WO1999056822A1 - Cardiac activity algorithm activation of a neurostimulator - Google Patents
Cardiac activity algorithm activation of a neurostimulator Download PDFInfo
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- WO1999056822A1 WO1999056822A1 PCT/US1999/009372 US9909372W WO9956822A1 WO 1999056822 A1 WO1999056822 A1 WO 1999056822A1 US 9909372 W US9909372 W US 9909372W WO 9956822 A1 WO9956822 A1 WO 9956822A1
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- Prior art keywords
- patient
- change
- seizure
- cardiac activity
- electrical
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/36128—Control systems
- A61N1/36135—Control systems using physiological parameters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
- A61N1/36064—Epilepsy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/36053—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for vagal stimulation
Definitions
- the present invention relates generally to implantable battery-operated medical devices employed as neurostimulators for treating or controlling medical, psychiatric or neurological disorders by application of modulating electrical signals to a selected nerve or nerves of the patient, and more particularly, to improved methods and devices for activating a neurostimulator to treat an epileptic attack in response to the sensing of a natural activity of the body indicative of onset of such an attack.
- Extra-physiologic electrical stimulation of the vagus nerve for treatment of epilepsy and various forms of involuntary movement disorders is disclosed in U.S. Patent 4,702,254 to J. Zabara (referred to herein as "the '254 patent"), exclusively licensed to the assignee of the present application.
- a device constituting an implantable NeuroCybernetic Prosthesis (NCPTM, a trademark of Cyberonics, Inc. of Houston, Texas) generator activates or controls certain nerves of the patient — for example, by use of neurocybernetic spectral discrimination in which the external current of the NCP generator is tuned to the electrochemical properties of a specific group of inhibitory nerves that affect the reticular system of the brain.
- These nerves may be embedded within a bundle of other nerves, and are selectively activated directly or indirectly by such tuning of the NCP generator to augment states of brain neural discharge, by which to control convulsions or seizures.
- the spectral discrimination analysis dictates that certain electrical parameters of the NCP generator are to be selected based on the electrochemical properties of the nerves desired to be activated.
- An improved implantable neurostimulator device is disclosed in U. S . Patent - 5,154,172 to R.S. Terry, Jr. et al. (referred to herein as "the '172 patent"), assigned to the assignee of the present application. The disclosure of the ' 172 patent is incorporated in its entirety by reference herein. In FIG.
- the stimulus generator 25 portion of device 10 which is generally of thin circular, oval, or rectangular shape and suitably sized for implantation, is typically implanted within a surgically- formed pocket just below the skin in the left pectoral region of a patient 12.
- the back side of stimulus generator 25 (or the front side, depending on the implanting physician's preference as to the direction in which an electrically conductive insulatively sheathed lead 16 of the neurostimulator device 10 will extend for implantation of electrode array 15 of the lead on the vagus nerve or other selected cranial nerve of the patient) resides against the pectoral muscle in this example.
- the generator housing 14 (typically referred to in the art as a “can” or “case”) is composed of biocompatible material (i.e., biologically compatible with the fluids and tissue of the patient's body), typically a metal such as titanium or medical grade stainless steel, and is hermetically sealed to prevent fluid penetration into the electronic components and battery(ies) (sometimes referred to herein as the "electronics package”) contained therein.
- biocompatible material i.e., biologically compatible with the fluids and tissue of the patient's body
- a metal such as titanium or medical grade stainless steel
- a male connector at the proximal end of lead or lead assembly 16 is inserted into a female connector in a header 51 on case 14, to electrically connect the nerve stimulating electrode array 15 at the distal end of lead 16 to the proper node(s) of the- electrical circuitry of the electronics package in the stimulus generator.
- the electrode array is preferably a bipolar stimulating electrode assembly, for example, of the type described in U.S. Patent 4,573,481 to Bullara.
- the electrical output pulse waveform of stimulus generator 25 is applied through the lead-electrode system to a selected cranial nerve or nerve bundle of the patient on which the electrode array has been implanted, such as in the cervical location of the vagus nerve shown in FIG. 1.
- the implanted neurostimulator device communicates by telemetry with a programmer and/or monitor (sometimes referred to herein as the "program console") external to the patient's body, by asynchronous serial communication, to selectively control and detect operating states of the device.
- a programmer and/or monitor sometimes referred to herein as the "program console"
- Conventional external components employed for such purposes may include, for example, a programming wand 18 which transmits parameter changes to device 10 and receives device parameter and signal information to be monitored, in conjunction with computer 20 of the program console.
- Conventional software installed in the computer facilitates physician-controlled adjustment of selected parameters and of communication with the implanted device.
- the stimulus generator 25 of implantable device 10 includes battery(ies) 32, such as a lithium carbon monofluoride cell, electrically connected to the input of a voltage regulator 33, which powers the device.
- the regulated output voltage is supplied to a logic and control section 35 and other electronic sections, including a microprocessor 36 that implements and controls the programmable functions of the device.
- Programmable functions may include the magnitude of current or voltage, the frequency, the pulse width, and the on-time and off-time of output pulses generated by the stimulus generator for application to the lead assembly and thence to the distal electrode array and the nerve on - which it is implanted.
- the programmability of the device enables the attending physician to selectively tailor its output pulse waveform to modulate the electrical activity of the vagus nerve to provide a prescribed therapy regimen for the disorder being treated — epilepsy, in this case.
- Timing of the logic and control and other functions of the stimulus generator is controlled by a precise output frequency signal of a crystal oscillator 37.
- a magnetically-actuatable reed switch 39 enables the patient to manually activate the generator for initiating the delivery of its output pulses to the nerve by means of an external magnet (not shown).
- Built-in antenna 40 is provided for use in bidirectional telemetry communication between the implanted stimulus generator and the external electronics of the program console, for supplying the programming signals necessary to set or change the output pulse parameters, and to detect device operation, via wand 18 (FIG. 1). Once the generator is programmed, it operates continuously at the programmed settings until they are re-programmed (by the attending physician) by means of the external program console.
- Logic/control section 35 controls output circuit 42 for producing the output pulse waveform according to the prescribed therapy.
- the stimulus generator When the stimulus generator is activated, which may be continuously or periodically to provide prophylactic/preventive treatment of the disorder, or which may be controlled by the patient's manual activation or by automatic activation upon sensing physiologic changes indicative of onset of the disorder, the programmed output waveform is delivered via the electrical connector in the header of the generator case to lead assembly 16 and stimulating electrode array 15 (FIG. 1). This electrical stimulation produces a predetermined modulation of the electrical activity of the nerve on which the electrodes are implanted to treat, control, and alleviate the disorder.
- the _ electrical activity of a cranial nerve such as the vagus nerve is modulated by initiation of the stimulus waveform in response to a set of detection criteria having been met, for the purpose of inhibiting or interrupting a seizure, or of lessening the frequency or severity of seizures.
- means for manually activating or deactivating the stimulus generator include a sensor such as an accelerometer or a piezoelectric element mounted to the inner surface of the generator case and adapted to detect light taps by the patient on the implant site. In this way, the patient is given limited but convenient control over the device operation, to an extent which will be determined by the attending physician.
- the '206 patent also discloses an automatic activation technique for the implanted device, in which random jerky movements of the patient that occur with some types of seizures, and which are not consistent with normal activity, are detected by a vibration sensor, accelerometer, or other means having programmable sensitivity.
- the sensor may thus be fine-tuned to the seizure characteristics of a particular patient without likelihood of being triggered by normal activity of the patient.
- the present invention is directed toward further improvements in automatic _ activation of an implanted neurostimulator device, particularly for treating epilepsy.
- a principal objective of the invention is to provide apparatus and methods for activation of an implanted stimulus generator for treating epileptic seizures by sensing changes in certain physiological parameters which can be a reliable precursor of an oncoming attack.
- the present invention is based upon the premise, borne out by empirical evidence, that the heart rate of an epileptic subject undergoes a sudden, rapid rate of change to an elevated rate immediately before or at the onset of a seizure. More broadly, according to the invention, the patient's cardiac activity is monitored, preferably by an implanted device, for characteristics of a sudden time rate of change of heart rate not physiologically consistent or compatible with physical exercise — most generally, a positive increase in time rate of change (i.e., slope, or first derivative) of heart rate, although a decrease (negative slope) in rate of change having those characteristics is also possible — and, to a lesser extent, a change in heart rate itself which is substantial and sustained.
- the device is arranged and adapted to respond with neurostimulation, and more specifically, to initiate stimulation of the patient's vagus nerve to modulate the electrical activity thereof according to a programmed impulse waveform for treating the expected impending seizure.
- a substantial, sustained change typically, an increase
- the device has or is electrically connected to one or more sensing electrodes for measuring the electrical waveform associated with cardiac activity of the heart.
- the metal case of the stimulus generator can be used as one sensing electrode of a bipolar configuration.
- the sensing is between the metal case and an active electrode of the array mounted on the vagus nerve, which serves to detect a large cardiac signal.
- EKG EKG
- these electrodes are located at predetermined spaced-apart points along the exterior of the device case, and not on a separate lead or leads external to the case.
- the only lead required to be implanted in the patient is the lead associated with the electrode array to be. implanted on the vagus (or other cranial) nerve for stimulation thereof.
- a signal obtained from the intrinsic cardiac activity (the "sense signal") is processed by the implanted device to develop and store a running average of heart rate, both short term and longer term, each with a programmable time constant. Because heart rate is typically lower when the patient is in a sleep state, these running averages may be used as a first order detector of patient sleep, to initiate delivery of nerve stimulation as a prophylactic measure.
- the short term running average is continuously compared within the device electronics to the long term running average, which aids in detecting an occurrence of sudden significant rate of change of heart rate (typically, as noted above, a positive slope) exceeding a programmed threshold level (e.g., a predetermined grade) that is taken to indicate onset of epileptic seizure.
- a programmed threshold level e.g., a predetermined grade
- the programmed threshold may, for example, be set at a slope or grade representative of, say, an increase in absolute heart rate from 80 beats per minute (bpm) to 100 bpm in a period of a few (e.g., ten) seconds.
- a microprocessor initiates activation of a stimulus generator in the device to apply the pre-programmed electrical waveform stimulus therapy to the electrode array implanted on the patient's vagus nerve, to appropriately modulate the nerve's electrical activity to inhibit, abort, or alleviate the seizure.
- an alternative embodiment of the implanted device is programmed to trigger neurostimulation upon detection of a sudden significant negative slope in the time rate of change of heart rate exceeding (i.e., in a negative direction) the programmed threshold level, or grade, deemed to indicate onset of epileptic seizure.
- the stimulus generator is activated to apply the preprogrammed electrical waveform stimulus to the nerve electrode array, with the above- described effect.
- the device may be programmed to stimulate and appropriately modulate electrical activity of the vagus nerve whenever the patient's heart rate exceeds or falls below the applicable programmed positive or negative slope threshold.
- the device may additionally be programmed to apply a periodic prophylactic stimulation of the nerve or nerve bundle to modulate its electrical activity in an appropriate manner for inhibiting seizures while the patient is sleeping, the sleep state being recognizable as a sustained period during which the sense signal is indicative of a _ heart rate lower by a predetermined margin than the average long term heart rate.
- a cranial nerve preferably the vagus nerve
- the epileptic patient in a predetermined manner in response to detection of a sudden time rate of change of the patient's heart rate, to inhibit, abort or alleviate a seizure.
- Detection of such rate of change of heart rate coupled with detection of a substantial and sustained increase in absolute heart rate, offers relative ease of detection, reliability as an indicator, and simplicity of the sensor and implant procedure.
- the sensed cardiac activity signal is subjected to spectral analysis, with particular attention devoted to the higher frequency band. If the high frequency peak of the cardiac activity exhibits an increase of predetermined magnitude and duration, this is deemed to be indicative of an oncoming seizure, and the stimulus generator is activated to apply its electrical output stimulus to the lead/electrode array and, thence, to the vagus nerve so as to suppress the seizure or to minimize its effect. On the other hand, if the high frequency peak displays a change, but in the form of a decrease in magnitude, the change is assumed to be induced by a commencement of physical activity or exercise by the patient. In the latter case, no vagal stimulation is initiated.
- FIG. 1 is a simplified illustration of a neurostimulator device for stimulus generation with associated lead-electrode system implanted in a patient's body, together with related external program console as described in the background section above;
- FIG. 2 is a simplified block diagram of an implantable stimulus generator of the type used in the device of FIG. 1, described in the background section above, to the extent of a prior art portion, and utilizing a sensing circuit according to the present invention;
- FIG. 3 is a side view of the front of the stimulus generator case showing the location of one set of sensing electrodes on the exterior of the generator according to the present invention
- FIG. 3 A is a fragmentary view of the back side of the case
- FIG. 4 is a simplified block diagram of a sensing circuit used in the stimulus generator of FIGS. 2 and 3;
- FIG. 5 is a flow diagram of the operation of a timing and state circuit used in the stimulus generator of FIG. 2 to assist the sensing circuit in distinguishing seizure- induced changes in cardiac activity, which may be detected in the patient's EKG, from the
- FIG.6 is a simplified block diagram of an alternative embodiment in which _ the detected cardiac activity is subjected to spectral analysis to differentiate between exercise-induced and seizure-induced changes in a patient's cardiac activity.
- a neurostimulator device 10 of the preferred embodiment of the invention includes a sensing circuit 45 for measuring the electrical signals 47 indicative of the patient's cardiac activity (e.g., as the EKG, or ECG). Details of the sensing circuit will be discussed in greater detail in the description of FIG. 4, below. For the present, however, it is sufficient to note that the circuit responds to an input exceeding a preset threshold slope
- the logic level output signal 48 is applied to a timing and state circuit 65 which is also arranged to receive a signal representing heart rate sequence similar to that applied to the sensing circuit, and to supply an output to logic and control section 35 from which the output circuit 42 is controlled. Operation of circuit 65 will be described in greater detail presently, with reference to FIG. 5.
- FIG. 3 A view of the front side of an implantable stimulus generator 25 of a neurostimulator device 10 implemented to treat epileptic seizures according to the invention is illustrated in FIG. 3.
- the generator 25 is equipped with one or more sensing electrodes for measuring the electrical impulses constituting the cardiac activity of the heart.
- the metal case (generator housing) 14 is used as one sensing electrode in either of two sensing implementations. In a preferred one of two alternatives, sensing is performed between metal case 14 and one of the two active
- the back side 21 of case 14 of generator 25, shown in FIG. 3A is preferably coated with a layer of biocompatible, electrically insulating material 22 of any conventional type for such purpose and use, to minimize muscle stimulation.
- the generator would be implanted with the insulated back side 21 facing "down", i.e., inwardly, toward the patient's ribs.
- a pair of additional sensing electrodes 49, 50 are exposed at the exterior surface of the case, one located in the header 51 and the other on the main body of the case but insulated therefrom, preferably along the edge of the case, so that the electrodes are positioned for greater sensitivity to the electrical activity of the heart regardless of whether the generator is implanted with the front (logo) side "up” (facing outwardly of the patient's body), or down.
- the exterior electrodes 49, 50 are preferably displaced by about 90 degrees (orthogonally) from each other about the periphery of the case along its edge, as shown in FIG. 3, to assure good sensitivity regardless of the orientation or alignment of the case relative to the field produced by the cardiac electrical activity. The purpose of these procedures is to enhance the detection of the cardiac signal by positioning the electrodes to be at points of its greatest magnitude.
- Electrode 49 is electrically insulated from the case by virtue of the electrically insulating character of the header 51 itself.
- two external electrodes 49, 50 may be connected in parallel so that they act effectively as
- sensing and automatic activation capability is provided upon implantation of the stimulus generator alone, without need for implantation of a separate lead and electrodes in direct contact with or in proximity to the heart.
- the sensing electrodes one of which is the stimulating electrode, or which are the two electrodes positioned externally on and electrically insulated from the case, are able to detect the electrical activity of the heart in the same way as a surface electrogram is obtained.
- the sense signal is supplied to a microprocessor 36 within the stimulus generator housing, to receive and record signal information indicative of the patient's heart rate, and time rate of changes thereof, and to maintain an ongoing average of both short term and long term heart rate with a programmable time interval for each.
- the monitoring preferably ranges up to 32 beats, and for the long term average, up to 124 beats. It may desirable to assess a twenty- four hour average with calculation of a standard deviation for modification of the trigger slope.
- an overly high sensitivity might result in continuous therapy.
- the time interval between consecutive applications of nerve stimuli should be programmed to assure that a suitable minimum off time is provided to prevent overstimulation.
- Rate of change of heart rate over the short term running average is continuously compared to the same calculation for the long term running average. If it is determined that a sudden change in heart rate surpasses the programmed threshold slope, the programmed therapy waveform is applied to the nerve electrode.
- slope detection is readily performed by the microprocessor
- the microprocessor is easily programmed, and such a technique and arrangement has the additional advantage of requiring fewer components and thus allowing implementation of the generator in a smaller package.
- additional noise elimination algorithms may be desirable.
- a sudden increase followed by a sudden decrease within a very short period of time may be attributable to movement artifacts.
- a requirement for a sudden and sustained increase or decrease in rate would serve to reject this type of noise.
- the algorithm should have characteristics of a capability to distinguish between increases that result from exercise or activity of the patient, as well as normally expected heart rate variability, and noise artifacts. For example, a 50 msec or greater change in interval between heart beats may be associated with breathing in normal healthy subjects.
- External electrodes 49 and 50 (connected in parallel) and case 14, or one of the nerve electrodes and the case, are electrically connected to the input terminals of
- sensing circuit 45 (FIG. 2).
- the sensing circuit may be implemented to provide an analog detection circuit.
- the sense signal derived by the respective sense electrodes is applied to a charge amplifier (e.g., a capacitive ramp generator) 60 having a fixed time constant for periodically generating slopes of heart rate over time.
- the output of the latter circuit is filtered by a slope detection filter 62 to examine only slopes indicative of rate changes in a preselected range above those reflecting normal exercise or activity, even of a strenuous nature.
- Each such slope (ramp) is compared in a ramp comparator 63 to a programmed threshold slope and, if the threshold is exceeded, to trigger the deliver of the therapeutic stimulus to the nerve electrode.
- the sensitivity of sensing circuit 45 may be varied by appropriately programming the gain of amplifier 60 and/or by adjusting the threshold slope of detector 63, using the external programming console.
- sensing circuit 45 in distinguishing seizure-induced rate of change of the patient's heart rate from change attributable to normal physical activity may be enhanced by the provision of timing and state circuit 65 (FIG.2).
- the latter circuit also receives the rate sequences indicative of cardiac activity from the sensors, as well as monitoring the output signal of sensing circuit 45.
- Circuit 65 also operates in conjunction with microprocessor 36 and associated random access memory (RAM) 66 within the logic and control section 35 of the stimulus generator.
- RAM random access memory
- timing and state circuit 65 Operation of timing and state circuit 65 is illustrated by the flow chart of FIG.5. Implementation of a circuit and/or software to perform the functions of the timing and state circuit according to this flow chart are readily achieved in various well known ways.
- the circuit 65 is essentially a multi-state machine which waits in the ready state 68
- a counter is initially cleared in advance of each input rate sequence to count R-waves in the patient's cardiac activity sense signal over a predetermined time interval.
- a timer having a predetermined maximum time interval (at which the timer "times out") is also held in a cleared state in preparation for measuring the time elapsed from the start of the latest time measurement interval in a sequence of such intervals.
- Detection of the first R-wave in the predetermined time interval moves the state machine to a waiting state (70) in which the R-wave detection is "debounced" to enhance detection of each R-wave as a single event.
- a waiting state 70
- the state machine On expiration of a preselected time interval of only a few milliseconds of the time counter (71), the state machine enters an increment state (72) in which the R-wave counter is incremented by one with detection of each individual R-wave.
- the increment state is exited upon the occurrence of either of two different conditions.
- the cardiac activity sequence of interest is examined to assess whether the patient's heart rate is undergoing a time rate of change which is consistent or inconsistent with physical exercise (e.g., walking, or even merely getting up from a sitting or lying position), or the heart rate is relatively constant so that no rate of change is being experienced. Occurrence of either of the first two conditions will produce an exit and cause an interrupt of the microprocessor (state 73) in the logic and control section.
- the R-wave count is divided by the time interval (either the time out interval or the interval up to the point that the maximum count is reached, as applicable),
- the microprocessor and associated logic control circuitry determines that the threshold slope (rate change) is exceeded (either independently, as is preferred, or confirming the finding of the sense circuit)
- the programmed nerve stimulation waveform is triggered.
- the absolute heart rate is monitored by the timing and state circuit to assess whether, when the threshold slope is exceeded, the rate is sustained for a preset interval of time. If so, the stimulus is generated from the output section of the implanted device in the form of the selected waveform therapy to appropriately modulate the vagal activity, whereby to inhibit a seizure if it has not commenced, or, if it has commenced, to abort it or reduce its severity and/or duration.
- stimulation pattern pulse sequences ranging from "on" time of 30 seconds followed by "off time of five minutes, to "on” time of seven second followed by “off time of 14 seconds, are well tolerated and within a range of suitability to achieve the desired effect.
- stimulation pattern sequence pulse sequences ranging from "on" time of 30 seconds followed by "off time of five minutes, to "on” time of seven second followed by "off time of 14 seconds.
- voice modulation and hoarseness can be minimized by
- vagal stimulation is triggered . solely by the threshold detection (in contrast to prophylactic treatment).
- a different automatic detection algorithm, or manual activation may be used in cases where the epileptic patient is also suffering from heart disease or disorder of a type which would render the cardiac activity algorithm inconclusive.
- Spectral analysis of heart rate variability may provide greater sensitivity for discrimination between exercise-induced and seizure-induced rate changes, but involves a more complex structure and analysis. It is postulated that a seizure-induced rate change increases the high frequency peak of the high frequency band of the spectrum, whereas an exercised-induced rate change causes a decrease in such peak of the high frequency band.
- Subjection of the detected cardiac activity to spectral analysis to differentiate between exercise-induced and seizure-induced changes in a patient's cardiac activity is illustrated in the block diagram of the alternative embodiment of FIG. 6.
- the sensed cardiac activity signal 80 is applied to a spectrum analyzer 82.
- the output of the analyzer is used to trigger vagal stimulation by the implanted stimulus generator 25 according to whether the signal 80 exhibits an increase in the high frequency peak of the high frequency band. If it does, the output stimulus of the generator 25 is enabled by a trigger signal at 85 to deliver the designated pulsed output to the nerve electrode array 15 via lead assembly 16 and, thus, to modulate the electrical activity of the vagus nerve in a manner to inhibit or suppress the oncoming seizure before the seizure can fully manifest itself in the patient's brain. In contrast, if by virtue of the spectral analysis cardiac activity signal 80 is detected to undergo a time rate of change of heart rate which exhibits a decrease in the high frequency peak of the high frequency band,
- the change is deemed to be exercised induced, and the stimulus generator 25 is disabled from generating its output stimulus by a disabling input signal applied at 87.
Abstract
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Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA2331020A CA2331020C (en) | 1998-05-02 | 1999-04-30 | Cardiac activity algorithm activation of a neurostimulator |
DK99920169.2T DK1087815T3 (en) | 1998-05-02 | 1999-04-30 | Activation of a neurostimulator by a cardiac activity algorithm |
AU37731/99A AU752688B2 (en) | 1998-05-02 | 1999-04-30 | Cardiac activity algorithm activation of a neurostimulator |
ES99920169T ES2402991T3 (en) | 1998-05-02 | 1999-04-30 | Activation of a neurostimulator using cardiac activity algorithm |
EP99920169A EP1087815B1 (en) | 1998-05-02 | 1999-04-30 | Cardiac activity algorithm activation of a neurostimulator |
JP2000546840A JP3571651B2 (en) | 1998-05-02 | 1999-04-30 | Activation of the cardiac activity algorithm of the neural stimulator |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US09/071,856 | 1998-05-02 | ||
US09/071,856 US5928272A (en) | 1998-05-02 | 1998-05-02 | Automatic activation of a neurostimulator device using a detection algorithm based on cardiac activity |
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WO1999056822A1 true WO1999056822A1 (en) | 1999-11-11 |
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PCT/US1999/009372 WO1999056822A1 (en) | 1998-05-02 | 1999-04-30 | Cardiac activity algorithm activation of a neurostimulator |
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US (1) | US5928272A (en) |
EP (2) | EP1087815B1 (en) |
JP (1) | JP3571651B2 (en) |
AU (1) | AU752688B2 (en) |
CA (1) | CA2331020C (en) |
DK (1) | DK1087815T3 (en) |
ES (1) | ES2402991T3 (en) |
WO (1) | WO1999056822A1 (en) |
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US7853329B2 (en) | 1998-08-05 | 2010-12-14 | Neurovista Corporation | Monitoring efficacy of neural modulation therapy |
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US8295934B2 (en) | 2006-11-14 | 2012-10-23 | Neurovista Corporation | Systems and methods of reducing artifact in neurological stimulation systems |
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US5928272A (en) | 1999-07-27 |
EP2258444B1 (en) | 2015-10-21 |
AU3773199A (en) | 1999-11-23 |
CA2331020A1 (en) | 1999-11-11 |
EP1087815B1 (en) | 2013-03-06 |
EP2258444A1 (en) | 2010-12-08 |
JP3571651B2 (en) | 2004-09-29 |
DK1087815T3 (en) | 2013-05-27 |
EP1087815A1 (en) | 2001-04-04 |
CA2331020C (en) | 2012-01-17 |
ES2402991T3 (en) | 2013-05-13 |
EP1087815A4 (en) | 2008-04-23 |
AU752688B2 (en) | 2002-09-26 |
JP2002513656A (en) | 2002-05-14 |
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