NL2001696C2

NL2001696C2 - 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: NL2001696C2
Application number: NL2001696A
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 with a stimulation matrix 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.

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 apnoea or mixed type sleep apnoea, treatment with CPAP is showing limited success. Modulating the air 15 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 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. Several stimulation devices are described. However, no matrix types are described.

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Summary of the invention

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 15 course of time when stimulation is always applied to the same point. Therefore, it is an object of the present invention to provide an improved stimulation device that can be used to generate a stimulus to human organs like the brain.

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

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The advantage of using a stimulation matrix is that the stimulus to the human body can be spread over an area instead of being apphed 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.

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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 30 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; 4

Figure 2 is a detail from figure 1;

Figures 3 shows a schematic block diagram of an electronic system according to the 5 invention.

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.

10

Figure 6 shows an alternative to the arrangement of figure 3.

Figure 7 shows a flexible substrate with some electronic components on top of it.

15 Description of embodiments.

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 20 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 25 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, laiyngospasm, hiccup, tremor associated with Parkinson’s disease, 30 epileptic seizure, absence type epilepsy, migraine, hypotension, syncope, haemorhagic shock (loss of blood), alternating hemiplegia, Alzheimers disease, depression, anorexia 5 nervosa, bulimia, autism, psychiatric disorders, sleep paralysis, insomnia, comatose states.

It is believed that the “aspiration reflex”, via strong activation of the inspiratory centre, 5 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 10 neuropsychic and somato -motor functions.

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.

15 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 20 brainstem may reverse the closure of the airways and restore normal breathing.

2. In patients with Transient Ischemic Attack (TLA), 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 25 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 intemeurons providing inhibitory 30 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 6 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 5 intemeurons 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.

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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 15 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.

Resuscitating stimulation may be performed in the area of the pharynx. As shown in 20 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).

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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 30 auditiva 5 indicated by the hatched lines in figure 2.

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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 5 14, as well as to a stimulation device 17 via suitable wires 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 10 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 15 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 20 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 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 function may be determined to detect the absence of breathing during a certain time 25 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 30 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 8 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.

5 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 10 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 include 15 but are not limited to parameters corresponding to muscle activity, parameters 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, the ear or any other suitable point on the body of a human being.

20 Parameters corresponding to muscle activity include but are not limited to movement 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 device known in the art such as devices conventionally used for detecting an 25 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 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, 30 frequency, repeatability of phasic activity, is processed in microprocessor 20.

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Parameters corresponding to breathing, include but are not limited to parameters 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 5 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 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 10 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.

In a further alternative embodiment of the detection device 16, the parameters corresponding to breathing activity to be detected may comprise sound. During 15 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 of a human 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 20 membrane.

In a further alternative embodiment of the invention an electro encephalogram may be 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 25 measured e.g. on the skin of the skull or the ear of a human being. Alternatively such signals may be recorded from the phaiynx 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.

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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 10 stimulation units 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 5 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 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 10 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 15 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.

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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 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 25 nasopharynx, more preferably the part of the nasopharynx in the proximity of the tubae 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 30 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 11 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 5 in the form of block waves, sinus waves or spikes of different length, frequency and amplitude, or combinations thereof.

Stimulation matrix.

10 Figure 5 shows a stimulation matrix 40 according to the invention. The stimulation matrix 40 is part of or 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.....1. The stimulation units are arranged in a matrix form. The arrangement shown comprises stimulation units 43(i) in a regular matrix pattern.

15 However, the invention is not restricted to this arrangement. Irregular patterns may be used instead. The only requirement is that the stimulation units 43(i) are arranged in a two dimensional pattern.

In an embodiment, the stimulation units are stimulation electrodes 43(i) for delivering an 20 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 be placed on the surface of the body or anchored in various tissues of the subject’s body. For stimulation 25 of acupuncture point GV26 on the nasal philtre and acupuncture points on the ear, for instance the auricle of the ear, the electrodes 43 (i) may be placed on the skin. Alternatively, electrodes 43(i) 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 phaiynx.

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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 12 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 will enhance the stimulatory effect. It also allows to let the device auto-optimise the stimulation position, 5 by optimising the effect as measured by the detection devices.

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 10 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 electrodes 43(i) may be electro-stimulation leads which are arranged to 15 be 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 threads, 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 20 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 25 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 30 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.

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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 5 movement when excited by an electrical current. Such mechanical stimulation units 43(i) may have the form of needles.

An 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 6, the casing 11 ’ of such 10 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’.

15 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 detect electric activity of the human body e.g. for the detection of an EEG.

20 The conductive casing 11 ’ may similarly be provided with the stimulation units 43(i) 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 resuscitating stimulation of the respiratory area of the brainstem with an 25 induction of an aspiration reflex, e.g. in the nasopharyngeal area.

In a further alternative embodiment, only the stimulation device 17’ is located inside casing 11 ’ and the stimulation units 43 (i) are located on the casing 11 ’ whereas detection circuit 16’ is located outside casing 11’ like in the arrangement shown in 30 figure 3.

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Casing 11 ’ may be made from a conducting material like titan or platina. In such a case, when the stimulation units 43(i) themselves are conductive too they should be electrically isolated from the conductive casing 11’. This can be done in any way known to a person skilled in the art.

5

In one embodiment, the casing 11,11 ’ that accommodates electronics 12, 12’ and battery 13,13’ 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 materials tolerated by the human body may be used instead.

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The advantage of using a flexible casing 11, 11’ is that it can well be used in implantable devices: it adapts itself to the form of the body where the casing 11,11’ 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. 15

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

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In such an embodiment, the battery 13, 13’ may be made flexible too. Alternatively, many small batteries may be joined to form a virtually flexible battery pack. The electronics 12, 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 25 board. Figure 7 shows such a flexible substrate 30 having electronic components 31 located on at least one surface. As shown in figure 6, the stimulation device 17’ may be located inside the casing 11 ’ too and be 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 30 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 15 detection device 16’ may be located inside the casing 1Γ 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 7 as well. The substrates with the electronic components of the electronics 12’, the detection device 16’ and the stimulation device 17’ may be 5 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 1Γ. This can be done by 10 providing silicone portions of the casing 11 ’ with doping materials like titan or platina.

Such an implantable device can be made auto-optimizing. The electronics 12, 12’ can be arranged to perform an impedance measurement on predetermined locations on the skin to locate one or more optimal stimulation points, i.e., points where an aspiration reflex 15 can be induced best. Such an impedance measurement can be performed by using the stimulation matrix and measuring impedance levels of the skin between several stimulation units 43(i). This renders a 2D pattern of impedance levels of the measured area on the skin. Areas with a lower impedance will be better points for providing the stimulus.

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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 25 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 30 the body stimulated by the stimulation units 43(i). This could reduce adaptation of the body to the generated stimuli and, thus, enhance efficiency of the device 10,10’.

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The device according to the invention may be at least partly implantable in a human body. Preferably the device is fully implantable in a human body. Implantation is especially suitable when using electrical and/or mechanical stimulation units 43(i). Complete implantation of the device will make its use easier for the subject as there will 5 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 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 10 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 method according to the invention is suitable for the treatment of one or more of 15 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, 20 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.

It should be understood that the embodiments presented in the examples above are 25 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.

17

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.

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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.

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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 18 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

A stimulation system, comprising a plurality of stimulation units (43 (i)) adapted to provide a stimulus to a human body, the stimulation units (43 (i)) being arranged in the form of a two-dimensional matrix.

The stimulation system of claim 1, wherein the stimulation units (43 (i)) are either monopolar or multipolar electrodes. 10

The stimulation system of claim 2, wherein the electrodes are arranged to be placed on a surface of a human body or to be anchored in a human tissue.

The stimulation system of claim 1, wherein the stimulation units (43 (i)) are mechanical stimulation units.

The stimulation system of claim 4, wherein the mechanical stimulation units (43 (i)) are electrostriction components. 20

The stimulation system of claim 1, wherein the stimulation units (43 (i)) are placed on a substrate (42).

7. Stimulation system according to any of the preceding claims, wherein the stimulation system comprises: • a housing (11, 11 '); • electronics (12; 12 ") arranged within the housing (11; 11") and comprising: o at least one memory (21) for storing instructions and data relating to a predetermined function; o a control unit (20) connected to the memory (21) to process the number of detected parameter values according to the predetermined function; • a stimulation device (17; 17 ') which is either connected to the stimulation units (43 (i)) or comprises these stimulation units (43 (i)); the electronics (12; 12 ') being arranged to receive one or more detected parameter values from a detection device (16; 16') relating to one or more functions of the human body and to receive a control signal for generate the stimulation device (17; 17 ') based on the detected parameter values.

The stimulation system of claim 7, wherein the stimulation units (43 (i)) are either embedded in or provided on the housing (11; 1Γ). 10

The stimulation system of claim 8, wherein the housing (11; 11 ") is made of a flexible material.

10. Stimulation system according to claim 9, wherein the housing is made of silicone.

The stimulation system of claim 10, wherein the stimulation units are electrodes that are electrically conductive silicone parts.

The stimulation system of claim 8, wherein the housing (11; 11 ") is made of a metal and the stimulation units are electrodes that are electrically insulated from the housing (11; 11").

13. Stimulation system according to any of claims 7-12, wherein the control unit (20) and the stimulation device (17; 17 ') are arranged to provide stimulation signals for the stimulation units (43 (i)). generate such that they provide different stimuli to the human body.

The stimulation system of claim 13, wherein the control unit (20) and the stimulation device (17; 17 ') are arranged to generate randomly varying stimulation signals for the stimulation units (43 (i)).

The stimulation system of claim 13, wherein the stimulation system is arranged as an auto-optimization system.

The stimulation system of any one of claims 7-15, wherein the electron-ca (12, 12 ') is arranged to perform impedance measurements in a predetermined area on the skin between a plurality of stimulation units (43 (i)) ), to obtain a 2D pattern of impedance levels of the measured area, and to derive suitable points for providing the stimulus from the impedance measurements. | Q ***********