO2010065604A1 (en) * | 2008-12-02 | 2010-06-10 | Purdue Research Foundation | Radio transparent sensor implant package |
WO2010065741A1 (en) * | 2008-12-04 | 2010-06-10 | Neurovista Corporation | Universal electrode array for monitoring brain activity |
US8412336B2 (en) | 2008-12-29 | 2013-04-02 | Autonomic Technologies, Inc. | Integrated delivery and visualization tool for a neuromodulation system |
US9320908B2 (en) * | 2009-01-15 | 2016-04-26 | Autonomic Technologies, Inc. | Approval per use implanted neurostimulator |
US20130110195A1 (en) * | 2009-01-15 | 2013-05-02 | Autonomic Technologies, Inc. | Neurostimulator system, apparatus, and method |
US20130116745A1 (en) * | 2009-01-15 | 2013-05-09 | Autonomic Technologies, Inc. | Neurostimulator system, apparatus, and method |
US8270814B2 (en) | 2009-01-21 | 2012-09-18 | The Nielsen Company (Us), Llc | Methods and apparatus for providing video with embedded media |
US8464288B2 (en) | 2009-01-21 | 2013-06-11 | The Nielsen Company (Us), Llc | Methods and apparatus for providing personalized media in video |
US9357240B2 (en) | 2009-01-21 | 2016-05-31 | The Nielsen Company (Us), Llc | Methods and apparatus for providing alternate media for video decoders |
US9161693B2 (en) | 2009-03-19 | 2015-10-20 | University Of Florida Research Foundation, Inc. | Miniaturized electronic device ingestible by a subject or implantable inside a body of the subject |
US20100250325A1 (en) | 2009-03-24 | 2010-09-30 | Neurofocus, Inc. | Neurological profiles for market matching and stimulus presentation |
US20100292545A1 (en) * | 2009-05-14 | 2010-11-18 | Advanced Brain Monitoring, Inc. | Interactive psychophysiological profiler method and system |
US10238822B2 (en) | 2009-05-29 | 2019-03-26 | Resmed Limited | PAP system |
WO2010149158A1 (en) * | 2009-06-26 | 2010-12-29 | Widex A/S | Eeg monitoring system and method of monitoring an eeg |
CA2921304C (en) | 2009-07-30 | 2018-06-05 | Tandem Diabetes Care, Inc. | Infusion pump system with disposable cartridge having pressure venting and pressure feedback |
US8655437B2 (en) * | 2009-08-21 | 2014-02-18 | The Nielsen Company (Us), Llc | Analysis of the mirror neuron system for evaluation of stimulus |
US10987015B2 (en) | 2009-08-24 | 2021-04-27 | Nielsen Consumer Llc | Dry electrodes for electroencephalography |
EP3388101A1 (en) | 2009-08-28 | 2018-10-17 | Resmed Limited | Pap system |
US20110106750A1 (en) | 2009-10-29 | 2011-05-05 | Neurofocus, Inc. | Generating ratings predictions using neuro-response data |
US9560984B2 (en) | 2009-10-29 | 2017-02-07 | The Nielsen Company (Us), Llc | Analysis of controlled and automatic attention for introduction of stimulus material |
US8209224B2 (en) | 2009-10-29 | 2012-06-26 | The Nielsen Company (Us), Llc | Intracluster content management using neuro-response priming data |
US8838217B2 (en) | 2009-11-10 | 2014-09-16 | Makor Issues And Rights Ltd. | System and apparatus for providing diagnosis and personalized abnormalities alerts and for providing adaptive responses in clinical trials |
EP2501535B1 (en) * | 2009-11-19 | 2017-11-15 | Stratasys, Inc. | Encoded consumable filaments for use in additive manufacturing systems |
US20110117268A1 (en) * | 2009-11-19 | 2011-05-19 | Stratasys, Inc. | Consumable materials having encoded markings for use with direct digital manufacturing systems |
US8335715B2 (en) | 2009-11-19 | 2012-12-18 | The Nielsen Company (Us), Llc. | Advertisement exchange using neuro-response data |
US8335716B2 (en) | 2009-11-19 | 2012-12-18 | The Nielsen Company (Us), Llc. | Multimedia advertisement exchange |
US8914115B2 (en) * | 2009-12-03 | 2014-12-16 | Medtronic, Inc. | Selecting therapy cycle parameters based on monitored brain signal |
US8886323B2 (en) * | 2010-02-05 | 2014-11-11 | Medtronic, Inc. | Electrical brain stimulation in gamma band |
WO2011112972A2 (en) * | 2010-03-11 | 2011-09-15 | Philometron, Inc. | Physiological monitor system for determining medication delivery and outcome |
WO2011133548A2 (en) | 2010-04-19 | 2011-10-27 | Innerscope Research, Inc. | Short imagery task (sit) research method |
US8655428B2 (en) | 2010-05-12 | 2014-02-18 | The Nielsen Company (Us), Llc | Neuro-response data synchronization |
US8552311B2 (en) | 2010-07-15 | 2013-10-08 | Advanced Bionics | Electrical feedthrough assembly |
US8386047B2 (en) * | 2010-07-15 | 2013-02-26 | Advanced Bionics | Implantable hermetic feedthrough |
US9095266B1 (en) * | 2010-08-02 | 2015-08-04 | Chi Yung Fu | Method for treating a patient |
US9037224B1 (en) * | 2010-08-02 | 2015-05-19 | Chi Yung Fu | Apparatus for treating a patient |
US8392251B2 (en) | 2010-08-09 | 2013-03-05 | The Nielsen Company (Us), Llc | Location aware presentation of stimulus material |
US8392250B2 (en) | 2010-08-09 | 2013-03-05 | The Nielsen Company (Us), Llc | Neuro-response evaluated stimulus in virtual reality environments |
US8396744B2 (en) | 2010-08-25 | 2013-03-12 | The Nielsen Company (Us), Llc | Effective virtual reality environments for presentation of marketing materials |
KR101304338B1 (en) * | 2010-10-21 | 2013-09-11 | 주식회사 엠아이텍 | LCP-based electro-optrode neural interface and Method for fabricating the same |
US8565886B2 (en) | 2010-11-10 | 2013-10-22 | Medtronic, Inc. | Arousal state modulation with electrical stimulation |
EP2663229B1 (en) | 2011-01-12 | 2021-08-11 | T&W Engineering A/S | Bi-hemispheric brain wave system and method of performing bi-hemispherical brain wave measurements |
KR101652571B1 (en) | 2011-01-20 | 2016-08-30 | 티앤더블유 엔지니어링 에이/에스 | Personal eeg monitoring device with electrode validation |
WO2012103224A1 (en) | 2011-01-25 | 2012-08-02 | Medtronic, Inc. | Target therapy delivery site selection |
WO2012109447A1 (en) | 2011-02-09 | 2012-08-16 | The Charles Stark Draper Laboratory, Inc. | Wireless, implantable electro-encephalography system |
CN103492022A (en) | 2011-04-04 | 2014-01-01 | 斯蒂维科技公司 | Implantable lead |
US20130172774A1 (en) * | 2011-07-01 | 2013-07-04 | Neuropace, Inc. | Systems and Methods for Assessing the Effectiveness of a Therapy Including a Drug Regimen Using an Implantable Medical Device |
US8723640B2 (en) | 2011-08-16 | 2014-05-13 | Elwha Llc | Distillation of status data relating to regimen compliance responsive to the presence and absence of wireless signals relating to one or more threshold frequencies |
WO2013040549A1 (en) | 2011-09-15 | 2013-03-21 | Stimwave Technologies Incorporated | Relay module for implant |
US20130072809A1 (en) * | 2011-09-19 | 2013-03-21 | Persyst Development Corporation | Method And System For Analyzing An EEG Recording |
RU2473304C1 (en) * | 2011-12-28 | 2013-01-27 | Учреждение Российской академии медицинских наук Научно-исследовательский институт нейрохирургии имени академика Н.Н. Бурденко РАМН | Method of diagnosing malignancy of neuroepithelial tumours of iii ventricle by data of electroencephalographic examination |
US9292858B2 (en) | 2012-02-27 | 2016-03-22 | The Nielsen Company (Us), Llc | Data collection system for aggregating biologically based measures in asynchronous geographically distributed public environments |
US9451303B2 (en) | 2012-02-27 | 2016-09-20 | The Nielsen Company (Us), Llc | Method and system for gathering and computing an audience's neurologically-based reactions in a distributed framework involving remote storage and computing |
US9569986B2 (en) | 2012-02-27 | 2017-02-14 | The Nielsen Company (Us), Llc | System and method for gathering and analyzing biometric user feedback for use in social media and advertising applications |
US9180242B2 (en) | 2012-05-17 | 2015-11-10 | Tandem Diabetes Care, Inc. | Methods and devices for multiple fluid transfer |
US9555186B2 (en) | 2012-06-05 | 2017-01-31 | Tandem Diabetes Care, Inc. | Infusion pump system with disposable cartridge having pressure venting and pressure feedback |
CN103747722A (en) * | 2012-06-05 | 2014-04-23 | 博伊雷尔有限责任公司 | Stress and burn-out analysis and diagnostic device |
US8989835B2 (en) | 2012-08-17 | 2015-03-24 | The Nielsen Company (Us), Llc | Systems and methods to gather and analyze electroencephalographic data |
US20140148723A1 (en) * | 2012-11-26 | 2014-05-29 | Persyst Development Corporation | Method And System For Displaying The Amount Of Artifact Present In An EEG Recording |
US9254393B2 (en) | 2012-12-26 | 2016-02-09 | Micron Devices Llc | Wearable antenna assembly |
US10039460B2 (en) | 2013-01-22 | 2018-08-07 | MiSleeping, Inc. | Neural activity recording apparatus and method of using same |
US9320450B2 (en) | 2013-03-14 | 2016-04-26 | The Nielsen Company (Us), Llc | Methods and apparatus to gather and analyze electroencephalographic data |
US9173998B2 (en) | 2013-03-14 | 2015-11-03 | Tandem Diabetes Care, Inc. | System and method for detecting occlusions in an infusion pump |
US20140276194A1 (en) * | 2013-03-15 | 2014-09-18 | Flint Hills Scientific, L.L.C. | Automated means to control responses to repetitive electrical stimulation and improve therapeutic efficacy |
US9687165B2 (en) * | 2013-03-15 | 2017-06-27 | Greatbatch Ltd. | Apparatus and method for electrocardiographic monitoring |
US9092552B2 (en) | 2013-04-26 | 2015-07-28 | Cyberonics, Inc. | System monitor for monitoring functional modules of a system |
AU2014273790A1 (en) * | 2013-05-28 | 2016-01-21 | Laszlo Osvath | Systems and methods for diagnosis of depression and other medical conditions |
US11229789B2 (en) | 2013-05-30 | 2022-01-25 | Neurostim Oab, Inc. | Neuro activator with controller |
CN105307719B (en) | 2013-05-30 | 2018-05-29 | 格雷厄姆·H.·克雷西 | Local nerve stimulation instrument |
US20140371544A1 (en) * | 2013-06-14 | 2014-12-18 | Medtronic, Inc. | Motion-based behavior identification for controlling therapy |
DK178081B9 (en) | 2013-06-21 | 2015-05-11 | Ictalcare As | Method of indicating the probability of psychogenic non-epileptic seizures |
US9601267B2 (en) | 2013-07-03 | 2017-03-21 | Qualcomm Incorporated | Wireless power transmitter with a plurality of magnetic oscillators |
US10929753B1 (en) | 2014-01-20 | 2021-02-23 | Persyst Development Corporation | System and method for generating a probability value for an event |
US9622702B2 (en) | 2014-04-03 | 2017-04-18 | The Nielsen Company (Us), Llc | Methods and apparatus to gather and analyze electroencephalographic data |
US10319475B1 (en) * | 2014-06-13 | 2019-06-11 | Enigami Systems, Inc. | Method and apparatus for determining relationships between medications and symptoms |
US11077301B2 (en) | 2015-02-21 | 2021-08-03 | NeurostimOAB, Inc. | Topical nerve stimulator and sensor for bladder control |
EP3277159A1 (en) * | 2015-03-31 | 2018-02-07 | Koninklijke Philips N.V. | System and method for automatic prediction and prevention of migraine and/or epilepsy |
US9936250B2 (en) | 2015-05-19 | 2018-04-03 | The Nielsen Company (Us), Llc | Methods and apparatus to adjust content presented to an individual |
US10542961B2 (en) | 2015-06-15 | 2020-01-28 | The Research Foundation For The State University Of New York | System and method for infrasonic cardiac monitoring |
DE102015010189A1 (en) * | 2015-08-04 | 2017-02-09 | Infineon Technologies Ag | Body parameter monitoring device |
US11045134B2 (en) | 2016-01-19 | 2021-06-29 | Washington University | Depression brain computer interface for the quantitative assessment of mood state and for biofeedback for mood alteration |
US11051712B2 (en) * | 2016-02-09 | 2021-07-06 | Verily Life Sciences Llc | Systems and methods for determining the location and orientation of implanted devices |
US11071869B2 (en) | 2016-02-24 | 2021-07-27 | Cochlear Limited | Implantable device having removable portion |
US10925538B2 (en) | 2016-03-14 | 2021-02-23 | The Nielsen Company (Us), Llc | Headsets and electrodes for gathering electroencephalographic data |
US10561333B2 (en) * | 2016-06-10 | 2020-02-18 | Mocxa Health Private Limited | Procedure and a portable apparatus for diagnosis of seizures |
US10067565B2 (en) * | 2016-09-29 | 2018-09-04 | Intel Corporation | Methods and apparatus for identifying potentially seizure-inducing virtual reality content |
WO2018067588A1 (en) * | 2016-10-03 | 2018-04-12 | Mirus Llc | Systems and methods for clinical planning and risk management |
CA3054004A1 (en) * | 2017-03-07 | 2018-09-13 | University Of Southampton | Intra-uterine monitoring system |
WO2018200723A1 (en) | 2017-04-25 | 2018-11-01 | Washington University | Resorbable implant for stimulating tissue, systems including such implant, and methods of using |
JP2021510608A (en) | 2017-11-07 | 2021-04-30 | ニューロスティム オーエービー インコーポレイテッド | Non-invasive nerve activator with adaptive circuit |
US11529523B2 (en) | 2018-01-04 | 2022-12-20 | Cardiac Pacemakers, Inc. | Handheld bridge device for providing a communication bridge between an implanted medical device and a smartphone |
US11457855B2 (en) | 2018-03-12 | 2022-10-04 | Persyst Development Corporation | Method and system for utilizing empirical null hypothesis for a biological time series |
US11219416B2 (en) | 2018-03-12 | 2022-01-11 | Persyst Development Corporation | Graphically displaying evoked potentials |
US10340408B1 (en) | 2018-05-17 | 2019-07-02 | Hi Llc | Non-invasive wearable brain interface systems including a headgear and a plurality of self-contained photodetector units configured to removably attach to the headgear |
US10420498B1 (en) | 2018-06-20 | 2019-09-24 | Hi Llc | Spatial and temporal-based diffusive correlation spectroscopy systems and methods |
US11213206B2 (en) | 2018-07-17 | 2022-01-04 | Hi Llc | Non-invasive measurement systems with single-photon counting camera |
US20200222703A1 (en) * | 2019-01-10 | 2020-07-16 | Stimwave Technologies Incorporated | Wireless implantable pulse generators |
US10849553B2 (en) | 2019-03-27 | 2020-12-01 | CeriBell, Inc. | Systems and methods for processing sonified brain signals |
EP3966590A1 (en) | 2019-05-06 | 2022-03-16 | Hi LLC | Photodetector architectures for time-correlated single photon counting |
EP3980849A1 (en) | 2019-06-06 | 2022-04-13 | Hi LLC | Photodetector systems with low-power time-to-digital converter architectures |
WO2020264214A1 (en) | 2019-06-26 | 2020-12-30 | Neurostim Technologies Llc | Non-invasive nerve activator with adaptive circuit |
WO2021076662A1 (en) | 2019-10-16 | 2021-04-22 | Invicta Medical, Inc. | Adjustable devices for treating sleep apnea, and associated systems and methods |
AU2020373042A1 (en) * | 2019-10-29 | 2022-06-16 | Synchron Australia Pty Limited | Systems and methods for configuring a brain control interface using data from deployed systems |
JP2023506713A (en) | 2019-12-16 | 2023-02-20 | ニューロスティム テクノロジーズ エルエルシー | Noninvasive nerve activator using booster charge delivery |
CN115066270A (en) * | 2020-02-13 | 2022-09-16 | 心脏起搏器股份公司 | Hermetically sealed implantable medical device and method of forming the same |
WO2021167893A1 (en) | 2020-02-21 | 2021-08-26 | Hi Llc | Integrated detector assemblies for a wearable module of an optical measurement system |
US11883181B2 (en) * | 2020-02-21 | 2024-01-30 | Hi Llc | Multimodal wearable measurement systems and methods |
US11630310B2 (en) | 2020-02-21 | 2023-04-18 | Hi Llc | Wearable devices and wearable assemblies with adjustable positioning for use in an optical measurement system |
US11950879B2 (en) | 2020-02-21 | 2024-04-09 | Hi Llc | Estimation of source-detector separation in an optical measurement system |
WO2021167876A1 (en) * | 2020-02-21 | 2021-08-26 | Hi Llc | Methods and systems for initiating and conducting a customized computer-enabled brain research study |
US11245404B2 (en) | 2020-03-20 | 2022-02-08 | Hi Llc | Phase lock loop circuit based signal generation in an optical measurement system |
US11903676B2 (en) | 2020-03-20 | 2024-02-20 | Hi Llc | Photodetector calibration of an optical measurement system |
US11864867B2 (en) | 2020-03-20 | 2024-01-09 | Hi Llc | Control circuit for a light source in an optical measurement system by applying voltage with a first polarity to start an emission of a light pulse and applying voltage with a second polarity to stop the emission of the light pulse |
US11187575B2 (en) | 2020-03-20 | 2021-11-30 | Hi Llc | High density optical measurement systems with minimal number of light sources |
US11877825B2 (en) | 2020-03-20 | 2024-01-23 | Hi Llc | Device enumeration in an optical measurement system |
WO2021188485A1 (en) | 2020-03-20 | 2021-09-23 | Hi Llc | Maintaining consistent photodetector sensitivity in an optical measurement system |
WO2021188486A1 (en) | 2020-03-20 | 2021-09-23 | Hi Llc | Phase lock loop circuit based adjustment of a measurement time window in an optical measurement system |
WO2021188487A1 (en) | 2020-03-20 | 2021-09-23 | Hi Llc | Temporal resolution control for temporal point spread function generation in an optical measurement system |
US11857348B2 (en) | 2020-03-20 | 2024-01-02 | Hi Llc | Techniques for determining a timing uncertainty of a component of an optical measurement system |
US11110271B1 (en) | 2020-10-23 | 2021-09-07 | Salvia Bioelectronics B.V. | Method for implanting a stimulator with a foil-like electrode portion |
US20220134102A1 (en) | 2020-11-04 | 2022-05-05 | Invicta Medical, Inc. | Implantable electrodes with remote power delivery for treating sleep apnea, and associated systems and methods |
EP4262968A1 (en) * | 2020-12-18 | 2023-10-25 | Brainconnect Pty Ltd | Implantable neurophysiology devices |
US11400299B1 (en) | 2021-09-14 | 2022-08-02 | Rainbow Medical Ltd. | Flexible antenna for stimulator |
Citations (94)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3498287A (en) * | 1966-04-28 | 1970-03-03 | Neural Models Ltd | Intelligence testing and signal analyzing means and method employing zero crossing detection |
US3863625A (en) * | 1973-11-02 | 1975-02-04 | Us Health | Epileptic seizure warning system |
US4494950A (en) * | 1982-01-19 | 1985-01-22 | The Johns Hopkins University | Plural module medication delivery system |
US4505275A (en) * | 1977-09-15 | 1985-03-19 | Wu Chen | Treatment method and instrumentation system |
US4566464A (en) * | 1981-07-27 | 1986-01-28 | Piccone Vincent A | Implantable epilepsy monitor apparatus |
US4573481A (en) * | 1984-06-25 | 1986-03-04 | Huntington Institute Of Applied Research | Implantable electrode array |
US4903702A (en) * | 1988-10-17 | 1990-02-27 | Ad-Tech Medical Instrument Corporation | Brain-contact for sensing epileptogenic foci with improved accuracy |
US4991582A (en) * | 1989-09-22 | 1991-02-12 | Alfred E. Mann Foundation For Scientific Research | Hermetically sealed ceramic and metal package for electronic devices implantable in living bodies |
US5082861A (en) * | 1989-09-26 | 1992-01-21 | Carter-Wallace, Inc. | Method for the prevention and control of epileptic seizure associated with complex partial seizures |
US5097835A (en) * | 1990-04-09 | 1992-03-24 | Ad-Tech Medical Instrument Corporation | Subdural electrode with improved lead connection |
US5179950A (en) * | 1989-11-13 | 1993-01-19 | Cyberonics, Inc. | Implanted apparatus having micro processor controlled current and voltage sources with reduced voltage levels when not providing stimulation |
US5181520A (en) * | 1987-12-22 | 1993-01-26 | Royal Postgraduate Medical School | Method and apparatus for analyzing an electro-encephalogram |
US5186170A (en) * | 1989-11-13 | 1993-02-16 | Cyberonics, Inc. | Simultaneous radio frequency and magnetic field microprocessor reset circuit |
US5188104A (en) * | 1991-02-01 | 1993-02-23 | Cyberonics, Inc. | Treatment of eating disorders by nerve stimulation |
US5190029A (en) * | 1991-02-14 | 1993-03-02 | Virginia Commonwealth University | Formulation for delivery of drugs by metered dose inhalers with reduced or no chlorofluorocarbon content |
US5193539A (en) * | 1991-12-18 | 1993-03-16 | Alfred E. Mann Foundation For Scientific Research | Implantable microstimulator |
US5193540A (en) * | 1991-12-18 | 1993-03-16 | Alfred E. Mann Foundation For Scientific Research | Structure and method of manufacture of an implantable microstimulator |
US5292772A (en) * | 1989-09-26 | 1994-03-08 | Carter-Wallace, Inc. | Method for the prevention and control of epileptic seizure associated with Lennox-Gastaut syndrome |
US5293879A (en) * | 1991-09-23 | 1994-03-15 | Vitatron Medical, B.V. | System an method for detecting tremors such as those which result from parkinson's disease |
US5299118A (en) * | 1987-06-26 | 1994-03-29 | Nicolet Instrument Corporation | Method and system for analysis of long term physiological polygraphic recordings |
US5392788A (en) * | 1993-02-03 | 1995-02-28 | Hudspeth; William J. | Method and device for interpreting concepts and conceptual thought from brainwave data and for assisting for diagnosis of brainwave disfunction |
US5486999A (en) * | 1994-04-20 | 1996-01-23 | Mebane; Andrew H. | Apparatus and method for categorizing health care utilization |
US5611350A (en) * | 1996-02-08 | 1997-03-18 | John; Michael S. | Method and apparatus for facilitating recovery of patients in deep coma |
US5704352A (en) * | 1995-11-22 | 1998-01-06 | Tremblay; Gerald F. | Implantable passive bio-sensor |
US5707400A (en) * | 1995-09-19 | 1998-01-13 | Cyberonics, Inc. | Treating refractory hypertension by nerve stimulation |
US5711316A (en) * | 1996-04-30 | 1998-01-27 | Medtronic, Inc. | Method of treating movement disorders by brain infusion |
US5713923A (en) * | 1996-05-13 | 1998-02-03 | Medtronic, Inc. | Techniques for treating epilepsy by brain stimulation and drug infusion |
US5715821A (en) * | 1994-12-09 | 1998-02-10 | Biofield Corp. | Neural network method and apparatus for disease, injury and bodily condition screening or sensing |
US5716377A (en) * | 1996-04-25 | 1998-02-10 | Medtronic, Inc. | Method of treating movement disorders by brain stimulation |
US5720294A (en) * | 1996-05-02 | 1998-02-24 | Enhanced Cardiology, Inc. | PD2I electrophysiological analyzer |
US5857978A (en) * | 1996-03-20 | 1999-01-12 | Lockheed Martin Energy Systems, Inc. | Epileptic seizure prediction by non-linear methods |
US5862803A (en) * | 1993-09-04 | 1999-01-26 | Besson; Marcus | Wireless medical diagnosis and monitoring equipment |
US5876424A (en) * | 1997-01-23 | 1999-03-02 | Cardiac Pacemakers, Inc. | Ultra-thin hermetic enclosure for implantable medical devices |
US6016449A (en) * | 1997-10-27 | 2000-01-18 | Neuropace, Inc. | System for treatment of neurological disorders |
US6018682A (en) * | 1998-04-30 | 2000-01-25 | Medtronic, Inc. | Implantable seizure warning system |
US6042579A (en) * | 1997-04-30 | 2000-03-28 | Medtronic, Inc. | Techniques for treating neurodegenerative disorders by infusion of nerve growth factors into the brain |
US6042548A (en) * | 1997-11-14 | 2000-03-28 | Hypervigilant Technologies | Virtual neurological monitor and method |
US6171239B1 (en) * | 1998-08-17 | 2001-01-09 | Emory University | Systems, methods, and devices for controlling external devices by signals derived directly from the nervous system |
US6176242B1 (en) * | 1999-04-30 | 2001-01-23 | Medtronic Inc | Method of treating manic depression by brain infusion |
US6201980B1 (en) * | 1998-10-05 | 2001-03-13 | The Regents Of The University Of California | Implantable medical sensor system |
US6205359B1 (en) * | 1998-10-26 | 2001-03-20 | Birinder Bob Boveja | Apparatus and method for adjunct (add-on) therapy of partial complex epilepsy, generalized epilepsy and involuntary movement disorders utilizing an external stimulator |
US6208893B1 (en) * | 1998-01-27 | 2001-03-27 | Genetronics, Inc. | Electroporation apparatus with connective electrode template |
US6339725B1 (en) * | 1996-05-31 | 2002-01-15 | The Board Of Trustees Of Southern Illinois University | Methods of modulating aspects of brain neural plasticity by vagus nerve stimulation |
US6341236B1 (en) * | 1999-04-30 | 2002-01-22 | Ivan Osorio | Vagal nerve stimulation techniques for treatment of epileptic seizures |
US6343226B1 (en) * | 1999-06-25 | 2002-01-29 | Neurokinetic Aps | Multifunction electrode for neural tissue stimulation |
US6353754B1 (en) * | 2000-04-24 | 2002-03-05 | Neuropace, Inc. | System for the creation of patient specific templates for epileptiform activity detection |
US6354299B1 (en) * | 1997-10-27 | 2002-03-12 | Neuropace, Inc. | Implantable device for patient communication |
US6356788B2 (en) * | 1998-10-26 | 2002-03-12 | Birinder Bob Boveja | Apparatus and method for adjunct (add-on) therapy for depression, migraine, neuropsychiatric disorders, partial complex epilepsy, generalized epilepsy and involuntary movement disorders utilizing an external stimulator |
US6356784B1 (en) * | 1999-04-30 | 2002-03-12 | Medtronic, Inc. | Method of treating movement disorders by electrical stimulation and/or drug infusion of the pendunulopontine nucleus |
US6358203B2 (en) * | 1999-06-03 | 2002-03-19 | Cardiac Intelligence Corp. | System and method for automated collection and analysis of patient information retrieved from an implantable medical device for remote patient care |
US6358281B1 (en) * | 1999-11-29 | 2002-03-19 | Epic Biosonics Inc. | Totally implantable cochlear prosthesis |
US20020035338A1 (en) * | 1999-12-01 | 2002-03-21 | Dear Stephen P. | Epileptic seizure detection and prediction by self-similar methods |
US20030004428A1 (en) * | 2001-06-28 | 2003-01-02 | Pless Benjamin D. | Seizure sensing and detection using an implantable device |
US6505077B1 (en) * | 2000-06-19 | 2003-01-07 | Medtronic, Inc. | Implantable medical device with external recharging coil electrical connection |
US20030009207A1 (en) * | 2001-07-09 | 2003-01-09 | Paspa Paul M. | Implantable medical lead |
US20030013981A1 (en) * | 2000-06-26 | 2003-01-16 | Alan Gevins | Neurocognitive function EEG measurement method and system |
US6510340B1 (en) * | 2000-01-10 | 2003-01-21 | Jordan Neuroscience, Inc. | Method and apparatus for electroencephalography |
US20030018367A1 (en) * | 2001-07-23 | 2003-01-23 | Dilorenzo Daniel John | Method and apparatus for neuromodulation and phsyiologic modulation for the treatment of metabolic and neuropsychiatric disease |
US6511424B1 (en) * | 1997-01-11 | 2003-01-28 | Circadian Technologies, Inc. | Method of and apparatus for evaluation and mitigation of microsleep events |
US20030028072A1 (en) * | 2000-08-31 | 2003-02-06 | Neuropace, Inc. | Low frequency magnetic neurostimulator for the treatment of neurological disorders |
US20030050549A1 (en) * | 2001-09-13 | 2003-03-13 | Jerzy Sochor | Implantable lead connector assembly for implantable devices and methods of using it |
US6678548B1 (en) * | 2000-10-20 | 2004-01-13 | The Trustees Of The University Of Pennsylvania | Unified probabilistic framework for predicting and detecting seizure onsets in the brain and multitherapeutic device |
US6684105B2 (en) * | 2001-08-31 | 2004-01-27 | Biocontrol Medical, Ltd. | Treatment of disorders by unidirectional nerve stimulation |
US6687538B1 (en) * | 2000-06-19 | 2004-02-03 | Medtronic, Inc. | Trial neuro stimulator with lead diagnostics |
US20040034368A1 (en) * | 2000-11-28 | 2004-02-19 | Pless Benjamin D. | Ferrule for cranial implant |
US20040039427A1 (en) * | 2001-01-02 | 2004-02-26 | Cyberonics, Inc. | Treatment of obesity by sub-diaphragmatic nerve stimulation |
US20040039981A1 (en) * | 2002-08-23 | 2004-02-26 | Riedl Daniel A. | Method and apparatus for identifying one or more devices having faults in a communication loop |
US20050004621A1 (en) * | 2002-05-09 | 2005-01-06 | Boveja Birinder R. | Method and system for modulating the vagus nerve (10th cranial nerve) with electrical pulses using implanted and external componants, to provide therapy for neurological and neuropsychiatric disorders |
US20050010261A1 (en) * | 2002-10-21 | 2005-01-13 | The Cleveland Clinic Foundation | Application of stimulus to white matter to induce a desired physiological response |
US20050015129A1 (en) * | 1999-12-09 | 2005-01-20 | Mische Hans A. | Methods and devices for the treatment of neurological and physiological disorders |
US20050015128A1 (en) * | 2003-05-29 | 2005-01-20 | Rezai Ali R. | Excess lead retaining and management devices and methods of using same |
US20050021104A1 (en) * | 1998-08-05 | 2005-01-27 | Dilorenzo Daniel John | Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease |
US20050021108A1 (en) * | 2002-06-28 | 2005-01-27 | Klosterman Daniel J. | Bi-directional telemetry system for use with microstimulator |
US20050021103A1 (en) * | 1998-08-05 | 2005-01-27 | Dilorenzo Daniel John | Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease |
US20050021313A1 (en) * | 2000-04-03 | 2005-01-27 | Nikitin Alexei V. | Method, computer program, and system for automated real-time signal analysis for detection, quantification, and prediction of signal changes |
US20050021105A1 (en) * | 2000-07-13 | 2005-01-27 | Firlik Andrew D. | Methods and apparatus for effectuating a change in a neural-function of a patient |
US20050027328A1 (en) * | 2000-09-26 | 2005-02-03 | Transneuronix, Inc. | Minimally invasive surgery placement of stimulation leads in mediastinal structures |
US20050033369A1 (en) * | 2003-08-08 | 2005-02-10 | Badelt Steven W. | Data Feedback loop for medical therapy adjustment |
US20050043772A1 (en) * | 2003-08-18 | 2005-02-24 | Stahmann Jeffrey E. | Therapy triggered by prediction of disordered breathing |
US20050043774A1 (en) * | 2003-05-06 | 2005-02-24 | Aspect Medical Systems, Inc | System and method of assessment of the efficacy of treatment of neurological disorders using the electroencephalogram |
US20060015034A1 (en) * | 2002-10-18 | 2006-01-19 | Jacques Martinerie | Analysis method and real time medical or cognitive monitoring device based on the analysis of a subject's cerebral electromagnetic use of said method for characterizing and differenting physiological and pathological states |
US20060015153A1 (en) * | 2004-07-15 | 2006-01-19 | Gliner Bradford E | Systems and methods for enhancing or affecting neural stimulation efficiency and/or efficacy |
US6990372B2 (en) * | 2002-04-11 | 2006-01-24 | Alfred E. Mann Foundation For Scientific Research | Programmable signal analysis device for detecting neurological signals in an implantable device |
US20060030904A1 (en) * | 2004-08-09 | 2006-02-09 | Sylvia Quiles | Secure remote access for an implantable medical device |
US7006872B2 (en) * | 2001-04-27 | 2006-02-28 | Medtronic, Inc. | Closed loop neuromodulation for suppression of epileptic activity |
US20070027514A1 (en) * | 2005-07-29 | 2007-02-01 | Medtronic, Inc. | Electrical stimulation lead with conformable array of electrodes |
US20070027367A1 (en) * | 2005-08-01 | 2007-02-01 | Microsoft Corporation | Mobile, personal, and non-intrusive health monitoring and analysis system |
US7174212B1 (en) * | 2003-12-10 | 2007-02-06 | Pacesetter, Inc. | Implantable medical device having a casing providing high-speed telemetry |
US7177701B1 (en) * | 2000-12-29 | 2007-02-13 | Advanced Bionics Corporation | System for permanent electrode placement utilizing microelectrode recording methods |
US20070035910A1 (en) * | 2005-08-15 | 2007-02-15 | Greatbatch-Sierra, Inc. | Feedthrough filter capacitor assembly with internally grounded hermetic insulator |
US20070043459A1 (en) * | 1999-12-15 | 2007-02-22 | Tangis Corporation | Storing and recalling information to augment human memories |
US7486986B1 (en) * | 1999-10-12 | 2009-02-03 | Flint Hills Scientific Llc | Bi-directional cerebral interface system |
US20100023089A1 (en) * | 1998-08-05 | 2010-01-28 | Dilorenzo Daniel John | Controlling a Subject's Susceptibility to a Seizure |
US7881798B2 (en) * | 2004-03-16 | 2011-02-01 | Medtronic Inc. | Controlling therapy based on sleep quality |
Family Cites Families (384)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL81678C (en) * | 1949-12-06 | |||
US3218638A (en) | 1962-05-29 | 1965-11-16 | William M Honig | Wireless passive biological telemetry system |
US3575162A (en) | 1968-12-23 | 1971-04-20 | Kenneth R Gaarder | Physiological monitors and method of using the same in treatment of disease |
US3522811A (en) | 1969-02-13 | 1970-08-04 | Medtronic Inc | Implantable nerve stimulator and method of use |
US3837922A (en) * | 1969-09-12 | 1974-09-24 | Inst Gas Technology | Implantable fuel cell |
US3967616A (en) | 1972-10-24 | 1976-07-06 | Ross Sidney A | Multichannel system for and a multifactorial method of controlling the nervous system of a living organism |
US3837331A (en) | 1972-10-24 | 1974-09-24 | S Ross | System and method for controlling the nervous system of a living organism |
US3850161A (en) | 1973-04-09 | 1974-11-26 | S Liss | Method and apparatus for monitoring and counteracting excess brain electrical energy to prevent epileptic seizures and the like |
US3882850A (en) | 1973-05-09 | 1975-05-13 | Howard Bailin | Brain wave feedback instrument |
US3918461A (en) | 1974-01-31 | 1975-11-11 | Irving S Cooper | Method for electrically stimulating the human brain |
US3993046A (en) | 1974-11-06 | 1976-11-23 | Heriberto Fernandez | Seizure suppression device |
JPS587291B2 (en) | 1977-10-08 | 1983-02-09 | 財団法人交通医学研究財団 | Automatic brain wave determination device |
JPS5573269A (en) | 1978-11-28 | 1980-06-02 | Matsushita Electric Ind Co Ltd | Living body feedback device |
US4201224A (en) | 1978-12-29 | 1980-05-06 | Roy John E | Electroencephalographic method and system for the quantitative description of patient brain states |
US4305402A (en) | 1979-06-29 | 1981-12-15 | Katims Jefferson J | Method for transcutaneous electrical stimulation |
US4279258A (en) | 1980-03-26 | 1981-07-21 | Roy John E | Rapid automatic electroencephalographic evaluation |
JPS57177735A (en) | 1981-04-27 | 1982-11-01 | Toyoda Chuo Kenkyusho Kk | Telemeter type brain nanometer |
US4421122A (en) | 1981-05-15 | 1983-12-20 | The Children's Medical Center Corporation | Brain electrical activity mapping |
US4408616A (en) | 1981-05-15 | 1983-10-11 | The Children's Medical Center Corporation | Brain electricaL activity mapping |
USRE34015E (en) | 1981-05-15 | 1992-08-04 | The Children's Medical Center Corporation | Brain electrical activity mapping |
US4407299A (en) | 1981-05-15 | 1983-10-04 | The Children's Medical Center Corporation | Brain electrical activity mapping |
US4793353A (en) | 1981-06-30 | 1988-12-27 | Borkan William N | Non-invasive multiprogrammable tissue stimulator and method |
US4612934A (en) | 1981-06-30 | 1986-09-23 | Borkan William N | Non-invasive multiprogrammable tissue stimulator |
SU1074484A1 (en) | 1981-08-19 | 1984-02-23 | Ленинградский Нейрохирургический Институт Им.Проф.А.Л.Поленова | Method of diagnosis of epilepsia |
US4556061A (en) | 1982-08-18 | 1985-12-03 | Cordis Corporation | Cardiac pacer with battery consumption monitor circuit |
EP0124663A1 (en) | 1983-05-04 | 1984-11-14 | General Foods Corporation | Compressed tablets |
US4545388A (en) | 1983-06-09 | 1985-10-08 | Roy John E | Self-normed brain state monitoring |
US4867164A (en) | 1983-09-14 | 1989-09-19 | Jacob Zabara | Neurocybernetic prosthesis |
US5025807A (en) | 1983-09-14 | 1991-06-25 | Jacob Zabara | Neurocybernetic prosthesis |
US4702254A (en) | 1983-09-14 | 1987-10-27 | Jacob Zabara | Neurocybernetic prosthesis |
WO1985001213A1 (en) | 1983-09-14 | 1985-03-28 | Jacob Zabara | Neurocybernetic prosthesis |
US4844075A (en) | 1984-01-09 | 1989-07-04 | Pain Suppression Labs, Inc. | Transcranial stimulation for the treatment of cerebral palsy |
US4579125A (en) | 1984-01-23 | 1986-04-01 | Cns, Inc. | Real-time EEG spectral analyzer |
US4590946A (en) | 1984-06-14 | 1986-05-27 | Biomed Concepts, Inc. | Surgically implantable electrode for nerve bundles |
US4768177A (en) | 1984-07-06 | 1988-08-30 | Kehr Bruce A | Method of and apparatus for alerting a patient to take medication |
US4768176A (en) | 1984-07-06 | 1988-08-30 | Kehr Bruce A | Apparatus for alerting a patient to take medication |
US4679144A (en) * | 1984-08-21 | 1987-07-07 | Q-Med, Inc. | Cardiac signal real time monitor and method of analysis |
US4686999A (en) * | 1985-04-10 | 1987-08-18 | Tri Fund Research Corporation | Multi-channel ventilation monitor and method |
US4817628A (en) | 1985-10-18 | 1989-04-04 | David L. Zealear | System and method for evaluating neurological function controlling muscular movements |
US5167229A (en) | 1986-03-24 | 1992-12-01 | Case Western Reserve University | Functional neuromuscular stimulation system |
US4735208B1 (en) * | 1987-01-09 | 1995-07-04 | Ad Tech Medical Instr Corp | Subdural strip electrode for determining epileptogenic foci |
US4785827A (en) | 1987-01-28 | 1988-11-22 | Minnesota Mining And Manufacturing Company | Subcutaneous housing assembly |
US5070873A (en) | 1987-02-13 | 1991-12-10 | Sigmedics, Inc. | Method of and apparatus for electrically stimulating quadriceps muscles of an upper motor unit paraplegic |
US4838272A (en) | 1987-08-19 | 1989-06-13 | The Regents Of The University Of California | Method and apparatus for adaptive closed loop electrical stimulation of muscles |
US4926865A (en) | 1987-10-01 | 1990-05-22 | Oman Paul S | Microcomputer-based nerve and muscle stimulator |
US5010891A (en) | 1987-10-09 | 1991-04-30 | Biometrak Corporation | Cerebral biopotential analysis system and method |
US5871472A (en) | 1987-11-17 | 1999-02-16 | Brown University Research Foundation | Planting devices for the focal release of neuroinhibitory compounds |
US4852573A (en) | 1987-12-04 | 1989-08-01 | Kennedy Philip R | Implantable neural electrode |
US5343064A (en) | 1988-03-18 | 1994-08-30 | Spangler Leland J | Fully integrated single-crystal silicon-on-insulator process, sensors and circuits |
US4920979A (en) | 1988-10-12 | 1990-05-01 | Huntington Medical Research Institute | Bidirectional helical electrode for nerve stimulation |
US4878498A (en) | 1988-10-14 | 1989-11-07 | Somatics, Inc. | Electroconvulsive therapy apparatus and method for automatic monitoring of patient seizures |
US4873981A (en) | 1988-10-14 | 1989-10-17 | Somatics, Inc. | Electroconvulsive therapy apparatus and method for automatic monitoring of patient seizures |
US5016635A (en) | 1988-11-29 | 1991-05-21 | Sigmedics, Inc. Of Delaware | Control of FNS via pattern variations of response EMG |
US5766573A (en) | 1988-12-06 | 1998-06-16 | Riker Laboratories, Inc. | Medicinal aerosol formulations |
US4955380A (en) | 1988-12-15 | 1990-09-11 | Massachusetts Institute Of Technology | Flexible measurement probes |
FR2645641B1 (en) | 1989-04-10 | 1991-05-31 | Bruno Comby | METHOD AND DEVICE FOR MEASURING VIBRATION, IN PARTICULAR MICROSCOPIC SHAKING OF LIVING ORGANISMS |
EP0399063B1 (en) | 1989-05-22 | 1994-01-05 | Pacesetter AB | Implantable medical device to stimulate contraction in tissues with an adjustable stimulation intensity, and process for using same |
US4978680A (en) | 1989-09-26 | 1990-12-18 | Carter-Wallace, Inc. | Method for the prevention and control of epileptic seizure |
US4979511A (en) | 1989-11-03 | 1990-12-25 | Cyberonics, Inc. | Strain relief tether for implantable electrode |
US5215088A (en) | 1989-11-07 | 1993-06-01 | The University Of Utah | Three-dimensional electrode device |
US5361760A (en) | 1989-11-07 | 1994-11-08 | University Of Utah Research Foundation | Impact inserter mechanism for implantation of a biomedical device |
US5235980A (en) | 1989-11-13 | 1993-08-17 | Cyberonics, Inc. | Implanted apparatus disabling switching regulator operation to allow radio frequency signal reception |
US5154172A (en) | 1989-11-13 | 1992-10-13 | Cyberonics, Inc. | Constant current sources with programmable voltage source |
US5031618A (en) | 1990-03-07 | 1991-07-16 | Medtronic, Inc. | Position-responsive neuro stimulator |
US5314458A (en) * | 1990-06-01 | 1994-05-24 | University Of Michigan | Single channel microstimulator |
IE912227A1 (en) | 1990-06-28 | 1992-01-01 | Verhoeven Jean Marie | Method and device for the treatment of epilepsy |
DE69209324T2 (en) | 1991-01-09 | 1996-11-21 | Medtronic Inc | Servo control for muscles |
US5263480A (en) | 1991-02-01 | 1993-11-23 | Cyberonics, Inc. | Treatment of eating disorders by nerve stimulation |
US5269303A (en) | 1991-02-22 | 1993-12-14 | Cyberonics, Inc. | Treatment of dementia by nerve stimulation |
US5222503A (en) | 1991-04-24 | 1993-06-29 | Beth Israel Hospital Association | Ambulatory electroencephalography system |
US5299569A (en) | 1991-05-03 | 1994-04-05 | Cyberonics, Inc. | Treatment of neuropsychiatric disorders by nerve stimulation |
US5335657A (en) | 1991-05-03 | 1994-08-09 | Cyberonics, Inc. | Therapeutic treatment of sleep disorder by nerve stimulation |
US5251634A (en) | 1991-05-03 | 1993-10-12 | Cyberonics, Inc. | Helical nerve electrode |
US5215086A (en) | 1991-05-03 | 1993-06-01 | Cyberonics, Inc. | Therapeutic treatment of migraine symptoms by stimulation |
US5269302A (en) | 1991-05-10 | 1993-12-14 | Somatics, Inc. | Electroconvulsive therapy apparatus and method for monitoring patient seizures |
US5205285A (en) | 1991-06-14 | 1993-04-27 | Cyberonics, Inc. | Voice suppression of vagal stimulation |
US5222494A (en) | 1991-07-31 | 1993-06-29 | Cyberonics, Inc. | Implantable tissue stimulator output stabilization system |
US5231988A (en) | 1991-08-09 | 1993-08-03 | Cyberonics, Inc. | Treatment of endocrine disorders by nerve stimulation |
US5269315A (en) | 1991-08-16 | 1993-12-14 | The Regents Of The University Of California | Determining the nature of brain lesions by electroencephalography |
US5215089A (en) | 1991-10-21 | 1993-06-01 | Cyberonics, Inc. | Electrode assembly for nerve stimulation |
US5458117A (en) | 1991-10-25 | 1995-10-17 | Aspect Medical Systems, Inc. | Cerebral biopotential analysis system and method |
US5304206A (en) | 1991-11-18 | 1994-04-19 | Cyberonics, Inc. | Activation techniques for implantable medical device |
US5237991A (en) | 1991-11-19 | 1993-08-24 | Cyberonics, Inc. | Implantable medical device with dummy load for pre-implant testing in sterile package and facilitating electrical lead connection |
US5312439A (en) | 1991-12-12 | 1994-05-17 | Loeb Gerald E | Implantable device having an electrolytic storage electrode |
US5330515A (en) | 1992-06-17 | 1994-07-19 | Cyberonics, Inc. | Treatment of pain by vagal afferent stimulation |
US5376359A (en) | 1992-07-07 | 1994-12-27 | Glaxo, Inc. | Method of stabilizing aerosol formulations |
SE500122C2 (en) * | 1992-08-27 | 1994-04-18 | Rudolf Valentin Sillen | Method and apparatus for individually controlled, adaptive medication |
US5476494A (en) | 1992-09-11 | 1995-12-19 | Massachusetts Institute Of Technology | Low pressure neural contact structure |
AU4626893A (en) | 1992-09-14 | 1994-03-24 | Aprex Corporation | Contactless communication system |
US5311876A (en) | 1992-11-18 | 1994-05-17 | The Johns Hopkins University | Automatic detection of seizures using electroencephalographic signals |
US6117066A (en) | 1992-12-04 | 2000-09-12 | Somatics, Inc. | Prevention of seizure arising from medical magnetoictal non-convulsive stimulation therapy |
US5342408A (en) | 1993-01-07 | 1994-08-30 | Incontrol, Inc. | Telemetry system for an implantable cardiac device |
US6167304A (en) | 1993-05-28 | 2000-12-26 | Loos; Hendricus G. | Pulse variability in electric field manipulation of nervous systems |
US6081744A (en) | 1993-05-28 | 2000-06-27 | Loos; Hendricus G. | Electric fringe field generator for manipulating nervous systems |
US5782874A (en) | 1993-05-28 | 1998-07-21 | Loos; Hendricus G. | Method and apparatus for manipulating nervous systems |
US5411540A (en) | 1993-06-03 | 1995-05-02 | Massachusetts Institute Of Technology | Method and apparatus for preferential neuron stimulation |
US5649068A (en) | 1993-07-27 | 1997-07-15 | Lucent Technologies Inc. | Pattern recognition system using support vectors |
US5549656A (en) | 1993-08-16 | 1996-08-27 | Med Serve Group, Inc. | Combination neuromuscular stimulator and electromyograph system |
US5365939A (en) | 1993-10-15 | 1994-11-22 | Neurotrain, L.C. | Method for evaluating and treating an individual with electroencephalographic disentrainment feedback |
US5349962A (en) | 1993-11-30 | 1994-09-27 | University Of Washington | Method and apparatus for detecting epileptic seizures |
US5578036A (en) * | 1993-12-06 | 1996-11-26 | Stone; Kevin T. | Method and apparatus for fixation of bone during surgical procedures |
US5513649A (en) | 1994-03-22 | 1996-05-07 | Sam Technology, Inc. | Adaptive interference canceler for EEG movement and eye artifacts |
US5769778A (en) | 1994-04-22 | 1998-06-23 | Somatics, Inc. | Medical magnetic non-convulsive stimulation therapy |
US5782891A (en) * | 1994-06-16 | 1998-07-21 | Medtronic, Inc. | Implantable ceramic enclosure for pacing, neurological, and other medical applications in the human body |
US6249703B1 (en) | 1994-07-08 | 2001-06-19 | Medtronic, Inc. | Handheld patient programmer for implantable human tissue stimulator |
US5571148A (en) * | 1994-08-10 | 1996-11-05 | Loeb; Gerald E. | Implantable multichannel stimulator |
US6009061A (en) * | 1994-08-25 | 1999-12-28 | Discovision Associates | Cartridge-loading apparatus with improved base plate and cartridge receiver latch |
US5531778A (en) | 1994-09-20 | 1996-07-02 | Cyberonics, Inc. | Circumneural electrode assembly |
US5540734A (en) | 1994-09-28 | 1996-07-30 | Zabara; Jacob | Cranial nerve stimulation treatments using neurocybernetic prosthesis |
US5555191A (en) | 1994-10-12 | 1996-09-10 | Trustees Of Columbia University In The City Of New York | Automated statistical tracker |
US5571150A (en) | 1994-12-19 | 1996-11-05 | Cyberonics, Inc. | Treatment of patients in coma by nerve stimulation |
US5638826A (en) | 1995-06-01 | 1997-06-17 | Health Research, Inc. | Communication method and system using brain waves for multidimensional control |
US5540730A (en) | 1995-06-06 | 1996-07-30 | Cyberonics, Inc. | Treatment of motility disorders by nerve stimulation |
NZ311474A (en) | 1995-06-09 | 1997-09-22 | Euro Celtique Sa | Formulations for providing prolonged local anesthesia |
GB9511964D0 (en) | 1995-06-13 | 1995-08-09 | Rdm Consultants Limited | Monitoring an EEG |
US5626627A (en) * | 1995-07-27 | 1997-05-06 | Duke University | Electroconvulsive therapy method using ICTAL EEG data as an indicator of ECT seizure adequacy |
US5700282A (en) | 1995-10-13 | 1997-12-23 | Zabara; Jacob | Heart rhythm stabilization using a neurocybernetic prosthesis |
US20020169485A1 (en) | 1995-10-16 | 2002-11-14 | Neuropace, Inc. | Differential neurostimulation therapy driven by physiological context |
US6480743B1 (en) | 2000-04-05 | 2002-11-12 | Neuropace, Inc. | System and method for adaptive brain stimulation |
US6944501B1 (en) | 2000-04-05 | 2005-09-13 | Neurospace, Inc. | Neurostimulator involving stimulation strategies and process for using it |
US5683432A (en) * | 1996-01-11 | 1997-11-04 | Medtronic, Inc. | Adaptive, performance-optimizing communication system for communicating with an implanted medical device |
US5995868A (en) | 1996-01-23 | 1999-11-30 | University Of Kansas | System for the prediction, rapid detection, warning, prevention, or control of changes in activity states in the brain of a subject |
US6066163A (en) | 1996-02-02 | 2000-05-23 | John; Michael Sasha | Adaptive brain stimulation method and system |
US6463328B1 (en) | 1996-02-02 | 2002-10-08 | Michael Sasha John | Adaptive brain stimulation method and system |
US6051017A (en) | 1996-02-20 | 2000-04-18 | Advanced Bionics Corporation | Implantable microstimulator and systems employing the same |
US5626145A (en) | 1996-03-20 | 1997-05-06 | Lockheed Martin Energy Systems, Inc. | Method and apparatus for extraction of low-frequency artifacts from brain waves for alertness detection |
US5743860A (en) | 1996-03-20 | 1998-04-28 | Lockheed Martin Energy Systems, Inc. | Apparatus and method for epileptic seizure detection using non-linear techniques |
US5690681A (en) | 1996-03-29 | 1997-11-25 | Purdue Research Foundation | Method and apparatus using vagal stimulation for control of ventricular rate during atrial fibrillation |
US5813993A (en) | 1996-04-05 | 1998-09-29 | Consolidated Research Of Richmond, Inc. | Alertness and drowsiness detection and tracking system |
US5824021A (en) | 1996-04-25 | 1998-10-20 | Medtronic Inc. | Method and apparatus for providing feedback to spinal cord stimulation for angina |
US6094598A (en) | 1996-04-25 | 2000-07-25 | Medtronics, Inc. | Method of treating movement disorders by brain stimulation and drug infusion |
US5683422A (en) | 1996-04-25 | 1997-11-04 | Medtronic, Inc. | Method and apparatus for treating neurodegenerative disorders by electrical brain stimulation |
US5735814A (en) | 1996-04-30 | 1998-04-07 | Medtronic, Inc. | Techniques of treating neurodegenerative disorders by brain infusion |
US6006134A (en) | 1998-04-30 | 1999-12-21 | Medtronic, Inc. | Method and device for electronically controlling the beating of a heart using venous electrical stimulation of nerve fibers |
US5690691A (en) * | 1996-05-08 | 1997-11-25 | The Center For Innovative Technology | Gastro-intestinal pacemaker having phased multi-point stimulation |
US5782798A (en) | 1996-06-26 | 1998-07-21 | Medtronic, Inc. | Techniques for treating eating disorders by brain stimulation and drug infusion |
DE19645371C1 (en) | 1996-10-23 | 1997-12-18 | Biotronik Mess & Therapieg | Implant, e.g. heart pacemaker, for mounting in human tissue |
US5800474A (en) | 1996-11-01 | 1998-09-01 | Medtronic, Inc. | Method of controlling epilepsy by brain stimulation |
US5752979A (en) | 1996-11-01 | 1998-05-19 | Medtronic, Inc. | Method of controlling epilepsy by brain stimulation |
US7630757B2 (en) | 1997-01-06 | 2009-12-08 | Flint Hills Scientific Llc | System for the prediction, rapid detection, warning, prevention, or control of changes in activity states in the brain of a subject |
US5957861A (en) * | 1997-01-31 | 1999-09-28 | Medtronic, Inc. | Impedance monitor for discerning edema through evaluation of respiratory rate |
US5950632A (en) | 1997-03-03 | 1999-09-14 | Motorola, Inc. | Medical communication apparatus, system, and method |
US7111009B1 (en) | 1997-03-14 | 2006-09-19 | Microsoft Corporation | Interactive playlist generation using annotations |
US5975085A (en) | 1997-05-01 | 1999-11-02 | Medtronic, Inc. | Method of treating schizophrenia by brain stimulation and drug infusion |
US6128537A (en) | 1997-05-01 | 2000-10-03 | Medtronic, Inc | Techniques for treating anxiety by brain stimulation and drug infusion |
US5815413A (en) | 1997-05-08 | 1998-09-29 | Lockheed Martin Energy Research Corporation | Integrated method for chaotic time series analysis |
US6052619A (en) * | 1997-08-07 | 2000-04-18 | New York University | Brain function scan system |
US6479523B1 (en) | 1997-08-26 | 2002-11-12 | Emory University | Pharmacologic drug combination in vagal-induced asystole |
US6622036B1 (en) * | 2000-02-09 | 2003-09-16 | Cns Response | Method for classifying and treating physiologic brain imbalances using quantitative EEG |
US6931274B2 (en) | 1997-09-23 | 2005-08-16 | Tru-Test Corporation Limited | Processing EEG signals to predict brain damage |
US5941906A (en) | 1997-10-15 | 1999-08-24 | Medtronic, Inc. | Implantable, modular tissue stimulator |
US5938688A (en) | 1997-10-22 | 1999-08-17 | Cornell Research Foundation, Inc. | Deep brain stimulation method |
US6230049B1 (en) | 1999-08-13 | 2001-05-08 | Neuro Pace, Inc. | Integrated system for EEG monitoring and electrical stimulation with a multiplicity of electrodes |
US6647296B2 (en) | 1997-10-27 | 2003-11-11 | Neuropace, Inc. | Implantable apparatus for treating neurological disorders |
US6427086B1 (en) | 1997-10-27 | 2002-07-30 | Neuropace, Inc. | Means and method for the intracranial placement of a neurostimulator |
US6459936B2 (en) | 1997-10-27 | 2002-10-01 | Neuropace, Inc. | Methods for responsively treating neurological disorders |
US6597954B1 (en) | 1997-10-27 | 2003-07-22 | Neuropace, Inc. | System and method for controlling epileptic seizures with spatially separated detection and stimulation electrodes |
US5931791A (en) | 1997-11-05 | 1999-08-03 | Instromedix, Inc. | Medical patient vital signs-monitoring apparatus |
FR2772484B1 (en) | 1997-12-12 | 2000-02-11 | Biospace Instr | AUTORADIOGRAPHY IMAGE PROCESSING METHOD |
DE69921449T2 (en) | 1998-01-12 | 2005-11-24 | Ronald P. Lesser | METHOD FOR THE TREATMENT OF HORN DRESSES BY MEANS OF CONTROLLED HEAT SUPPLY |
US5978710A (en) | 1998-01-23 | 1999-11-02 | Sulzer Intermedics Inc. | Implantable cardiac stimulator with safe noise mode |
US6227203B1 (en) | 1998-02-12 | 2001-05-08 | Medtronic, Inc. | Techniques for controlling abnormal involuntary movements by brain stimulation and drug infusion |
US5971594A (en) | 1998-03-24 | 1999-10-26 | Innovative Medical Devices, Inc. | Medication dispensing system |
US6266556B1 (en) | 1998-04-27 | 2001-07-24 | Beth Israel Deaconess Medical Center, Inc. | Method and apparatus for recording an electroencephalogram during transcranial magnetic stimulation |
US6374140B1 (en) | 1998-04-30 | 2002-04-16 | Medtronic, Inc. | Method and apparatus for treating seizure disorders by stimulating the olfactory senses |
US6411854B1 (en) | 1998-04-30 | 2002-06-25 | Advanced Bionics Corporation | Implanted ceramic case with enhanced ceramic case strength |
US6006124A (en) | 1998-05-01 | 1999-12-21 | Neuropace, Inc. | Means and method for the placement of brain electrodes |
US5938689A (en) | 1998-05-01 | 1999-08-17 | Neuropace, Inc. | Electrode configuration for a brain neuropacemaker |
US5928272A (en) | 1998-05-02 | 1999-07-27 | Cyberonics, Inc. | Automatic activation of a neurostimulator device using a detection algorithm based on cardiac activity |
US9415222B2 (en) * | 1998-08-05 | 2016-08-16 | Cyberonics, Inc. | Monitoring an epilepsy disease state with a supervisory module |
US7242984B2 (en) | 1998-08-05 | 2007-07-10 | Neurovista Corporation | Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease |
US6366813B1 (en) | 1998-08-05 | 2002-04-02 | Dilorenzo Daniel J. | Apparatus and method for closed-loop intracranical stimulation for optimal control of neurological disease |
US7231254B2 (en) * | 1998-08-05 | 2007-06-12 | Bioneuronics Corporation | Closed-loop feedback-driven neuromodulation |
US7747325B2 (en) * | 1998-08-05 | 2010-06-29 | Neurovista Corporation | Systems and methods for monitoring a patient's neurological disease state |
US8762065B2 (en) | 1998-08-05 | 2014-06-24 | Cyberonics, Inc. | Closed-loop feedback-driven neuromodulation |
US9375573B2 (en) | 1998-08-05 | 2016-06-28 | Cyberonics, Inc. | Systems and methods for monitoring a patient's neurological disease state |
US7324851B1 (en) * | 1998-08-05 | 2008-01-29 | Neurovista Corporation | Closed-loop feedback-driven neuromodulation |
US7403820B2 (en) | 1998-08-05 | 2008-07-22 | Neurovista Corporation | Closed-loop feedback-driven neuromodulation |
AU5900299A (en) | 1998-08-24 | 2000-03-14 | Emory University | Method and apparatus for predicting the onset of seizures based on features derived from signals indicative of brain activity |
DE19844296A1 (en) | 1998-09-18 | 2000-03-23 | Biotronik Mess & Therapieg | Arrangement for patient monitoring |
US6668191B1 (en) | 1998-10-26 | 2003-12-23 | Birinder R. Boveja | Apparatus and method for electrical stimulation adjunct (add-on) therapy of atrial fibrillation, inappropriate sinus tachycardia, and refractory hypertension with an external stimulator |
US6366814B1 (en) | 1998-10-26 | 2002-04-02 | Birinder R. Boveja | External stimulator for adjunct (add-on) treatment for neurological, neuropsychiatric, and urological disorders |
US6496724B1 (en) | 1998-12-31 | 2002-12-17 | Advanced Brain Monitoring, Inc. | Method for the quantification of human alertness |
US6280198B1 (en) * | 1999-01-29 | 2001-08-28 | Scientific Learning Corporation | Remote computer implemented methods for cognitive testing |
US6650779B2 (en) | 1999-03-26 | 2003-11-18 | Georgia Tech Research Corp. | Method and apparatus for analyzing an image to detect and identify patterns |
US6923784B2 (en) | 1999-04-30 | 2005-08-02 | Medtronic, Inc. | Therapeutic treatment of disorders based on timing information |
US6109269A (en) | 1999-04-30 | 2000-08-29 | Medtronic, Inc. | Method of treating addiction by brain infusion |
US6161045A (en) | 1999-06-01 | 2000-12-12 | Neuropace, Inc. | Method for determining stimulation parameters for the treatment of epileptic seizures |
DE19930263A1 (en) * | 1999-06-25 | 2000-12-28 | Biotronik Mess & Therapieg | Method and device for data transmission between an electromedical implant and an external device |
US6587719B1 (en) | 1999-07-01 | 2003-07-01 | Cyberonics, Inc. | Treatment of obesity by bilateral vagus nerve stimulation |
US6221011B1 (en) | 1999-07-26 | 2001-04-24 | Cardiac Intelligence Corporation | System and method for determining a reference baseline of individual patient status for use in an automated collection and analysis patient care system |
CA2314517A1 (en) | 1999-07-26 | 2001-01-26 | Gust H. Bardy | System and method for determining a reference baseline of individual patient status for use in an automated collection and analysis patient care system |
US6304775B1 (en) * | 1999-09-22 | 2001-10-16 | Leonidas D. Iasemidis | Seizure warning and prediction |
US6473644B1 (en) | 1999-10-13 | 2002-10-29 | Cyberonics, Inc. | Method to enhance cardiac capillary growth in heart failure patients |
US6882881B1 (en) | 1999-10-19 | 2005-04-19 | The Johns Hopkins University | Techniques using heat flow management, stimulation, and signal analysis to treat medical disorders |
US6386882B1 (en) | 1999-11-10 | 2002-05-14 | Medtronic, Inc. | Remote delivery of software-based training for implantable medical device systems |
US6309406B1 (en) | 1999-11-24 | 2001-10-30 | Hamit-Darwin-Fresh, Inc. | Apparatus and method for inducing epileptic seizures in test animals for anticonvulsant drug screening |
JP2003516206A (en) | 1999-12-07 | 2003-05-13 | クラスノウ インスティテュート | Adaptive electric field regulation of the nervous system |
US6873872B2 (en) | 1999-12-07 | 2005-03-29 | George Mason University | Adaptive electric field modulation of neural systems |
WO2001048676A1 (en) | 1999-12-24 | 2001-07-05 | Medtronic, Inc. | Central network to facilitate remote collaboration with medical instruments |
US8002700B2 (en) | 1999-12-30 | 2011-08-23 | Medtronic, Inc. | Communications system for an implantable medical device and a delivery device |
US6471645B1 (en) | 1999-12-30 | 2002-10-29 | Medtronic, Inc. | Communications system for an implantable device and a drug dispenser |
US7483743B2 (en) * | 2000-01-11 | 2009-01-27 | Cedars-Sinai Medical Center | System for detecting, diagnosing, and treating cardiovascular disease |
US6328699B1 (en) | 2000-01-11 | 2001-12-11 | Cedars-Sinai Medical Center | Permanently implantable system and method for detecting, diagnosing and treating congestive heart failure |
US20010027384A1 (en) | 2000-03-01 | 2001-10-04 | Schulze Arthur E. | Wireless internet bio-telemetry monitoring system and method |
US6473639B1 (en) | 2000-03-02 | 2002-10-29 | Neuropace, Inc. | Neurological event detection procedure using processed display channel based algorithms and devices incorporating these procedures |
US6973342B1 (en) | 2000-03-02 | 2005-12-06 | Advanced Neuromodulation Systems, Inc. | Flexible bio-probe assembly |
US6484132B1 (en) | 2000-03-07 | 2002-11-19 | Lockheed Martin Energy Research Corporation | Condition assessment of nonlinear processes |
DE60107062T2 (en) * | 2000-03-31 | 2005-11-24 | Advanced Bionics Corp., Sylmar | COMPLETELY IMPLANTABLE COCHLEA MICROPROTHESIS WITH A VARIETY OF CONTACTS |
AU2001249785A1 (en) | 2000-04-03 | 2001-10-15 | Flint Hills Scientific, L.L.C. | Method, computer program, and system for automated real-time signal analysis fordetection, quantification, and prediction of signal changes |
US6466822B1 (en) | 2000-04-05 | 2002-10-15 | Neuropace, Inc. | Multimodal neurostimulator and process of using it |
US7660621B2 (en) * | 2000-04-07 | 2010-02-09 | Medtronic, Inc. | Medical device introducer |
US6441747B1 (en) * | 2000-04-18 | 2002-08-27 | Motorola, Inc. | Wireless system protocol for telemetry monitoring |
US6442421B1 (en) | 2000-04-27 | 2002-08-27 | Centre National De La Recherche Scientifique | Method for the medical monitoring in real time of a patient from the analysis of electroencephalograms to characterize and differentiate between physiological or pathological conditions, and a method for anticipating epileptic seizures |
US6453198B1 (en) | 2000-04-28 | 2002-09-17 | Medtronic, Inc. | Power management for an implantable medical device |
CA2408097A1 (en) * | 2000-05-08 | 2001-11-15 | Brainsgate Ltd. | Method and apparatus for stimulating the sphenopalatine ganglion to modify properties of the bbb and cerebral blood flow |
US6306403B1 (en) | 2000-06-14 | 2001-10-23 | Allergan Sales, Inc. | Method for treating parkinson's disease with a botulinum toxin |
US6782292B2 (en) | 2000-06-20 | 2004-08-24 | Advanced Bionics Corporation | System and method for treatment of mood and/or anxiety disorders by electrical brain stimulation and/or drug infusion |
US7010351B2 (en) * | 2000-07-13 | 2006-03-07 | Northstar Neuroscience, Inc. | Methods and apparatus for effectuating a lasting change in a neural-function of a patient |
US6402678B1 (en) | 2000-07-31 | 2002-06-11 | Neuralieve, Inc. | Means and method for the treatment of migraine headaches |
US6811562B1 (en) | 2000-07-31 | 2004-11-02 | Epicor, Inc. | Procedures for photodynamic cardiac ablation therapy and devices for those procedures |
EP1355571A2 (en) | 2000-08-15 | 2003-10-29 | The Regents Of The University Of California | Method and apparatus for reducing contamination of an electrical signal |
WO2002014635A1 (en) * | 2000-08-17 | 2002-02-21 | Biometix Pty Ltd. | A security container for medicines and system for filling prescriptions |
US6443891B1 (en) | 2000-09-20 | 2002-09-03 | Medtronic, Inc. | Telemetry modulation protocol system for medical devices |
US6488617B1 (en) | 2000-10-13 | 2002-12-03 | Universal Hedonics | Method and device for producing a desired brain state |
WO2002038031A2 (en) | 2000-10-30 | 2002-05-16 | Neuropace, Inc. | System and method for determining stimulation parameters for the treatment of epileptic seizures |
US7089059B1 (en) | 2000-11-03 | 2006-08-08 | Pless Benjamin D | Predicting susceptibility to neurological dysfunction based on measured neural electrophysiology |
US6534693B2 (en) | 2000-11-06 | 2003-03-18 | Afmedica, Inc. | Surgically implanted devices having reduced scar tissue formation |
US6591137B1 (en) | 2000-11-09 | 2003-07-08 | Neuropace, Inc. | Implantable neuromuscular stimulator for the treatment of gastrointestinal disorders |
US6529774B1 (en) | 2000-11-09 | 2003-03-04 | Neuropace, Inc. | Extradural leads, neurostimulator assemblies, and processes of using them for somatosensory and brain stimulation |
US6618623B1 (en) | 2000-11-28 | 2003-09-09 | Neuropace, Inc. | Ferrule for cranial implant |
US6594524B2 (en) | 2000-12-12 | 2003-07-15 | The Trustees Of The University Of Pennsylvania | Adaptive method and apparatus for forecasting and controlling neurological disturbances under a multi-level control |
CA2431420C (en) | 2000-12-21 | 2011-10-11 | Insulet Corporation | Medical apparatus remote control and method |
US6788975B1 (en) * | 2001-01-30 | 2004-09-07 | Advanced Bionics Corporation | Fully implantable miniature neurostimulator for stimulation as a therapy for epilepsy |
US6571125B2 (en) | 2001-02-12 | 2003-05-27 | Medtronic, Inc. | Drug delivery device |
US20040176359A1 (en) * | 2001-02-20 | 2004-09-09 | University Of Kentucky Research Foundation | Intranasal Benzodiazepine compositions |
US6597953B2 (en) | 2001-02-20 | 2003-07-22 | Neuropace, Inc. | Furcated sensing and stimulation lead |
US7299096B2 (en) * | 2001-03-08 | 2007-11-20 | Northstar Neuroscience, Inc. | System and method for treating Parkinson's Disease and other movement disorders |
US6901292B2 (en) | 2001-03-19 | 2005-05-31 | Medtronic, Inc. | Control of externally induced current in an implantable pulse generator |
US6889086B2 (en) * | 2001-04-06 | 2005-05-03 | Cardiac Pacemakers, Inc. | Passive telemetry system for implantable medical device |
US7916013B2 (en) * | 2005-03-21 | 2011-03-29 | Greatbatch Ltd. | RFID detection and identification system for implantable medical devices |
US7369897B2 (en) | 2001-04-19 | 2008-05-06 | Neuro And Cardiac Technologies, Llc | Method and system of remotely controlling electrical pulses provided to nerve tissue(s) by an implanted stimulator system for neuromodulation therapies |
US6572528B2 (en) | 2001-04-20 | 2003-06-03 | Mclean Hospital Corporation | Magnetic field stimulation techniques |
US6901296B1 (en) * | 2001-05-25 | 2005-05-31 | Advanced Bionics Corporation | Methods and systems for direct electrical current stimulation as a therapy for cancer and other neoplastic diseases |
US6901294B1 (en) * | 2001-05-25 | 2005-05-31 | Advanced Bionics Corporation | Methods and systems for direct electrical current stimulation as a therapy for prostatic hypertrophy |
US20050124863A1 (en) * | 2001-06-28 | 2005-06-09 | Cook Daniel R. | Drug profiling apparatus and method |
US6694159B2 (en) * | 2001-07-16 | 2004-02-17 | Art, Advanced Research Technologies Inc. | Choice of wavelengths for multiwavelength optical imaging |
WO2003009207A1 (en) | 2001-07-20 | 2003-01-30 | Medical Research Group | Ambulatory medical apparatus and method using a robust communication protocol |
US6622047B2 (en) | 2001-07-28 | 2003-09-16 | Cyberonics, Inc. | Treatment of neuropsychiatric disorders by near-diaphragmatic nerve stimulation |
US6622038B2 (en) | 2001-07-28 | 2003-09-16 | Cyberonics, Inc. | Treatment of movement disorders by near-diaphragmatic nerve stimulation |
US8190695B2 (en) * | 2001-08-02 | 2012-05-29 | Sony Corporation | Remote control system and remote control method, device for performing remote control operation and control method therefor, device operable by remote control operation and control method therefor, and storage medium |
US6622041B2 (en) | 2001-08-21 | 2003-09-16 | Cyberonics, Inc. | Treatment of congestive heart failure and autonomic cardiovascular drive disorders |
US6600956B2 (en) | 2001-08-21 | 2003-07-29 | Cyberonics, Inc. | Circumneural electrode assembly |
US6547746B1 (en) | 2001-08-27 | 2003-04-15 | Andrew A. Marino | Method and apparatus for determining response thresholds |
US6760626B1 (en) | 2001-08-29 | 2004-07-06 | Birinder R. Boveja | Apparatus and method for treatment of neurological and neuropsychiatric disorders using programmerless implantable pulse generator system |
US6832200B2 (en) * | 2001-09-07 | 2004-12-14 | Hewlett-Packard Development Company, L.P. | Apparatus for closed-loop pharmaceutical delivery |
US7136695B2 (en) | 2001-10-12 | 2006-11-14 | Pless Benjamin D | Patient-specific template development for neurological event detection |
US20030083716A1 (en) | 2001-10-23 | 2003-05-01 | Nicolelis Miguel A.L. | Intelligent brain pacemaker for real-time monitoring and controlling of epileptic seizures |
US6591132B2 (en) | 2001-11-30 | 2003-07-08 | Stellate Systems Inc. | Artifact detection in encephalogram data using an event model |
US6721603B2 (en) | 2002-01-25 | 2004-04-13 | Cyberonics, Inc. | Nerve stimulation as a treatment for pain |
AU2003217253A1 (en) | 2002-01-25 | 2003-09-02 | Intellipatch, Inc. | Evaluation of a patient and prediction of chronic symptoms |
US20030144711A1 (en) | 2002-01-29 | 2003-07-31 | Neuropace, Inc. | Systems and methods for interacting with an implantable medical device |
US7110820B2 (en) | 2002-02-05 | 2006-09-19 | Tcheng Thomas K | Responsive electrical stimulation for movement disorders |
US7024249B2 (en) * | 2002-02-21 | 2006-04-04 | Alfred E. Mann Foundation For Scientific Research | Pulsed magnetic control system for interlocking functions of battery powered living tissue stimulators |
US20030176806A1 (en) | 2002-02-26 | 2003-09-18 | Pineda Jaime A. | Method and system for an intelligent supervisory control system |
DE10215115A1 (en) | 2002-04-05 | 2003-10-16 | Oliver Holzner | Method and device for the prevention of epileptic seizures |
US7146222B2 (en) | 2002-04-15 | 2006-12-05 | Neurospace, Inc. | Reinforced sensing and stimulation leads and use in detection systems |
US6735467B2 (en) | 2002-04-15 | 2004-05-11 | Persyst Development Corporation | Method and system for detecting seizures using electroencephalograms |
US20030195588A1 (en) | 2002-04-16 | 2003-10-16 | Neuropace, Inc. | External ear canal interface for the treatment of neurological disorders |
IL164685A0 (en) * | 2002-04-22 | 2005-12-18 | Marcio Marc Aurelio Martins Ab | Apparatus and method for measuring biologic parameters |
US6937891B2 (en) | 2002-04-26 | 2005-08-30 | Medtronic, Inc. | Independent therapy programs in an implantable medical device |
US6950706B2 (en) | 2002-04-26 | 2005-09-27 | Medtronic, Inc. | Wave shaping for an implantable medical device |
US7191012B2 (en) | 2003-05-11 | 2007-03-13 | Boveja Birinder R | Method and system for providing pulsed electrical stimulation to a craniel nerve of a patient to provide therapy for neurological and neuropsychiatric disorders |
US6921538B2 (en) | 2002-05-10 | 2005-07-26 | Allergan, Inc. | Therapeutic treatments for neuropsychiatric disorders |
US7373198B2 (en) * | 2002-07-12 | 2008-05-13 | Bionova Technologies Inc. | Method and apparatus for the estimation of anesthetic depth using wavelet analysis of the electroencephalogram |
US7209861B2 (en) | 2002-07-12 | 2007-04-24 | Ut-Battelle Llc | Methods for improved forewarning of critical events across multiple data channels |
US7139677B2 (en) | 2002-07-12 | 2006-11-21 | Ut-Battelle, Llc | Methods for consistent forewarning of critical events across multiple data channels |
US6934580B1 (en) | 2002-07-20 | 2005-08-23 | Flint Hills Scientific, L.L.C. | Stimulation methodologies and apparatus for control of brain states |
US7460903B2 (en) | 2002-07-25 | 2008-12-02 | Pineda Jaime A | Method and system for a real time adaptive system for effecting changes in cognitive-emotive profiles |
US7263467B2 (en) | 2002-09-30 | 2007-08-28 | University Of Florida Research Foundation Inc. | Multi-dimensional multi-parameter time series processing for seizure warning and prediction |
WO2004036804A2 (en) | 2002-08-27 | 2004-04-29 | University Of Florida | Optimization of multi-dimensional time series processing for seizure warning and prediction |
US20060200038A1 (en) | 2002-09-13 | 2006-09-07 | Robert Savit | Noninvasive nonlinear systems and methods for predicting seizure |
US7277748B2 (en) | 2002-09-13 | 2007-10-02 | Neuropace, Inc. | Spatiotemporal pattern recognition for neurological event detection and prediction in an implantable device |
US7209790B2 (en) | 2002-09-30 | 2007-04-24 | Medtronic, Inc. | Multi-mode programmer for medical device communication |
US7460904B2 (en) * | 2002-10-09 | 2008-12-02 | Wake Forest University Health Sciences | Wireless systems and methods for the detection of neural events using onboard processing |
EP1579608A4 (en) | 2002-10-11 | 2012-09-05 | Flint Hills Scient Llc | Method, computer program, and system for intrinsic timescale decomposition, filtering, and automated analysis of signals of arbitrary origin or timescale |
WO2004032720A2 (en) | 2002-10-11 | 2004-04-22 | Flint Hills Scientific, L.L.C. | Multi-modal system for detection and control of changes in brain state |
US8543214B2 (en) | 2002-10-15 | 2013-09-24 | Medtronic, Inc. | Configuring and testing treatment therapy parameters for a medical device system |
AU2003287159A1 (en) | 2002-10-15 | 2004-05-04 | Medtronic Inc. | Synchronization and calibration of clocks for a medical device and calibrated clock |
WO2004036370A2 (en) | 2002-10-15 | 2004-04-29 | Medtronic Inc. | Channel-selective blanking for a medical device system |
AU2003285872A1 (en) | 2002-10-15 | 2004-05-04 | Medtronic Inc. | Treatment termination in a medical device |
WO2004034882A2 (en) | 2002-10-15 | 2004-04-29 | Medtronic Inc. | Measuring a neurological event using clustering |
WO2004034998A2 (en) | 2002-10-15 | 2004-04-29 | Medtronic Inc. | Control of treatment therapy during start-up and during operation of a medical device system |
EP1558132B1 (en) | 2002-10-15 | 2011-12-21 | Medtronic, Inc. | Medical device system for scoring of sensed neurological events |
WO2004036376A2 (en) | 2002-10-15 | 2004-04-29 | Medtronic Inc. | Multi-modal operation of a medical device system |
AU2003285888A1 (en) | 2002-10-15 | 2004-05-04 | Medtronic Inc. | Medical device system with relaying module for treatment of nervous system disorders |
EP1558121A4 (en) | 2002-10-15 | 2008-10-15 | Medtronic Inc | Signal quality monitoring and control for a medical device system |
EP1558128B1 (en) | 2002-10-15 | 2014-04-30 | Medtronic, Inc. | Signal quality monitoring and control for a medical device system |
WO2004034879A2 (en) | 2002-10-15 | 2004-04-29 | Medtronic Inc. | Screening techniques for management of a nervous system disorder |
US20050049649A1 (en) | 2002-10-21 | 2005-03-03 | The Cleveland Clinic Foundation | Electrical stimulation of the brain |
EP1556127A2 (en) | 2002-10-21 | 2005-07-27 | The Cleveland Clinic Foundation | Electrical stimulation of the brain |
US7212851B2 (en) * | 2002-10-24 | 2007-05-01 | Brown University Research Foundation | Microstructured arrays for cortex interaction and related methods of manufacture and use |
WO2004043536A1 (en) | 2002-11-12 | 2004-05-27 | Neuropace, Inc. | System for adaptive brain stimulation |
US20040243146A1 (en) | 2002-11-18 | 2004-12-02 | Chesbrough Richard M | Method and apparatus for supporting a medical device |
TR200202651A2 (en) | 2002-12-12 | 2004-07-21 | Met�N�Tulgar | the vücutádışındanádirekátedaviásinyaliátransferliáábeyinápil |
US7294101B2 (en) | 2002-12-21 | 2007-11-13 | Neuropace, Inc. | Means and methods for treating headaches |
US7149581B2 (en) * | 2003-01-31 | 2006-12-12 | Medtronic, Inc. | Patient monitoring device with multi-antenna receiver |
US7269455B2 (en) * | 2003-02-26 | 2007-09-11 | Pineda Jaime A | Method and system for predicting and preventing seizures |
US20040199212A1 (en) | 2003-04-01 | 2004-10-07 | Fischell David R. | External patient alerting system for implantable devices |
US20050055035A1 (en) * | 2003-05-23 | 2005-03-10 | Cosman Eric Richard | Image-based stereotactic frame for non-human animals |
US7117108B2 (en) * | 2003-05-28 | 2006-10-03 | Paul Ernest Rapp | System and method for categorical analysis of time dependent dynamic processes |
US20050004622A1 (en) | 2003-07-03 | 2005-01-06 | Advanced Neuromodulation Systems | System and method for implantable pulse generator with multiple treatment protocols |
US20050059867A1 (en) * | 2003-09-13 | 2005-03-17 | Cheng Chung Yuan | Method for monitoring temperature of patient |
US7617002B2 (en) | 2003-09-15 | 2009-11-10 | Medtronic, Inc. | Selection of neurostimulator parameter configurations using decision trees |
US7252090B2 (en) | 2003-09-15 | 2007-08-07 | Medtronic, Inc. | Selection of neurostimulator parameter configurations using neural network |
US7502650B2 (en) | 2003-09-22 | 2009-03-10 | Cvrx, Inc. | Baroreceptor activation for epilepsy control |
US7129836B2 (en) | 2003-09-23 | 2006-10-31 | Ge Medical Systems Information Technologies, Inc. | Wireless subject monitoring system |
US20050070970A1 (en) | 2003-09-29 | 2005-03-31 | Knudson Mark B. | Movement disorder stimulation with neural block |
US7187967B2 (en) * | 2003-09-30 | 2007-03-06 | Neural Signals, Inc. | Apparatus and method for detecting neural signals and using neural signals to drive external functions |
US8190248B2 (en) * | 2003-10-16 | 2012-05-29 | Louisiana Tech University Foundation, Inc. | Medical devices for the detection, prevention and/or treatment of neurological disorders, and methods related thereto |
US20050113744A1 (en) | 2003-11-21 | 2005-05-26 | Cyberkinetics, Inc. | Agent delivery systems and related methods under control of biological electrical signals |
US20050113885A1 (en) | 2003-11-26 | 2005-05-26 | Haubrich Gregory J. | Patient notification of medical device telemetry session |
US7813799B2 (en) | 2003-12-08 | 2010-10-12 | Cardiac Pacemakers, Inc. | Adaptive safety pacing |
US20050182422A1 (en) * | 2004-02-13 | 2005-08-18 | Schulte Gregory T. | Apparatus for securing a therapy delivery device within a burr hole and method for making same |
JP2007522249A (en) * | 2004-02-13 | 2007-08-09 | ニューロモレキュラー・インコーポレイテッド | Combination of an NMDA receptor antagonist and an antidepressant MAO inhibitor or GADPH inhibitor for the treatment of psychiatric conditions |
US20050187789A1 (en) | 2004-02-25 | 2005-08-25 | Cardiac Pacemakers, Inc. | Advanced patient and medication therapy management system and method |
US20050203584A1 (en) * | 2004-03-10 | 2005-09-15 | Medtronic, Inc. | Telemetry antenna for an implantable medical device |
US20050203366A1 (en) * | 2004-03-12 | 2005-09-15 | Donoghue John P. | Neurological event monitoring and therapy systems and related methods |
US8055348B2 (en) | 2004-03-16 | 2011-11-08 | Medtronic, Inc. | Detecting sleep to evaluate therapy |
US7805196B2 (en) * | 2004-03-16 | 2010-09-28 | Medtronic, Inc. | Collecting activity information to evaluate therapy |
US7387608B2 (en) | 2004-04-06 | 2008-06-17 | David A Dunlop | Apparatus and method for the treatment of sleep related disorders |
WO2005099816A1 (en) | 2004-04-07 | 2005-10-27 | Cardiac Pacemakers, Inc. | System and method for rf transceiver duty cycling in an implantable medical device |
US7283856B2 (en) | 2004-04-09 | 2007-10-16 | Neuro Pace, Inc. | Implantable lead system with seed electrodes |
US20050231374A1 (en) | 2004-04-15 | 2005-10-20 | Diem Bjorn H | Data management system |
US7272435B2 (en) | 2004-04-15 | 2007-09-18 | Ge Medical Information Technologies, Inc. | System and method for sudden cardiac death prediction |
US7532936B2 (en) | 2004-04-20 | 2009-05-12 | Advanced Neuromodulation Systems, Inc. | Programmable switching device for implantable device |
WO2005104779A2 (en) | 2004-04-28 | 2005-11-10 | Transoma Medical, Inc. | Implantable medical devices and related methods |
US7463917B2 (en) * | 2004-04-28 | 2008-12-09 | Medtronic, Inc. | Electrodes for sustained delivery of energy |
US20050245984A1 (en) | 2004-04-30 | 2005-11-03 | Medtronic, Inc. | Implantable medical device with lubricious material |
WO2005117693A1 (en) | 2004-05-27 | 2005-12-15 | Children's Medical Center Corporation | Patient-specific seizure onset detection system |
US7450991B2 (en) | 2004-05-28 | 2008-11-11 | Advanced Neuromodulation Systems, Inc. | Systems and methods used to reserve a constant battery capacity |
US7283867B2 (en) | 2004-06-10 | 2007-10-16 | Ndi Medical, Llc | Implantable system and methods for acquisition and processing of electrical signals from muscles and/or nerves and/or central nervous system tissue |
WO2006019822A2 (en) | 2004-07-14 | 2006-02-23 | Arizona Technology Enterprises | Pacemaker for treating physiological system dysfunction |
US7751891B2 (en) | 2004-07-28 | 2010-07-06 | Cyberonics, Inc. | Power supply monitoring for an implantable device |
US20060049957A1 (en) | 2004-08-13 | 2006-03-09 | Surgenor Timothy R | Biological interface systems with controlled device selector and related methods |
US7463927B1 (en) | 2004-09-02 | 2008-12-09 | Intelligent Neurostimulation Microsystems, Llc | Self-adaptive system for the automatic detection of discomfort and the automatic generation of SCS therapies for chronic pain control |
WO2006035392A1 (en) * | 2004-09-27 | 2006-04-06 | Koninklijke Philips Electronics N. V. | Biosensors for the analysis of samples |
WO2006041738A2 (en) * | 2004-10-04 | 2006-04-20 | Cyberkinetics Neurotechnology Systems, Inc. | Biological interface system |
ATE479387T1 (en) * | 2004-11-02 | 2010-09-15 | Medtronic Inc | TECHNIQUES FOR USER-ACTIVATED DATA RETENTION IN AN IMPLANTABLE MEDICAL DEVICE |
US20060122469A1 (en) * | 2004-11-16 | 2006-06-08 | Martel Normand M | Remote medical monitoring system |
US20060129056A1 (en) * | 2004-12-10 | 2006-06-15 | Washington University | Electrocorticography telemitter |
US8112153B2 (en) * | 2004-12-17 | 2012-02-07 | Medtronic, Inc. | System and method for monitoring or treating nervous system disorders |
US20060293578A1 (en) | 2005-02-03 | 2006-12-28 | Rennaker Robert L Ii | Brian machine interface device |
US7493167B2 (en) * | 2005-03-22 | 2009-02-17 | Greatbatch-Sierra, Inc. | Magnetically shielded AIMD housing with window for magnetically actuated switch |
US20060253096A1 (en) | 2005-04-15 | 2006-11-09 | Blakley Daniel R | Intelligent medical cabinet |
EP3827747A1 (en) | 2005-04-28 | 2021-06-02 | Otsuka Pharmaceutical Co., Ltd. | Pharma-informatics system |
US8644941B2 (en) * | 2005-06-09 | 2014-02-04 | Medtronic, Inc. | Peripheral nerve field stimulation and spinal cord stimulation |
US20070055320A1 (en) * | 2005-09-07 | 2007-03-08 | Northstar Neuroscience, Inc. | Methods for treating temporal lobe epilepsy, associated neurological disorders, and other patient functions |
US9042974B2 (en) * | 2005-09-12 | 2015-05-26 | New York University | Apparatus and method for monitoring and treatment of brain disorders |
US7729773B2 (en) * | 2005-10-19 | 2010-06-01 | Advanced Neuromodualation Systems, Inc. | Neural stimulation and optical monitoring systems and methods |
US20080319281A1 (en) | 2005-12-20 | 2008-12-25 | Koninklijle Philips Electronics, N.V. | Device for Detecting and Warning of Medical Condition |
US8725243B2 (en) | 2005-12-28 | 2014-05-13 | Cyberonics, Inc. | Methods and systems for recommending an appropriate pharmacological treatment to a patient for managing epilepsy and other neurological disorders |
US20070149952A1 (en) | 2005-12-28 | 2007-06-28 | Mike Bland | Systems and methods for characterizing a patient's propensity for a neurological event and for communicating with a pharmacological agent dispenser |
US8868172B2 (en) | 2005-12-28 | 2014-10-21 | Cyberonics, Inc. | Methods and systems for recommending an appropriate action to a patient for managing epilepsy and other neurological disorders |
US8078618B2 (en) * | 2006-01-30 | 2011-12-13 | Eastman Kodak Company | Automatic multimode system for organizing and retrieving content data files |
US7787945B2 (en) * | 2006-03-08 | 2010-08-31 | Neuropace, Inc. | Implantable seizure monitor |
US8002701B2 (en) * | 2006-03-10 | 2011-08-23 | Angel Medical Systems, Inc. | Medical alarm and communication system and methods |
US8209018B2 (en) * | 2006-03-10 | 2012-06-26 | Medtronic, Inc. | Probabilistic neurological disorder treatment |
US20070217121A1 (en) * | 2006-03-14 | 2007-09-20 | Greatbatch Ltd. | Integrated Filter Feedthrough Assemblies Made From Low Temperature Co-Fired (LTCC) Tape |
WO2007115224A2 (en) * | 2006-03-30 | 2007-10-11 | Sri International | Method and apparatus for annotating media streams |
US7796769B2 (en) | 2006-05-30 | 2010-09-14 | Sonitus Medical, Inc. | Methods and apparatus for processing audio signals |
US20080027347A1 (en) * | 2006-06-23 | 2008-01-31 | Neuro Vista Corporation, A Delaware Corporation | Minimally Invasive Monitoring Methods |
US7885706B2 (en) * | 2006-09-20 | 2011-02-08 | New York University | System and device for seizure detection |
US20080091090A1 (en) * | 2006-10-12 | 2008-04-17 | Kenneth Shane Guillory | Self-contained surface physiological monitor with adhesive attachment |
US8380311B2 (en) * | 2006-10-31 | 2013-02-19 | Medtronic, Inc. | Housing for implantable medical device |
US8321032B2 (en) | 2006-11-09 | 2012-11-27 | Greatbatch Ltd. | RFID-enabled AIMD programmer system for identifying MRI compatibility of implanted leads |
US20080161712A1 (en) * | 2006-12-27 | 2008-07-03 | Kent Leyde | Low Power Device With Contingent Scheduling |
US9913593B2 (en) * | 2006-12-27 | 2018-03-13 | Cyberonics, Inc. | Low power device with variable scheduling |
US8075499B2 (en) * | 2007-05-18 | 2011-12-13 | Vaidhi Nathan | Abnormal motion detector and monitor |
US20080221876A1 (en) * | 2007-03-08 | 2008-09-11 | Universitat Fur Musik Und Darstellende Kunst | Method for processing audio data into a condensed version |
US8036736B2 (en) | 2007-03-21 | 2011-10-11 | Neuro Vista Corporation | Implantable systems and methods for identifying a contra-ictal condition in a subject |
US7917218B2 (en) | 2007-03-21 | 2011-03-29 | Medtronic, Inc. | Filtering capacitor feedthrough assembly |
US9259591B2 (en) | 2007-12-28 | 2016-02-16 | Cyberonics, Inc. | Housing for an implantable medical device |
US20090171168A1 (en) | 2007-12-28 | 2009-07-02 | Leyde Kent W | Systems and Method for Recording Clinical Manifestations of a Seizure |
-
2007
- 2007-06-21 US US11/766,751 patent/US20080027347A1/en not_active Abandoned
- 2007-06-21 WO PCT/US2007/071833 patent/WO2007150003A2/en active Application Filing
- 2007-06-21 US US11/766,760 patent/US7676263B2/en active Active
- 2007-06-21 EP EP07812246A patent/EP2034885A4/en not_active Withdrawn
- 2007-06-21 US US11/766,756 patent/US20080021341A1/en not_active Abandoned
- 2007-06-21 US US11/766,742 patent/US20080027515A1/en not_active Abandoned
- 2007-06-21 US US11/766,761 patent/US20080027348A1/en not_active Abandoned
-
2010
- 2010-01-21 US US12/691,650 patent/US20100125219A1/en not_active Abandoned
-
2011
- 2011-03-17 US US13/050,839 patent/US20110166430A1/en not_active Abandoned
-
2015
- 2015-03-10 US US14/644,058 patent/US9480845B2/en active Active
Patent Citations (99)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3498287A (en) * | 1966-04-28 | 1970-03-03 | Neural Models Ltd | Intelligence testing and signal analyzing means and method employing zero crossing detection |
US3863625A (en) * | 1973-11-02 | 1975-02-04 | Us Health | Epileptic seizure warning system |
US4505275A (en) * | 1977-09-15 | 1985-03-19 | Wu Chen | Treatment method and instrumentation system |
US4566464A (en) * | 1981-07-27 | 1986-01-28 | Piccone Vincent A | Implantable epilepsy monitor apparatus |
US4494950A (en) * | 1982-01-19 | 1985-01-22 | The Johns Hopkins University | Plural module medication delivery system |
US4573481A (en) * | 1984-06-25 | 1986-03-04 | Huntington Institute Of Applied Research | Implantable electrode array |
US5299118A (en) * | 1987-06-26 | 1994-03-29 | Nicolet Instrument Corporation | Method and system for analysis of long term physiological polygraphic recordings |
US5181520A (en) * | 1987-12-22 | 1993-01-26 | Royal Postgraduate Medical School | Method and apparatus for analyzing an electro-encephalogram |
US4903702A (en) * | 1988-10-17 | 1990-02-27 | Ad-Tech Medical Instrument Corporation | Brain-contact for sensing epileptogenic foci with improved accuracy |
US4991582A (en) * | 1989-09-22 | 1991-02-12 | Alfred E. Mann Foundation For Scientific Research | Hermetically sealed ceramic and metal package for electronic devices implantable in living bodies |
US5082861A (en) * | 1989-09-26 | 1992-01-21 | Carter-Wallace, Inc. | Method for the prevention and control of epileptic seizure associated with complex partial seizures |
US5292772A (en) * | 1989-09-26 | 1994-03-08 | Carter-Wallace, Inc. | Method for the prevention and control of epileptic seizure associated with Lennox-Gastaut syndrome |
US5186170A (en) * | 1989-11-13 | 1993-02-16 | Cyberonics, Inc. | Simultaneous radio frequency and magnetic field microprocessor reset circuit |
US5179950A (en) * | 1989-11-13 | 1993-01-19 | Cyberonics, Inc. | Implanted apparatus having micro processor controlled current and voltage sources with reduced voltage levels when not providing stimulation |
US5097835A (en) * | 1990-04-09 | 1992-03-24 | Ad-Tech Medical Instrument Corporation | Subdural electrode with improved lead connection |
US5188104A (en) * | 1991-02-01 | 1993-02-23 | Cyberonics, Inc. | Treatment of eating disorders by nerve stimulation |
US5190029A (en) * | 1991-02-14 | 1993-03-02 | Virginia Commonwealth University | Formulation for delivery of drugs by metered dose inhalers with reduced or no chlorofluorocarbon content |
US5293879A (en) * | 1991-09-23 | 1994-03-15 | Vitatron Medical, B.V. | System an method for detecting tremors such as those which result from parkinson's disease |
US5193539A (en) * | 1991-12-18 | 1993-03-16 | Alfred E. Mann Foundation For Scientific Research | Implantable microstimulator |
US5193540A (en) * | 1991-12-18 | 1993-03-16 | Alfred E. Mann Foundation For Scientific Research | Structure and method of manufacture of an implantable microstimulator |
US5392788A (en) * | 1993-02-03 | 1995-02-28 | Hudspeth; William J. | Method and device for interpreting concepts and conceptual thought from brainwave data and for assisting for diagnosis of brainwave disfunction |
US5862803A (en) * | 1993-09-04 | 1999-01-26 | Besson; Marcus | Wireless medical diagnosis and monitoring equipment |
US5486999A (en) * | 1994-04-20 | 1996-01-23 | Mebane; Andrew H. | Apparatus and method for categorizing health care utilization |
US5715821A (en) * | 1994-12-09 | 1998-02-10 | Biofield Corp. | Neural network method and apparatus for disease, injury and bodily condition screening or sensing |
US5707400A (en) * | 1995-09-19 | 1998-01-13 | Cyberonics, Inc. | Treating refractory hypertension by nerve stimulation |
US5704352A (en) * | 1995-11-22 | 1998-01-06 | Tremblay; Gerald F. | Implantable passive bio-sensor |
US5611350A (en) * | 1996-02-08 | 1997-03-18 | John; Michael S. | Method and apparatus for facilitating recovery of patients in deep coma |
US5857978A (en) * | 1996-03-20 | 1999-01-12 | Lockheed Martin Energy Systems, Inc. | Epileptic seizure prediction by non-linear methods |
US5716377A (en) * | 1996-04-25 | 1998-02-10 | Medtronic, Inc. | Method of treating movement disorders by brain stimulation |
US5711316A (en) * | 1996-04-30 | 1998-01-27 | Medtronic, Inc. | Method of treating movement disorders by brain infusion |
US5720294A (en) * | 1996-05-02 | 1998-02-24 | Enhanced Cardiology, Inc. | PD2I electrophysiological analyzer |
US5713923A (en) * | 1996-05-13 | 1998-02-03 | Medtronic, Inc. | Techniques for treating epilepsy by brain stimulation and drug infusion |
US6339725B1 (en) * | 1996-05-31 | 2002-01-15 | The Board Of Trustees Of Southern Illinois University | Methods of modulating aspects of brain neural plasticity by vagus nerve stimulation |
US6511424B1 (en) * | 1997-01-11 | 2003-01-28 | Circadian Technologies, Inc. | Method of and apparatus for evaluation and mitigation of microsleep events |
US5876424A (en) * | 1997-01-23 | 1999-03-02 | Cardiac Pacemakers, Inc. | Ultra-thin hermetic enclosure for implantable medical devices |
US6042579A (en) * | 1997-04-30 | 2000-03-28 | Medtronic, Inc. | Techniques for treating neurodegenerative disorders by infusion of nerve growth factors into the brain |
US6016449A (en) * | 1997-10-27 | 2000-01-18 | Neuropace, Inc. | System for treatment of neurological disorders |
US6360122B1 (en) * | 1997-10-27 | 2002-03-19 | Neuropace, Inc. | Data recording methods for an implantable device |
US6354299B1 (en) * | 1997-10-27 | 2002-03-12 | Neuropace, Inc. | Implantable device for patient communication |
US20020002390A1 (en) * | 1997-10-27 | 2002-01-03 | Fischell Robert E. | Implantable neurostimulator having a data communication link |
US6042548A (en) * | 1997-11-14 | 2000-03-28 | Hypervigilant Technologies | Virtual neurological monitor and method |
US6208893B1 (en) * | 1998-01-27 | 2001-03-27 | Genetronics, Inc. | Electroporation apparatus with connective electrode template |
US6337997B1 (en) * | 1998-04-30 | 2002-01-08 | Medtronic, Inc. | Implantable seizure warning system |
US6018682A (en) * | 1998-04-30 | 2000-01-25 | Medtronic, Inc. | Implantable seizure warning system |
US20050021103A1 (en) * | 1998-08-05 | 2005-01-27 | Dilorenzo Daniel John | Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease |
US20050021104A1 (en) * | 1998-08-05 | 2005-01-27 | Dilorenzo Daniel John | Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease |
US20100023089A1 (en) * | 1998-08-05 | 2010-01-28 | Dilorenzo Daniel John | Controlling a Subject's Susceptibility to a Seizure |
US6171239B1 (en) * | 1998-08-17 | 2001-01-09 | Emory University | Systems, methods, and devices for controlling external devices by signals derived directly from the nervous system |
US6201980B1 (en) * | 1998-10-05 | 2001-03-13 | The Regents Of The University Of California | Implantable medical sensor system |
US6356788B2 (en) * | 1998-10-26 | 2002-03-12 | Birinder Bob Boveja | Apparatus and method for adjunct (add-on) therapy for depression, migraine, neuropsychiatric disorders, partial complex epilepsy, generalized epilepsy and involuntary movement disorders utilizing an external stimulator |
US6205359B1 (en) * | 1998-10-26 | 2001-03-20 | Birinder Bob Boveja | Apparatus and method for adjunct (add-on) therapy of partial complex epilepsy, generalized epilepsy and involuntary movement disorders utilizing an external stimulator |
US6341236B1 (en) * | 1999-04-30 | 2002-01-22 | Ivan Osorio | Vagal nerve stimulation techniques for treatment of epileptic seizures |
US6176242B1 (en) * | 1999-04-30 | 2001-01-23 | Medtronic Inc | Method of treating manic depression by brain infusion |
US6356784B1 (en) * | 1999-04-30 | 2002-03-12 | Medtronic, Inc. | Method of treating movement disorders by electrical stimulation and/or drug infusion of the pendunulopontine nucleus |
US6358203B2 (en) * | 1999-06-03 | 2002-03-19 | Cardiac Intelligence Corp. | System and method for automated collection and analysis of patient information retrieved from an implantable medical device for remote patient care |
US6343226B1 (en) * | 1999-06-25 | 2002-01-29 | Neurokinetic Aps | Multifunction electrode for neural tissue stimulation |
US7486986B1 (en) * | 1999-10-12 | 2009-02-03 | Flint Hills Scientific Llc | Bi-directional cerebral interface system |
US6358281B1 (en) * | 1999-11-29 | 2002-03-19 | Epic Biosonics Inc. | Totally implantable cochlear prosthesis |
US20020035338A1 (en) * | 1999-12-01 | 2002-03-21 | Dear Stephen P. | Epileptic seizure detection and prediction by self-similar methods |
US20050015129A1 (en) * | 1999-12-09 | 2005-01-20 | Mische Hans A. | Methods and devices for the treatment of neurological and physiological disorders |
US20070043459A1 (en) * | 1999-12-15 | 2007-02-22 | Tangis Corporation | Storing and recalling information to augment human memories |
US6510340B1 (en) * | 2000-01-10 | 2003-01-21 | Jordan Neuroscience, Inc. | Method and apparatus for electroencephalography |
US20050021313A1 (en) * | 2000-04-03 | 2005-01-27 | Nikitin Alexei V. | Method, computer program, and system for automated real-time signal analysis for detection, quantification, and prediction of signal changes |
US6353754B1 (en) * | 2000-04-24 | 2002-03-05 | Neuropace, Inc. | System for the creation of patient specific templates for epileptiform activity detection |
US6505077B1 (en) * | 2000-06-19 | 2003-01-07 | Medtronic, Inc. | Implantable medical device with external recharging coil electrical connection |
US6687538B1 (en) * | 2000-06-19 | 2004-02-03 | Medtronic, Inc. | Trial neuro stimulator with lead diagnostics |
US20030013981A1 (en) * | 2000-06-26 | 2003-01-16 | Alan Gevins | Neurocognitive function EEG measurement method and system |
US20050021105A1 (en) * | 2000-07-13 | 2005-01-27 | Firlik Andrew D. | Methods and apparatus for effectuating a change in a neural-function of a patient |
US20030028072A1 (en) * | 2000-08-31 | 2003-02-06 | Neuropace, Inc. | Low frequency magnetic neurostimulator for the treatment of neurological disorders |
US20050027328A1 (en) * | 2000-09-26 | 2005-02-03 | Transneuronix, Inc. | Minimally invasive surgery placement of stimulation leads in mediastinal structures |
US7333851B2 (en) * | 2000-10-20 | 2008-02-19 | The Trustees Of The University Of Pennsylvania | Unified probabilistic framework for predicting and detecting seizure onsets in the brain and multitherapeutic device |
US6678548B1 (en) * | 2000-10-20 | 2004-01-13 | The Trustees Of The University Of Pennsylvania | Unified probabilistic framework for predicting and detecting seizure onsets in the brain and multitherapeutic device |
US20040034368A1 (en) * | 2000-11-28 | 2004-02-19 | Pless Benjamin D. | Ferrule for cranial implant |
US7177701B1 (en) * | 2000-12-29 | 2007-02-13 | Advanced Bionics Corporation | System for permanent electrode placement utilizing microelectrode recording methods |
US20040039427A1 (en) * | 2001-01-02 | 2004-02-26 | Cyberonics, Inc. | Treatment of obesity by sub-diaphragmatic nerve stimulation |
US7006872B2 (en) * | 2001-04-27 | 2006-02-28 | Medtronic, Inc. | Closed loop neuromodulation for suppression of epileptic activity |
US20070016094A1 (en) * | 2001-06-28 | 2007-01-18 | Neuropace, Inc. | Seizure sensing and detection using an implantable device |
US20030004428A1 (en) * | 2001-06-28 | 2003-01-02 | Pless Benjamin D. | Seizure sensing and detection using an implantable device |
US20030009207A1 (en) * | 2001-07-09 | 2003-01-09 | Paspa Paul M. | Implantable medical lead |
US20030018367A1 (en) * | 2001-07-23 | 2003-01-23 | Dilorenzo Daniel John | Method and apparatus for neuromodulation and phsyiologic modulation for the treatment of metabolic and neuropsychiatric disease |
US6684105B2 (en) * | 2001-08-31 | 2004-01-27 | Biocontrol Medical, Ltd. | Treatment of disorders by unidirectional nerve stimulation |
US20030050549A1 (en) * | 2001-09-13 | 2003-03-13 | Jerzy Sochor | Implantable lead connector assembly for implantable devices and methods of using it |
US6990372B2 (en) * | 2002-04-11 | 2006-01-24 | Alfred E. Mann Foundation For Scientific Research | Programmable signal analysis device for detecting neurological signals in an implantable device |
US20050004621A1 (en) * | 2002-05-09 | 2005-01-06 | Boveja Birinder R. | Method and system for modulating the vagus nerve (10th cranial nerve) with electrical pulses using implanted and external componants, to provide therapy for neurological and neuropsychiatric disorders |
US20050021108A1 (en) * | 2002-06-28 | 2005-01-27 | Klosterman Daniel J. | Bi-directional telemetry system for use with microstimulator |
US20040039981A1 (en) * | 2002-08-23 | 2004-02-26 | Riedl Daniel A. | Method and apparatus for identifying one or more devices having faults in a communication loop |
US20060015034A1 (en) * | 2002-10-18 | 2006-01-19 | Jacques Martinerie | Analysis method and real time medical or cognitive monitoring device based on the analysis of a subject's cerebral electromagnetic use of said method for characterizing and differenting physiological and pathological states |
US20050010261A1 (en) * | 2002-10-21 | 2005-01-13 | The Cleveland Clinic Foundation | Application of stimulus to white matter to induce a desired physiological response |
US20050043774A1 (en) * | 2003-05-06 | 2005-02-24 | Aspect Medical Systems, Inc | System and method of assessment of the efficacy of treatment of neurological disorders using the electroencephalogram |
US20050015128A1 (en) * | 2003-05-29 | 2005-01-20 | Rezai Ali R. | Excess lead retaining and management devices and methods of using same |
US20050033369A1 (en) * | 2003-08-08 | 2005-02-10 | Badelt Steven W. | Data Feedback loop for medical therapy adjustment |
US20050043772A1 (en) * | 2003-08-18 | 2005-02-24 | Stahmann Jeffrey E. | Therapy triggered by prediction of disordered breathing |
US7174212B1 (en) * | 2003-12-10 | 2007-02-06 | Pacesetter, Inc. | Implantable medical device having a casing providing high-speed telemetry |
US7881798B2 (en) * | 2004-03-16 | 2011-02-01 | Medtronic Inc. | Controlling therapy based on sleep quality |
US20060015153A1 (en) * | 2004-07-15 | 2006-01-19 | Gliner Bradford E | Systems and methods for enhancing or affecting neural stimulation efficiency and/or efficacy |
US20060030904A1 (en) * | 2004-08-09 | 2006-02-09 | Sylvia Quiles | Secure remote access for an implantable medical device |
US20070027514A1 (en) * | 2005-07-29 | 2007-02-01 | Medtronic, Inc. | Electrical stimulation lead with conformable array of electrodes |
US20070027367A1 (en) * | 2005-08-01 | 2007-02-01 | Microsoft Corporation | Mobile, personal, and non-intrusive health monitoring and analysis system |
US20070035910A1 (en) * | 2005-08-15 | 2007-02-15 | Greatbatch-Sierra, Inc. | Feedthrough filter capacitor assembly with internally grounded hermetic insulator |
Cited By (89)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100217348A1 (en) * | 1998-08-05 | 2010-08-26 | Neurovista Corporation | Systems for Monitoring a Patient's Neurological Disease State |
US8762065B2 (en) | 1998-08-05 | 2014-06-24 | Cyberonics, Inc. | Closed-loop feedback-driven neuromodulation |
US8781597B2 (en) | 1998-08-05 | 2014-07-15 | Cyberonics, Inc. | Systems for monitoring a patient's neurological disease state |
US20100023089A1 (en) * | 1998-08-05 | 2010-01-28 | Dilorenzo Daniel John | Controlling a Subject's Susceptibility to a Seizure |
US9415222B2 (en) | 1998-08-05 | 2016-08-16 | Cyberonics, Inc. | Monitoring an epilepsy disease state with a supervisory module |
US20060293720A1 (en) * | 1998-08-05 | 2006-12-28 | Dilorenzo Daniel J | Closed-loop feedback-driven neuromodulation |
US8565867B2 (en) | 2005-01-28 | 2013-10-22 | Cyberonics, Inc. | Changeable electrode polarity stimulation by an implantable medical device |
US20110213437A9 (en) * | 2005-01-28 | 2011-09-01 | Armstrong Randolph K | Changeable electrode polarity stimulation by an implantable medical device |
US20090192564A1 (en) * | 2005-01-28 | 2009-07-30 | Armstrong Randolph K | Changeable electrode polarity stimulation by an implantable medical device |
US9586047B2 (en) | 2005-01-28 | 2017-03-07 | Cyberonics, Inc. | Contingent cardio-protection for epilepsy patients |
US9592004B2 (en) | 2005-12-28 | 2017-03-14 | Cyberonics, Inc. | Methods and systems for managing epilepsy and other neurological disorders |
US9044188B2 (en) | 2005-12-28 | 2015-06-02 | Cyberonics, Inc. | Methods and systems for managing epilepsy and other neurological disorders |
US7996079B2 (en) | 2006-01-24 | 2011-08-09 | Cyberonics, Inc. | Input response override for an implantable medical device |
US8150508B2 (en) | 2006-03-29 | 2012-04-03 | Catholic Healthcare West | Vagus nerve stimulation method |
US9289599B2 (en) | 2006-03-29 | 2016-03-22 | Dignity Health | Vagus nerve stimulation method |
US9533151B2 (en) | 2006-03-29 | 2017-01-03 | Dignity Health | Microburst electrical stimulation of cranial nerves for the treatment of medical conditions |
US20090177252A1 (en) * | 2006-03-29 | 2009-07-09 | Catholic Healthcare West (D/B/A St. Joseph's Hospital And Medical Center) | Synchronization of vagus nerve stimulation with the cardiac cycle of a patient |
US8615309B2 (en) | 2006-03-29 | 2013-12-24 | Catholic Healthcare West | Microburst electrical stimulation of cranial nerves for the treatment of medical conditions |
US8660666B2 (en) | 2006-03-29 | 2014-02-25 | Catholic Healthcare West | Microburst electrical stimulation of cranial nerves for the treatment of medical conditions |
US8280505B2 (en) | 2006-03-29 | 2012-10-02 | Catholic Healthcare West | Vagus nerve stimulation method |
US8738126B2 (en) | 2006-03-29 | 2014-05-27 | Catholic Healthcare West | Synchronization of vagus nerve stimulation with the cardiac cycle of a patient |
US20070233193A1 (en) * | 2006-03-29 | 2007-10-04 | Catholic Healthcare West (D/B/A St. Joseph's Hospital And Medical Center) | Microburst electrical stimulation of cranial nerves for the treatment of medical conditions |
US20070233194A1 (en) * | 2006-03-29 | 2007-10-04 | Catholic Healthcare West (D/B/A St. Joseph's Hospital And Medical Center) | Synchronization of vagus nerve stimulation with the cardiac cycle of a patient |
US8219188B2 (en) | 2006-03-29 | 2012-07-10 | Catholic Healthcare West | Synchronization of vagus nerve stimulation with the cardiac cycle of a patient |
US20070233192A1 (en) * | 2006-03-29 | 2007-10-04 | Catholic Healthcare West (D/B/A St. Joseph's Hospital And Medical Center) | Vagus nerve stimulation method |
US9108041B2 (en) | 2006-03-29 | 2015-08-18 | Dignity Health | Microburst electrical stimulation of cranial nerves for the treatment of medical conditions |
US7962220B2 (en) | 2006-04-28 | 2011-06-14 | Cyberonics, Inc. | Compensation reduction in tissue stimulation therapy |
US20070255351A1 (en) * | 2006-04-28 | 2007-11-01 | Cyberonics, Inc. | Threshold optimization for tissue stimulation therapy |
US7869885B2 (en) | 2006-04-28 | 2011-01-11 | Cyberonics, Inc | Threshold optimization for tissue stimulation therapy |
US9480845B2 (en) | 2006-06-23 | 2016-11-01 | Cyberonics, Inc. | Nerve stimulation device with a wearable loop antenna |
US20110166430A1 (en) * | 2006-06-23 | 2011-07-07 | Harris John F | System and methods for analyzing seizure activity |
US20100125219A1 (en) * | 2006-06-23 | 2010-05-20 | Harris John F | Minimally invasive system for selecting patient-specific therapy parameters |
US7869867B2 (en) | 2006-10-27 | 2011-01-11 | Cyberonics, Inc. | Implantable neurostimulator with refractory stimulation |
US8855775B2 (en) | 2006-11-14 | 2014-10-07 | Cyberonics, Inc. | Systems and methods of reducing artifact in neurological stimulation systems |
US20080114417A1 (en) * | 2006-11-14 | 2008-05-15 | Leyde Kent W | Systems and methods of reducing artifact in neurological stimulation systems |
US8295934B2 (en) | 2006-11-14 | 2012-10-23 | Neurovista Corporation | Systems and methods of reducing artifact in neurological stimulation systems |
US9898656B2 (en) | 2007-01-25 | 2018-02-20 | Cyberonics, Inc. | Systems and methods for identifying a contra-ictal condition in a subject |
US20110172554A1 (en) * | 2007-01-25 | 2011-07-14 | Leyde Kent W | Patient Entry Recording in an Epilepsy Monitoring System |
US9622675B2 (en) | 2007-01-25 | 2017-04-18 | Cyberonics, Inc. | Communication error alerting in an epilepsy monitoring system |
US20080208074A1 (en) * | 2007-02-21 | 2008-08-28 | David Snyder | Methods and Systems for Characterizing and Generating a Patient-Specific Seizure Advisory System |
US9445730B2 (en) | 2007-03-21 | 2016-09-20 | Cyberonics, Inc. | Implantable systems and methods for identifying a contra-ictal condition in a subject |
US8036736B2 (en) | 2007-03-21 | 2011-10-11 | Neuro Vista Corporation | Implantable systems and methods for identifying a contra-ictal condition in a subject |
US8543199B2 (en) | 2007-03-21 | 2013-09-24 | Cyberonics, Inc. | Implantable systems and methods for identifying a contra-ictal condition in a subject |
US20080269839A1 (en) * | 2007-04-27 | 2008-10-30 | Armstrong Randolph K | Dosing Limitation for an Implantable Medical Device |
US7974701B2 (en) | 2007-04-27 | 2011-07-05 | Cyberonics, Inc. | Dosing limitation for an implantable medical device |
US9788744B2 (en) | 2007-07-27 | 2017-10-17 | Cyberonics, Inc. | Systems for monitoring brain activity and patient advisory device |
US11406317B2 (en) | 2007-12-28 | 2022-08-09 | Livanova Usa, Inc. | Method for detecting neurological and clinical manifestations of a seizure |
US20090171420A1 (en) * | 2007-12-28 | 2009-07-02 | David Brown | Housing for an Implantable Medical Device |
US20090171168A1 (en) * | 2007-12-28 | 2009-07-02 | Leyde Kent W | Systems and Method for Recording Clinical Manifestations of a Seizure |
US9259591B2 (en) | 2007-12-28 | 2016-02-16 | Cyberonics, Inc. | Housing for an implantable medical device |
US9314633B2 (en) | 2008-01-25 | 2016-04-19 | Cyberonics, Inc. | Contingent cardio-protection for epilepsy patients |
US8260426B2 (en) | 2008-01-25 | 2012-09-04 | Cyberonics, Inc. | Method, apparatus and system for bipolar charge utilization during stimulation by an implantable medical device |
US8204603B2 (en) | 2008-04-25 | 2012-06-19 | Cyberonics, Inc. | Blocking exogenous action potentials by an implantable medical device |
US8874218B2 (en) | 2008-10-20 | 2014-10-28 | Cyberonics, Inc. | Neurostimulation with signal duration determined by a cardiac cycle |
US8457747B2 (en) | 2008-10-20 | 2013-06-04 | Cyberonics, Inc. | Neurostimulation with signal duration determined by a cardiac cycle |
US20100168603A1 (en) * | 2008-12-23 | 2010-07-01 | Himes David M | Brain state analysis based on select seizure onset characteristics and clinical manifestations |
US8849390B2 (en) | 2008-12-29 | 2014-09-30 | Cyberonics, Inc. | Processing for multi-channel signals |
US9289595B2 (en) | 2009-01-09 | 2016-03-22 | Cyberonics, Inc. | Medical lead termination sleeve for implantable medical devices |
US8588933B2 (en) | 2009-01-09 | 2013-11-19 | Cyberonics, Inc. | Medical lead termination sleeve for implantable medical devices |
US20100179627A1 (en) * | 2009-01-09 | 2010-07-15 | Jared Floyd | Medical Lead Termination Sleeve for Implantable Medical Devices |
US10653883B2 (en) | 2009-01-23 | 2020-05-19 | Livanova Usa, Inc. | Implantable medical device for providing chronic condition therapy and acute condition therapy using vagus nerve stimulation |
US8786624B2 (en) | 2009-06-02 | 2014-07-22 | Cyberonics, Inc. | Processing for multi-channel signals |
US8884767B2 (en) * | 2009-12-02 | 2014-11-11 | Widex A/S | Method and apparatus for alerting a person carrying an EEG assembly |
CN102665533A (en) * | 2009-12-02 | 2012-09-12 | 唯听助听器公司 | Method and apparatus for alerting a person carrying an EEG assembly |
US20120235820A1 (en) * | 2009-12-02 | 2012-09-20 | Preben Kidmose | Method and apparatus for alerting a person carrying an eeg assembly |
WO2011066852A1 (en) * | 2009-12-02 | 2011-06-09 | Widex A/S | Method and apparatus for alerting a person carrying an eeg assembly |
AU2010344006B2 (en) * | 2010-02-01 | 2013-12-19 | T&W Engineering A/S | Portable EEG monitor system with wireless communication |
WO2011091856A1 (en) * | 2010-02-01 | 2011-08-04 | Widex A/S | Portable eeg monitor system with wireless communication |
KR101533874B1 (en) * | 2010-02-01 | 2015-07-03 | 비덱스 에이/에스 | Portable eeg monitor system with wireless communication |
US9643019B2 (en) | 2010-02-12 | 2017-05-09 | Cyberonics, Inc. | Neurological monitoring and alerts |
US20110218820A1 (en) * | 2010-03-02 | 2011-09-08 | Himes David M | Displaying and Manipulating Brain Function Data Including Filtering of Annotations |
US20110219325A1 (en) * | 2010-03-02 | 2011-09-08 | Himes David M | Displaying and Manipulating Brain Function Data Including Enhanced Data Scrolling Functionality |
US8684921B2 (en) | 2010-10-01 | 2014-04-01 | Flint Hills Scientific Llc | Detecting, assessing and managing epilepsy using a multi-variate, metric-based classification analysis |
US8562523B2 (en) | 2011-03-04 | 2013-10-22 | Flint Hills Scientific, Llc | Detecting, assessing and managing extreme epileptic events |
US9504390B2 (en) | 2011-03-04 | 2016-11-29 | Globalfoundries Inc. | Detecting, assessing and managing a risk of death in epilepsy |
US8562524B2 (en) | 2011-03-04 | 2013-10-22 | Flint Hills Scientific, Llc | Detecting, assessing and managing a risk of death in epilepsy |
US11596314B2 (en) | 2012-04-23 | 2023-03-07 | Livanova Usa, Inc. | Methods, systems and apparatuses for detecting increased risk of sudden death |
US10448839B2 (en) | 2012-04-23 | 2019-10-22 | Livanova Usa, Inc. | Methods, systems and apparatuses for detecting increased risk of sudden death |
US11096619B2 (en) * | 2013-07-12 | 2021-08-24 | Innara Health, Inc. | Neural analysis and treatment system |
US20150018705A1 (en) * | 2013-07-12 | 2015-01-15 | Innara Health | Neural analysis and treatment system |
EP3110323A4 (en) * | 2014-02-27 | 2017-08-09 | New York University | Minimally invasive subgaleal extra-cranial electroencephalography (eeg) monitoring device |
US11723579B2 (en) | 2017-09-19 | 2023-08-15 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement |
US11717686B2 (en) | 2017-12-04 | 2023-08-08 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement to facilitate learning and performance |
US11318277B2 (en) | 2017-12-31 | 2022-05-03 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement to enhance emotional response |
US11478603B2 (en) | 2017-12-31 | 2022-10-25 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement to enhance emotional response |
US11273283B2 (en) | 2017-12-31 | 2022-03-15 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement to enhance emotional response |
US11364361B2 (en) | 2018-04-20 | 2022-06-21 | Neuroenhancement Lab, LLC | System and method for inducing sleep by transplanting mental states |
US11452839B2 (en) | 2018-09-14 | 2022-09-27 | Neuroenhancement Lab, LLC | System and method of improving sleep |
US11786694B2 (en) | 2019-05-24 | 2023-10-17 | NeuroLight, Inc. | Device, method, and app for facilitating sleep |
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EP2034885A4 (en) | 2010-12-01 |
US7676263B2 (en) | 2010-03-09 |
EP2034885A2 (en) | 2009-03-18 |
US9480845B2 (en) | 2016-11-01 |
US20080027515A1 (en) | 2008-01-31 |
US20100125219A1 (en) | 2010-05-20 |
US20080033502A1 (en) | 2008-02-07 |
WO2007150003A3 (en) | 2008-11-06 |
WO2007150003A2 (en) | 2007-12-27 |
US20080027347A1 (en) | 2008-01-31 |
US20110166430A1 (en) | 2011-07-07 |
US20080021341A1 (en) | 2008-01-24 |
US20150182753A1 (en) | 2015-07-02 |
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