NL2001695C2

NL2001695C2 - Implantable electronic system useful for producing stimulation signal to human, has controller for processing parameter values to generate control signal for stimulation device based on detected parameter values

Info

Publication number: NL2001695C2
Application number: NL2001695A
Authority: NL
Inventors: Gerrit Johannis De Vos
Original assignee: Kerphos B V
Priority date: 2008-06-18
Filing date: 2008-06-18
Publication date: 2009-12-22

Abstract

The system has silicon casing (11) that includes upper surface (50) and lower surface (51) which are arranged in parallel and connected to one another by side surface (52). The casing is provided with electronics to receive one or more detected parameter values from detection device relating to one or more functions of subject. A controller is provided for processing number of detected parameter values to generate control signal for stimulation device based on detected parameter values in accordance with preset function.

Description

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

Field of the invention 5

The invention relates to an electronic system for producing a stimulation signal to the human body. Such a stimulation signal may relate to an aspiration reflex in human beings, a pacemaker signal or a cardiovertor/defibrillator signal.

10 Background of the invention

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 15 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 20 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 25 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 30 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 2 the upper airways by strong negative suction pressures. 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 5 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 10 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 apnea or mixed type sleep apnea, treatment with CPAP is showing limited success. Modulating the air pressure 15 (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 20 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 25 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, 30 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).

3 PCT/NL2006/000599, which has not been published prior to the date of filing of the application relating to the present invention, describes the surprising discovery that a resuscitating stimulation of the brainstem with an induced aspiration reflex in order to 5 obtain resuscitating physiological effects also works in human beings. That document also describes some devices designed for treating apnoea and related cardio-respiratory syndromes in humans via activation of the respiratory centre of the brainstem followed by an induced aspiration reflex.

10 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.

Many other implantable devices are available these days, among which pacemakers and 15 defibrillators. Such devices have been described in a wide variety of documents. As far as the inventor is aware of, no such document has disclosed or suggested using a flexible casing for such an implantable device.

Summary of the invention 20

The object of the present invention is to provide improved implantable devices that can be used to generate a stimulus to human organs like the brain and the heart.

To that end, the invention provides an electronic system as claimed in claim 1.

25

The advantage of using a flexible casing 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.

30 4

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 5 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; 10

Figure 3 shows a schematic block diagram of an electronic system according to the invention.

Figure 4 shows an example of electronics that can be used in the present invention.

15

Figure 5 shows a flexible substrate with some electronic components on top of it.

Figures 6a-6c show different embodiments of the invention.

20 Description of embodiments.

The present invention can advantageously be applied in an implantable device used to induce an aspiration reflex in a subject. Despite the fact that the invention can be applied equally well in other types of implantable devices, hereinafter a detailed description of its 25 application in a device for inducing an aspiration reflex will be provided.

The present invention, among others, relates to devices 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 30 of the human organism via inducing a sniff- and 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 5 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, 5 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 10 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 15 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.

20

As indicated in PCT/NL2006/000599, 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.

25 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. 30 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 periferal 6 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 5 Parkinson's disease may be inhibited by impulses from the inspiratory centre via the reticular formation, transmitted through intemeurons 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 intemeurons activates the descending part of the 10 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 intemeurons influences the ascending part of the reticular formation. This 15 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.

20 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 25 strong and short inspiratory efforts comparable to that occurring before or during one or more of gasp, sniff, sigh or augmented breath.

Resuscitating stimulation may be performed 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 30 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 7 oropharynx (roughly situated behind the oral cavity between arrows 2 and 3) and the laiyngopharynx (roughly situated behind the larynx between arrows 3 and 4).

Figure 2 shows the preferred location of resuscitating stimulation of the pharynx.

5 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.

10 Figure 3 shows 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.

15

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.

20

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 25 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 30 determine suitable functions on the basis of which a response is required as a function of the determined parameter values. E.g. the function may relate the absence of certain parameter values below a certain threshold value to a certain time frame. Such a δ 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 5 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 10 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 15 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 20 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 include but are not limited to parameters corresponding to muscle activity, parameters 25 corresponding to breathing, or parameters corresponding to cerebral activity, such as electrical activity of neural cells including brain cells, or electrical activity recorded from the pharynx or other parts of the body.

Parameters corresponding to muscle activity include but are not limited to movement 30 and electrical activity of muscles. Movement of muscles may be detected by any detection device 16 suitable for detecting movement, such as a number of accelerometers. Electrical activity of muscles may be detected by use of any suitable 9 device known in the art such as devices conventionally used for detecting an electromyogram (EMG), including an electrocardiogram (ECG), electroneurogram (ENG), actogram indicating contraction, etc. In one embodiment, the detection device 16 is arranged to record an electromyogram (EMG) detected by a detection electrode 5 connected to the detection device 16. The detection electrode 16 may be suitable for attachment to the human diaphragm. The EMG data, including for instance intensity, frequency, repeatability of phasic activity, is processed in microprocessor 20.

Parameters corresponding to breathing, include but are not limited to parameters 10 corresponding to activity of muscles involved in breathing activity such as the diaphragm, the intercostal muscles, musculus pectoralis, abdominal muscles, muscles of the upper and lower airways and other muscles involved. The parameters corresponding to muscle activity as discussed above are suitable. In an alternative embodiment of the device according to the invention, the parameter corresponding to breathing activity may 15 comprise gas flow in the airways and/or in the vicinity of the inlets/ outlets of the subject’s airways. It must be understood that the inlets/outlets of the subject’s airways comprise normally the nostrils and/or mouth or a tracheal tube in some patients. The skilled person will be familiar with suitable devices for determining gas flow, e.g. by a pneumotachograph or thermometer, such as a thermistor, PtlOO, PtlOOO and other.

20

In a further alternative embodiment of the device 16, the parameters corresponding to breathing activity to be detected may comprise sound. During breathing sounds are created. Respiratory sounds include but are not limited to snoring, inspiratory and expiratory stridor, groaning, etc. These sounds may be used to detect breathing activity 25 of a hiim.gr> being. Suitable detecting devices 16 for detecting sounds are microphones, a membrane connected to a coil/magnet system or any other device comprising a membrane with the possibility to register movement or displacement of this membrane.

In a further alternative embodiment of the invention an electro encephalogram may be 30 used by electronics 12. If so, detection device 16 is also arranged to detect electrical activity of the brainstem. Cerebral activity produces electrical fields which can be measured e.g. on the skin of the skull or the ear of a human being. Alternatively such 10 signals may be recorded from the pharynx of a human being. Suitable devices for detecting electrical activity from the skin of the pharynx are conductive patches connected to a suitable amplifier and filter. The skilled person will be familiar with suitable devices for determining electrical activity of the brain from the skin.

5

The stimulation device 17 is arranged to provide a response as a function of the number of processed parameter values. The stimulation device may comprise a number of stimulation units designed to provide resuscitating stimulation in order to stimulate and/or reactivate the inspiratory centre of the brainstem. The primary preferred 10 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 intemeurons 15 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.

20 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 25 brainstem and other parts of the brain such that resuscitation and/or autoresuscitation may be induced.

Preferably the resuscitating stimulation of the inspiratory centre of the brainstem is at a location distant from said inspiratory centre. Examples of such areas include the upper 30 airways, preferably the pharynx, acupuncture point GV26 on the nasal philtre and acupuncture points on the ear, for instance the auricle of the ear. Stimulation of the nasopharynx, more preferably the part of the nasopharynx in the proximity of the tubae 11 auditivae, is preferred 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 5 electrical stimulation device may include a separate power source. A suitable power source may be an array of charged capacitors, 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 10 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.

15 The stimulation device 17 may further include or be connected to one or more stimulation electrodes for delivering an electrical stimulation to the body of the subject. Such electrodes receive suitable stimulation signals based on the control signal received from the electronics 12. Electrodes may be mono-polar or multipolar, including bipolar electrodes, and may be placed on the surface of the body or anchored in various tissues 20 of the subject’s body. For stimulation of acupuncture point GV26 on the nasal philtre and acupuncture points on the ear, for instance the auricle of the ear, the electrodes may be placed on the skin. Alternatively electrodes may have the form of needles arranged to at least partially penetrate the subject’s skin. For stimulation of the pharynx the electrode may be anchored in the subject’s pharynx.

25

In an embodiment, the stimulation device 17 comprises a plurality of stimulation electrodes. By using a plurality of stimulation electrodes more complex stimulation currents can be provided to the body. This also provides the possibility of precise definition of the area to be stimulated. If a plurality of stimulation electrodes is used it is 30 preferred that there is some distance between said electrodes. Due to this distance the electrical current will travel over that distance through the subject’s body. This will enhance the stimulatory effect.

12

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)( Befiacka and Tomori, 1995). Sinus waves of various 5 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.

The stimulation electrode may be an electro-stimulation lead which is arranged to be 10 anchored to a selected area of the subject’s body by means of an anchoring unit. Any suitable anchoring unit as known in the art for anchoring an electro-stimulation lead to a mammalian body, including a human body, is suitable. Suitable examples are screw treads, which can be used to screw the electro-stimulation lead in the selected tissue, such as a muscle. Alternative anchoring means are flabs (e.g. 4 parts in a cross form at 15 the end of the electrode) that will grow into the muscle, or stitching, etc. In a further example, the electro-stimulation lead is suitable to be anchored in the dorsolateral area of the nasopharynx.

In an embodiment, the microprocessor 20 is designed to activate the wave function 20 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 25 as a sinus wave, block wave, spike train or any combination in a suitable frequency, duration and amplitude that is guided through electrical wires to its stimulation electrode.

Flexible implantable devices.

The device according to the invention is at least partly implantable in a human body, i.e., at least casing 11 with its components inside. Preferably the device is fully implantable in 30 13 a human body. Implantation is especially suitable when using electrical and/or mechanical stimulation means. Complete implantation of the device will make its use easier for the subject as there will be no parts on the surface of the subject’s body. An implanted device may serve as an alternative for a positive pressure supplying device 5 preventing airway obstruction giving the subject the same freedom as everybody else has. 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, 10 approximately 70% of the pacemaker’s volume is taken up by the battery and connectors.

In one embodiment, the implantable device is arranged as shown in figure 3 where the casing 11 that accommodates electronics 12 and battery 13 is made of a flexible 15 material. A suitable material is silicone since that is found to be well tolerated by the human body. However, other flexible materials tolerated by the human body may be used instead.

The advantage of using a flexible casing is that it adapts itself to the form of the body 20 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.

In an embodiment, when the invention relates to a device for resuscitating stimulation of 25 the inspiratory neurons of the brainstem such a flexible casing 11 is designed to be implantable behind the nasopharynx. Implanting such a casing can be done via the nose.

In such an embodiment, the battery may be made flexible too. The electronics 12 may be made of flexible components as well or at least electronic components may be provided 30 on a flexible substrate, e.g., a flexible printed circuit board. Figure 5 shows such a flexible substrate 30 having electronic components 31 located on at least one surface. The stimulation device 17 may be located inside the casing 11 too and be made of 14 electronic components on a flexible substrate too. Then, the stimulation device 17 may be arranged as shown in figure 5 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 5 be a single substrate. The battery 13 may be provided on that substrate too. The detection device 16 may be located inside the casing 11 too and be made of electronic components on a third flexible substrate too. Then, the detection device 16 may be arranged as shown in figure 5 as well. The substrates with the electronic components of the electronics 12, the detection device 16 and the stimulation device 17 may be separate 10 substrates. Alternatively, however, they may be one single substrate.

An implantable device 10 according to the invention may be designed such that it does not comprise any external detection or stimulation leads. As shown in figure 6a, the casing 11 ’ of such a device 10’, then, accommodates all components including the 15 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’. Then, the casing 11 ’ may be partly conductive. For instance, the casing 11 ’ may be provided with conductive pads 33 connected to the detection device 16’ and operating as an antenna to 20 detect electric activity of the human body e.g. for the detection of an EEG. The conductive casing 11 ’ may similarly be provided with electrical pads 34 connected to the stimulation device 17’ which are used to guide an electric stimulation current to the part of the human body in its direct proximity. Such a device 10’ may be implanted in a part of the human body where electric stimulation may suitably be applied to obtain 25 resuscitating stimulation of the respiratory area of the brainstem with an induction of an aspiration reflex, e.g. in the nasopharyngeal area.

It is observed that the idea of using a flexible casing can be used in other implantable devices as well, like pacemakers and implantable cardiovertors/defibrillators (ICD).

30 Such devices have, in principal, the structure as the one shown in figure 3. An embodiment thereof, however, is shown in figure 6b. In such cases detection device 16” is arranged to measure one or more suitable parameters relating to the operation of the 15 heart which are processed by electronics 12” in a known way to generate a suitable control signal to a stimulation device 17”. The stimulation device 17” is arranged within the casing 11” and arranged to provide a suitable stimulation signal to the heart via any suitable stimulation unit, e.g., one or more electrodes 18 implanted in the heart. When 5 the device is a pacemaker the stimulation signal is a pacemaker signal to the heart. When the device is a cardiovertor/defibrillator the stimulation signal is a defibrillating signal to the heart. Many such pacemakers or ICDs are known from the prior art and need no detailed discussion here. The invention is applicable to any such known or yet to be developed device.

10

Nowadays, such devices have a metal casing, usually made of titan. In most cases, such pacemakers and ICDs are implanted subcutaneously in a human’s body below a collarbone. However, such devices have a tendency of lowering in the human body which may cause irritation to the user. Moreover, in some cases decubitus may occur, 15 i.e., the pacemaker may come outward through the skin. A solution to that as applied nowadays is to implant the pacemaker or ICD under a muscle below the collarbone. However, when sleeping this may cause irritation to the wearer of the pacemaker or ICD, for instance, due to by turning over of the pacemaker or ICD.

20 By making at least the casing 11” more flexible, as proposed by the present invention, such disadvantages are overcome. Even if the pacemaker or ICD is made larger, this device may still be more comfortable if it is made from a flexible material like silicone.

To enhance the flexibility of the entire device 10” also at least one of the electronics 12”, the stimulation device 17” and the battery 13” may be (partly) made from a flexible 25 material. Alternatively, an array of smaller batteries may be joined to form a virtually flexible battery pack. To that end, the electronics 12” and the stimulation device 17” may be made on a flexible substrate like a printed circuit board. In an embodiment, the electronics 12” and the stimulation device 17” are made on a single flexible substrate like a printed circuit board. The electronics 12” and stimulation device 17” may be 30 arranged as shown in figure 5.

16

Sometimes, i.e. when the pacemaker is an unipolar pacemaker or in unipolar mode, its casing 11” is made of an electrically conductive material like platina or titan since it should allow a current produced by the stimulation device 17” and applied to the heart via the electrode 18 to flow back to the stimulation device 17” within the casing 11”.

5 This return current may flow back to the pacemaker through body tissue and flow via a wire 19 connected between the casing 11” and the stimulation device 17”. Even in such a case, the casing 11” can be made of a flexible material, be it that at least a part of it should be made of an electrically conductive material. This can be realized by at least partly doping the flexible material like silicone of the casing 11” with a conductive 10 material, for instance platina or titan. Alternatively, the flexible material can be provided with thin, flexible strips of electrically conductive material, for instance platina or titan that are connected to the wire 19.

Figure 6c shows a further alternative embodiment of the invention which may relate to a 15 pacemaker or a cardiovertor/defibrillator. The electronic system as shown in figure 6c is identical to the one shown in figure 6c apart from the following. The casing 11” is shown to comprise first electrical conductive portion 32 connected to the stimulation device 17” for allowing the return current to flow back to the stimulation device 17” as explained above. The first electrically conductive portion 32 may comprises one or more 20 separate first conductive pads. The detection device 16” is now accommodated in the casing 11” too and connected to a second electrically conductive portion 33. The second electrically conductive portion 33 may comprise one or more separate second conductive pads. The second electrically conductive portion 33 is arranged to sense one or more parameter values relating to one or more functions of the human body.

25

It is observed that the invention also relates to an embodiment in which only the detection device 16,16’, 16” is accommodated in the casing 11” and the stimulation device 17’, 17” outside the casing 11,11’, 11”.

30 The method according to the invention is suitable for the treatment of 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), 17 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 5 be construed to encompass alleviation of discomfort or provide reversal of life threatening functional disorders.

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 10 of the invention which is only limited by the annexed claims and its technical equivalents.

18

References

Arita H., Oshima T., Kita I., Sakamoto M.: Generation of hiccup by electrical stimulation in medulla of cats. Neurosci. Lett. 175: 67-70,1994.

5

Batsel H.L., Lines A.J.: Bulbar respiratory neurons participating in the sniff reflex in the cat, J. Exper. Neurol 39:469-481,1973' R. Benacka, Disorders of central regulation of breathing and their influencing by upper 10 airway reflexes (in Slovak). Orbis Medince S; No.: 53 - 63,2004, R. Benacka and Z. Tomori, The sniff-like aspiration reflex evoked by electrical stimulation of the nasopharynx, Respir. Physiol. 102: 163-174,1995.

15 J. Jakus, Z. Tomori and A. Stransky, Neural determinants of breathing, coughing and related motor behaviours, Monograph, Wist, Martin, 2004.

Sridhar R., Thach B.T. et al.: Characterization of successful and failed autoresuscitation in human infants including those dying of SIDS. Pediatr. Pulmon. 36:113-122, 2003.

20

St John W.M., Bledsoe T.A., Sokol H.W: Identification of medullary loci critical for neurogenesis of gasping J. Appl. Physiol. 56:1008-1019,1984.

Z. Tomori, M. Kurpas, V. Doni. and R. BeAa.ka, Reflex reversal of apnoeic episodes by 25 electrical stimulation of upper airway in cats, Respir. Physiol. 102:175-185,1995.

Z. Tomori, R. Benacka, V. Doni. and J. Jakus, Contribution of upper airway reflexes to apnoea reversal, arousal, and resuscitation, Monaldi Arch. Chest Dis. 55: 398-403, 2000.

Z. Tomori, R. Benacka and V. Doni., Mechanisms and clinicophysiological implications of the sniff- and gasp-like aspiration reflex, Respir. Physiol. 114: 83-98,1998.

30 19 Z. Tomori and J.G. Widdicombe, Muscular, bronchomotor and cardiovascular reflexes elicited by mechanical stimulation of the respiratory tract, J. Physiol 200: 25-49,1969.

5 Xie J., Weil M.H., Sun S., Yu T., Yang W.: Spontaneous gasping generates cardiac output during cardiac arrest, Crit. Care Med. 32: 238- 240, 2004.

Claims

An implantable electronic system, comprising: 5. a housing (11; 1Γ; 11 "); • electronics (12; 12 '; 12 ") arranged inside the housing (11; 1Γ; 11") and comprising: o at least one memory (21) for storing instructions and data relating to a predetermined function; 10. a control unit (20) connected to the memory (21) to process the number of detected parameter values according to the predetermined function; • a battery (13; 13 "; 13"); wherein the electronics (12; 12 '; 12 ") is arranged to detect one or more detected parameter values from a detection device (16; 16'; 16") that relate to one or more functions of a human body and to generate a control signal for a stimulation device (17; 17 '; 17 ") based on the detected parameter values, the housing (11; 11', 11") being made of a flexible material.

The electronic system of claim 1, wherein the flexible material is silicone.

An electronic system according to claim 1 or 2, wherein the electronics (12; 12 "; 12") comprise first electronic components (31) on a first flexible substrate (30).

The electronic system of claim 1, 2 or 3, wherein the battery (13; 13 ", 13") is a flexible battery. 30

The electronic system of claim 1, 2 or 3, wherein the battery is implemented as a series of batteries to provide a flexible battery pack.

The electronic system of any one of the preceding claims, wherein the electronics (12; 12 '; 12 ") comprises a microprocessor (20) connected to a wave function generator (23), the wave function generator (23) being arranged to to produce a control signal having a waveform selected from at least one of a sine wave, square wave, needle pulse train or any combination thereof with a predetermined frequency, duration and amplitude.

7. Electronic system as claimed in any of the foregoing claims, wherein the electronic system comprises the stimulation device (17 "; 17") arranged inside the housing (11 "; 11").

The electronic system of claim 7, wherein the stimulation device (17 "; 17") comprises second electronic components on a second flexible substrate.

The electronic system of claim 7 or 8, wherein the housing (11 ") is provided with at least a first electrically conductive portion (32) connected to the stimulation device (17") to allow a reverse flow from the human body to the stimulation device (17 ") can flow.

The electronic system of any one of claims 7-9, wherein the electronic system comprises a plurality of electrical contact surfaces (34) for supplying an electrical stimulation current to a body.

11. Electronic system as claimed in any of the foregoing claims, wherein the electronic system comprises the detection device (16 ') which is arranged within the I / II / III / III / III (III).

The electronic system of claim 11, wherein the detection device (16 ") comprises third electronic components on a third flexible substrate. 30

The electronic system according to claim 11 or 12, wherein the housing (11 ') is provided with at least a second electrically conductive portion (33) connected to the detection device (16 ") to determine the one or more parameter values to detect.

An electronic system according to any one of the preceding claims, wherein the stimulation device (17; 17 ') is designed to provide one of a respiratory region of a human brain stem respiratory region, a pacemaker signal to a human heart and a defibrillation signal to a human heart.

The electronic system of claim 14, wherein the detector device (16; 16 ') is a brain activity sensor adapted to detect EEG signals from the pharynx, preferably the nasopharynx, more preferably from the nasopharynx around one or both tubae auditivae and the stimulation device (17; 17 ') is designed to provide stimulation of the pharynx, preferably the oropharynx or nasopharynx, more preferably the nasopharynx, most preferably the nasopharyngeal region around one or both tubae auditivae . ** $ ***********