Source: http://www.docstoc.com/docs/53228960/Vagal-Nerve-Stimulation-Techniques-For-Treatment-Of-Epileptic-Seizures---Patent-6587727
Timestamp: 2014-12-20 19:30:15
Document Index: 548188912

Matched Legal Cases: ['art.\n5', 'art.\n6', 'art.\n12', 'art.\n18', 'art.\n19', 'art.\n26', 'art.\n31', 'art 55']

Vagal Nerve Stimulation Techniques For Treatment Of Epileptic Seizures - Patent 6587727
United States Patent: 6587727
10/047,179
607/45  ; 607/17
A61N 1/36&amp;nbsp(20060101); A61N 001/365&amp;nbsp()
607/9,45,17
Handforth et al., &quot;Vagus Nerve Stimulation Therapy for Partial Onset Seizures: A randomized Active Control Trial,&quot; J. Neurology, vol. 5, pp.
48-55 (1998).
Salinskey et al., &quot;Vagus Nerve Stimulation Has No Effect on Awake EEG Rhythms in Humans,&quot; J. Epilespia, vol. 34(2), pp. 229-304 (1993).
Michael H. Chase et al., &quot;Afferent Vagal Stimulatuion neurographic Correlates if Induced EEG Synchronization and Desynchronization,&quot; Brain Research pp. 236-249 (1967).
Ruda, Anti, &quot;A Real-Time Microprocessor QRS Detector System with a 1-ms Timing Accuracy for the Measurement of Ambulatory HRV,&quot; IEEE Transactions on Biomedical Engineering, vol. 44, Nos. 3, pp. 159-167 (Mar. 1997).
Accornero et al., &quot;Selective Activation of Peripheral Nerve Fibre Groups of Different Diameter by Triangular Shaped Pulses,&quot; J. Physiol., pp. 539-560 (1977).
Bures et al., &quot;Electrophysiological Methods n Biological Research&quot; Academic Press New York, London pp. 338-339 (3rd ed. 1967).
Jones et al., &quot;Heart Rate Responses to Selective Stimulation of Cardiac Vagal C Fibers in Anaesthetized Cats, Rats and Rabbits,&quot; J. Physiol (London) 489. 1:203-214 (1995).
Jalife J. Antzelevitch C., &quot;Pacemaker Annihilation: Diagnostic and Therapeutic Implications,&quot; Am Heart J 100: 128-130 (1980).
Mark V. Kamath, &quot;Neurocardiac Responses to Vagoafferent Electrostimulation in Humans,&quot; PACE, vol. 15, Oct. (1992) p. 1581..
09/302,516, filed Apr. 30, 1999, now U.S. Pat. No. 6,341,236 for which
1.  A method of pacing a heart with a pacemaker comprising the steps of: (a) monitoring an electrocardiogram signal of the heart;  (b) processing the signal to determine whether a vagus
nerve is being stimulated;  and (c) if the vagus nerve is being stimulated, operating the pacemaker to maintain a heart beat parameter at a predetermined level.
2.  A system for controlling the operation of a heart during vagus nerve stimulation comprising in combination: (a) an implantable pacemaker coupled to stimulate the heart;  (b) at least one sensor coupled to the pacemaker capable of measuring an
electrocardiogram signal;  and (c) means for processing the signal to determine whether the vagus nerve is being stimulated, whereby the pacemaker may control the heart during vagus nerve stimulation.
3.  The system of claim 2, further comprising: (d) means for providing a sensory stimulus responsive to the sensor signal for alerting the patient of an undesired effect on the heart from the vagus nerve.
4.  The system of claim 2, further comprising: (d) a control algorithm responsive to the sensor for activating the pacemaker to regulate the heart.
5.  The system of claim 2, wherein the sensor is capable of measuring a heart rate of the heart.
6.  The system of claim 2, wherein the sensor is capable of detecting a QRS.
7.  The system of claim 2, wherein the sensor is capable of detecting an R-wave.
8.  The system of claim 2, wherein the sensor is capable of measuring blood pressure.
9.  The system of claim 2, wherein the sensor is capable of measuring R--R variability.
10.  A method of pacing a heart with a pacemaker comprising the steps of: (a) monitoring a characteristic of the heart;  (b) processing the signal to determine whether a vagus nerve is being stimulated;  and (c) if the vagus nerve is being
stimulated, operating the pacemaker to maintain a heart beat parameter at a predetermined level.
11.  The method of claim 10, wherein the step of monitoring includes the step of monitoring a heart rate of the heart.
12.  The method of claim 11, wherein the step of monitoring the heart rate includes the step of monitoring QRS detection.
13.  The method of claim 11, wherein the step of monitoring the heart rate includes the step of monitoring R-wave detection.
14.  The method of claim 10, wherein the step of monitoring includes the step of monitoring blood pressure.
15.  The method of claim 10, wherein the step of monitoring includes the step of monitoring R--R variability .
16.  A method of monitoring a heart with a pacemaker comprising the steps of: (a) monitoring a characteristic of the heart for changes that are indicative of an occurrence of a seizure;  (b) identifying abnormal heart function indicative of a
possible occurrence of the seizure;  and (c) warning the patient of the possible occurrence of the seizure, whereby the patient may act accordingly to minimize a risk injury or sudden unexpected death.
17.  The method of claim 16, wherein the step of monitoring includes the step of monitoring an electro-cardiogram signal of the heart.
18.  The method of claim 16, wherein the step of monitoring includes the step of monitoring a he art rate of the heart.
19.  The method of claim 18, wherein the step of monitoring the heart rate includes the step of monitoring QRS detection.
20.  The method of claim 18, wherein the step of monitoring the heart rate includes the step of monitoring R-wave detection.
21.  The method of claim 16, wherein the step of monitoring includes the step of monitoring blood pressure.
22.  The method of claim 16, wherein the step of monitoring includes the step of monitoring R--R variability.
23.  The method of claim 16, further comprising the step of: (d) enabling the patient to deactivate operation of a vagus nerve stimulator (VNS).
24.  A system for controlling operation of a heart during vagus nerve stimulation comprising in combination: (a) an implantable signal generator providing stimulation energy;  (b) at least one electrode having a proximal end coupled to the signal
generator and a distal end adapted to provide the stimulation energy to a vagus nerve of a patient;  (c) at least one sensor coupled to a pacemaker capable of measuring a characteristic of the heart indicative that the signal generator is stimulating the
vagus nerve;  and (d) an implantable pacemaker coupled to regulate the heart in response to the sensor.
25.  The system of claim 24, wherein the sensor is capable of measuring a heart rate of the heart.
26.  The system of claim 24, wherein the sensor is capable of detecting a QRS.
27.  The system of claim 24, wherein the sensor is capable of detecting an R-wave.
28.  The system of claim 24, wherein the sensor is capable of measuring blood pressure.
29.  The system of claim 24, wherein the sensor is capable of measuring R--R variability.
30.  The system of claim 24, wherein the sensor provides indication that the signal generator is stimulating the vagus nerve further comprising: (e) a control algorithm responsive to the sensor for activating the pacemaker to regulate the heart.
31.  The system of claim 24, wherein the sensor provides indication that the signal generator is stimulating the vagus nerve further comprising: (e) a control algorithm responsive to undesirable heart activity during vagus nerve stimulation to
shut down the vagus nerve stimulation.
32.  The system of claim 24 further comprising: (e) a sensory stimulus responsive to the sensor signal and alerting the patient of an undesired effect on the heart from the vagus nerve.  Description
The neuro-cybemetic prosthesis (NCP) is the primary vagus nerve stimulation (VNS) system that is presently available.  This presently available VNS treatment technique for the treatment of epilepsy, however, has limited therapeutic efficacy and
value of 1 in this graph indicates that the instantaneous heart rate (IHR) at that point in time is equal to the median IHR for the current vagus nerve stimulator (VNS) device cycle (i.e., for the current 51/2 minute window).  The graph shows that during
vagus nerve stimulation from time 0 to 50, the heart rate drops to as low as 0.8 of its background rate.  Similarly, FIG. 1B is a graph of the instantaneous heart rates (defined herein) of a patient as a function of time over an 8 hour period.  The sharp
drops that occur periodically along the bottom of the graphed line correspond to times when the vagus nerve stimulation device is reset or turned &quot;on&quot;.  These sharp drops illustrate the effect that vagus nerve stimulation has on the heart.  Notably, the
Zabara patents recognize that the heart rate slows as a result of the stimulation.  This effect that vagus nerve stimulation has on the heart is undesirable due to negative short- or long-term effects on the patient.  For example, the heart may become
less adaptable to stresses due to the vagus nerve stimulation, which may lead to arrhythmia, asystole (heart stoppage), and possibly even to sudden death.  See Asconape et al, &quot;Early Experience with Vagus Nerve Stimulation for the Treatment of Epilepsy;
Cardiac Complications, AES Proceedings, p. 193 (1998) (incorporated herein by reference in its entirety).
No Effect on Awage EEG Rythms in Humans,&quot; J. Epilespia, Vol. 34 (2), p. 299-304 (1993).  Adequate stimulation of the vagus nerve induces either synchronization or desynchronization of brain rhythms depending on the stimulation parameters used.  See
alterations in the heart electrocardiogram (EKG) reading.  Given the shape of the pulse, its biphasic nature and the intensity settings available in the NCP, selective stimulation of slow conducting nerve fibers (a necessary condition for EEG
such as heart rate.  The heart rate information from the sensor can be used to determine whether the vagus nerve stimulation is adversely affecting the heart.  Once threshold parameters are met, the vagus nerve stimulation maybe stopped or adjusted.  In
In yet another embodiment, EKG rhythms may be sensed so as to minimize EKG changes via cybernetic techniques.  In another embodiment, the present invention may selectively stimulate certain fiber groups within the vagus nerve to block the
Referring to FIG. 2, a system 10 made in accordance with a preferred embodiment maybe implanted below the skin of a patient.  System 10 generally includes a sensor 15 for sensing a characteristic of the heart 55 of the patient, a signal generator
20, and one or more stimulation electrodes 25.  System 10 may be a modified version of the devices disclosed in the Zabara patents and are incorporated herein by reference.
Triangular Shaped Pulses,&quot; J. Phyisiol., pp.  539-560 (1977).  Simply stated, anodal currents causes a functional nerve block.
Alternatively, a modification of the above technique may be implemented which rests on the Alaw of independent conduction@ of nerve fibers.  Bures et al., &quot;Electrophysiological Methods in Biological Research,&quot; Academic Press N.Y., London, pp
selected in accordance with the techniques disclosed in U.S.  Pat.  Nos.  4,628,942 entitled Asymmetric Shielded Two Electrode Cuff&quot;; U.S.  Pat.  No. 4,649,936 entitled &quot;Asymmetric Single Electrode Cuff For Generation Of Unidirectionally Propagating
precision).  At 705, the digital EKG signal (y(k), k=1, 2, 3, .  . . ) is then passed into a first order statistic filter (preferably a median filter of order 0.0625 seconds, i.e., 15 data points at 240 Hz sampling rate).  At 707, the input to and output
for k=8, 9, 10, .  . . . At 715, the e(k) sequence is then passed into a second order statistic filter (preferably of order 1/3 second, i.e., 81 data points at 240 Hz sampling rate).  The output of this filter is denoted as fg(k) and is referred
to as the foreground sequence.  At 720, this output is sampled every 2 second (i.e. decimated by a factor of 120) and at 725 passed through a third order statistic filter of order 2 minutes (i.e., of order 240) to produce a moving background sequence,
5), and the system determines that the stimulation is &quot;on&quot; when R(k).sub..  5 and &quot;off&quot; when R(k)&amp;lt;5.  FIG. 11A is a graph showing a raw EKG signal with the VNS artifact on the left side.  FIG. 11B is another graph showing the difference between the
raw signal and the output of the first median filter 705.  FIG. 11C is another graph showing the output ratio R(k) (from the divider 730) and the threshold of 5 to determine when the device is &quot;on&quot; or &quot;off&quot;.  As can be seen in this graph, the VNS is &quot;on&quot;
at roughly time t=5 seconds through t=41 seconds.  Known periodicities of the VNS device can be compared with the detected on times to verify whether the VNS is operating in accordance with a desired schedule and stimulation parameters.  Accordingly,
under this embodiment, the present invention may be implemented to modify a pacemaker that can be used with existing VNS devices or with VNS devices of the present invention.
has the lowest effect on the heart.  This testing can be done by physician in clinic during or after implant or it maybe programmed to automatically perform within the signal generator 20.  See Jalife J, Anzelevitch C., &quot;Phase resetting and annihilation
cardio-vascular regulation, cause changes in heart rate, R--R variability and blood pressure.  The heart can thereby by monitored for these changes that are indicative of the occurrence of a seizure.  Specifically, the changes in the heart rate that may
Vagal nerve stimulation techniques for treatment of epileptic seizures, Osorio, et al., Ivan Osorio, Mark G. Frei, Application number 10 047-179, Surgery: LightThermal And Electrical Application, vagus nerve, vagus nerve stimulation, electrical stimulation, nerve stimulation, implantable medical device, Patent Search, medical device, Patent Attorney, Recently Added, atrial fibrillation
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