|Número de publicación||US20030028072 A1|
|Tipo de publicación||Solicitud|
|Número de solicitud||US 10/245,992|
|Fecha de publicación||6 Feb 2003|
|Fecha de presentación||17 Sep 2002|
|Fecha de prioridad||31 Ago 2000|
|También publicado como||US6591138, US7601116, US9033861, US20060205993, US20090318747, US20150217127|
|Número de publicación||10245992, 245992, US 2003/0028072 A1, US 2003/028072 A1, US 20030028072 A1, US 20030028072A1, US 2003028072 A1, US 2003028072A1, US-A1-20030028072, US-A1-2003028072, US2003/0028072A1, US2003/028072A1, US20030028072 A1, US20030028072A1, US2003028072 A1, US2003028072A1|
|Inventores||David Fischell, Adrian Upton|
|Cesionario original||Neuropace, Inc.|
|Exportar cita||BiBTeX, EndNote, RefMan|
|Citas de patentes (5), Citada por (135), Clasificaciones (21), Eventos legales (1)|
|Enlaces externos: USPTO, Cesión de USPTO, Espacenet|
 This is a division of U.S. Application Ser. No. 09/652,964, filed on Aug. 31, 2000.
 This invention is in the field of devices for the treatment of neurological disorders in human subjects, particularly those disorders that originate in the brain.
 The current state of the art in treating neurological disorders such as epilepsy or Parkinson's disease involves either drugs, destructive nigral lesions or the open-loop electrical stimulation of neurological tissue. Drug therapy has been shown to have significant short and long-term side effects and is often ineffective. In U.S. Pat. No. 3,850,161, Liss describes a continuous closed-loop feedback system which will always feedback part of the brain EEG signal to separate electrodes so that if a large EEG signal occurs it will be fed back in an attempt to cancel out the original signal. This system does not take advantage of recently developed digital signal processing and microcomputer technology by which feedback signals can be activated only when a neurological event occurs, nor does it provide a practical way to recognize and intervene during early stages in the evolution of a neurological event. In addition, the Liss device is not programmable and it does not provide any capability to record EEG signals. Examples of a “neurological event” are the occurrence of an epileptic seizure, a tremor or the occurrence of a migraine aura or migraine headache. A “neurological event” is defined herein as either the precursor of an event such as an epileptic seizure, or the event itself. This concept of detecting an electrical precursor that is a first type of neurological event that occurs some time before the “real” event (i.e. anomalous brain electrical activity or a particular pattern of neural activity associated with clinical symptoms) is an important aspect of the present invention. It has been shown that both epileptic seizures and Parkinson's tremors have precursors that occur before and can be used to predict the onset of the clinical symptom. It is also very likely that other neurological events such as migraine headaches and depression would have anomalous electrical activity predictive of the onset of clinical symptoms. Methods for prediction of epileptic seizures have been published by Elger and Lehnertz (in Elger, C. E., and Lehnertz, K., “Seizure prediction by non-linear time series analysis of brain electrical activity,” Eur. J. Neurosci. February 1998; 10(2):786-9, and Osorio, Frei and Wilkinson (in Osorio, I., et al., “Real-time automated detection and quantitative analysis of seizures and short-term prediction of clinical onset,” Epilepsia June 1998 ; 39(6):615-27.
 Maurer and Sorenson in U.S. Pat. No. 4,019,518 describe a combined internal/external system for electrical stimulation of the body with biphasic pulses but do not describe any means of detecting neurological events. Fischell in U.S. Pat. No. 4,373,527 describes a programmable medication infusion system but does not anticipate its use in response to a detected neurological event.
 More recently, a device has been approved for human use to stimulate the vagus nerve in a continuous fashion with the objective of decreasing the rate of epileptic seizures. Clinical reports on such devices indicate only a modest degree of success in that only 50% of the patients experience a greater than 20% reduction in the rate of epileptic seizures. Another device that has been recently introduced into clinical practice utilizes intermittent or continuous stimulation of the thalamus for the treatment of involuntary motion disorders such as Parkinson's syndrome. Neither of these two open-loop devices described above is highly effective for the treatment of a neurological disorder such as epilepsy, and neither anticipates the use of decision making in order to optimize a response to terminate the precursor of a neurological event or the neurological event itself; nor does either device allow for the recording of EEG signals. In addition, both known devices use stimulation frequencies above 10 Hz, which for the reasons set forth in detail below, are not optimal.
 Fischell et al in U.S. Pat. No. 6,016,449, which is incorporated herein by reference, teaches a fully implantable neurostimulator capable of responsive treatment of neurological disorders. However, Fischell does not discuss in detail the advantageous use of low frequency stimulation as a means of inhibiting epileptiform activity.
 It is well known that slow wave potentials in the brain are often inhibitory in nature yet all known stimulation attempts to treat epilepsy in humans have used relatively high frequency stimulation, in most cases greater than 20 Hz. These higher frequencies, while effective for a brain mapping type procedure, have significant potential to induce epileptogenic activity. In fact, Hallett in “Transcranial magnetic stimulation and the human brain,” Nature, Vol. 406, 13 July 2000, states that while “rapid repetitive transcranial magnetic stimulation (rTMS), at frequencies of 5 Hz and higher, will transiently enhance motor excitability . . . slow rTMS, at 1 Hz will transiently depress excitability.”
 There is good evidence that slow wave activity is inhibitory in the central nervous system of man (Staton, R. D. et al., “The electroencephalographic pattern during electroconvulsive therapy: V. Observations on the origins of phase III delta energy and the mechanism of action of ECT,” Clin. Electroencephalogr. October 1988; 19(4):176-198 and animals (Buzsaki, G. et al., “Depth profiles of hippocampal rhythmic slow activity (‘theta rhythm’) depend on behaviour,” Electroencephalogr. Clin. Neurophysiol. July 1985; 61(1):77-88) including such stimulation applied to the hippocampus (Leung, L. S. et al., “Theta-frequency resonance in hippocampal CA1 neurons in vitro demonstrated by sinusoidal current injection,” J. Neurophysiol. March 1998; 79(3):1592-6). These slow waves may be at theta frequencies (4 to 7 Hz—Buzsaki et al. 1985), delta frequencies (1 to 3 Hz—Staton et al. 1988), or even at less then 1 Hz (Contreras, D. et al., “Cellular basis of EEG slow rhythms: a study of dynamic corticothalamic relationships,” J. Neurosci. January 1995; 15(1 Pt 2):604-22). Paatta et al. (in “Control of chronic experimental focal epilepsy by feedback caudatum stimulation,” Epilepsia August 1983; 24(4):444-54) describe successful ictal spike depression by 5 Hz stimulation of the caudate nucleus (CN) in cat brains. The article also states that stimulation of the thalamus, mesencephalic reticular formation or hypothalamus was not effective. Finally, Hallett (in “Transcranial magnetic stimulation and the human brain,” Nature 2000; 406 (July 13): 147-150) discusses the inhibitory effects of low frequency pulsing from a transcranial magnetic stimulator.
 The present invention includes transcranial stimulation, or direct brain stimulation from multiple electrodes, in either an open or closed-loop system for the treatment of certain neurological disorders such as epilepsy, migraine headaches and Parkinson's disease. A purpose of the present invention is to overcome the shortcomings of all known devices for the treatment of such disorders. Specifically, the present invention utilizes slow wave potentials (low frequency stimulation in a range of approximately 1 to 10 Hz) to prevent or abort a neurological event.
 One embodiment of the present invention envisions a multiplicity of brain electrodes placed either within the brain, on the surface of the brain itself, or on the dura mater that surrounds the brain. Some or all of these brain electrodes may be used to directly detect an abnormal neurological event such as an epileptic seizure, or they may be used to detect a pattern of electrical activity that precedes or accompanies an abnormal neurological event. A stimulation signal can also be applied to any one, several, or all elements of such an electrode array. The stimulation signals sent to each electrode may be identical or they may be programmed to differ in amplitude, frequency, waveform, phase and time duration. It is also envisioned that sensing electrodes may be entirely separate from the electrodes used for responsive stimulation.
 It is also envisioned that appropriate selection (i.e., location) of electrode sites can be used to enhance the reliability for detection and termination of a neurological event. Thus, the present invention envisions enhancement of detection by the use of the spatial domain as it applies to the positioning of detection and treatment electrodes.
 A specific capability of this system is to provide electrical stimulation to a specific portion of the brain as the means of stopping a neurological event. It is believed that the earliest possible detection of a seizure and treatment of aberrant electrical activity from an epileptic focus has the highest probability of aborting the occurrence of a full seizure. It is envisioned that either through specific placement of treatment electrodes or by adjusting the phase of signals applied to an array of electrodes, stimulation can be directed to the location(s) within the brain that offer the highest probability of stopping the seizure. Detection of an abnormal neurological event would allow detection of specific but apparently normal patterns of electrical activity, which are reliable producers of the abnormal event; stimulation during the appearance of such patterns may prevent the occurrence of the event.
 A novel aspect of a preferred embodiment of this invention is that the entire implantable portion of this system for treating neurological disorders is implanted under the patient's scalp or intracranially. Such placement will either have the device located between the scalp and the cranium or the within a hole in the cranium. Because of size constraints, the intracranial location is the preferred embodiment.
 The implantable portion of the system includes: (1) electrodes that lie in close proximity to or actually within the brain, (2) a control module that contains a battery and all the electronics for sensing, recording and controlling brain activity, (3) electrically conducting wires that connect the control module to the electrodes, (4) a buzzer providing an acoustic signal or electrical “tickle” indicating that a neurological event has been detected, and (5) an input-output wire coil (or antenna) used for communication of the implanted system with any and all external equipment. The battery that provides power for the system and an electronics module are both contained within a metal shell that lies, in one embodiment, under the patient's scalp. The metal shell, which contains the electronics module and the battery collectively, forms the control module.
 All electrodes connect by way of electrically conducting wires to electrical terminals that are formed into the metal shell. The electronics module is electrically joined to the brain electrodes by way of the shell's electrical terminals, which are electrically joined to the wires that connect to the brain electrodes.
 An important aspect of the preferred embodiment of this device is the fact that the shell containing the electronics module and the battery, i.e. the control module, is to be placed in the cranium of the skull at a place where a significant volume of bone is removed. By placing the entire system within the cranium, (as opposed to having some wires extending into or through the patient's neck to a control module in the chest) the probability of wire breakage due to repeated wire bending is significantly reduced. However, the present invention also envisions the placement in the chest or abdomen of a control module if a large battery or a large volume electronics module dictates such a large size for the control module that it cannot be conveniently placed within the cranium. Such a thoracic or abdominal placement of a control module would typically require wires to be run through the patient's neck.
 The present invention also envisions the utilization of an intracranial system for the treatment of certain diseases without placing wires through the neck. Specifically, an alternative embodiment of the invention envisions the use of electrodes in or on the brain with an intracranial control module used in conjunction with a remote sensor/actuator device implanted elsewhere in the patient's body. For example, blood pressure could be sensed with a threshold of, for example, 150 mm Hg, and if that pressure is exceeded, a signal transmitted by electrical conduction through the body from the remote sensor/actuator device could be received at the control module, which would initiate brain stimulation in such a way as to reduce the blood pressure. Conversely, if the brain perceives pain and generates a corresponding signal detectable by the intracranial control module, a signal could be sent by electrical conduction through the body to the remote sensor/actuator device, which would provide responsive electrical stimulation to locally stimulate a nerve, thereby reducing the perception of that pain. In still another embodiment, if a precursor of an epileptic seizure is detected, the remote sensor/actuator could be used to electrically stimulate one or both vagus nerves so as to stop the epileptic seizure from occurring. Such a remote device could be located in the trunk of the patient's body. In an embodiment of the invention, a remote sensor/actuator may be used to deliver instantaneous, intravenous, intraperitoneal, subdural or intraventricular (of the brain) therapeutic chemicals, including medication, neurotransmitters and ionic substances, alone or in conjunction with electrical stimulation. Such a remote sensor/actuator is disclosed in the above referenced U.S. Pat. No. 6,016,449 by Fischell et al.
 It is also envisioned the ideal stimulation to prevent or abort a neurological event has a low frequency (e.g., 1 to 8 Hz) that would resemble slow wave inhibitory potentials and be significantly less likely to induce epileptiform activity. In one embodiment of the invention, the stimulation waveform is substantially sinusoidal and has minimal higher-order harmonics, and hence little energy above the fundamental frequency. In an alternative embodiment, the low frequency stimulation comprises a sequence of short duration biphasic pulses having a repetition rate of less than about ten pulses per second (10 Hz). Such stimulation could be applied to the caudate nucleus or other structures of the brain, including the hippocampus. As patients suffering from Parkinson's have an extremely low incidence of epilepsy and one manifestation of Parkinson's is characterized by a 5 Hz electrical oscillation that begins in the Thalamus, it is conceived that low frequency stimulation of the Thalamus could, in fact, be inhibitory to epileptiform activity. Such stimulation could be responsive to the detection of a precursor to a clinical seizure or the epileptiform activity from the seizure itself. Alternately, periodic slow wave stimulation applied without detection could prevent the brain from generating seizure activity. Although epilepsy is currently believed to be the most applicable use of such slow wave stimulation, it could also be successful for migraines, pain, tremor, Parkinson's, depression or other neurological disorders.
 It is also envisioned that while the standard treatment would have a constant amplitude for the duration of the low frequency stimulation, it may be advantageous to have the amplitude begin high and decrease over the duration, begin low and increase over the duration, or vary according to any desired treatment plan. The typical duration of low frequency stimulation that would be used to stop a neurological event would be between 100 ms and 10 seconds.
 Another embodiment of the present invention that would be significantly less invasive involves the use of Transcranial Magnetic Stimulation (TMS) from an external coil TMS stimulator. Such a device could be incorporated into a bicycle type helmet and could be used at the time a pre-event aura is sensed by the patient. Alternately, such an external system could be used in a repetitive or continuous mode for patients with serious disorders who often wear protective helmets. A TMS device could be extremely effective if it is pulsed on and off at frequencies below 10 Hz.
 Thus it is an object of this invention to provide appropriate slow wave stimulation of the human brain in response to a detected neurological event in order to cause the cessation of that neurological event. The pattern and frequency of stimulation can be modified to provide optimal control of the unwanted neurological event in each patient.
 Another object of this invention is to use periodic slow wave stimulation of the brain to treat neurological disorders.
 Another object of this invention is to use continuous slow wave stimulation of the brain to treat neurological disorders.
 Still another object of this invention is to have a system of electrodes connected by wires to a control module, the entire system being placed under the scalp or intracranially, and being substantially contained within an opening in the cranium.
 Still another object of this system is to have essentially no flexure of interconnecting wires so as to enhance system reliability.
 These and other objects and advantages of this invention will become apparent to a person of ordinary skill in this art upon careful reading of the detailed description of this invention including the drawings as presented herein.
FIG. 1 is a top view of a human head showing the configuration of an implantable system for the treatment of neurological disorders, as it would be situated in the human skull.
FIG. 2 is a block diagram of the implanted and external portions of the system.
FIG. 3 is a cross section of an embodiment of the present invention showing a magnetic depolarizer system within a helmet on the head of a patient.
FIG. 4A is a longitudinal cross section of the magnetic depolarizer.
FIG. 4B is a top view of the magnetic depolarizer.
FIG. 5 is a simplified circuit diagram of the main components of a magnetic depolarizer system.
FIG. 1 illustrates the configuration of an implantable system 10 for the treatment of neurological disorders as it would be situated under the scalp of a human head 9, the system including a control module 20, electrodes 15A, 15B, 15C, 15N and 16 with wires 17A, 17B, 17C, 17N and 18 connected through a connector 8 to the control module 20. It is envisioned that the control module 20 is permanently implanted into the top of the patient's skull in a location where the skull is fairly thick. It is also envisioned that the control module 20 could be located in the trunk of the patient's body like a heart pacemaker with the connecting wires being run through the patient's neck, under the patient's skin or otherwise. Each of the electrodes 15A, 15B, 15C, 15N and 16 would be placed under the cranium and above the dura mater (i.e., placed epidurally) or placed deep into the brain. The connecting wires 17A, 17B, 17C, 17N and 18 would be run from the control module 20 underneath the scalp and then be connected to the electrodes placed beneath the patient's cranium. Although FIG. 1 shows only four active electrodes 15A, 15B, 15C, 15N with connecting wires 17A, 17B, 17C, 17N, more than four active electrodes with connecting wires may be used with the present invention. The electrode 16 (having the connecting wire 18) could be considered a common or indifferent electrode.
 Throughout the detailed description of the present invention, the terminology “the electrodes 15A through 15N” is meant to include all electrodes 15A, 15B, 15C, . . . to 15N, inclusive, where N may be any integer greater than or equal to 1. Similar terminology using the words “through” or “to” for other groups of objects (i.e., wires 17A through 17N) will have a similar inclusive meaning.
 Throughout FIGS. 1 through 25, inclusive, lines connecting boxes on block diagrams or on software flow charts will each be labeled with an element number. Lines without arrows between boxes or other elements shall indicate a single wire.
 Lines with arrows connecting boxes or other elements are used to represent any of the following:
 1. A physical connection, namely a wire or group of wires (data bus) over which analog or digital signals may be sent.
 2. A data stream sent from one hardware element to another. Data streams include messages, analog or digital signals, commands, EEG information, and software downloads to change system operation and parameters.
 3. A transfer of information between software modules. Such transfers include software subroutine calls with and without the passing of parameters, and the reading and writing of memory locations.
 In each case, the descriptive text herein will indicate each specific use of a line with an arrow.
FIG. 2 is a block diagram of the implantable system 10 and the external equipment 11. The wires 17A through 17N from the electrodes 15A through 15N, and the wire 18 from the common electrode 16, are shown connected to both an event detection sub-system 30 and a stimulation sub-system 40. In one embodiment of the invention, it is also envisioned to use the case of the control module 20 of FIG. 1 as the common (or indifferent) electrode 16. The wires 17A through 17N carry EEG signals 21A through 21N from the electrodes 15A through 15N to the event detection sub-system 30. The electrodes 15A through 15N can be energized by the stimulation sub-system 40 via the wires 17A through 17N to electrically stimulate the patient's brain using the stimulation signals 412A through 412N respectively. Although the electrodes 15A through 15N and 16 shown here are connected to both the event detection sub-system 30 and the stimulation sub-system 40, it should be apparent that a separate set of electrodes and associated wires could be used with each sub-system. Furthermore, it is envisioned that any one or more of the electrodes 15A through 15N could be electrically connected (i.e., shorted) to the electrode 16 or to each other. This would be accomplished by appropriate switching circuitry in the stimulation sub-system 40.
 The event detection sub-system 30 receives the EEG signals 21A through 21N (referenced to a system ground 19 connected to the wire 18 from the common electrode 16) and processes them to identify neurological events such as an epileptic seizure or its precursor. A central processing system 50 with a central processor 51 and memory 55 acts to control and coordinate all functions of the implantable system 10. A first interconnection 52 is used to transmit programming parameters and instructions to the event detection sub-system 30 from the central processing system 50. A second interconnection 53 is used to transmit signals to the central processing system 50 identifying the detection of a neurological event by the event detection sub-system 30. The second interconnection 53 is also used to transmit EEG and other related data for storage in the memory 55.
 When an event is detected by the event detection sub-system 30 (by processing such as that disclosed and described in U.S. Pat. No. 6,016,449 to Fischell, et al., referenced above), the central processor 51 can command the stimulation sub-system 40 via a third interconnection 54 to transmit electrical signals to any one or more of the electrodes 15A through 15N via the wires 17A through 17N. It is anticipated that, if appropriate, electrical signals 412A to 412N, inclusive, are transmitted to certain locations in or near the brain, thereby aborting the normal progression of an epileptic seizure. It may also be necessary for the stimulation sub-system 40 to temporarily disable the event detection sub-system 30 via a fourth interconnection 29 when stimulation is imminent so that the stimulation signals are not inadvertently interpreted as a neurological event by the event detection sub-system 30.
 The stimulation sub-system 40 may also be engaged to perform continuous or periodic stimulation to the brain electrodes 15A through 15N, inclusive. In one embodiment of the invention, electrical stimulation from the stimulation sub-system 40 can include any of a wide range of frequencies from approximately 2 Hz to approximately 200 Hz. Details of a signal generator capable of generating waveforms over such a frequency range are well known in the art of electronics design. In connection with the invention, it is, however, highly desirable to use stimulation at frequencies below 10 Hz. In particular, 5 Hz stimulation has been shown to be inhibitory to ictal spikes in cat brains, and it is believed to be similarly effective in human patients. It is also known to be less likely for low frequency stimulation to induce epileptiform activity.
 In one embodiment of the invention, the low-frequency stimulation applied by an apparatus according to the invention comprises a substantially sinusoidal waveform having little or no energy in higher-frequency harmonics.
 A power supply 90 provides power to each component of the system 10. Power supplies for comparable implantable devices such as heart pacemakers and heart defibrillators are well known in the art of implantable electronic devices. Such a power supply typically utilizes a primary (non-rechargeable) storage battery with an associated d-c to d-c converter to obtain any voltages required for the implantable system 10. However, it should be understood that in an alternative embodiment of the invention, the power supply could use a rechargeable battery that is charged by means of a coil of wire in the control module 20 that receives energy by magnetic induction from an external coil that is placed outside the patient but in close proximity to the control module 20. The implanted coil of wire could also be located remotely from control module 20 but joined to it by electrical wires. Such technology is well known from the rechargeable cardiac pacemaker. Furthermore, the same pair of coils of wire could be used to provide power to the implanted system 10 when it is desired to read out stored telemetry or reprogram some portion of the implanted system 10.
 The central processing system 50 is connected to a data communication sub-system 60, thereby allowing data stored in the memory 55 to be retrieved by the patient's physician via a wireless communication link 72. An external data interface 70 can be directly connected to the physician's workstation 80 via a traditional serial data connection 74 (such as an RS-232 interface). Alternately, the serial connection may be made trans-telephonically, via modems 85 and 750 and a phone line 75 from the patient's home to the physician's workstation 80. Software in the computer section of the physician's workstation 80 allows the physician to read out a history of events detected by the implantable system 10, including EEG information before, during and after each event, as well as specific information relating to the detection of the event, such as the time evolving energy spectrum of the patient's EEG. In a preferred embodiment of the invention, the physician's workstation 80 also allows the physician to specify or alter any programmable parameters of the implantable system 10.
 As shown in FIGS. 1 and 2, a buzzer 95 connected to the central processor 51 via a link 92 can be used to notify the patient that a neurological event has occurred, the implanted system 10 is about to deliver stimulation, or that the implanted system 10 is not functioning properly. In alternative embodiments, the buzzer could provide a mechanical vibration (typically an acoustic signal) or an electrical stimulation “tickle,” either of which could be perceived by the patient. By placing the buzzer 95 near the ear and on the top of, below, or within a burr hole in the cranium, an acoustic signal emitted by the buzzer 95 would be transmitted via bone conduction and detectable by the patient's ear. This sound by itself can be an automatic means for stopping an epileptic seizure.
 A real time clock 91 is used for timing and synchronizing various portions of the implanted system 10 and also to enable the system to provide the exact date and time corresponding to each neurological event that is detected by the implantable system 10 and recorded in the memory 55. A fifth interconnection 96 is used to send data from the central processor 51 to the real time clock 91 in order to set the correct date and time in the clock 91.
 The various interconnections between sub-systems (e.g., the illustrated interconnections 29, 52, 53, 54, 56, 57, 92, 93 and 96) may be either analog or digital, single wire or multiple wires (a “data bus”).
 In an embodiment of the invention, the operation of the system 10 of FIG. 2 for detecting and treating a neurological event such as an epileptic seizure would typically be as follows:
 1. The event detection sub-system 30 continuously processes the EEG signals 21A through 21N carried by the wires 17A through 17N from the N electrodes 15A through 15N.
 2. When an event is detected, the event detection sub-system 30 notifies the central processor 51 via the second interconnection 53 that an event has occurred.
 3. The central processor 51 then triggers the stimulation sub-system 40 via the third interconnection 54 to electrically stimulate the patient's brain with low frequency electrical signals in order to stop the neurological event, using any one, several or all of the electrodes 15A through 15N.
 4. The stimulation sub-system 40 also sends a signal via the fourth interconnection 29 to the event detection sub-system 30 to disable event detection during stimulation to avoid an undesired input into the event detection sub-system 30.
 5. The central processor system 50 will store EEG signals and event related data received from the event detection sub-system 30 via the second interconnection 53 over a time from X minutes before the event to Y minutes after the event for later analysis by the patient's physician. The value of X and Y may be set from as little as approximately 0.1 minutes to as long as approximately 30 minutes.
 6. The central processor 51 may generate a “buzz” to notify the patient that an event has occurred by sending a signal via the link 92 to the buzzer 95.
 An alternative embodiment of the invention is shown in FIG. 3, which illustrates the head of a patient showing a cross section of a non-invasive transcranial magnetic depolarizer system 100 as it would be contained within a helmet 111 of the type used by bicycle riders. The magnetic depolarizer system 100 consists of a magnetic depolarizer coil assembly 112, a battery 114, electronic circuitry 115, a recharging receptacle 116 and interconnecting wires 117. The magnetic depolarizer system 100 is contained within the helmet 111 by means of an elastic support 113 that passes between a front support 111A and a rear support 111B. The purpose of the elastic support 113 is to keep the magnetic depolarizer coil 112 in comparatively tight contact with the patient's head and at a specific location relative to the patient's cerebral cortex.
FIG. 4A is a longitudinal cross section of the magnetic depolarizer 112 of FIG. 3. The magnetic depolarizer coil assembly 112 consists of a first coil 121 placed into a figure-eight configuration with a second coil 122. The two coils 121 and 122 are electrically connected in series in such a way as to create north magnetic poles 121A and 122A in essentially opposite directions when electric current is flowing through the coils 121 and 122. This orientation of coils 121 and 122 can produce a comparatively strong magnetic field onto the cortex of the brain for a distance of a few centimeters beneath the cranium. If the magnetic field changes rapidly in time, it produces an electric current in the brain that can cause excited neurons to be depolarized. Ideally, slow TMS, at 1 to 5 Hz, will transiently depress excitability. In an embodiment of the invention, the intensity of the magnetic field at the surface of the brain should be between 0.1 and 10 Tesla. It is therefore an object of the present invention to use a device such as shown in FIG. 3 pulsed at a slow rate such as 1 or 2 Hz as an external means for treating a neurological disorder; preferably, this frequency is set and evaluated by the patient's physician. Such a device could be worn all the time for chronic epileptics where periodic slow stimulation would act to keep the focal region in a depressed condition, thus preventing a hyper-excited state associated with an epileptic seizure. For patients exhibiting an aura, the helmet could be put on as needed.
 It should also be understood that the patient could use one or more elastic bands (without a helmet) to place the magnetic depolarizer coil assembly 112 at an appropriate location onto his or her head.
FIG. 4B is a top view of the magnetic depolarizer coil assembly 112 showing as dotted lines the outline of the coils 121 and 122. In both FIGS. 3A and 3B, it is shown that the coils 121 and 122 could be encapsulated into a plastic housing 125. Furthermore, FIG. 3A shows a magnetic core 123 in the coil 121 and a separate magnetic core 124 in the coil 122. These cores 123 and 124 are not required for the device to perform its intended purpose of generating a depolarizing electric current within the cerebral cortex, but their presence facilitates the generation of a high-intensity magnetic field in the brain at a lower level of electric current in the coils 121 and 122. To be effective at the high frequency of the magnetic pulses that are used to stimulate the cortex, the cores 123 and 124 would typically be formed from powdered iron or equivalent ferromagnetic material that has low eddy current and hysteresis losses.
 Although FIGS. 4A and 4B show a race-track, figure eight type of design for the magnetic depolarizer coil assembly 112, it should be understood that a simple cylindrical coil (and other shaped coils as well) with or without a ferromagnetic core could be used generate the desired time-varying magnetic field.
FIG. 5 is a simplified electrical diagram of the magnetic depolarizer system 100. The rechargeable battery 114 can be recharged through the receptacle 116 by receiving a plug from a conventional AC adapter (not shown) that connects to a-c line voltage (e.g., 115 volts) and delivers an appropriate d-c voltage to recharge the rechargeable battery 114. When the patient is experiencing an aura of a migraine headache or other symptoms of a neurological disorder, he or she can throw the ON-OFF switch 129 to the ON position. That would cause the d-c to d-c converter 130 to activate and generate a high voltage for rapidly charging the capacitor 126. When the control circuitry 128 senses that the appropriate voltage has been reached, it moves the switch 127 from position A to position B thus discharging the capacitor 126 through the coils 121 and 122 of the magnetic depolarizer 112. As previously described, the coils 121 and 122 could have air cores or they could use magnetically permeable cores 123 and 124. The control circuitry 128 can be used to set the repetition rate for causing magnetic pulses to be delivered. For example, a pulse from the capacitor might last for 70 microseconds and could be repeated at the slow frequency rates between approximately 0.1 and 10 Hz. A frequency of 1 Hz has been shown to be effective in depolarizing brain neurons and may be ideal for some patients. However, other patients might find other repetition rates to be more effective. It is even possible that a single magnetic pulse having a time duration between 10 and 1,000 microseconds could be used to stop an aura, thereby preventing the occurrence of a neurological event.
 In an embodiment of the invention, the TMS administered through a non-invasive magnetic depolarizer system according to the invention comprises a low-frequency signal (between approximately 0.1 Hz and 10 Hz) modulated, via amplitude modulation or frequency modulation, onto a carrier frequency on the order of 100 Hz. It should be recognized that the carrier frequency given here is considered representative of a beneficial and advantageous carrier signal, and that various other carrier frequencies and modulation schemes are possible. Various waveforms are also possible for both the TMS waveform and the carrier waveform, including the substantially sinusoidal wave described above. Circuits capable of generating such stimulus signals are well known to practitioners skilled in the art of electronic circuit design.
 Although FIGS. 3 and 5 show a battery operated magnetic depolarizer system 100, the system 100 could be operated by plugging into a receptacle at (typically) 115 or 230 volts a-c. Such a system might or might not use a battery as part of its circuitry.
 Additional objects and advantages of the present invention will become apparent to those skilled in the art to which this invention relates from the subsequent description of the preferred embodiments and the appended claims, taken in conjunction with the accompanying drawings.
|Patente citada||Fecha de presentación||Fecha de publicación||Solicitante||Título|
|US2151733||4 May 1936||28 Mar 1939||American Box Board Co||Container|
|CH283612A *||Título no disponible|
|FR1392029A *||Título no disponible|
|FR2166276A1 *||Título no disponible|
|GB533718A||Título no disponible|
|Patente citante||Fecha de presentación||Fecha de publicación||Solicitante||Título|
|US6926660||5 Mar 2004||9 Ago 2005||Neuronetics, Inc.||Facilitating treatment via magnetic stimulation|
|US7153256||8 Sep 2003||26 Dic 2006||Neuronetics, Inc.||Reducing discomfort caused by electrical stimulation|
|US7313442||29 Abr 2005||25 Dic 2007||Advanced Neuromodulation Systems, Inc.||Method of treating mood disorders and/or anxiety disorders by brain stimulation|
|US7320664||4 Mar 2004||22 Ene 2008||Neuronetics, Inc.||Reducing discomfort caused by electrical stimulation|
|US7346395||18 Jun 2004||18 Mar 2008||Advanced Neuromodulation Systems, Inc.||Method of treating depression, mood disorders and anxiety disorders using neuromodulation|
|US7396326||17 May 2005||8 Jul 2008||Neuronetics, Inc.||Ferrofluidic cooling and acoustical noise reduction in magnetic stimulators|
|US7520848||9 Abr 2004||21 Abr 2009||The Board Of Trustees Of The Leland Stanford Junior University||Robotic apparatus for targeting and producing deep, focused transcranial magnetic stimulation|
|US7560058||4 Ene 2006||14 Jul 2009||Neuronetics, Inc.||Magnetic core for medical procedures|
|US7601115||24 May 2004||13 Oct 2009||Neuronetics, Inc.||Seizure therapy method and apparatus|
|US7614996||5 Dic 2003||10 Nov 2009||Neuronetics, Inc.||Reducing discomfort caused by electrical stimulation|
|US7651459||6 Ene 2004||26 Ene 2010||Neuronetics, Inc.||Method and apparatus for coil positioning for TMS studies|
|US7653433||1 Sep 2006||26 Ene 2010||Advanced Neuromodulation Systems, Inc.||Method of treating depression, mood disorders and anxiety disorders using neuromodulation|
|US7676263||9 Mar 2010||Neurovista Corporation||Minimally invasive system for selecting patient-specific therapy parameters|
|US7684866||2 Ago 2004||23 Mar 2010||Advanced Neuromodulation Systems, Inc.||Apparatus and methods for applying neural stimulation to a patient|
|US7729773||18 Oct 2006||1 Jun 2010||Advanced Neuromodualation Systems, Inc.||Neural stimulation and optical monitoring systems and methods|
|US7747325||28 Sep 2005||29 Jun 2010||Neurovista Corporation||Systems and methods for monitoring a patient's neurological disease state|
|US7756584||27 Sep 2002||13 Jul 2010||Advanced Neuromodulation Systems, Inc.||Methods and apparatus for effectuating a lasting change in a neural-function of a patient|
|US7824324||27 Jul 2005||2 Nov 2010||Neuronetics, Inc.||Magnetic core for medical procedures|
|US7831305||15 Oct 2002||9 Nov 2010||Advanced Neuromodulation Systems, Inc.||Neural stimulation system and method responsive to collateral neural activity|
|US7853329||29 Dic 2006||14 Dic 2010||Neurovista Corporation||Monitoring efficacy of neural modulation therapy|
|US7857746||29 Oct 2004||28 Dic 2010||Nueronetics, Inc.||System and method to reduce discomfort using nerve stimulation|
|US7930035||2 May 2007||19 Abr 2011||Neurovista Corporation||Providing output indicative of subject's disease state|
|US7963903||26 Ago 2005||21 Jun 2011||Neuronetics, Inc.||Magnetic core for medical procedures|
|US7974696||23 Jul 2005||5 Jul 2011||Dilorenzo Biomedical, Llc||Closed-loop autonomic neuromodulation for optimal control of neurological and metabolic disease|
|US7976451||16 Jun 2005||12 Jul 2011||The United States Of America As Represented By The Department Of Health And Human Services||Transcranial magnetic stimulation system and methods|
|US8036736||21 Mar 2008||11 Oct 2011||Neuro Vista Corporation||Implantable systems and methods for identifying a contra-ictal condition in a subject|
|US8052591||5 May 2006||8 Nov 2011||The Board Of Trustees Of The Leland Stanford Junior University||Trajectory-based deep-brain stereotactic transcranial magnetic stimulation|
|US8073546||12 Jul 2010||6 Dic 2011||Advanced Neuromodulation Systems, Inc.||Methods and apparatus for effectuating a lasting change in a neural-function of a patient|
|US8088058||20 Ene 2005||3 Ene 2012||Neuronetics, Inc.||Articulating arm|
|US8118722||25 Oct 2005||21 Feb 2012||Neuronetics, Inc.||Reducing discomfort caused by electrical stimulation|
|US8177702||15 Abr 2004||15 May 2012||Neuronetics, Inc.||Method and apparatus for determining the proximity of a TMS coil to a subject's head|
|US8190264||12 Ene 2010||29 May 2012||Advanced Neuromodulation Systems, Inc.||Method of treating depression, mood disorders and anxiety disorders using neuromodulation|
|US8195300||5 May 2011||5 Jun 2012||Advanced Neuromodulation Systems, Inc.||Systems and methods for automatically optimizing stimulus parameters and electrode configurations for neuro-stimulators|
|US8246529||29 Sep 2010||21 Ago 2012||Neuronetics, Inc.||Magnetic core for medical procedures|
|US8262714||27 Feb 2009||11 Sep 2012||Advanced Neuromodulation Systems, Inc.||Techniques for selecting signal delivery sites and other parameters for treating depression and other neurological disorders, and associated systems and methods|
|US8265910||9 Oct 2008||11 Sep 2012||Cervel Neurotech, Inc.||Display of modeled magnetic fields|
|US8267850||26 Nov 2008||18 Sep 2012||Cervel Neurotech, Inc.||Transcranial magnet stimulation of deep brain targets|
|US8295934||14 Nov 2006||23 Oct 2012||Neurovista Corporation||Systems and methods of reducing artifact in neurological stimulation systems|
|US8315703||30 Abr 2009||20 Nov 2012||Advanced Neuromodulation Systems, Inc.||Methods for targeting deep brain sites to treat mood and/or anxiety disorders|
|US8326431||28 Abr 2006||4 Dic 2012||Medtronic, Inc.||Implantable medical device for the concurrent treatment of a plurality of neurological disorders and method therefore|
|US8343027||30 Ene 2012||1 Ene 2013||Ivivi Health Sciences, Llc||Methods and devices for providing electromagnetic treatment in the presence of a metal-containing implant|
|US8412335||4 Jun 2012||2 Abr 2013||Advanced Neuromodulation Systems, Inc.||Systems and methods for automatically optimizing stimulus parameters and electrode configurations for neuro-stimulators|
|US8415123||15 Mar 2010||9 Abr 2013||Ivivi Health Sciences, Llc||Electromagnetic treatment apparatus and method for angiogenesis modulation of living tissues and cells|
|US8430805||20 May 2009||30 Abr 2013||Emkinetics, Inc.||Method and apparatus for magnetic induction therapy|
|US8435166||20 May 2009||7 May 2013||Emkinetics, Inc.||Method and apparatus for magnetic induction therapy|
|US8467878||23 May 2012||18 Jun 2013||Advanced Neuromodulation Systems, Inc.||Method of treating depression, mood disorders and anxiety disorders using neuromodulation|
|US8506468||27 May 2008||13 Ago 2013||Neuronetics, Inc.||Ferrofluidic cooling and acoustical noise reduction in magnetic stimulators|
|US8517908||12 Ene 2012||27 Ago 2013||Neuronetics, Inc.||Reducing discomfort caused by electrical stimulation|
|US8523753||15 Ago 2012||3 Sep 2013||Cervel Neurotech, Inc.||Transcranial magnet stimulation of deep brain targets|
|US8538537||8 Dic 2008||17 Sep 2013||Advanced Neuromodulations Systems, Inc.||Systems and methods for providing targeted neural stimulation therapy to address neurological disorders, including neuropyschiatric and neuropyschological disorders|
|US8538547||28 Oct 2008||17 Sep 2013||Forschungszentrum Juelich Gmbh||Apparatus for the stimulation of neural networks|
|US8543199||2 Sep 2011||24 Sep 2013||Cyberonics, Inc.||Implantable systems and methods for identifying a contra-ictal condition in a subject|
|US8588884||28 May 2010||19 Nov 2013||Emkinetics, Inc.||Microneedle electrode|
|US8588933||11 Ene 2010||19 Nov 2013||Cyberonics, Inc.||Medical lead termination sleeve for implantable medical devices|
|US8608634||21 Mar 2008||17 Dic 2013||The United States Of America, As Represented By The Secretary, Department Of Health And Human Services||Coil for magnetic stimulation and methods for using the same|
|US8657731||5 Jun 2009||25 Feb 2014||Neuronetics, Inc.||Magnetic core for medical procedures|
|US8690748 *||2 Ago 2010||8 Abr 2014||Chi Yung Fu||Apparatus for measurement and treatment of a patient|
|US8723628||7 Ene 2010||13 May 2014||Cervel Neurotech, Inc.||Shaped coils for transcranial magnetic stimulation|
|US8725243||28 Dic 2005||13 May 2014||Cyberonics, Inc.||Methods and systems for recommending an appropriate pharmacological treatment to a patient for managing epilepsy and other neurological disorders|
|US8762065||22 Jun 2005||24 Jun 2014||Cyberonics, Inc.||Closed-loop feedback-driven neuromodulation|
|US8781597||5 May 2010||15 Jul 2014||Cyberonics, Inc.||Systems for monitoring a patient's neurological disease state|
|US8786624||2 Jun 2010||22 Jul 2014||Cyberonics, Inc.||Processing for multi-channel signals|
|US8788044||20 Ene 2006||22 Jul 2014||Michael Sasha John||Systems and methods for tissue stimulation in medical treatment|
|US8795148||26 Oct 2010||5 Ago 2014||Cervel Neurotech, Inc.||Sub-motor-threshold stimulation of deep brain targets using transcranial magnetic stimulation|
|US8845508||11 Mar 2009||30 Sep 2014||The Board Of Trustees Of The Leland Stanford Junior University||Robotic apparatus for targeting and producing deep, focused transcranial magnetic stimulation|
|US8849390||29 Dic 2009||30 Sep 2014||Cyberonics, Inc.||Processing for multi-channel signals|
|US8855775||23 Oct 2012||7 Oct 2014||Cyberonics, Inc.||Systems and methods of reducing artifact in neurological stimulation systems|
|US8864641||10 Jul 2013||21 Oct 2014||Neuronetics, Inc.||Reducing discomfort caused by electrical stimulation|
|US8868172||28 Dic 2005||21 Oct 2014||Cyberonics, Inc.||Methods and systems for recommending an appropriate action to a patient for managing epilepsy and other neurological disorders|
|US8956273||20 Ago 2008||17 Feb 2015||Cervel Neurotech, Inc.||Firing patterns for deep brain transcranial magnetic stimulation|
|US8956274||16 Jul 2010||17 Feb 2015||Cervel Neurotech, Inc.||Transcranial magnetic stimulation field shaping|
|US8961385||5 Abr 2011||24 Feb 2015||Ivivi Health Sciences, Llc||Devices and method for treatment of degenerative joint diseases with electromagnetic fields|
|US9002477||20 Nov 2013||7 Abr 2015||Emkinetics, Inc.||Methods and devices for performing electrical stimulation to treat various conditions|
|US9005102||26 Abr 2012||14 Abr 2015||Emkinetics, Inc.||Method and apparatus for electrical stimulation therapy|
|US9037224||2 Ago 2010||19 May 2015||Chi Yung Fu||Apparatus for treating a patient|
|US9042988||17 Nov 2005||26 May 2015||Cyberonics, Inc.||Closed-loop vagus nerve stimulation|
|US9044188||12 May 2014||2 Jun 2015||Cyberonics, Inc.||Methods and systems for managing epilepsy and other neurological disorders|
|US9095266||2 Ago 2010||4 Ago 2015||Chi Yung Fu||Method for treating a patient|
|US9113801||29 Dic 2006||25 Ago 2015||Cyberonics, Inc.||Methods and systems for continuous EEG monitoring|
|US9132277||7 Abr 2014||15 Sep 2015||Cerval Neurotech, Inc.||Shaped coils for transcranial magnetic stimulation|
|US20030074032 *||15 Oct 2002||17 Abr 2003||Gliner Bradford Evan||Neural stimulation system and method responsive to collateral neural activity|
|US20030088274 *||30 Sep 2002||8 May 2003||Vertis Neuroscience, Inc.||Method and apparatus for electrically stimulating cells implanted in the nervous system|
|US20040199041 *||8 Sep 2003||7 Oct 2004||Riehl Mark Edward||Reducing discomfort caused by electrical stimulation|
|US20040199042 *||5 Dic 2003||7 Oct 2004||Riehl Mark Edward||Reducing discomfort caused by electrical stimulation|
|US20040204625 *||4 Mar 2004||14 Oct 2004||Riehl Mark Edward||Reducing discomfort caused by electrical stimulation|
|US20050021103 *||20 Nov 2003||27 Ene 2005||Dilorenzo Daniel John||Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease|
|US20050021104 *||5 Abr 2004||27 Ene 2005||Dilorenzo Daniel John||Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease|
|US20050075679 *||7 May 2004||7 Abr 2005||Gliner Bradford E.||Methods and apparatuses for treating neurological disorders by electrically stimulating cells implanted in the nervous system|
|US20050148808 *||6 Ene 2004||7 Jul 2005||Allan Cameron||Method and apparatus for coil positioning for TMS studies|
|US20050154426 *||7 Mar 2005||14 Jul 2005||Boveja Birinder R.||Method and system for providing therapy for neuropsychiatric and neurological disorders utilizing transcranical magnetic stimulation and pulsed electrical vagus nerve(s) stimulation|
|US20050222626 *||25 May 2005||6 Oct 2005||Dilorenzo Daniel J||Cloosed-loop feedback-driven neuromodulation|
|US20050234286 *||15 Abr 2004||20 Oct 2005||Riehl Mark E||Method and apparatus for determining the proximity of a TMS coil to a subject's head|
|US20050240242 *||12 Jul 2004||27 Oct 2005||Dilorenzo Daniel J||Closed-loop feedback-driven neuromodulation|
|US20050261542 *||24 May 2004||24 Nov 2005||Riehl Mark E||Seizure therapy method and apparatus|
|US20060064138 *||29 Abr 2005||23 Mar 2006||Francisco Velasco||Method of treating mood disorders and/or anxiety disorders by brain stimulation|
|US20060094924 *||29 Oct 2004||4 May 2006||Riehl Mark E||System and method to reduce discomfort using nerve stimulation|
|US20060122454 *||25 Oct 2005||8 Jun 2006||Neuronetics, Inc.||Reducing discomfort caused by electrical stimulation|
|US20060161039 *||20 Ene 2005||20 Jul 2006||Neuronetics, Inc.||Articulating arm|
|US20060199159 *||1 Mar 2005||7 Sep 2006||Neuronetics, Inc.||Head phantom for simulating the patient response to magnetic stimulation|
|US20060212090 *||1 Mar 2006||21 Sep 2006||Functional Neuroscience Inc.||Method of treating cognitive disorders using neuromodulation|
|US20060212091 *||1 Mar 2006||21 Sep 2006||Functional Neuroscience Inc.||Method of treating depression, mood disorders and anxiety disorders using neuromodulation|
|US20060217780 *||11 Oct 2005||28 Sep 2006||Gliner Bradford E||Methods for treating essential tremor|
|US20060264692 *||17 May 2005||23 Nov 2006||Neuronetics, Inc.||Ferrofluidic cooling and acoustical noise reduction in magnetic stimulators|
|US20060287566 *||16 Jun 2005||21 Dic 2006||Abraham Zangen||Transcranial magnetic stimulation system and methods|
|US20060293720 *||22 Jun 2005||28 Dic 2006||Dilorenzo Daniel J||Closed-loop feedback-driven neuromodulation|
|US20070005115 *||1 Sep 2006||4 Ene 2007||Lozano Andres M||Method of treating depression, mood disorders and anxiety disorders using neuromodulation|
|US20070027353 *||26 Ago 2005||1 Feb 2007||Neuronetics, Inc.||Magnetic core for medical procedures|
|US20070027354 *||4 Ene 2006||1 Feb 2007||Neuronetics, Inc.||Magnetic core for medical procedures|
|US20070027355 *||27 Jul 2005||1 Feb 2007||Neuronetics, Inc.||Magnetic core for medical procedures|
|US20070032834 *||20 Abr 2006||8 Feb 2007||Northstar Neuroscience, Inc.||Systems and methods for automatically optimizing stimulus parameters and electrode configurations for neuro-stimulators|
|US20070073355 *||15 Nov 2006||29 Mar 2007||Bioneuronics Corporation||Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease|
|US20070088403 *||19 Oct 2005||19 Abr 2007||Allen Wyler||Methods and systems for establishing parameters for neural stimulation|
|US20100113959 *||7 Mar 2007||6 May 2010||Beth Israel Deaconess Medical Center, Inc.||Transcranial magnetic stimulation (tms) methods and apparatus|
|US20100210894 *||1 Dic 2007||19 Ago 2010||Beth Israel Deaconess Medical Center, Inc.||Transcranial magnetic stimulation (TMS) methods and apparatus|
|US20100256436 *||30 Jul 2008||7 Oct 2010||Partsch Michael J||Device and method for treating hypertension via non-invasive neuromodulation|
|US20110301402 *||18 Feb 2009||8 Dic 2011||Meizhou Cornley Hi-Tech Co., Ltd.||Ultra-low frequency magnetic stimulating device and operational method thereof|
|US20130338424 *||18 Ene 2013||19 Dic 2013||Children's Medical Center Corporation||Transcranial magnetic stimulation (tms) methods and apparatus|
|US20140316188 *||30 Jun 2014||23 Oct 2014||The Trustees Of Columbia University In The City Of New York||Methods, apparatus, and systems for magnetic stimulation|
|US20150123608 *||9 Ene 2015||7 May 2015||Alfred E. Mann Foundation For Scientific Research||Microprocessor controlled class e driver|
|EP1703940A1 *||28 Dic 2004||27 Sep 2006||Jacob Zabara||Systems and methods for therapeutically treating neuro-psychiatric disorders and other illnesses|
|EP1708787A2 *||6 Ene 2005||11 Oct 2006||Neuronetics, Inc.||Method and apparatus for coil positioning for tms studies|
|EP2240239A2 *||30 Ene 2009||20 Oct 2010||Great Lakes Biosciences, LLC||Brain-related chronic pain disorder treatment method and apparatus|
|EP2240239A4 *||30 Ene 2009||27 Nov 2013||Great Lakes Biosciences Llc||Brain-related chronic pain disorder treatment method and apparatus|
|EP2544764A2 *||11 Mar 2011||16 Ene 2013||Ronald J. Weinstock||Emf probe configurations for electro-modulation of ionic channels of cells and methods of use thereof|
|EP2547397A2 *||18 Mar 2011||23 Ene 2013||Ronald J. Weinstock||System for diagnosing and treatment of diabetic symptoms|
|WO2005105013A2 *||26 Abr 2005||10 Nov 2005||A Dimino Andre||Electromagnetic treatment induction apparatus and method|
|WO2007007058A1 *||7 Jul 2006||18 Ene 2007||Isis Innovation||Method and apparatus for regulating blood pressure|
|WO2007103475A2 *||7 Mar 2007||13 Sep 2007||Beth Israel Hospital||Transcranial magnetic stimulation (tms) methods and apparatus|
|WO2008070001A2 *||1 Dic 2007||12 Jun 2008||Beth Israel Hospital||Transcranial magnetic stimulation (tms) methods and apparatus|
|WO2008145436A1 *||31 Mar 2008||4 Dic 2008||Okm Ortungstechni Krauss & Mue||Arrangement for supporting, stimulating, and influencing brain activities|
|WO2009026386A1 *||20 Ago 2008||26 Feb 2009||Neostim Inc||Firing patterns for deep brain transcranial magnetic stimulation|
|WO2009056106A1||28 Oct 2008||7 May 2009||Forschungszentrum Juelich Gmbh||Apparatus for the stimulation of neural networks|
|WO2009143503A2 *||26 May 2009||26 Nov 2009||Neostim, Inc.||Transcranial magnetic stimulation by enhanced magnetic field perturbations|
|WO2011098638A1 *||9 Feb 2011||18 Ago 2011||Pneuma Research, S.L.||Portable digital transducer device that is programmable, has high discrimination at low frequency and low intensity|
|WO2013067512A1 *||5 Nov 2012||10 May 2013||Ivivi Health Sciences, Llc||Method and apparatus for electromagnetic treatment of cognition and neurological injury|
|Clasificación de EE.UU.||600/13, 600/15|
|Clasificación internacional||A61N2/00, A61N1/36, A61N2/02, A61N1/32, A61N2/04|
|Clasificación cooperativa||A61N1/36021, A61N2/02, A61N1/36082, A61N1/32, A61N1/36025, A61N2/006, A61N1/36071, A61N2/008|
|Clasificación europea||A61N1/36Z3C, A61N1/36E4, A61N1/36Z, A61N2/00T2, A61N2/02, A61N1/32|
|25 May 2006||AS||Assignment|
Owner name: NEUROPACE, INC., CALIFORNIA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:FISCHELL, DAVID R.;UPTON, ADRIAN R.M.;REEL/FRAME:017678/0105;SIGNING DATES FROM 20000825 TO 20000830