WO2018038930A1

WO2018038930A1 - Device for brain electrical monitoring with or without combined brain fluid drainage

Info

Publication number: WO2018038930A1
Application number: PCT/US2017/046329
Authority: WO
Inventors: Axel Rosengart; Ueli Rutishauser
Original assignee: Cedars-Sinai Medical Center
Priority date: 2016-08-24
Filing date: 2017-08-10
Publication date: 2018-03-01

Abstract

Disclosed is an external ventricular drainage device that includes intracranial electrodes attached to the drain itself for monitoring brain activity. The device includes different types of electrodes at different depths for monitoring different portions of brain electrical activity. For instance, the device includes microwire electrodes for monitoring single neural unit cortical activity while the device simultaneously drains cerebrospinal fluid.

Description

DEVICE FOR BRAIN ELECTRICAL MONITORING WITH OR WITHOUT

COMBINED BRAIN FLUID DRAINAGE

FIELD

[0001] The present invention is directed to devices and methods for brain function monitoring and brain fluid drainage.

BACKGROUND

[0002] The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.

[0003] Brain-injured patients admitted to the acute care setting often experience elevated intracranial (i.e., inside the skull) pressure from brain swelling, bleeding or obstruction of brain fluid (i.e., cerebrospinal fluid (CSF)). As elevated brain pressure causes secondary brain injury and death an external ventricular drain (EVD) is inserted through the skull to relieve CSF and pressure. An EVD, also known as ventriculostomy, is a small plastic tube (e.g., 3 mm outer diameter) which is inserted via a stylet through a small skull burr hole piercing all brain layers (from the cortex through the underlying white matter) to end in the inner brain fluid spaces (ventricles) for CSF drainage and pressure readings. Placing an EVD is very commonly the first and life-saving procedure indicated in many patients with moderate to severe brain injury or obstruction of brain fluid (hydrocephalus) of many types.

[0004] Furthermore, patients with brain injury are at higher risks for deleterious seizures, both clinically visible (convulsive) and nonvisible (non-convulsive). To monitor for this treatable brain problem and also to understand the injured brain's general neuronal activity and recovery potentials surface electroencephalography (EEG) is used by placing multiple electrode pads on the scalp and obtaining brain electrical waves. Unfortunately, EEG is not a very sensitive method to obtain brain electrical activities (both seizures and post- injury resting states) as it captures only electrical potentials from larger brain networks strong enough to emerge from the brain's surface to penetrate the skull and scalp. For instance, electrical activates and potentials generated from smaller or individual neurons, i.e., in deeper brain regions or from the cortex, allowing more precise electrical brain monitoring is not possible with surface EEG.

SUMMARY

[0005] Currently, no device exists that allows for routine invasive electrical seizure or cortical neuron activity monitoring in brain-injured patients admitted to the acute care setting. Currently, surface electroencephalography (EEG) is used to monitor for seizures and baseline brain activity. However EEG has several drawbacks including: (1) it poorly detects deep- seated brain seizures; (2) it needs 21 surface electrodes throughout the skull competing with other brain monitoring equipment for space and accessibility; (3) it is prone to artifacts; (4) it frequently interferes with care, (4) it entails risks of skull skin breakdown if performed for prolonged periods of time; (5) it does not allow single neuron studies; and (6) it is a poor localizer and prognosticator of brain pathology. However, research and intraoperative monitoring delineates that intracranial (e.g., direct) brain electrical activity monitoring is superior to EEG; unfortunately, there is no method available to do so in critically-ill, brain- injured patients.

[0006] Accordingly, disclosed are systems and methods that allow continuous deep and single neuronal brain recordings combine with or without CSF drainage and suitable for patients cared for in the acute injury settings (e.g., neuroscience ICU). Thus, the disclosed systems and methods enhance the usefulness of brain fluid drainage systems (EVDs) by combining CSF drainage with intracranial monitoring of neuronal network electrical activities (e.g., seizures) and continuous recording of single cortical neurons, a hybrid device named 'ventrode,' short for the combination of ventriculostomy and electrode. The proposed ventrode can be used as a stand-alone device for either CSF drainage or continuous recording of electric brain activity or can be utilized for both functions simultaneously.

[0007] The disclosed device includes intracranial multichannel (multi-contact) electrodes that enable simultaneous cortical and deep brain electrical activity monitoring. In contrast to already existing brain monitoring technology, this device can be used concurrently as a brain fluid (CSF) drainage device similar to commercially available EVD systems. Such a combination device does not currently exist and brain-injured patients would benefit from the ability to monitor intracranial electrical activity while simultaneously obtaining CSF drainage and pressure. The system enables recording of electrical fields both throughout the brain parenchyma (e.g., to detect seizures) and single neuronal recordings to detect cortical activities in the acute care setting. It is envisioned that one target population benefiting from such a device include adults and children with moderate to severe acute brain injury of any type.

[0008] Furthermore, cortical single neuron recordings have not been established in the acute care setting and would provide very unique prognostic and treatment parameters. For example, the ability to survey cortical neuronal activities after acute brain injury may uniquely enable the clinician to prognosticate whether a coma state in an individual patient may or may not be reversible. Combining this unique and novel electrical brain monitoring approach with a device and procedure which is clinically commonly employed - the ventriculostomy - and hence avoiding an additional invasive procedure for electrical monitoring will be provide an attractive clinical advantage.

BRIEF DESCRIPTION OF THE DRAWINGS

[0009] The accompanying drawings, which are incorporated in and constitute a part of this specification, exemplify the embodiments of the present invention and, together with the description, serve to explain and illustrate principles of the invention. The drawings are intended to illustrate major features of the exemplary embodiments in a diagrammatic manner. The drawings are not intended to depict every feature of actual embodiments nor relative dimensions of the depicted elements, and are not drawn to scale.

[0010] FIGS. 1 A - ID depict, a prior art process for inserting an external ventricular drainage (EVD) tube into the patient's cerebrospinal fluid (CSF) spaces (ventricles) located in the center of the brain. FIG. 1A illustrates a perspective view of a patient with hydrocephalus and a surgeon making an incision into the skin to expose the skull; FIG. IB depicts a perspective view of a surgeon drilling a hole through the patient's skull exposing the meningeal membranes and subarachnoid CSF-filled space; FIG. 1C depicts a perspective view of a surgeon inserting an EVD through the patient's brain; and FIG. ID depicts a perspective view of an EVD inserted into a patient's ventricular spaces for CSF drainage;

[0011] FIG. 2A depicts, in accordance with various embodiments, a perspective view of an EVD device (drainage tube with stylet inserted); [0012] FIG. 2B depicts, in accordance with various embodiments, a perspective view of the distal (innermost) portion of an EVD device including the multiple holes for CSF drainage; and

[0013] FIG. 2C depicts, in accordance with various embodiments, a cross sectional schematic view of five functional segments of a ventrode. These segments include: (1) the outermost segment that harbors connectors on the ventrode to connect to external wires and then penetrates through the skin and skull hole; this segments connects to; (2) the subarachnoid segment where multiple micro- and millimeter-long, perpendicular electrodes reaching over the brain's cortex to capture surface electrical (network) potentials; 3) the cortical segment where multiple, perpendicular microelectrodes reach into the various cortical cell layers to obtain individual recordings from cortical neurons; 4) the subcortical segment which extends from below the cortical layers up to the ventricular lining where multiple ring electrodes captures deep electrical (network) potentials; and 5) the ventricular segment where CSF drainage occurs but also may contain sensors to measure brain temperature, CSF pressure or to discharge/record electrical signals facilitating inter-electrode communications such as impedance measurements;

[0014] FIG. 3 depicts, in accordance with various embodiments, a perspective view of a ventrode with multiple electrode regions; functional segments depict are subarachnoid (330) containing perpendicular electrodes reaching over the brain's surface, cortical (320) micro-electrodes inserting themselves into the cortical cell layer for recordings from individual cortical neurons, subcortical (310) ring electrodes for larger network recordings, and ventricular (255) segments for CSF drainage and electrode tips to record pressure, temperature and other physical modalities or to emit strategic currents throughout the brain (segment lengths not to scale);

[0015] FIG. 4A depicts, in accordance with various embodiments, a perspective view of sheath deployment of micro-electrodes within the subarachnoid and cortical segment of the ventrode; and

[0016] FIG. 4B depicts, in accordance with various embodiments, a perspective view of a rotating sheath deployment of micro-electrodes within the subarachnoid and cortical segment of the ventrode; and [0017] FIG. 4C depicts, in accordance with various embodiments, a perspective view of a spring-loaded deployment of micro-electrodes within the subarachnoid and cortical segment of the ventrode;

[0018] In the drawings, the same reference numbers and any acronyms identify elements or acts with the same or similar structure or functionality for ease of understanding and convenience. To easily identify the discussion of any particular element or act, the most significant digit or digits in a reference number refer to the Figure number in which that element is first introduced.

DETAILED DESCRIPTION

[0019] Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Szycher's Dictionary of Medical Devices CRC Press, 1995, may provide useful guidance to many of the terms and phrases used herein. One skilled in the art will recognize many methods and materials similar or equivalent to those described herein, which could be used in the practice of the present invention. Indeed, the present invention is in no way limited to the methods and materials specifically described.

[0020] In some embodiments, properties such as dimensions, shapes, relative positions, and so forth, used to describe and claim certain embodiments of the invention are to be understood as being modified by the term "about."

[0021] Various examples of the invention will now be described. The following description provides specific details for a thorough understanding and enabling description of these examples. One skilled in the relevant art will understand, however, that the invention may be practiced without many of these details. Likewise, one skilled in the relevant art will also understand that the invention can include many other obvious features not described in detail herein. Additionally, some well-known structures or functions may not be shown or described in detail below, so as to avoid unnecessarily obscuring the relevant description.

[0022] The terminology used below is to be interpreted in its broadest reasonable manner, even though it is being used in conjunction with a detailed description of certain specific examples of the invention. Indeed, certain terms may even be emphasized below; however, any terminology intended to be interpreted in any restricted manner will be overtly and specifically defined as such in this Detailed Description section.

[0023] While this specification contains many specific implementation details, these should not be construed as limitations on the scope of any inventions or of what may be claimed, but rather as descriptions of features specific to particular implementations of particular inventions. Certain features that are described in this specification in the context of separate implementations can also be implemented in combination in a single implementation. Conversely, various features that are described in the context of a single implementation can also be implemented in multiple implementations separately or in any suitable sub-combination. Moreover, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination can in some cases be excised from the combination, and the claimed combination may be directed to a sub-combination or variation of a sub-combination.

[0024] Similarly, while operations may be depicted in the drawings in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order, or that all illustrated operations be performed, to achieve desirable results. In certain circumstances, multitasking and parallel processing may be advantageous. Moreover, the separation of various system components in the implementations described above should not be understood as requiring such separation in all implementations, and it should be understood that the described program components and systems can generally be integrated together in a single software product or packaged into multiple software products.

Overview

[0025] Patients with acute brain injury experience increased intracranial pressure and obstruction of brain fluid or cerebrospinal fluid (CSF) outflow which is treated with an external ventricular drain (EVD) inserted via a skull burr hole and through the brain tissue to reach the inner brain fluid spaces (ventricles) in order to release excess CSF and to monitor pressure. Currently, brain electrical activity monitoring to detect seizures and to identify post- injury brain activity is performed using "scalp EEG" with electrodes attached to a patient's head. However, as discussed above, scalp based EEG is relatively insensitive as it only detects larger brain network activity (therefore, missing weak and emerging activities generated by injured brains), does not allow for monitoring single neuron activities, and is rather insensitive to precise spatial or prognostic information.

[0026] Accordingly, disclosed is an EVD (ventriculostomy)-electrode hybrid

("ventrode") that includes intracranial electrodes as part of the EVD design in order to record brain electrical activity - both network and individual neuron recordings. The disclosed EVD design (or "ventrode" as used herein) includes different types of electrodes at different depths along the intracranial (inside the skull) segment of the device for monitoring different portions of brain electrical activity separately. Accordingly, the electrodes that are included into the ventrode will be able to simultaneously record electrical brain activities and drain CSF (and measure CSF pressure) without the need for installing an additional electrical monitoring device. However, it is pointed out that the disclosed ventrode can be used only as an electrical recording or only as CSF drainage (EVD) device.

[0027] This is a very efficient and effective method of monitoring brain electrical activity without increasing the invasiveness of the procedure as an EVD is inserted into the brain to drain CSF anyway. As routine intracerebral network and single-cell neural recordings have not been accomplished in the acute care setting, the disclosed device will provide additional diagnostic, prognostic and other useful information helpful to managing the care of acutely brain-injured patients.

[0028] FIGS. 1A - ID illustrate an example of a procedure for placement of a conventional EVD device through a patient's skull to drain CSF from the brain's innermost fluid spaces (ventricles). FIG. 1A illustrates a surgeon making an incision into the scalp, exposing the skull bone and then drilling a burr hole as illustrated in FIG. IB. Then, a catheter or EVD may be inserted as illustrated in FIG. 1C. FIG. ID and FIG. 2C illustrate the path the EVD device may take as it enters the ventricles as illustrated. Once the EVD is properly positioned into the ventricles, CSF will begin to drain indicating correct EVD positioning.

[0029] As illustrated, the EVD enters the skull and therefore passes through several intracranial spaces: the subarachnoid space filled with CSF and located between the inner skull and the brain's surface, then traversing the cortex (the initial or most superficial 3 mm of the brain), and finally the subcortical white matter before ending within the ventricle (see also FIG. C). Accordingly, the EVD traverses each of the layers of the brain and therefore is an ideal vehicle to attach electrodes at different depths to monitor and measure brain activity separately at each level or for each type of tissue.

[0030] FIGS. 2A - 2B illustrate a ventrode tube 200. The disclosed devices herein may be constructed from silicon tubing or other soft to semi-rigid materials with an inner diameter of 0.8 to 3 mm, wall thickness of 0.5 to 3 mm and outer diameter from 2 to 5 mm. Other suitable sizes may be utilized for similar procedures to accommodate varying sizes of incisions. In other examples, the disclosed devices may be made from rigid materials. In some examples, the total length of the device (that is, including the part outside of the head) may range from 20 to 40 cm. The ventrode tubing is quite flexible and therefore generally requires a guidewire (stylet) for insertion of the device into the skull; however, the ventrode may be rigid in some or all of its segments and therefore, a guidewire for insertion may not be needed.

[0031] As illustrated in FIG. 2A, the ventrode 200 includes an intracranial portion

210 that is inserted into a patient's skull to a depth of about 6 cm. Generally, about 0.5 cm of the intracranial ventrode 210 part is located within the subarachnoid space between the brain's surface and the inner skull, about 4 cm is needed to penetrate the brain tissue (cortex and subcortical white matter), and the remaining 1.5 cm usually lies within the ventricular fluid space. If desired, the ventrode may be connected (e.g., with a Luer connector) to a drainage and reservoir system for capturing CSF fluid and measure intracranial pressure.

[0032] The ventrode 200 also includes an extracranial portion 220 used to secure the

EVD to the patient's head. Once the ventrode 200 is placed properly inside the patient's skull the guidewire is removed to provide an unobstructed path for CSF outflow.

[0033] FIG. 2B illustrates a CSF drainage segment 255 of the intracranial portion 210 that includes multiple holes 250 for the CSF fluid to drain inside the ventrode 200. In some examples, the CSF drainage segment 255 may be the innermost 1 - 2 cm of the ventrode, or other suitable ranges and may include drainage holes 250 or other orifices.

[0034] A ventrode tube 200 may include numerical length markers at each centimeter to facilitate insertion, radiopaque stripes along the longitudinal axis for imaging recognition, small pressure and temperature sensors at the tip of the ventrode tube 200 to measure intracranial pressure and brain temperature, an electrode tip which allows emission of defined electrical currents, i.e., to measure brain impedance or to abort seizures, and antibiotic impregnation of the outer tubing structure to reduce the risk of catheter-related infections.

Electrodes and Signal Processing

[0035] FIG. 3 illustrates a ventrode 300 that may incorporate the features of an EVD

200 and additionally include electrodes placed at various depths along the ventrode 300. For instance, the ventrode 300 may include the following electrodes or various combinations starting from the most distal portion, inside of the CSF drainage segment 255 which may not include electrodes:

(1) white matter ring electrodes 315 that monitor the white matter larger neuronal networks for abnormalities such as seizures;

(2) cortical microwire electrodes 325 that monitor single cortical cells of the cortex/grey matter;

(3) subarachnoid microwire electrodes 335 located in the subarachnoid space (between the brain surface and inside of the skull) that monitor larger cortical fields; and

(4) electrode coating, i.e., employing pliable polymeric materials, on the outside and along the longitudinal length of a conventional ventriculostomy or similar drainage tubing casing the complete or partial length of the tube.

[0036] In some examples, the ventrode 300 may only include cortical microwire electrodes 320 or other combinations of the above electrodes. Each electrode is connected with a tiny wire that may be embedded or connected to the ventrode 300 wall that travels to the proximal portion of the ventrode 300 outside the head and connects to neuronal recording equipment. In some examples, if the wires are not embedded in the ventrode 300 wall, they may be covered with insulation to prevent interference.

[0037] Neural monitoring equipment may include any suitable equipment for monitoring a multitude of leads using different signal processing techniques based on the type and location of electrodes. For instance, the microwire electrodes may be connected to a cathode follower amplifier or other various specialized amplifiers to accommodate high impedance. Then, these signals may be fed to an analog to digital converter, and then processed to identify and analyze the signal neural signals or other signals. [0038] Additionally, the data processing units will be utilized to identify electrodes that have good signal quality and those that are not in good contact with a single neuron or are receiving good signal. For instance, the spike detection algorithms disclosed in "Adaptive Movable Neural Interfaces for Monitoring Single Neurons in the Brain", by Muthuswamy available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168918/ may provide one example of algorithms that could identify leads that have good signals for single unit recordings and which is incorporated by reference herein in its entirety. These electrode signals may be processed to identify seizures and other abnormal brain activity such as slowing.

Electrodes - Subcortical (White Matter) Ring Electrodes

[0039] As illustrated in FIG. 3, the ventrode 300 may include subcortical ring electrodes 315 that are proximal from the CSF drainage portion 255 and that span a white matter segment 310 of the ventrode 300. These white matter ring electrodes 315 may be metal ring electrodes or micro-contact electrodes that monitor larger neuronal networks for abnormalities such as seizures or may apply small currents to restricted, targeted brain areas, i.e., to treat patients for movement disorders.

[0040] These ring electrodes 315 may be structures etched into the outer circumference of the ventrode 300 and plated from conductive, inert materials such as platinum-iridium, copper, and others. The ring electrode 315 width may range from 500 nm to 2 mm, and the inter-ring distances may range from a few millimeters to centimeters. Each electrode may connect to a wire that runs or is embedded inside the non-conductive ventrode 300 tube to connect to neural monitoring equipment.

Electrodes - Cortical Microwire

[0041] Proximal to the white matter ring electrodes 315, the ventrode 300 may include cortical microwire electrodes 325 that span a cortical segment 320. The cortical segment 320 may be 1 to 3 cm in length although the cortical layer is only 2 to 3 mm in length (spanning about 6 horizontal cortical cell layers with an average cell body size of 20 μιη). These microwire electrodes 325 may detect electrical activity from single neurons in this cortex area. [0042] Single cell neuronal recordings are acquired by bringing microwires within

100 μιη or less to the cell body of an individual neuron without causing membrane injury. Conventional single cell brain research focuses on intraoperative settings where electrode wires are connected to the recording system and incrementally advanced into the brain tissue until single cell recordings at the target location.

[0043] Alternatively, the outer surface of the ventriculostomy tubing are coated with arrays of polymeric microelectrodes strips. Depending on the arrangement and design of these electrode strips single or groups of neurons are recorded and monitored. These strips may cover the partial or complete length of the ventriculostomy tube to reach from the distal tip to the proximal (outside) tube ending. At the proximal end the electrode strips or their respective wire extensions are connected to the amplifier and recording systems.

[0044] Because the average ventrode insertion depth to obtain CSF can vary by usually ± 10 mm between individuals (i.e., due to head size, shift of brain tissue, etc.) the ventrode microwires segment for single cell cortical recordings is designed to be several times longer than the actual cortical thickness of 3 mm. This approach will drastically increase the probability that some cortical microwires are by default positioned within the brain's cortex despite the ventrode insertion depth variability between individuals. For example, 100 to 200 microwires distributed over a 20 mm ventrode 300 cortical segment will provide in the majority of all ventrode insertion depths cortical placement of about 20 electrodes microwires per 1 mm ventrode 300 length which, in turn, equals the presence of 40 to 60 microwires within the cortical thickness of 2-3 mm.

[0045] Furthermore, as the human cortex has ridges and folds with various angulations a perpendicular to the skull inserted ventrode may -by chance- penetrate the brain's cortical layer more than once (i.e., at both sides of a fold) and hence, providing excess ventrode cortical segment-to-cortical thickness ratio will increase the likelihood that microwires are positioned within the brain's cortex.

[0046] Currently, there is no device or technology that allows single cell monitoring of the brain cortex in patients with acute brain injury. Cortical recordings are important because the cortex is the location of memory, attention, consciousness, perception, motor execution, language and thought processing, among other important functions. It is also of great clinical importance for prognostication after brain trauma, for assessments of level of coma and anesthesia depth, and for understanding the function of anesthetics or defining cortical recovery from injury.

[0047] In some examples, the cortical microwire electrodes 325 will protrude (e.g. perpendicularly) from the outer surface of a ventrode 300 and be arranged in a recurrent circumferential or semi/full spiral pattern or other suitable pattern. The electrode density along the cortical segment 320 may be 1, 10, 20, or 200 microwires per 1 mm ventrode 300 segment (along a longitudinal axis). The microwires may have a protrusion depth from 50 nm to 2 mm, a thickness from 10 to hundreds of nm, and inter-electrode distances may vary from 0.1 μιη ΐο 1000 μιη.

[0048] The cortical microwires 325 may be designed to retain or spring to a shape once released from a restraint (e.g. shape memory metals to resume a perpendicular position once released from a flattened position parallel to the longitudinal axis of the ventrode 300 by way of a cover or sleeve). The materials may include materials coated with Teflon, polyethylimine, laminin, or uncoated inert materials such as conductive polymers, silicon, platinum, iridium, polyimide, ceramic, and gold. Electrodes coated with materials may advantageously reduce electrode-induced trauma and foreign body reactions in the cortical layers. The wires may have different shapes, including uniform microwires, planar shanks, and wires that taper to a thin tip from a wider base.

Electrodes - Subarachnoid Microwire

[0049] Proximal from the cortical microwire electrodes 325, the ventrode 300 may include subarachnoid microwire electrodes 335 that span the subarachnoid segment 330 of the ventrode 300. These subarachnoid microwire electrodes 335 are similar to the cortical microwire electrodes 325 but may be longer in length to lie on or to reach over the surface of the brain in order to obtain cortical potentials.

[0050] These subarachnoid microwire electrodes 335 may also contain self-expanding electrodes similar to the cortical microwire electrodes 325 and may unfold after release as an umbrella-like structure. The subarachnoid microwires 335 may be several millimeters in length to improve detection of electrical activities over the cortical surface but may otherwise be similar to the cortical microwire electrodes 325. Electrodes - Cortical Microwires and Deployment

[0051] In some instances, the microwire electrodes that deployed in the subarachnoid space or the cortex may be shielded by a protection sleeve 410. The protective sleeve 410 may cover the ends of the microwires completely so they are folded under the sleeve 410 until it is removed or withdrawn after ventrode deployment. The sleeve may be removed or adjusted by the operator after obtaining CSF flow but before suturing and draping the ventrode 300 onto the scalp.

[0052] This sleeve 410 embodiment may prevent damage to the recording wires during ventrode 300 handling and insertion, and prevent damage to the adjacent cortical layers during insertion. For instance, proper EVD positioning into the brain (which is done without any guidance apparatus) to drain CSF frequently requires multiple insertion attempts, which could result both in abrasion of the cortical tissue from and damage to the microwires. In other examples, the microwires may remain extended and uncovered as the short length of the microwires may not cause damage to the cortical tissue.

[0053] FIG 4 A illustrates an embodiment of a sleeve 410 that covers microwire electrodes 325 that fold underneath the sleeve 410. Accordingly, when sleeve 410 is withdrawn, the microwire electrodes 325 extend out perpendicularly or near perpendicularly to single neural units for electrical contact. Accordingly, in this embodiment, the protective sleeve 410 remains in place during insertion (placement) until the ventrode' s 300 final position has been determined, for example, by good CSF return.

[0054] To release the sleeve 410 and the electrodes 325, the sleeve 410 may then be retracted until it has fully exited the skull at which point it may be removed from the ventrode 300 (for example by sliding off or breaking off). After the sleeve is removed 410, as illustrated, the tips of the microelectrode 325 wires may regain their prior shape in an extended (e.g. perpendicular) position to the ventrode 300.

[0055] FIG. 4B illustrates another example where the sleeve 410 remains part of the ventrode structure after insertion into the brain. For microwire deployment the sleeve is instead rotated to expose or extend the microwires out from holes or slots in the sleeve 410 so that they may contact the cortex (surface or cell layers). As illustrated, the sleeve may be rotated so that the wires uncoil and extend further out of slots or holes of the sleeve 410. In some examples, this deployment method may also be utilized to retract the microwires before removal of the ventrode 300 to protect the brain tissue from microwire abrasion during withdrawal.

[0056] In a further example in FIG. 4C, the wires themselves may be coiled in a matter that a guidewire (i.e., inserted into the ventrode lumen) or other mechanism restrains them until released. Then, once released, the coiled wires may at least partially uncoil, extending through holes or slots in a sleeve 410.

[0057] The electrodes contained within the ventrode, specifically the subarachnoid and cortical microwires, subcortical ring and distal ventrode tip electrodes, are designed to function both as electrodes capable of recording and emitting electrical currents. In some instances, some of these electrode contacts may actually serve as a brain blood flow analyzer; here, a single or set of electrodes generate a well-defined temperature signal whereas neighboring (receiving) electrodes serve as temperature sensor in which case the electrode unit functions as a measure of brain blood flow by estimating dissipation of heat (via blood perfusion) between two electrodes by evaluating the delta change of expected versus recorded temperatures. In other examples, inter-electrode electric flux or current can be employed to determine the brain impedance and hence, provide indirect measures of brain water content and density. In yet other example, current emitting electrodes may be used to stimulate certain brain areas in or to induce a brain function or to abort abnormal brain electrical activities (i.e., electroshock to abort seizures). Whereas other electrodes may be designated to measure and record actual brain temperature and CSF pressure. In yet other applications biosensor and bioreceptor systems may be included into the ventrode in order to measure the cortical and subcortical tissue biochemistry.

Computer & Hardware Implementation of Disclosure

[0058] It should initially be understood that the disclosure herein, including the neural recording and processing equipment may be implemented with any type of hardware and/or software, and may be a pre-programmed general purpose computing device. For example, the system may be implemented using a server, a personal computer, a portable computer, a thin client, or any suitable device or devices. The disclosure and/or components thereof may be a single device at a single location, or multiple devices at a single, or multiple, locations that are connected together using any appropriate communication protocols over any communication medium such as electric cable, fiber optic cable, or in a wireless manner. [0059] It should also be noted that the disclosure is illustrated and discussed herein as having a plurality of modules which perform particular functions. It should be understood that these modules are merely schematically illustrated based on their function for clarity purposes only, and do not necessary represent specific hardware or software. In this regard, these modules may be hardware and/or software implemented to substantially perform the particular functions discussed. Moreover, the modules may be combined together within the disclosure, or divided into additional modules based on the particular function desired. Thus, the disclosure should not be construed to limit the present invention, but merely be understood to illustrate one example implementation thereof.

[0060] The computing system can include clients and servers. A client and server are generally remote from each other and typically interact through a communication network. The relationship of client and server arises by virtue of computer programs running on the respective computers and having a client-server relationship to each other. In some implementations, a server transmits data (e.g., an HTML page) to a client device (e.g., for purposes of displaying data to and receiving user input from a user interacting with the client device). Data generated at the client device (e.g., a result of the user interaction) can be received from the client device at the server.

[0061] Implementations of the subject matter described in this specification can be implemented in a computing system that includes a back-end component, e.g., as a data server, or that includes a middleware component, e.g., an application server, or that includes a front-end component, e.g., a client computer having a graphical user interface or a Web browser through which a user can interact with an implementation of the subject matter described in this specification, or any combination of one or more such back-end, middleware, or front-end components. The components of the system can be interconnected by any form or medium of digital data communication, e.g., a communication network. Examples of communication networks include a local area network ("LAN") and a wide area network ("WAN"), an inter-network (e.g., the Internet), and peer-to-peer networks (e.g., ad hoc peer-to-peer networks).

[0062] Implementations of the subject matter and the operations described in this specification can be implemented in digital electronic circuitry, or in computer software, firmware, or hardware, including the structures disclosed in this specification and their structural equivalents, or in combinations of one or more of them. Implementations of the subject matter described in this specification can be implemented as one or more computer programs, i.e., one or more modules of computer program instructions, encoded on computer storage medium for execution by, or to control the operation of, data processing apparatus. Alternatively or in addition, the program instructions can be encoded on an artificially-generated propagated signal, e.g., a machine-generated electrical, optical, or electromagnetic signal that is generated to encode information for transmission to suitable receiver apparatus for execution by a data processing apparatus. A computer storage medium can be, or be included in, a computer-readable storage device, a computer-readable storage substrate, a random or serial access memory array or device, or a combination of one or more of them. Moreover, while a computer storage medium is not a propagated signal, a computer storage medium can be a source or destination of computer program instructions encoded in an artificially-generated propagated signal. The computer storage medium can also be, or be included in, one or more separate physical components or media (e.g., multiple CDs, disks, or other storage devices).

[0063] The operations described in this specification can be implemented as operations performed by a "data processing apparatus" on data stored on one or more computer-readable storage devices or received from other sources.

[0064] The term "data processing apparatus" encompasses all kinds of apparatus, devices, and machines for processing data, including by way of example a programmable processor, a computer, a system on a chip, or multiple ones, or combinations, of the foregoing The apparatus can include special purpose logic circuitry, e.g., an FPGA (field programmable gate array) or an ASIC (application-specific integrated circuit). The apparatus can also include, in addition to hardware, code that creates an execution environment for the computer program in question, e.g., code that constitutes processor firmware, a protocol stack, a database management system, an operating system, a cross-platform runtime environment, a virtual machine, or a combination of one or more of them. The apparatus and execution environment can realize various different computing model infrastructures, such as web services, distributed computing and grid computing infrastructures.

[0065] A computer program (also known as a program, software, software application, script, or code) can be written in any form of programming language, including compiled or interpreted languages, declarative or procedural languages, and it can be deployed in any form, including as a stand-alone program or as a module, component, subroutine, object, or other unit suitable for use in a computing environment. A computer program may, but need not, correspond to a file in a file system. A program can be stored in a portion of a file that holds other programs or data (e.g., one or more scripts stored in a markup language document), in a single file dedicated to the program in question, or in multiple coordinated files (e.g., files that store one or more modules, sub-programs, or portions of code). A computer program can be deployed to be executed on one computer or on multiple computers that are located at one site or distributed across multiple sites and interconnected by a communication network.

[0066] The processes and logic flows described in this specification can be performed by one or more programmable processors executing one or more computer programs to perform actions by operating on input data and generating output. The processes and logic flows can also be performed by, and apparatus can also be implemented as, special purpose logic circuitry, e.g., an FPGA (field programmable gate array) or an ASIC (application-specific integrated circuit).

[0067] Processors suitable for the execution of a computer program include, by way of example, both general and special purpose microprocessors, and any one or more processors of any kind of digital computer. Generally, a processor will receive instructions and data from a read-only memory or a random access memory or both. The essential elements of a computer are a processor for performing actions in accordance with instructions and one or more memory devices for storing instructions and data. Generally, a computer will also include, or be operatively coupled to receive data from or transfer data to, or both, one or more mass storage devices for storing data, e.g., magnetic, magneto-optical disks, or optical disks. However, a computer need not have such devices. Moreover, a computer can be embedded in another device, e.g., a mobile telephone, a personal digital assistant (PDA), a mobile audio or video player, a game console, a Global Positioning System (GPS) receiver, or a portable storage device (e.g., a universal serial bus (USB) flash drive), to name just a few. Devices suitable for storing computer program instructions and data include all forms of non-volatile memory, media and memory devices, including by way of example semiconductor memory devices, e.g., EPROM, EEPROM, and flash memory devices; magnetic disks, e.g., internal hard disks or removable disks; magneto-optical disks; and CD-ROM and DVD-ROM disks. The processor and the memory can be supplemented by, or incorporated in, special purpose logic circuitry. CONCLUSION

[0068] The various methods and techniques described above provide a number of ways to carry out the invention. Of course, it is to be understood that not necessarily all objectives or advantages described can be achieved in accordance with any particular embodiment described herein. Thus, for example, those skilled in the art will recognize that the methods can be performed in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other objectives or advantages as taught or suggested herein. A variety of alternatives are mentioned herein. It is to be understood that some embodiments specifically include one, another, or several features, while others specifically exclude one, another, or several features, while still others mitigate a particular feature by inclusion of one, another, or several advantageous features.

[0069] Furthermore, the skilled artisan will recognize the applicability of various features from different embodiments. Similarly, the various elements, features and steps discussed above, as well as other known equivalents for each such element, feature or step, can be employed in various combinations by one of ordinary skill in this art to perform methods in accordance with the principles described herein. Among the various elements, features, and steps some will be specifically included and others specifically excluded in diverse embodiments.

[0070] Although the application has been disclosed in the context of certain embodiments and examples, it will be understood by those skilled in the art that the embodiments of the application extend beyond the specifically disclosed embodiments to other alternative embodiments and/or uses and modifications and equivalents thereof.

[0071] In some embodiments, the terms "a" and "an" and "the" and similar references used in the context of describing a particular embodiment of the application (especially in the context of certain of the following claims) can be construed to cover both the singular and the plural. The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (for example, "such as") provided with respect to certain embodiments herein is intended merely to better illuminate the application and does not pose a limitation on the scope of the application otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the application.

[0072] Certain embodiments of this application are described herein. Variations on those embodiments will become apparent to those of ordinary skill in the art upon reading the foregoing description. It is contemplated that skilled artisans can employ such variations as appropriate, and the application can be practiced otherwise than specifically described herein. Accordingly, many embodiments of this application include all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the application unless otherwise indicated herein or otherwise clearly contradicted by context.

[0073] Particular implementations of the subject matter have been described. Other implementations are within the scope of the following claims. In some cases, the actions recited in the claims can be performed in a different order and still achieve desirable results. In addition, the processes depicted in the accompanying figures do not necessarily require the particular order shown, or sequential order, to achieve desirable results.

[0074] All patents, patent applications, publications of patent applications, and other material, such as articles, books, specifications, publications, documents, things, and/or the like, referenced herein are hereby incorporated herein by this reference in their entirety for all purposes, excepting any prosecution file history associated with same, any of same that is inconsistent with or in conflict with the present document, or any of same that may have a limiting affect as to the broadest scope of the claims now or later associated with the present document. By way of example, should there be any inconsistency or conflict between the description, definition, and/or the use of a term associated with any of the incorporated material and that associated with the present document, the description, definition, and/or the use of the term in the present document shall prevail.

[0075] In closing, it is to be understood that the embodiments of the application disclosed herein are illustrative of the principles of the embodiments of the application. Other modifications that can be employed can be within the scope of the application. Thus, by way of example, but not of limitation, alternative configurations of the embodiments of the application can be utilized in accordance with the teachings herein. Accordingly, embodiments of the present application are not limited to that precisely as shown and described.

Claims

1. A ventrode for simultaneous drainage of CSF fluid and neural monitoring, the ventrode comprising: a catheter tube with a central lumen, the distal end of the catheter tube comprising a drainage segment with holes in fluid communication with the central lumen; and a cortical microelectrode segment positioned relative to the drainage portion on the catheter tube to allow at least a portion of the cortical microelectrode segment contact a cortex of a patient when deployed inside the patient to drain cerebrospinal fluid, the cortical microelectrode segment comprising cortical microelectrode wires extended from the catheter tube and in electrical communication with wires that extend to the proximal end of the tube.

2. The ventrode of claim 1, further comprising a ring electrode segment positioned relative to the drainage segment on the catheter tube to allow at least a portion of the ring electrode segment to contact a white matter of the patient when deployed to drain cerebrospinal fluid, the ring electrode segment comprising ring electrodes in electrical communication with wires that extend to the proximal end of the tube.

3. The ventrode of claim 2, further comprising a subarachnoid microelectrode segment positioned relative to the drainage segment on the catheter tube to allow at least a portion of the subarachnoid microelectrode segment to contact a surface of the cortex of the patient when deployed to drain cerebrospinal fluid, the subarachnoid microelectrode segment comprising subarachnoid microelectrode wires extended from the catheter tube and in electrical communication with wires that extend to the proximal end of the tube, the subarachnoid microelectrode wires extending further away from an outside surface of the catheter tube than the wires extending from the cortex microelectrode segment.

4. The ventrode of claim 1, further comprising a sleeve that removably covers the microelectrode segment.

5. The ventrode of claim 1, further comprising a signal processing unit in electrical communication with the wires extending to the proximal end of the tube.

6. The ventrode of claim 5, the signal processing unit comprising: a memory containing machine readable medium comprising machine executable code having stored thereon instructions for performing a method of analyzing neural electrical activity; an analog to digital converter in communication with the wires extending to the proximal end of the tube from analog to digital; and a processor coupled to the memory, the processor configured to execute the machine executable code to cause the processor to identify electrode signals output from the analog digital converter that represent signal neural unit activity.

7. The ventrode of claim 1, wherein the catheter comprises silicon.

8. The ventrode of claim 1, wherein the catheter includes a pressure sensor.

9. The ventrode of claim 1, wherein at least one of the electrodes generates a defined temperature signal and at least a second of the electrodes functions as a temperature sensor and wherein the processor determines a measure of blood perfusion based on the difference between the expected and measured temperature.

10. A method of simultaneously draining the cerebrospinal fluid from a patient's skull while recording cortical activity from single neural units, the method comprising: positioning a catheter into a patient's head so at least a portion of a drainage segment on the catheter is located in a ventricle of the patient and cerebrospinal fluid begins to drain through a lumen of the catheter; detecting, with microwire electrodes positioned on the catheter proximal to the drainage segment, signal neural unit activity from the cortex of the patient; processing, with a control system, the signal neural unit activity to diagnose a condition based on the signal neural unit activity; and outputting, to a display, a representation of the diagnosis.

11. The method of claim 10, further comprising: detecting, with ring electrodes positioned on the catheter proximal to the drainage segment, electrical activity from the white matter; processing, with a control system, signals output from the ring electrodes to determine an indication of whether the patient is having a seizure; and sending an alert to a patient status device if the control system determines the patient is having a seizure.

12. The method of claim 10, further comprising: detecting, with at least one subarachnoid microwire electrode positioned on the catheter proximal to the drainage segment, electrical activity from the surface of the cortex; processing, with a control system, signals output from the microwire electrodes to determine an indication of whether the patient is having a seizure; and sending an alert to a patient status device if the control system determines the patient is having a seizure.

13. The method of claim 10, further comprising manipulating a sleeve positioned to cover the at least one microwire electrode after positioning the catheter in order to allow the tips of the at least one microwire electrodes to extend outward from the catheter.

14. The method of claim 13, wherein manipulating comprises withdrawing.

15. The method of claim 13, wherein manipulating comprises rotating.

16. The method of claim 10, further comprising deploying the at least one microwire electrode by allowing a coiled portion of wires inside the catheter body to release and extend the tips of the microwire electrodes outward from the surface of an outside surface of the catheter.

17. The method of claim 13, wherein the microwire electrodes are folder underneath the sleeve prior to deployment.

18. The method of claim 13, wherein the microwire electrodes are retained in sheaths of the sleeve prior to deployment.