WO2009154456A1

WO2009154456A1 - A flexible electronic system for producing a stimulation signal to the human body.

Info

Publication number: WO2009154456A1
Application number: PCT/NL2009/050356
Authority: WO
Inventors: Gerrit Johannis De Vos
Original assignee: Kerphos B.V.
Priority date: 2008-06-18
Filing date: 2009-06-18
Publication date: 2009-12-23

Abstract

An implantable electronic system has electronics (12), a detection device (16) and a stimulation device (17) within a casing (11). The electronics (12) receive detected parameter values from the detection device (16) relating to one or more functions of a human body. A controller (20) processes the parameter values and generates a control signal for the stimulation device (17) based on the detected parameter values in accordance with the predetermined function. The casing (11) is made of a flexible material.The casing (11) is made of a flexible biocompatible material, and has an upper surface (50) and a lower surface (51) which are substantially parallel to one another and connected to one another by means of a side surface (52).

Description

A flexible electronic system for producing a stimulation signal to the human body.

Field of the invention

The invention relates to a flexible electronic system for producing a stimulation signal to the human body.

Background of the invention

The present invention relates to a flexible implantable stimulation device.

Many implantable devices are available these days, among which pacemakers and defibrillators. Such devices have been described in a wide variety of documents. Using flexible implantable devices have been disclosed in, for instance, CA 2 507 142 Al and US 2006/0217779 Al . However, the flexible devices shown in these prior art documents are shaped like a hose and not suitable to be placed in every location in the human body where a stimulation device should be located.

One important location where a stimulation device can be implanted is in the pharyngeal area of the human body to provoke an induced aspiration reflex by a resuscitating stimulation of the respiratory area of the human brain stem, as described in PCT/NL2006/000599, which has not been published prior to the claimed priority date of the application relating to the present invention. Embodiments of the devices described in PCT/NL2006/000599 relate to implantable devices. However, this document is silent as to how such implantable devices may be constructed.

It is observed that auto -optimization of stimulation devices is known as such from WO 2007/146213.

Summary of the invention

To that end, the invention provides an electronic system as claimed in claim 1. The advantage of using a flexible casing as defined in claim 1 is that it adapts itself to the form of the body where the casing is implanted. Thus, it does not, or hardly, perform any mechanical pressure to the human body after implantation, which would cause discomfort or even undesired stimulation by pressure.

When stimulating a predetermined point of the human body in the course of time, irritation of that point may occur. Moreover, the stimulation effect may reduce in the course of time when stimulation is always applied to the same point. This is especially true for stimulating an area of the pharynx where it is not easy to identify the best location for stimulation and which can be damaged by the stimulation over time easily. Therefore, it is an object of an embodiment of the present invention to provide an improved implantable device with stimulation device that can be used to generate a stimulus to a human brain via an area in the pharynx.

To that end, in an embodiment, the invention provides an electronic system with a stimulation matrix.

The advantage of using a stimulation matrix is that the stimulus can be spread over an area instead of being applied to a point. This reduces irritation when used during longer time periods. Moreover, the applied stimulus pattern can be changed, thus avoiding adaptation of the body to and reduced efficiency of the stimulus. Moreover, integrating the stimulation matrix in the casing of the implantable device saves space and provides a device that can be implanted more easily. Also, stimulation waves of all kinds can be applied from one point to one or more of the other points on the matrix. This can be employed to produce more complex stimulation patterns.

Brief description of the drawings

The invention will be explained in detail with reference to some drawings that are only intended to show embodiments of the invention and not to limit the scope. The scope of the invention is defined in the annexed claims and by its technical equivalents.

Figure 1 is a schematic cross section of a part of the human head and neck. Figure 2 is a detail from figure 1.

Figure 3 a shows a schematic block diagram of an electronic system. Figures 3b and 3c show alternative shapes of a casing of an implantable device. Figure 4 shows an example of electronics that can be used in the present invention. Figure 5 shows a substrate with stimulation units arranged in the form of a matrix. Figure 6 shows an electronic arrangement according to the invention. Figure 7 shows a flexible substrate with some electronic components on top of it. Figure 8 shows a portion of a flexible casing with sensors and stimulation electrodes.

Description of embodiments.

The following detailed specification will explain the invention with reference to a stimulation device being implantable in the pharyngeal area of a subject, although application of the present invention is not restricted to this as will be explained further below.

The brainstem contains a number of central mechanisms regulating a number of vital physiological functions. Disorders in the regulation of the cardio -pulmonary system can result in a number of pathological conditions some of which may be potentially life threatening.

People suffering from sleep apnoea have cardio -pulmonary disorders manifesting with breathing irregularities and even frequent stops of breathing (apnoea), particularly during sleep, but also during the day. The apnoeic episodes during the day-time are less dangerous, because they can be self-managed by conscious actions, apnoeas during the night are more dangerous. Patients can feel very sick in everyday life, due to oxygen deprivation. During episodes of apnoea, blood pressure can collapse and subsequently the heart may stop its function, resulting in inadequate brain perfusion, loss of consciousness and even sudden death. At least 4% of the adult population in developed countries suffers from sleep apnoea.

There are several types of apnoea. One type, central apnoea, involves a dysfunction of the respiratory muscles (including the diaphragm) for lack of command from the respiratory centre in the brainstem. This is the type occurring in approximately 10 percent of the cases. Another type, obstructive apnoea, occurs in 80% of cases, when in spite of respiratory movements there is no supply of air to the lungs, due to collapse of the upper airways. The third type, a mixed apnoea, occurs in the rest of the patients.

It is known, that apnoea can be counteracted by stimulation of the patient in various ways. In infants shaking is usually enough to arouse the baby from sleep and restart the process of automatic breathing and even provoke gasps, which induces resuscitation from asphyxia. Adults suffering from sleep apnoea now sleep with a mask, tightly connected to the facial contours, so a slight over-pressure of air from a device can continuously be applied (Continuous Positive Airway Pressure- CPAP). This keeps the airways open and allows air supply by spontaneous breathing. In any case these patients have to sleep attached to their breathing apparatus, limiting their freedom of movement during sleep. For patients with sleep apnoea travelling means carrying the breathing apparatus with them. For patients suffering from central sleep apnoea or mixed type sleep apnoea, treatment with CPAP is showing limited success. Modulating the air pressure (BIPAP) offers only a slightly better success rate.

Research in cats has shown that breathing can be stopped by inhalation of anoxic mixtures for over 1 minute, with subsequently a severe drop in blood pressure and heart rate. Mechanical or electrical stimulation of the nasopharynx can induce a sniff- and gasp-like "aspiration reflex" (Tomori and Widdicombe, 1969, Benacka & Tomori, 1995, Tomori et al. 1995, 1998, 2000). Due to resuscitation effects, the blood pressure returns to normal, heart rhythm normalizes, respiration and neuro-behavioral functions return to normal. The anesthetized cat seems to be in good condition, even after as long as three minutes without adequate blood pressure, heart rate and breathing. This experiment can be repeated over 10 times on the same cat, without any noticeable negative consequences.

Provocation of such an aspiration reflex has been indicated as a possible means for interruption of apnoea in cats (Tomori et al., 1991, 1995, Benacka & Tomori, 1995, Jakus et al., 2004). Alternatively, similar resuscitation may be induced by (electro)- acupuncture, (electro)-acupressure or mechanical stimulation of the nasal philtre in cats, inducing spasmodic inspiration (Benacka & Tomori, 1997).

The present invention relates to devices that are, among others, suitable for inducing autoresuscitation in a subject in need thereof. The term autoresuscitation should be understood to comprise resuscitation by activation of natural compensatory mechanisms of the human organism via inducing a sniff- and/or gasp-like aspiration reflex, or its alternative forms in various species, similar to that provided by means of spontaneous gasping autoresuscitation observed in non-human animals and human infants (Sridhar et al, 2003; Xie et al, 2004). When referring to induction of autoresuscitation in this specification the term resuscitation may be used. Subjects that may benefit from induction of autoresuscitation are subjects suffering from and/or having a predisposition for functional disorders, such as hyper and hypo-function of the: a) respiratory system, b) cardiovascular system, c) neurobehavioral changes and d) psychiatric disorders. These include one or more of apnoea, transient ischemic attacks (TIA), bronchospasm also in asthmatics, laryngospasm, hiccup, tremor associated with Parkinson's disease, epileptic seizure, absence type epilepsy, migraine, hypotension, syncope, haemorhagic shock (loss of blood), alternating hemiplegia, Alzheimers disease, depression, anorexia nervosa, bulimia, autism, psychiatric disorders, sleep paralysis, insomnia, comatose states.

It is believed that the "aspiration reflex", via strong activation of the inspiratory centre, causes the controlling functions of the brainstem to be reset, similar to activation of brainstem centres during autoresuscitation induced by gasping. In rapid and strong inspiratory efforts during a gasp or a provoked aspiration reflex, activation of the inspiratory centre in the brainstem resets the failing centres of other vital functions, including the centres controlling cardiac activity, blood pressure, as well as various neuropsychic and somato-motor functions.

As indicated in PCT/NL2006/000599 referred to in the introduction of the present document, without wishing to be bound by any theory, it is believed that inducing the aspiration reflex may be helpful in relation to the following 5 groups of disorders of the human body. 1. In patients with apnoea and hypopnoea caused by transient inactivity of the inspiratory neurons in the brainstem, induction of the aspiration reflex can reverse the apnoea or hypopnoea and restore spontaneous breathing. In patients with obstructive apnoea, the stimulation of the inspiratory centre in the brainstem may reverse the closure of the airways and restore normal breathing.

2. In patients with Transient Ischemic Attack (TIA), syncope, hypotension, migraine and hemorrhagic shock the aspiration reflex activates, via the respiratory centre, the brainstem vasomotor centre to evoke peripheral vasoconstriction and vaso-dilatation in the brain and heart, resulting in increase of blood pressure and consequently increased brain and heart perfusion, interrupting, terminating or at least alleviating the pathological condition. 3. Bronchospasm, laryngospasm, hiccup, epileptic seizures, and tremor in

Parkinson's disease may be inhibited by impulses from the inspiratory centre via the reticular formation, transmitted through interneurons providing inhibitory influence to the relevant control centres in the brainstem and elsewhere. 4. In alternating hemiplegia, sleep paralysis and absence type epilepsy: stimulation via the inspiratory centre and interneurons activates the descending part of the reticular formation, which activates motoneurons, terminating, or at least alleviating the attack. 5. In comatose states, depression, insomnia, Alzheimers disease, anorexia nervosa, bulimia, and autism, stimulation via the inspiratory centre and interneurons influences the ascending part of the reticular formation. This inhibits or provides relief in depression, bulimia, anorexia nervosa and increases concentration and other cognitive functions. This improves some comatose states, may inhibit the development of Alzheimer's disease and autism and has a positive influence on insomnia and psychiatric disorders.

Resuscitating stimulation of the inspiratory neurons of the brainstem should be understood to mean stimulation of the human body such that the aspiration reflex or its alternatives are induced, which will influence various brainstem centres. Through such stimulation other parts of the brain relevant for the conditions treatable with the device are influenced. The aspiration reflex and its alternatives have as a common feature strong and short inspiratory efforts comparable to that occurring before or during one or more of gasp, sniff, sigh or augmented breath.

In accordance with a first embodiment of the present invention, the device is designed to provide resuscitating stimulation in the area of the pharynx. As shown in figure 1 the pharynx of the human body is situated from the underside of the skull to the level of cervical vertebra C6. The pharynx may be divided in three compartments, the nasopharynx (roughly situated behind the nasal cavity between arrows 1 and 2), the oropharynx (roughly situated behind the oral cavity between arrows 2 and 3) and the laryngopharynx (roughly situated behind the larynx between arrows 3 and 4).

Figure 2 shows the preferred location of resuscitating stimulation of the pharynx. Resuscitating stimulation is preferably administered in the area of the nasopharynx enclosed by reference marks A, B, C, D surrounding the tuba auditiva 5. More preferably resuscitating stimulation is administered in the direct proximity of the tuba auditiva 5 indicated by the hatched lines in figure 2.

Figure 3 a shows a schematic overview of an implantable device 10 with a casing 11. Enclosed in the casing 11 is a battery 13 which is connected to electronics 12. The battery 13 may comprise lithium iodine with nanocrystaline cathode components, as generally used in cardiac pacemakers. The electronics 12 are connected to a detection device 16 via suitable wires 14, as well as to a stimulation device 17 via suitable wires 15.

Figure 3b shows a first physical embodiment of the casing 11 of the present invention. The casing 11 is made of a flexible biocompatible polymer like silicone. However, the invention is not restricted to silicone. Other such flexible biocompatible materials known to persons skilled in the art or still to be developed may be used instead. The form of the casing 11 is box shaped. I.e., casing 11 has an upper surface 50 and a lower surface 51 which are substantially parallel and connected to one another via a side surface 52. The casing is designed such that it is flexible in three dimensions. The embodiment shown in figure 3b is shaped such that the upper surface 50 and lower surface 51 are either circular or oval.

Figure 3 c shows an alternative embodiment in which the upper surface 50 and lower surface 51 have rectangular shape.

It is observed that the invention is not restricted to the shapes shown in figures 3b and 3c. Every box shaped form of casing 11 is considered to fall within the scope of the present invention where the box has substantially parallel upper and lower surfaces. Moreover, side surface 52 need not be flat but may be curved seen in a cross sectional view in a direction perpendicular to upper surface 50 and lower surface 51.

Is will be evident to persons skilled in the art, the flexible casing 11 as proposed by the present invention is very suitable to be used in an implantable device 10 to be implanted in body areas as volatile as a (human) pharynx. Due to the flexibility, its form adapts itself to the surrounding tissue thus causing less irritation and health problems than in cases where a non- flexible casing is used.

The electronics 12 may be implemented by means of an analogue circuit, a digital circuit or a computer arrangement with a processor instructed by a suitable computer program, or any combination thereof. Figure 4 shows an embodiment based on a computer arrangement.

As shown in figure 4, the electronics 11 comprise a controller, e.g., in the form of a microprocessor 20 which is connected to a memory 21. Moreover, the microprocessor 20 is connected to a wave function generator 23 via suitable wires 22, which has an output connected to the wires 15 that are connectable to stimulation device 17.

The memory 21 may be implemented as several memory units of different types (RAM, ROM, etc.). The memory 21 stores instructions of a program to allow the microprocessor 20 to perform one or more functions. Optionally, memory 21 stores a number of detected parameter values as obtained from detection device 16. The memory 21 may be any suitable memory for storing a predetermined function such as a computer readable memory. The predetermined function may be a mathematical function or correlation. Suitable functions may be functions that are suitable for determining whether a determined parameter value is equal to, greater than or smaller than a predetermined threshold value. Based on his knowledge the skilled person will be able to determine suitable functions on the basis of which a response is required as a function of determined parameter values of parameters sensed by the detection device 16. E.g. the function may relate the absence of certain parameter values below a certain threshold value to a certain time frame. Such a function may be determined to detect the absence of breathing during a certain time period e.g. 2 seconds and longer, 5 seconds and longer or 10 seconds and longer.

Based on the program as stored in the memory 21, the microprocessor 20 is able to process the number of detected parameter values as obtained from the detection device 16 in said function. For this, the detected parameter values are loaded into the microprocessor 20 either directly from the detection device 16 or alternatively from the memory 21 into which the detected parameter values were previously loaded. The function is loaded in the microprocessor 20 from the memory 21 or in an alternative embodiment the predetermined function may be embedded in said microprocessor 20. In the latter embodiment at least one memory is (partially) integrated in the microprocessor 20.

The detection device 16 may be any suitable device for detecting a number of parameter values. In the present specification, a "number" shall mean one or more unless explicitly stated otherwise. In use, the detection device 16 provides an output signal on wire 14, representing determined parameter values in response to determined parameter values. The determined parameter values are values of a parameter as measured/determined by the detection device 16 within a certain time frame. The parameter may be any parameter on the basis of which it may be determined whether a subject is in need of induction of autoresuscitation.

Parameters suitable for determining whether a subject is in need of resuscitation are parameters corresponding to electrical activity recorded from, for instance, the pharynx indicating a level of cerebral activity. Suitable devices for detecting electrical activity from the surface of the pharynx are conductive patches connected to a suitable amplifier and filter. Alternatively, sensors may be anchored inside the nasopharynx. The microprocessor 20 is arranged to, as instructed by a suitable program stored in memory 21, receive values of such parameters from the detection device 16 and establish whether or not the subject is in need of autoresuscitation. However, the detection device may, alternatively, be arranged to detect at least one of a gas flow, a gas composition, a gas pressure, a gas temperature, a body temperature, a body part movement and sound. Signals delivered by detecting device 16 may, thus, be a measure of breathing activity, EEG data, EMG data, ECG data, or neural activity.

The stimulation device 17 is arranged to provide a response as a function of the number of processed parameter values as instructed by a suitable control signal received from electronics 12. The stimulation device 17 comprises a number of stimulation units which may be designed to provide resuscitating stimulation in order to stimulate and/or reactivate the inspiratory centre of the brainstem. The primary preferred stimulation as provided by the stimulation device 17 goes from the upper airways, preferably the pharynx, to the inspiratory centre in the brainstem. In the brainstem there are other controlling centres, such as the vasomotor centre and the neurons controlling cardiac activity, which will as a result also be influenced secondarily to the stimulation of the inspiratory centre. Furthermore, the inspiratory centre is connected by interneurons to the reticular formation (RF). The descending part of the RF connects to the peripheral nervous system, such as various motor and sensory neurons; the ascending part connects to higher centres controlling e.g. sensation, perception and cognitive functions.

Stimulation of certain locations distant from the brainstem, like in the pharynx, results in induction of resuscitation because in certain locations of the mammalian body afferent nerves connected to the inspiratory centre of the brainstem are present. Stimulation of such afferent nerves or their receptive zones results in activation of the inspiratory centre of the brainstem and through this in influencing of the other centres in the brainstem and other parts of the brain such that resuscitation and/or autoresuscitation may be induced. Stimulation of the nasopharynx, more preferably the part of the nasopharynx in the proximity of the tubae auditivae, is a suitable option as it provides the strongest resuscitation effect with induction of the aspiration reflex.

The stimulation device 17 may be a mechanical or an electrical stimulation device. The electrical stimulation device may include a separate power source. A suitable power source may be an array of charged capacitors connected to a battery, allowing voltage selection for the stimulation, in case spikes are used. This separate power source may, alternatively, be absent in which case the stimulation device 17 will be connected to the battery 13 within casing 11 via wiring 15. The wave generator 23 as shown in figure 4 may be part of the stimulation device 17. In combination with such a power source, the wave generator 23 is arranged to produce a desired control signal for the stimulation device 17, for instance in the form of block waves, sinus waves or spikes of different length, frequency and amplitude, or combinations thereof.

Figure 5 shows a stimulation matrix 40 which is used in an embodiment of the invention. The stimulation matrix 40 is connected to the stimulation device 17. As shown in figure 5, the stimulation matrix 40 has a substrate 42 provided with a plurality of stimulation units 43(i), i = 1, 2, 3, ..., I. The stimulation units 43(i) are arranged in a matrix form. The arrangement shown comprises stimulation units 43 (i) in a regular matrix pattern. However, the invention is not restricted to this arrangement. Irregular patterns may be used instead.

In an embodiment, the stimulation units are stimulation electrodes 43 (i) for delivering an electrical stimulation to the body of the subject. Such electrodes 43(i) receive suitable stimulation signals via wires 41 from electronics 44 within stimulation device 17 based on the control signal received from the electronics 12 via wire 15. Electrodes 43(i) may be mono-polar or multipolar, including bipolar electrodes, and may, in use, be placed on the surface of the pharynx. For stimulation of the pharynx the electrodes may be anchored in the subject's pharynx. By using a plurality of stimulation electrodes 43 (i) arranged in the form of a two dimensional matrix more complex stimulation currents can be provided to the body. This also provides the possibility of precise definition of the area to be stimulated. There is some distance between the electrodes 43(i). Due to this distance the electrical current will travel over that distance through the subject's body. This may enhance the stimulatory effect. It also allows to let the device auto-optimise the stimulation position, by optimising the effect as measured by the detection devices, as explained hereinafter.

If spikes are used for the control signal, variations in the amplitude and duration of the spikes, i.e. the amount of energy can be made, apart from trains of spikes over an extended period of time (seconds) (Benacka and Tomori, 1995). Sinus waves of various frequencies and duration, block waves, spikes, spike trains and any combination of these can be used. It is preferred to not just transfer energy, but to stimulate the targeted response centres more complexly to elicit the desired physiological response.

In an embodiment, the microprocessor 20 is designed to activate the wave function generator 23 if an EMG as detected by detection device 16 does not satisfy a predetermined criterion, such as a lack of normal EMG activity for >10 sec (central apnoea) or extremely strong EMG activity accompanied by stop of airflow (obstructive apnoea) as detected by detection device 16. Then, upon activation the wave function generator 23 may generate the control signal in the form of a predetermined wave, such as a sinus wave, block wave, spike train or any combination in a suitable frequency, duration and amplitude that is guided through electrical wires 41 to its stimulation electrode.

In an embodiment, the stimulation units 43 (i) are mechanical stimulation units arranged to provide a mechanical stimulus to the human body. Such mechanical stimulation units 43 (i) may be formed by electrostriction components which produce a mechanical movement when excited by an electrical current. Such mechanical stimulation units 43(i) may have the form of needles. An implantable device 10 according to the invention may be a fully integrated implantable device. Such a fully integrated implantable device is shown in figure 6 in which like components as in figure 3 are indicated with the same reference numbers, however provided with a prime. As shown in figure 6, the casing 11 ' of such a device 10', then, accommodates all components including the detection device 16', the electronics 12', the battery 13' and the stimulation device 17'. The battery 13' is shown to be connected to the electronics 12' but may equally well be connected to the detection device 16' and the stimulation device 17'.

Moreover, the casing 11 ' is shaped and made like casing 11.

The casing 11 ' may be partly conductive. For instance, the casing 11 ' may be provided with sensors 33 in the form of conductive areas, for instance in the form of conductive pads on the casing 11 'of the detection device 16' and operating as sensors to detect electric activity of the human body e.g. for the detection of an EEG. The sensors 33 may be formed by providing suitable conductive coating portions on casing 11 '. If the casing itself is also conductive, or in part conductive, then, sensors 33 should be electrically isolated from the casing 11 '. However, the invention is not restricted to this embodiment. Cf. for instance figure 8. It is observed that one or more of the sensors could be arranged such as to be usable as stimulators too. This also holds for other embodiments explained here.

In an alternative embodiment, the detection device 16' is connected to one or more small microphones to sense sound, small piezo-electric sensors to convert mechanical pressure into electric signals, or strain gages, etc. that are integrated in or placed on top of the casing 11'.

Alternatively, the detection device 16' is connected to a sensor to measure oxygen saturation in the blood of the subject. This can be done in any way known to a person skilled in the art. In the embodiment where the apparatus is implanted in the pharyngeal area this is possible with a sensor having a light source directed to a blood vessel, as is evident to persons skilled in the art. Measuring oxygen saturation is a good indication of whether or not apnoea is present. Sensors arranged in a matrix arrangement may especially be suitable to measure EMG or neural activity.

The casing 11 ' is also provided with the stimulation units 43 (i) connected to the stimulation device 17' which may be arranged in the form of a matrix and used to guide an electric stimulation current to the part of the pharynx in its direct proximity. The stimulation units 43 (i) may also be formed by providing suitable conductive coating portions on casing 11 '. If the casing itself is also conductive, then, sensors 33 should be electrically isolated from the casing 11 '. However, the invention is not restricted to this embodiment. Cf. for instance figure 8.

Both the sensors 33 and the stimulation units 43 (i) may be provided on a separate, insulating, flexible substrate 42 (cf. figure 5) which is attached to the outside of the casing 11 '. The wirings to the detection device 16' and stimulation device 17', respectively, are then guided through suitable through holes in casing 11 '.

The sensors 33 may also be arranged in a two dimensional matrix. The sensors 33 and the stimulation units 43 (i) may be arranged in matrices separate from one another. However, they may be arranged in a single mixed matrix arrangement with a plurality of electrically conductive areas where some of the electrically conductive areas are connected as sensors 33 and the others as stimulation units 43 (i).

In an embodiment, the device 10' is designed to be implanted in the pharyngeal area of the human body where electric stimulation may suitably be applied to obtain resuscitating stimulation of the respiratory area of the brainstem with an induction of an aspiration reflex, e.g. in the nasopharyngeal area.

To that effect the flexible casing 11 ' of the device will easily adapt to the local form of the pharyngeal area of the body concerned. The area on the casing 11 ' where the sensors 33 and the stimulation units 43(i) are located is arranged to cover the pharyngeal area A-B-C-D as indicated in figure 2, and preferably at least the area in the direct proximity of the tuba auditiva 5, for instance within a distance of 5 mm from the tuba auditiva 5.

The flexible casing 11 ' may be designed to be implantable in or behind the nasopharynx. In an embodiment, the casing 11, 11 'is sized and designed such that it may be implanted in or behind the nasopharynx via a human nose or throat.

As indicated above, the casing 11 ' that accommodates electronics 2' and battery 13' is made of a flexible material. A suitable material is silicone since that is found to be well tolerated by the human body. However, other flexible biocompatible materials tolerated by the human body may be used instead.

The advantage of using a flexible casing 11 ' is that it can well be used in implantable devices: it adapts itself to the form of the body where the casing 11 ' is implanted. Thus, it does not, or hardly, perform any mechanical pressure to the human body after implantation, which would cause discomfort or even undesired stimulation by pressure.

In an embodiment, the battery 13' may be made flexible too. Alternatively, many small batteries may be joined to form a virtually flexible battery pack. From cardiac pacemakers it is known that the battery life can be as long as 10 years. With devices for resuscitating stimulation of the inspiratory neurons of the brainstem the battery life can be expected to be much longer, or the device can be made much smaller, as it does not have to stimulate as often as a cardiac pacemaker. In cardiac pacemakers, approximately 70% of the pacemaker's volume is taken up by the battery and connectors.

The electronics 12' may be made of flexible components as well or at least electronic components may be provided on a flexible substrate, e.g., a flexible printed circuit board 30. Figure 7 shows such a flexible substrate 30 having electronic components 31 located on at least one surface of the substrate 30. As shown in figure 6, the stimulation device 17' is located inside the casing 11 ' too and is made of electronic components on a flexible substrate too. Then, the stimulation device 17' may be arranged as shown in figure 7 as well.

The electronic components of the electronics 12' may be arranged on a first flexible substrate and the stimulation device 17' may be arranged on a second flexible substrate. However, these first and second substrates may be a single substrate. The battery 13' may be provided on that substrate too.

As also shown in figure 6, the detection device 16' is located inside the casing 11 ' too and is made of electronic components on a third flexible substrate. Then, the detection device 16' may be arranged as shown in figure 7 as well. The substrates with the electronic components of the electronics 12', the detection device 16' and the stimulation device 17' may be separate substrates. Alternatively, however, they may be one single substrate.

In the embodiment where the casing is made of silicone and the stimulation units are stimulation electrodes 43 (i), these stimulation electrodes 43 (i) can be made as electrically conductive silicone portions in the silicone casing 11, 11 '. This can be done by providing silicone portions of the casing 11, 11 ' with doping materials like titan or platina. Such an embodiment is shown in Figure 8. Figure 8 shows a portion of a cross section of the flexible casing 11, 11 ' with sensors 33 and stimulation electrodes 43 (i). In this embodiment, both the casing 11, 11 ' and the sensors 33 and the stimulations electrodes 43(i) are made of silicone. They are all produced from a silicone substrate in which predetermined portions are doped with a suitable doping material like titan or platina to become sensors 33 and stimulation electrodes 43(i). Suitable conductive wirings are connected to these latter portions for electrically connecting the sensors 33 to the detection device 16, 16'and the stimulation electrodes 43(i) to the stimulation device 17, 17'.

Such a device can be made auto -optimizing. The electronics 12, 12' can be arranged to perform a feedback measurement, such that stimulation can be performed at a point where the aspiration reflex can be elicited best. In one embodiment the electronics will, through a suitable sensor, register the strength of the aspiration reflex; this can for example be performed by measuring airflow through the nose or mouth, measuring sound, heart rate, blood pressure etc. Impedance of the stimulation point may be a guide for finding the optimal point. In this case the device may use impedance measurement to find suitable points for stimulation.

The electronics 12, 12' can be arranged to send different types of stimulation signals to the stimulation units 43(i), either in form or in amplitude or both. The effect of the different stimulation signals per stimulation unit 43 (i) can be measured by detection device 16, 16' and be evaluated by electronics 12, 12'. Electronics 12, 12' can be programmed to amend these stimulation signals by amending its control signal as output to the stimulation device 17, 17'.

Moreover, the electronics 12, 12' can be programmed to randomly vary its generated control signal such that the stimulation signals produce random stimuli over the area of the pharynx stimulated by the stimulation units 43(i). This could reduce adaptation of the pharynx to the generated stimuli and, thus, enhance efficiency of the device 10, 10'.

The method according to the invention is suitable for the treatment of several disorders including one or more of but not limited to apnoea, such as central apnoea or obstructive apnoea, transient ischemic attacks (TIA), hypotension, syncope, haemorhagic shock (loss of blood), bronchospasm, laryngospasm, hiccup, tremor associated with Parkinson's disease, epileptic seizure, absence type epilepsy, migraine, alternating hemiplegia, Alzheimers disease, depression, anorexia nervosa, bulimia, autism, psychiatric disorders, insomnia, sleep paralysis, comatose states. As used in this specification the term treatment should be construed to encompass alleviation of discomfort or provide reversal of life threatening functional disorders. Depending on the application concerned, the microprocessor 20 is programmed to analyse received signals from sensors 33 and establish from them whether or not the subject concerned is in need of autoresuscitation. If so, the microprocessor 20 will produce suitable control signals and send them to the stimulation device 17, 17' which, then, produces suitable stimulation signals for the stimulation units 43(i). It should be understood that the embodiments presented in the examples above are solely intended to illustrate the present invention and are not intended to limit the scope of the invention which is only limited by the annexed claims and its technical equivalents.

For instance, the device as presented above, can be used in a pacemaker arrangement where at least the electronics 12 are located within the flexible casing 11 but the stimulation device 17 is outside casing 11. If so, the sensors may located outside the casing 11 as well or on top of or in casing 11 to sense parameters indicating whether or not the subject concerned is in need of a pacemaker stimulation signal. The stimulation device 17 may have any form suitable to provide the heart with a suitable pacing signal, as known from the prior art. In that case, the detecting device 16, 16' is at least arranged to sense an ECG signal from some part of the subject's body. Sensing and pacing may be done by one single electrode located in the heart wall as is known to a person skilled in the art.

Moreover, the device 10, 10' may be implanted at other locations in the subject to stimulate one or more predetermined nerves, etc.

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Claims

1. Implantable electronic system comprising:

• a casing (11; 11 '), • a detection device (16; 16') connected to at least one sensor (33),

• a stimulation device (17; 17') connected to at least one stimulation unit (43(i)),

• electronics (12; 12') arranged within said casing (11; 11 ') and arranged to receive one or more detected parameter values from said detection device (16; 16') relating to one or more functions of a subject, and comprising a controller (20) for processing the number of detected parameter values and to generate a control signal for said stimulation device (17') based on said detected parameter values in accordance with said predetermined function, wherein said casing (11; 11 ') is made of a flexible biocompatible material, and has an upper surface (50) and a lower surface (51) which are substantially parallel to one another and connected to one another by means of a side surface (52).

2. Implantable electronic system according to claim 1, wherein the upper and lower surfaces (50, 51) have a shape selected from a circular shape, an oval shape and a rectangular shape.

3. Implantable electronic system according to claim 1 or 2, wherein the detection device (16') is located within said casing (11 '), the at least one sensor (33) being arranged either embedded in or provided on at least one of said lower, upper and side surfaces of the casing (11 ').

4. Implantable electronic system according to claim 1, 2 or 3, wherein the stimulation device (17') is located within said casing and connected to a plurality of stimulation units (43 (i)) arranged in a matrix arrangement either embedded in or provided on at least one of said lower, upper and side surfaces of said casing (11 ').

5. Implantable electronic system according to any of the preceding claims, wherein the casing (11 ') is designed to be implantable in a human pharyngeal area.

6. Implantable electronic system according to claim 1, wherein the detection device (16') is located within said casing (11 '), the at least one sensor (33) being arranged either embedded in or provided on at least one of said lower, upper and side surfaces of the casing (11 '), the stimulation device (IV) is located within said casing and connected to a plurality of stimulation units (43 (i)) arranged in a matrix arrangement either embedded in or provided on one of said lower, upper and side surfaces of said casing (11 '), and the system is designed to be implantable in a human pharyngeal area via either a human nose or a human throat.

7. Implantable electronic system according to claim 4 or 6, wherein the stimulation units (43(i)) are located on a flexible substrate (42) attached to said casing (11 ').

8. Implantable electronic system according to claim 4 or 6, wherein said casing (11 ') is a silicone casing and said stimulation units (43(i)) are electrodes which are electrically conductive silicone portions in said silicone casing (11 ').

9. Implantable electronic system according to claim 4, 6, 7 or 8, wherein said system is arranged as an auto -optimizing system, and said stimulation system is arranged to identify a best location to provide a stimulus based on feedback signals from the detection device.

10. Implantable electronic system according to any of the preceding claims, wherein said electronics (12; 12') comprise electronic components (31) on a further flexible substrate (30).

11 Implantable electronic system according to claim 3 or 6, wherein said casing (11 ') is a silicone casing and said at least one sensor (33) comprises one or more electrically conductive silicone portions in said silicone casing (11 ').

12. Implantable electronic system according to any of the preceding claims, wherein the detector device (16') is one of a cerebral activity sensor arranged to sense EEG signals, an EMG sensor, an ECG sensor, a sensor to measure temperature, a sensor to measure pressure, a sensor to measure neural activity and a sound sensor.

13. Implantable electronic system according to any of the preceding claims, wherein the controller (20) and the stimulation device (IV) are arranged to generate randomly varying stimulation signals.

14. Implantable electronic system according to any of the preceding claims, wherein the at least one sensor (33) comprises a plurality of sensors arranged in a matrix arrangement.

15. Implantable electronic system according to claim 1, wherein the at least one sensor comprises a plurality of sensors (33) and the at least one stimulation unit comprises a plurality of stimulation units (43(i)), the plurality of sensors and the plurality of stimulation units being arranged in a mixed matrix arrangement.

16. Implantable electronic system according to any of the preceding claims, wherein the controller (20) is arranged to establish whether said subject is suffering from at least one of a set of disorders including apnoea, such as central apnoea or obstructive apnoea, heart failure, transient ischemic attacks (TIA), hypotension, syncope, haemorhagic shock, bronchospasm, laryngospasm, hiccup, tremor associated with Parkinson's disease, epileptic seizure, absence type epilepsy, migraine, alternating hemiplegia, Alzheimers disease, depression, anorexia nervosa, bulimia, autism, psychiatric disorders, insomnia, sleep paralysis, comatose states.