Methods, systems and apparatuses for detecting increased risk of sudden death

Information

  • Patent Grant
  • 11596314
  • Patent Number
    11,596,314
  • Date Filed
    Friday, October 18, 2019
    4 years ago
  • Date Issued
    Tuesday, March 7, 2023
    a year ago
Abstract
Methods, systems, and apparatuses for detecting seizure events are disclosed, including a system for identification of an increased risk of a severe neurological event. The system may include an electroencephalogram (“EEG”) monitoring unit configured to collect EEG data from the patient during at least a postictal phase or one or more seizures and a processing unit configured to receive the EEG data from the EEG monitoring unit. The processing unit is configured to detect postictal EEG suppression from the EEG data and to identify the increased risk of the severe neurological event based on the detected postictal EEG suppression. Other embodiments are described and claimed.
Description
FIELD OF THE DISCLOSURE

The present disclosure relates generally to systems, methods, and apparatuses for detecting medical conditions. More particularly, the disclosure relates to systems, methods and apparatuses for detecting medical conditions relating to seizures, especially conditions that may place a patient experiencing a seizure at greater risk of sudden death.


BACKGROUND OF THE DISCLOSURE

The embodiments described herein relate generally to the field of medical detection systems for patients experiencing seizures. “A seizure is an abnormal, unregulated electrical charge that occurs within the brain's cortical gray matter and transiently interrupts normal brain function.” The Merck Manual of Diagnosis and Therapy, 1822 (M. Beers Editor in Chief, 18th ed. 2006) (“Merck Manual”). Epilepsy is a chronic disease characterized by such seizures, but not caused by an event such as a stroke, drug use or physical injury. Seizures may vary in frequency and scope and may range from involving no impairment of consciousness at all to complete loss of consciousness. Typically, a seizure resolves within a few minutes and extraordinary medical intervention, other than that needed for the comfort of the patient and to promote unobstructed breathing, is not needed. (See, generally, Merck Manual at 1822-1827, incorporated herein by reference.)


But in some cases, a seizure may lead to death. Asphyxia is an impairment or absence of the oxygen and carbon dioxide exchange in the body, which can occur, for example, during suffocation. Asphyxia is considered to be the leading cause of Sudden Unexplained Death in Epileptic Patients (“SUDEP”) and may indeed trigger SUDEP. But the mechanism and relationship of SUDEP with cardiorespiratory and cerebral function has been poorly understood. SUDEP does not occur during or, generally, immediately after an initial phase of a seizure but as the patient appears to be recovering from the seizure. In addition, SUDEP may occur at night, while the patient is sleeping. Such sudden unexplained death is not necessarily limited to seizure patients and may be underreported in the general population. But seizure patients, including those with epilepsy, seem to be at a higher risk for sudden unexplained death than the general population.


In a typical seizure condition, there are three phases: ictal, post ictal (or “postictal”), and interictal. The ictal phase is the initial portion of the seizure, where a patient may display symptoms, if any, such as convulsions. Generally speaking, the interictal phase is the period between seizures when the patient has substantially recovered.


A postictal phase takes place immediately after the ictal phase of the seizure, where symptoms have subsided, but the patient has not yet returned to normal. During the postictal period, the patient may be relaxed or lying down and may appear to be sleeping. In the postictal period, the patient's heart rate may typically take a few minutes to return to the patient's non-seizure baseline. The same is true of the patient's electrocardiogram (“EKG” or “ECG”) measurements, if the patient should happen to be undergoing EKG testing at the time of the seizure. EKG measurements provide a record of the heart's integrated action over a period of time. Cardiac and respiratory readings for the patient soon appear to be normal as the patient progresses in the postictal period. Such measurements and readings, along with visual observation, would support a view that a patient is coming out of the seizure in a normal fashion and is not at risk for SUDEP. One might thus conclude that no medical intervention is necessary. But in some cases, such measurements, readings and observations would be deceptive and the patient is at risk of SUDEP.


If a condition in a patient that leads to an increased risk of SUDEP can be detected, timely measures may be taken that would reduce that risk and possibly save the patient.


Accordingly, a need is present for methods, systems and apparatuses to detect one or more conditions in a patient that may lead to SUDEP and/or overcome issues discussed above.


SUMMARY

The embodiments of the disclosure described herein include a system for identification of an increased risk of a severe neurological event. The system may include an electroencephalogram (“EEG”) monitoring unit configured to collect EEG data from the patient during at least a postictal phase of one or more seizures and a processing unit configured to receive the EEG data from the EEG monitoring unit. The processing unit is configured to detect postictal EEG suppression from the EEG data and to identify the increased risk of the severe neurological event based on the detected postictal EEG suppression.


The embodiments of the disclosure described herein also include a system for identification of an increased risk of a severe neurological event. The system includes an electroencephalogram (“EEG”) monitoring unit, a processing unit, a respiratory monitoring unit and an electrocardiogram (“EKG”) monitoring unit. The electroencephalogram (“EEG”) monitoring unit is configured to collect EEG data from the patient's brain during at least a postictal phase of one or more seizures. The processing unit is configured to receive the EEG data from the EEG monitoring unit and to detect postictal EEG suppression from the EEG data when the EEG data crosses an EEG threshold for at least a predetermined time period. The respiratory monitoring unit is configured to collect respiratory data from the patient's respiration during at least the postictal phase of the one or more seizures in response to detection of the postictal EEG suppression. The processing unit receives the respiratory data from the respiratory monitoring unit and determines whether the respiratory data crosses a respiratory threshold. The electrocardiogram (“EKG”) monitoring unit is configured to collect EKG data for the patient's heart. The processing unit is configured to receive the EKG data from the EKG monitoring unit and to determine whether the EKG data crosses an EKG threshold. The processing unit is further configured to determine whether the EKG data crosses the EKG threshold in response to a determination that the respiration data crosses the respiration threshold. The processor may identify the increased risk of the severe neurological event based on the detected postictal EEG suppression, the determination that the respiration data crosses the respiration threshold, and the determination that the EKG data crosses the EKG threshold.


The embodiments of the disclosure described herein also include a method for detecting a condition in a patient that poses an increased risk of sudden unexplained death in epilepsy (SUDEP), including collecting encephalogram (“EEG”) data from a patient during at least a postictal phase of one or more seizures, and determining whether the EEG data indicates postictal EEG suppression when the EEG data crosses an EEG threshold.


Other aspects and advantages of the embodiments described herein will become apparent from the following description and the accompanying drawings, illustrating the principles of the embodiments by way of example only.





BRIEF DESCRIPTION OF THE DRAWINGS

Features and advantages of the present disclosure will become apparent from the appended claims, the following detailed description of one or more example embodiments, and the corresponding figures.



FIG. 1 is a graph depicting EEG measurements where a first patient is recovering normally and a second and third patient start exhibiting EEG suppression indicative of an increased risk of SUDEP.



FIG. 2 is a depiction of relationships between some conditions that may be related to SUDEP.



FIGS. 3A-C are depictions of flowcharts for a process and methods in accordance with one or more embodiments of the present disclosure.



FIG. 4 is a depiction of a system for a patient in a medical facility in accordance with one or more embodiments of the present disclosure.



FIG. 5 is a depiction of a system for a patient outside of a medical facility, in accordance with one or more embodiments of the present disclosure.





While the disclosure is subject to various modifications and alternative forms, specific embodiments thereof are shown by way of example in the drawings and the accompanying detailed description. It should be understood, however, that the drawings and detailed description are not intended to limit the invention to the particular embodiments. This disclosure is instead intended to cover all modifications, equivalents, and alternatives falling within the scope of the present invention as defined by the appended claims.


DETAILED DESCRIPTION

The drawing figures are not necessarily to scale and certain features may be shown exaggerated in scale or in somewhat generalized or schematic form in the interest of clarity and conciseness. In the description which follows, like parts may be marked throughout the specification and drawing with the same reference numerals. The foregoing description of the figures is provided for a more complete understanding of the drawings. It should be understood, however, that the embodiments are not limited to the precise arrangements and configurations shown. Although the design and use of various embodiments are discussed in detail below, it should be appreciated that the present disclosure provides many inventive concepts that may be embodied in a wide variety of contexts. The specific aspects and embodiments discussed herein are merely illustrative of ways to make and use the disclosure, and do not limit the scope of the disclosure. It would be impossible or impractical to include all of the possible embodiments and contexts in this disclosure. Upon reading this disclosure, many alternative embodiments of the present disclosure will be apparent to persons of ordinary skill in the art.













TABLE 1






Mean EEG
Clinical





Seizure
Seizure
EKG Seizure
Postictal


Identification
Duration
Duration
Duration
Breathing (Y/N)







1 (10 sz)
2.24 min.
1.96 min 
4.85 min 
Y


2 (11 sz)
1.89 min.
1.69 min.
4.18 min.
Y


3 (7 sz)
1.77 min 
1.71 min.
4.02 min.
Y









Table 1 compares seizure duration as determined by different types of measurements. These measurements include EKG measurements, clinical measurements which are based on visual observations of the patient, and electroencephalogram (“EEG”) readings. In contrast to EKG devices which measure heart activity, EEG devices measure brain activity, often in several parts of the brain at once. Note that the mean EEG seizure duration differs from both the clinical and EKG measurements in these examples being longer than clinical duration and shorter than EKG seizure duration. This is because the brain behavior of patients having seizures can be quite different from the patient's cardiac and respiratory behavior. The EEG indications of seizure are considered the most accurate and EEG variation will typically begin a few seconds before a patient begins experiencing physical symptoms, i.e. when the clinical duration begins. The EKG measurements in the EKG seizure duration column indicate that the heart generally takes longer to return to baseline than either the EEG measurements or the clinical observations would indicate. The far right hand column of Table 1 indicates that postictal breathing was present.



FIG. 1 is a graph 100 depicting EEG measurements where a first patient is recovering normally and a second and third patient start exhibiting EEG suppression indicative of an increased risk of SUDEP. The graph 100 includes three EEG waveforms. A first EEG waveform 102 shows EEG data of a patient having seizures and recovering normally. A second EEG waveform 104 shows EEG data of a patient having multiple seizures and experiencing at least one EEG suppression during the postictal phase of each seizure. A third EEG waveform 106 shows EEG data of a patient having seizures and experiencing multiple EEG suppressions during the postictal and interictal phase after a single seizure. Waveforms 102, 104, and 106 each start with a normal EEG signal during an interictal phase. The interictal phase ends at time 108 and the ictal phase begins with the onset of a seizure. The seizure shown in waveforms 102, 104, and 106 ends at time 110 and the patients enter a postictal phase. The EEG waveform 102 shows a normal recovery during the postictal phase. The EEG waveform 104 shows a period of EEG suppression 112 and EEG waveform 106 also shows a period of EEG suppression 114. During EEG suppression periods 112 and 114, the amplitudes of the corresponding EEG waveforms are greatly suppressed and appear flat. These EEG suppression periods indicate a significant reduction in brain activity of the patient. The EEG waveforms 104 and 106 show that the patients EEG signal returns to normal and each of the EEG waveforms 102, 104, and 106 may transition into the interictal phase.


A time lapse 116 is provided to skip to the next seizure occurring in EEG waveforms 102 and 104. The EEG waveform 106 indicates that the patient is still in the interictal phase and that a subsequent seizure has not occurred. The second seizure shown in the EEG waveform 102 ends at time 118 and shows normal recovery during the postictal phase. The second seizure shown in the EEG waveform 104 ends at time 118 and enters an EEG suppression period 120 that is longer than the previous EEG suppression period 112. The EEG waveform 106 transitions from an interictal phase at time 118 and enters an EEG suppression period 122 that is longer than the previous EEG suppression period 114 without any intervening seizures. This increase in the duration of the EEG suppression periods in the EEG waveforms 104 and 106 may be indicative of a progressive or worsening condition that may lead to a severe neurological event, such as SUDEP.


While FIG. 1 depicts one EEG signal for each of the scenarios, EEG readings are typically performed on many channels representing measurements from many EEG sensors. Whether one channel, two or more channels or all channels will be suppressed in a condition leading to SUDEP, or whether there will be a cascading effect, may depend on the particular pathology of the patient or the severity of the patient's current condition. One set of channels may exhibit a suppressive behavior pattern. The suppressive behavior pattern may migrate to another location or could propagate, with additional channels exhibiting the suppressive behavior. Often a higher number of channels being involved indicates that the case may be more serious.


By detecting a period of postictal EEG suppression, one may be able to intervene to assist the patient and prevent SUDEP. But any assistance must be prompt because potential remedies for SUDEP may not be effective unless they are applied in a timely manner. Possible treatments include activating an implanted medical device, such as a neurostimulator described in U.S. Pat. No. 5,304,206, an injection of an appropriate dosage of medicine, CPR and/or defibrillation, use of an external device, such as a helmet for cooling the brain, or EMS (electromagnetic stimulation). The treatment could be increased or changed if the patient does not respond. For example, the neurostimulator could include successive rounds of stimulation at higher currents if the postictal EEG suppression continues. Appropriate medication could be injected via a pump device, with an additional dose being added if the patient is not responsive. Depending on the patient and the treating physician's evaluation, more than one treatment may be used, either in combination or sequentially, for some patients.



FIG. 2 is a depiction of relationships between conditions that may be related to SUDEP 222 and to postictal EEG suppression 220. Conditions which may be related to SUDEP 222 and postictal EEG suppression 220 include postictal apnea 200, postictal hypoxia 210 and postictal bradycardia 215. Postictal apnea 200, which is an absence of breathing, can give rise to both postictal hypoxia 210, which is decreased levels of oxygen in a person, and postictal bradycardia 215, which is a slowing of a person's heart rate. Both postictal hypoxia 210 and postictal bradycardia 215 can in turn increase postictal apnea 200. Postictal hypoxia 210 can also increase postictal bradycardia 215. All of these conditions may also contribute to, or be indicative of, postictal EEG suppression 220 and may be present before, or during, SUDEP 222. This may explain why postictal EEG suppression 220 may also be indicative of SUDEP 222.



FIG. 3A is a depiction of a flowchart for a process in accordance with one or more embodiments of the present disclosure. A patient's EEG readings are monitored 300 during at least postictal portions of a seizure and preferably starting within the ictal period of the seizure. Many techniques could be used to detect an EEG suppression, such as a nonlinear signal analysis or a recurrence quantification analysis. The EEG suppression may last for a relatively long time or it may comprise shorter, re-occurring periods of suppression, interspersed with periods of normal activity. In the latter case, the re-occurring periods of suppression may progressively get worse. While an EEG suppression is most likely during the postictal phase, it may occur at other times as well. In several typical scenarios, the EEG suppression may occur 45-95 minutes after a seizure has occurred. Accordingly, in various embodiments of the disclosure, monitoring may occur outside of the postictal phase or may be continuous. The EEG suppression may be progressive exhibiting a trend of generally increasing duration of successive suppression periods. A single suppression period may occur after each seizure where each suppression period after each successive seizure generally increases in duration. Alternatively, multiple suppression periods may occur after a single seizure exhibiting the trend of generally increasing duration. The multiple suppression periods may be interleaved with non-suppression periods where the non-suppression periods exhibit a trend of generally decreasing duration.


If there is detection 310 of an EEG suppression, then a respiratory or other physiological sensor is activated 315 to measure breathing rate (“BR”) of the patient. If the breathing rate falls 320 below a first predetermined threshold, such as a respiratory threshold, then EKG and/or accelerator measurements 325 may be taken 325 of the patient. If EKG readings are less than a second predetermined threshold 330, such as an EKG threshold, and/or accelerator measurements are less than 330 a third predetermined threshold, then a warning is issued 335 by a warning device. The warning can be audible, visual and/or vibrational. A warning device could also send messages, such as recorded telephone calls or e-mail messages or text messages to designated persons. The messages in one or more embodiments of the present disclosure may include information about measurements done on the patient. The warning may be local in nature, alerting the patient (if conscious) and/or those in immediate attendance upon the patient and/or may be sent to appropriate medical responders not in the immediate vicinity of the patient.


In other embodiments, the breathing rate and/or the EKG measurements may be monitored differently, such as continuously or while EEG measurements are taken.



FIG. 3B is a depiction of one embodiment of a method for detecting a condition in a patient that poses an increased risk of a severe neurological event, such as sudden unexplained death in epilepsy (SUDEP). The method collects EEG data from a patient during at least a postictal phase of one or more seizures at 340. The method further determines whether the EEG data indicates postictal EEG suppression when the EEG data crosses an EEG threshold, at 345, where the postictal EEG suppression is progressive postictal EEG suppression comprised of multiple suppression periods interleaved with non-suppression periods. The postictal EEG suppression may be progressive when the suppression is characterized by a trend of generally increasing duration with time of the multiple suppression periods. The method further activates a warning device when the EEG data indicates postictal EEG suppression for a predetermined period of time at 350.



FIG. 3C is a depiction of another embodiment of a method for detecting a condition in a patient that poses an increased risk of a severe neurological event, such as sudden unexplained death in epilepsy (SUDEP). The method collects EEG data from a patient during at least a postictal phase of one or more seizures, at 355, and determines whether the EEG data indicates postictal EEG suppression when the EEG data crosses an EEG threshold, at 360. The method further collects respiratory data from the patient's respiration, at 365, and determines whether the respiratory data crosses a first threshold, at 370. The method further collects EKG data for the patient's heart, at 375, and determines whether the EKG data crosses a second threshold, at 380. The method activates a warning device when the EEG data indicates postictal EEG suppression for a predetermined period of time, the respiratory data crosses the first threshold, and the EKG data crosses the second threshold, at 385.



FIG. 4 is a depiction of a system for a patient in a medical facility or at home, for use during sleep, for example, in accordance with one or more embodiments of the present disclosure. A patient 400, who may be asleep or between seizures or in an ictal or postictal portion of a seizure, has EEG sensors 405 placed on the patient's body in appropriate locations for taking EEG measurements. The EEG sensors 405 are attached to an EEG monitoring unit 410, via an EEG lead 415. Although two EEG sensors 405 and EEG leads 415 are depicted in FIG. 4, there may be many EEG sensors 405 and EEG leads 415. Although EEG leads 415 are currently used for transmitting information from the EEG sensors 405 to the EEG monitoring unit 410, it may be practical in the future to transmit information from the EEG sensors 405 to the EEG monitoring unit 410 wirelessly. Wearable EEG monitors for personal or home use are becoming available commercially. (See e.g. the HealthPals™ device by Olga Epikhina.)


In alternate embodiments, an EEG helmet or headgear may be used and may include many sensors. Alternatively, in the absence of EEG data or in addition thereto, heart and respiration measurements may be used as surrogate markers. For example, during EEG suppression, respiration may proceed in a pattern from tachycardia, to bradycardia, and back to tachycardia.


In the embodiment depicted in FIG. 4, the patient 400 is also monitored by an EKG monitoring unit 420 having EKG sensors 422 placed on the patient's body to monitor the patient's heart activity and linked to the EKG monitoring unit 420 through one or more EKG leads 425. Although two EKG sensors 422 and EKG leads 425 are depicted in FIG. 4, there may be many EKG sensors 422 and EKG leads 425. While EKG's have traditionally been used in a hospital setting, handheld EKG's for home use are now commercially available, some with only a single EKG sensor 422. Although EKG leads 425 are currently used for transmitting information from the EKG sensors 422 to the EKG monitoring unit 420, it may be practical in the future to transmit information from the EKG sensors 422 to the EKG monitoring unit 420 wirelessly.


Continuing to refer to FIG. 4, in this embodiment of the present disclosure, the respiration of the patient 400 is also monitored through a respiratory monitoring unit 430, which includes one or more respiratory sensors 432 attached to the patient's body 400 through one or more respiratory leads 435. Respiration may be monitored in many ways, for example, by use of a nose clip, by a chest band to determine chest expansion, by measuring the temperature of the inhale versus the temperature of the exhale, indirectly by use of an oximeter, or by impedance measurements using chest electrodes. There are some caveats to using respiration measurements in embodiments of the disclosure, but a treating physician can evaluate these factors in determining how to treat a specific patient. For example, respiration could be subject to natural cycles and certain conditions, such as obstructive sleep apnea or central sleep apnea, may mimic SUDEP conditions, resulting in a false SUDEP warning. But considered carefully, respiration measurements may be helpful in different embodiments of the present disclosure.


Signals from the EEG monitoring unit, the EKG monitor unit and the respiratory monitoring unit are fed through one or more signal lines 438 to a processor 440 (or processing unit). Alternatively, the signals could be sent to the processor 440 in a wireless fashion. The processor 440 runs software preferably capable of determining three conditions, including whether: (1) the EEG measurements indicate a period of postictal suppression; (2) the respiration of the patient has fallen below a first threshold and (3) the EKG measurements have fallen below a second threshold. If all three conditions are met, the processor 440 activates an alarm 445, signaling the need for immediate medical intervention. In alternative embodiments, the processor 440 is set so that it signals the alarm if two of the three conditions are met. For example, if EEG measurements are not available or show no change, but heart rate cycles and respiration cycles become longer, more progressive and more extreme, a warning should be triggered.


In some cases, the alarm may be triggered if just one of the conditions is met or if the EEG suppression is prolonged, even if the other two conditions are not met. The EEG suppression is typically the most specific and earliest marker, and in some embodiments of the present disclosure, detection of EEG suppression may alone trigger the alarm. Severe or progressive deterioration of respiration or heart rate may also warrant alarm activation in some patients.


In alternative embodiments, different alarms or messages may be activated for each of the different kinds of measurements being taken of a patient. In alternative embodiments, other physiological measurements with related thresholds may be substituted for the respiratory measurements and the EKG measurements.



FIG. 5 is a depiction of a system for a patient outside of a medical facility, in accordance with one or more embodiments of the present disclosure. In FIG. 5, a person 500 is wearing a headgear 510 containing one or more sensors, which take EEG measurements of the person 500, preferably on a real time basis. The EEG measurements are sent, preferably wirelessly 515, but alternatively through wired connections, to a one or more EEG monitoring units 520, 530, which may include a remote monitor 520 and/or a local monitor 530, such as a handheld device 530, either or both of which can store and analyze the EEG measurements. Should the person's 500 EEG measurements fall below a predetermined threshold, such as an EEG threshold, alarms or alerts 535 are executed by the handheld device 530 and the remote monitor 520. The EEG threshold may include falling below a level of brain activity for a predetermined time period. Additional alerts 535 could be sent to specified recipients such as medical responders and/or family members and/or other designated persons. The person's location could also be provided to the recipients using a GPS or other locator which might be a function included with the handheld device 530 or provided on a separate device in communication with the handheld device 530.


Continuing to refer to FIG. 5, should no help arrive within a pre-determined period of time and/or the person's EEG measurements remain suppressed during the pre-determined period of time, an optional personal medical delivery system 540 could automatically introduce an emergency remedy into the patient's system in an attempt to avert imminent death. The personal medical delivery system 540 could, for example, comprise a neurostimulator, such as that described in U.S. Pat. No. 5,304,206, or an implantable medical device for delivery of a premeasured dosage of medicine, a brain cooling system, CPR and/or defibrillation or EMS (electromagnetic stimulation). The headgear 510 could continue to monitor the patient's condition, with successive or alternative therapy being delivered by the optional personal medical delivery system 540 as needed, until and unless deactivated by medical personnel.


In one or more embodiments of the disclosure, the alert device could also provide written or verbal instructions to those attending to the person. The processor of the present disclosure could maintain a record of measurements made by the system for display, downloading or transmittal to other sites.


In light of the principles and example embodiments described and illustrated herein, it will be recognized that the example embodiments can be modified in arrangement and detail without departing from such principles. Also, the foregoing discussion has focused on particular embodiments, but other configurations are contemplated. In particular, even though expressions such as “in one embodiment,” “in another embodiment,” or the like are used herein, these phrases are meant to generally reference embodiment possibilities, and are not intended to limit the disclosure to particular embodiment configurations. As used herein, these terms may reference the same or different embodiments that are combinable into other embodiments.


Similarly, although example processes have been described with regard to particular operations performed in a particular sequence, numerous modifications could be applied to those processes to derive numerous alternative embodiments of the present invention. For example, alternative embodiments may include processes that use fewer than all of the disclosed operations, processes that use additional operations, and processes in which the individual operations disclosed herein are combined, subdivided, rearranged, or otherwise altered.


This disclosure also described various benefits and advantages that may be provided by various embodiments. One, some, all, or different benefits or advantages may be provided by different embodiments.


In view of the wide variety of useful permutations that may be readily derived from the example embodiments described herein, this detailed description is intended to be illustrative only, and should not be taken as limiting the scope of the invention. What is claimed as the invention, therefore, are all implementations that come within the scope of the following claims, and all equivalents to such implementations.

Claims
  • 1. A system for identification of an increased risk of a severe neurological event, comprising a processing unit configured to: receive, from one or more electroencephalogram (EEG) sensors adapted to sense neurological activity of a patient, EEG data during at least a postictal phase of each of one or more seizures;receive at least one of: respiratory data during at least the postictal phase of each of the one or more seizures from one or more respiration sensors adapted to sense respiratory activity of the patient, orelectrocardiogram (EKG) data during at least the postictal phase of each of the one or more seizures from one or more EKG sensors adapted to sense heart activity of the patient;detect, from the EEG data, at least one postictal EEG suppression period, wherein a postictal EEG suppression period is detected when the EEG data crosses an EEG threshold for at least a predetermined time period;detect, from the at least one of the respiratory data or the EKG data, that at least one of a respiration of the patient has fallen below a first threshold or an EKG measurement of the patient has fallen below a second threshold;identify the increased risk of the severe neurological event based on the detected at least one postictal suppression period and the at least one of the respiration falling below the first threshold or the EKG measurement falling below the second threshold; andprovide, responsive to identifying the increased risk of the severe neurological event, at least one of an alert indicating the increased risk of the severe neurological event of the patient or a stimulation to the patient to assist in preventing the severe neurological event.
  • 2. The system of claim 1, wherein the severe neurological event is sudden unexplained death in epilepsy (SUDEP).
  • 3. The system of claim 1, wherein the processing unit is further configured to detect a plurality of postictal EEG suppression periods interleaved with postictal EEG non-suppression periods during each of at least one postictal phase of the one or more seizures from the EEG data.
  • 4. The system of claim 3, wherein the processing unit is further configured to: detect a trend of generally increasing duration with time of the plurality of postictal EEG suppression periods during the postictal phase of one or more seizures;wherein the increased risk of the severe neurological event is further identified based on the trend.
  • 5. The system of claim 4, wherein the trend is a first trend and the processing unit is further configured to: detect a second trend of generally decreasing duration with time of the plurality of postictal EEG non-suppression periods during the postictal phase of the one or more seizures;wherein the increased risk of the severe neurological event is further identified based on the second trend.
  • 6. The system of claim 3, wherein at least a first EEG suppression period of the plurality of postictal EEG suppression periods occurs after a first seizure and at least a second EEG suppression period of the plurality of postictal EEG suppression periods occurs after a second seizure, the second seizure occurring after the first seizure.
  • 7. The system of claim 1, wherein the processing unit is further configured to trigger an alarm in response to identifying the increased risk of the severe neurological event.
  • 8. The system of claim 1, wherein the processing unit is further configured to activate a personal medical delivery system in response to identifying the increased risk of the severe neurological event.
  • 9. The system of claim 1, wherein the processing unit is configured to receive the EEG data and the at least one of the respiratory data or the EKG data remotely.
  • 10. The system of claim 1, wherein the processing unit is configured to receive the at least one of the respiratory data or the EKG data and detect that the at least one of the respiratory data of the patient has fallen below the first threshold or the EKG measurement of the patient has fallen below the second threshold in response to detecting the at least one postictal EEG suppression period.
  • 11. A method for identifying an increased risk of a severe neurological event, comprising: receiving, from one or more EEG sensors adapted to sense neurological activity of a patient, EEG data during at least a postictal phase of each of one or more seizures;receiving at least one of: respiratory data during at least the postictal phase of each of the one or more seizures from one or more respiration sensors adapted to sense respiratory activity of the patient; orEKG data during at least the postictal phase of each of the one or more seizures from one or more EKG sensors adapted to sense heart activity of the patient;detecting, from the EEG data, at least one postictal EEG suppression period, wherein a postictal EEG suppression period is detected when the EEG data crosses an EEG threshold for at least a predetermined time period;detecting, from the at least one of the respiratory data or the EKG data, that at least one of a respiration of the patient has fallen below a first threshold or an EKG measurement of the patient has fallen below a second threshold;identifying the increased risk of the severe neurological event based on the detected at least one postictal suppression period and the at least one of the respiration falling below the first threshold or the EKG measurement falling below the second threshold; andproviding, responsive to identifying the increased risk of the severe neurological event, at least one of an alert indicating the increased risk of the severe neurological event of the patient or a stimulation to the patient to assist in preventing the severe neurological event.
  • 12. The method of claim 11, wherein the severe neurological event is sudden unexplained death in epilepsy (SUDEP).
  • 13. The method of claim 11, further comprising detecting a plurality of postictal EEG suppression periods interleaved with postictal EEG non-suppression periods during each of at least one postictal phase of the one or more seizures from the EEG data.
  • 14. The method of claim 13, further comprising detecting a trend of generally increasing duration with time of the plurality of postictal EEG suppression periods during the postictal phase of one or more seizures; wherein the increased risk of the severe neurological event is further identified based on the trend.
  • 15. The method of claim 13, wherein at least a first EEG suppression period of the plurality of postictal EEG suppression periods occurs after a first seizure and at least a second EEG suppression period of the plurality of postictal EEG suppression periods occurs after a second seizure, the second seizure occurring after the first seizure.
  • 16. The method of claim 11, further comprising triggering an alarm in response to identifying the increased risk of the severe neurological event.
  • 17. The method of claim 11, further comprising activating a personal medical delivery system in response to identifying the increased risk of the severe neurological event.
  • 18. The method of claim 11, wherein receiving the EEG data comprises receiving the EEG data remotely, and wherein receiving the at least one of the respiratory data or the EKG data comprises receiving the at least one of the respiratory data or the EKG data remotely.
  • 19. The method of claim 11, wherein receiving the at least one of the respiratory data or the EKG data comprises receiving the at least one of the respiratory data or the EKG data in response to detecting the at least one postictal EEG suppression period; and wherein detecting that the at least one of the respiratory data of the patient has fallen below the first threshold or the EKG measurement of the patient has fallen below the second threshold comprises detecting that the at least one of the respiration of the patient has fallen below the first threshold or the EKG measurement of the patient has fallen below the second threshold in response to detecting the at least one postictal EEG suppression period.
  • 20. A system for identification of an increased risk of a severe neurological event, comprising: an electroencephalogram (EEG) monitoring unit configured to receive EEG data generated by one or more EEG sensors adapted to sense neurological activity of a patient during at least a postictal phase of each of one or more seizures;at least one of: a respiration monitoring unit configured to receive respiration data generated by one or more respiration sensors adapted to sense respiratory activity of the patient during at least the postictal phase of each of the one or more seizures, oran electrocardiogram (EKG) monitoring unit configured to receive EKG data generated by one or more EKG sensors adapted to sense EKG activity of the patient during at least the postictal phase of each of the one or more seizures; anda processing unit configured to:receive the EEG data from the EEG monitoring unit;receive the at least one of the respiratory data from the respiratory monitoring unit or the EKG data from the EKG monitoring unit;detect, from the EEG data, at least one postictal EEG suppression period, wherein a postictal EEG suppression period is detected when the EEG data crosses an EEG threshold for at least a predetermined time period;detect, from the at least one of the respiratory data or the EKG data, that at least one of a respiration of the patient has fallen below a first threshold or an EKG measurement of the patient has fallen below a second threshold;identify the increased risk of the severe neurological event based on the detected at least one postictal suppression period and the at least one of the respiration falling below the first threshold or the EKG measurement falling below the second threshold; andprovide, responsive to identifying the increased risk of the severe neurological event, at least one of an alert indicating the increased risk of the severe neurological event of the patient or a stimulation to the patient to assist in preventing the severe neurological event.
CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No. 13/453,746, titled “Methods, Systems and Apparatuses for Detecting Increased Risk of Sudden Death,” filed Apr. 23, 2012, the disclosure of which is incorporated by reference herein in its entirety.

US Referenced Citations (626)
Number Name Date Kind
4172459 Hepp Oct 1979 A
4197856 Northrop Apr 1980 A
4291699 Geddes et al. Sep 1981 A
4295474 Fischell Oct 1981 A
4320766 Alihanka et al. Mar 1982 A
4541432 Molina-Negro et al. Sep 1985 A
4573481 Bullara Mar 1986 A
4702254 Zabara Oct 1987 A
4867164 Zabara Sep 1989 A
4920979 Bullara May 1990 A
4949721 Toriu et al. Aug 1990 A
4979511 Terry, Jr. Dec 1990 A
5025807 Zabara Jun 1991 A
5062169 Kennedy et al. Nov 1991 A
5113869 Nappholz et al. May 1992 A
5137020 Wayne et al. Aug 1992 A
5154172 Terry et al. Oct 1992 A
5179950 Stanislaw Jan 1993 A
5186170 Varrichio et al. Feb 1993 A
5188104 Wernicke et al. Feb 1993 A
5194847 Taylor et al. Mar 1993 A
5203326 Collins Apr 1993 A
5205285 Baker, Jr. Apr 1993 A
5213568 Lattin et al. May 1993 A
5215086 Terry, Jr. et al. Jun 1993 A
5215089 Baker, Jr. Jun 1993 A
5222494 Baker, Jr. Jun 1993 A
5231988 Wernicke et al. Aug 1993 A
5235980 Varrichio et al. Aug 1993 A
5237991 Baker et al. Aug 1993 A
5243980 Mehra Sep 1993 A
5251634 Weinberg Oct 1993 A
5263480 Wernicke et al. Nov 1993 A
5269302 Swartz et al. Dec 1993 A
5299569 Wernicke et al. Apr 1994 A
5304206 Baker, Jr. et al. Apr 1994 A
5307263 Brown Apr 1994 A
5313953 Yomtov et al. May 1994 A
5330507 Schwartz Jul 1994 A
5330515 Rutecki et al. Jul 1994 A
5334221 Bardy Aug 1994 A
5335657 Terry, Jr. et al. Aug 1994 A
5357427 Langen et al. Oct 1994 A
5404877 Nolan et al. Apr 1995 A
5425373 Causey, III Jun 1995 A
5441047 David et al. Aug 1995 A
5513649 Gevins et al. May 1996 A
5522862 Testerman et al. Jun 1996 A
5523742 Simkins et al. Jun 1996 A
5531778 Maschino et al. Jul 1996 A
5540730 Terry, Jr. et al. Jul 1996 A
5540734 Zabara Jul 1996 A
5544649 David et al. Aug 1996 A
5544661 Davis et al. Aug 1996 A
5553609 Yaobin et al. Sep 1996 A
5571150 Wernicke et al. Nov 1996 A
5601435 Quy Feb 1997 A
5610590 Johnson et al. Mar 1997 A
5611350 John Mar 1997 A
5645077 Foxlin Jul 1997 A
5645570 Corbucci Jul 1997 A
5651378 Matheny et al. Jul 1997 A
5658318 Stroetmann et al. Aug 1997 A
5683422 Rise Nov 1997 A
5690681 Geddes et al. Nov 1997 A
5690688 Noren et al. Nov 1997 A
5700282 Zabara Dec 1997 A
5707400 Terry, Jr. et al. Jan 1998 A
5716377 Rise et al. Feb 1998 A
5720771 Snell Feb 1998 A
5722999 Snell Mar 1998 A
5743860 Hively et al. Apr 1998 A
5748113 Torch May 1998 A
5759199 Snell et al. Jun 1998 A
5800474 Benabid et al. Sep 1998 A
5807284 Foxlin Sep 1998 A
5808552 Wiley et al. Sep 1998 A
5792186 Rise Nov 1998 A
5833709 Rise et al. Nov 1998 A
5853005 Scanlon Dec 1998 A
5879309 Johnson et al. Mar 1999 A
5905436 Dwight et al. May 1999 A
5913876 Taylor et al. Jun 1999 A
5916181 Socci et al. Jun 1999 A
5916239 Geddes et al. Jun 1999 A
5928272 Adkins et al. Jul 1999 A
5941906 Barreras et al. Aug 1999 A
5942979 Luppino Aug 1999 A
5978702 Ward et al. Nov 1999 A
5978972 Stewart et al. Nov 1999 A
5987352 Klein et al. Nov 1999 A
5995868 Dorfmeister et al. Nov 1999 A
6016449 Fischell et al. Jan 2000 A
6018682 Rise Jan 2000 A
6048324 Socci et al. Apr 2000 A
6061593 Fischell et al. May 2000 A
6073048 Kieval et al. Jun 2000 A
6083249 Familoni Jul 2000 A
6091992 Bourgeois et al. Jul 2000 A
6095991 Krausman et al. Aug 2000 A
6104956 Naritoku et al. Aug 2000 A
6115628 Stadler et al. Sep 2000 A
6115630 Stadler et al. Sep 2000 A
6128538 Fischell et al. Oct 2000 A
6134474 Fischell et al. Oct 2000 A
6162191 Foxlin Dec 2000 A
6163281 Torch Dec 2000 A
6167311 Rezai Dec 2000 A
6171239 Humphrey Jan 2001 B1
6175764 Loeb et al. Jan 2001 B1
6200331 Swartz et al. Mar 2001 B1
6205359 Boveja Mar 2001 B1
6208894 Schulman et al. Mar 2001 B1
6208902 Boveja Mar 2001 B1
6221908 Kilgard et al. Apr 2001 B1
6246344 Torch Jun 2001 B1
6248080 Miesel et al. Jun 2001 B1
6253109 Gielen Jun 2001 B1
6264614 Albert et al. Jul 2001 B1
6269270 Boveja Jul 2001 B1
6272379 Fischell et al. Aug 2001 B1
6304775 Iasemidis et al. Oct 2001 B1
6315740 Singh Nov 2001 B1
6324421 Stadler et al. Nov 2001 B1
6337997 Rise Jan 2002 B1
6339725 Naritoku et al. Jan 2002 B1
6341236 Osorio et al. Jan 2002 B1
6356784 Lozano et al. Mar 2002 B1
6356788 Boveja Mar 2002 B2
6358203 Bardy Mar 2002 B2
6361507 Foxlin Mar 2002 B1
6361508 Johnson et al. Mar 2002 B1
6366813 DiLorenzo Apr 2002 B1
6366814 Boveja et al. Apr 2002 B1
6374140 Rise Apr 2002 B1
6397100 Stadler et al. May 2002 B2
6427086 Fischell et al. Jul 2002 B1
6429217 Puskas Aug 2002 B1
6441731 Hess Aug 2002 B1
6449512 Boveja Sep 2002 B1
6459936 Fischell et al. Oct 2002 B2
6463328 John Oct 2002 B1
6466822 Pless Oct 2002 B1
6473639 Fischell et al. Oct 2002 B1
6473644 Terry et al. Oct 2002 B1
6477418 Plicchi et al. Nov 2002 B2
6480743 Kirkpatrick et al. Nov 2002 B1
6484132 Hively et al. Nov 2002 B1
6497655 Linberg et al. Dec 2002 B1
6501983 Natarajan et al. Dec 2002 B1
6505074 Boveja et al. Jan 2003 B2
6532388 Hill et al. Mar 2003 B1
6539263 Schiff et al. Mar 2003 B1
6542081 Torch Apr 2003 B2
6542774 Hill et al. Apr 2003 B2
6549804 Osorio et al. Apr 2003 B1
6556868 Naritoku et al. Apr 2003 B2
6560486 Osorio et al. May 2003 B1
6564102 Boveja May 2003 B1
6587719 Barrett et al. Jul 2003 B1
6587727 Osorio et al. Jul 2003 B2
6594524 Esteller et al. Jul 2003 B2
6599250 Webb et al. Jul 2003 B2
6600956 Maschino et al. Jul 2003 B2
6609025 Barrett et al. Aug 2003 B2
6610713 Tracey Aug 2003 B2
6611715 Boveja Aug 2003 B1
6611783 Kelly et al. Aug 2003 B2
6615081 Boveja Sep 2003 B1
6615085 Boveja Sep 2003 B1
6622038 Barrett et al. Sep 2003 B2
6622041 Terry, Jr. et al. Sep 2003 B2
6622047 Barrett et al. Sep 2003 B2
6628985 Sweeney et al. Sep 2003 B2
6628987 Hill et al. Sep 2003 B1
6629990 Putz et al. Oct 2003 B2
6647296 Fischell et al. Nov 2003 B2
6656125 Misczynski et al. Dec 2003 B2
6656960 Puskas Dec 2003 B2
6668191 Bogeja Dec 2003 B1
6671555 Gielen et al. Dec 2003 B2
6671556 Osorio et al. Dec 2003 B2
6684105 Cohen et al. Jan 2004 B2
6721603 Zabara et al. Apr 2004 B2
6730047 Socci et al. May 2004 B2
6731979 MacDonald May 2004 B2
6735474 Loeb et al. May 2004 B1
6738671 Christopherson et al. May 2004 B2
6760626 Boveja Jul 2004 B1
6763256 Kimball et al. Jul 2004 B2
6768969 Nikitin et al. Jul 2004 B1
6786877 Foxlin Sep 2004 B2
6788975 Whitehurst et al. Sep 2004 B1
6793670 Osorio et al. Sep 2004 B2
6819953 Yonce et al. Nov 2004 B2
6819956 DiLorenzo Nov 2004 B2
6832114 Whitehurst et al. Dec 2004 B1
6836685 Fitz Dec 2004 B1
6850601 Jones et al. Feb 2005 B2
6879850 Kimball Apr 2005 B2
6885888 Rezai Apr 2005 B2
6904390 Nikitin et al. Jun 2005 B2
6920357 Osorio et al. Jul 2005 B2
6923784 Stein Aug 2005 B2
6931274 Williams Aug 2005 B2
6934580 Osorio et al. Aug 2005 B1
6934585 Schloss et al. Aug 2005 B1
6944501 Pless Sep 2005 B1
6957107 Rogers et al. Oct 2005 B2
6959215 Gliner et al. Oct 2005 B2
6961618 Osorio et al. Nov 2005 B2
6976958 Quy Dec 2005 B2
6984993 Ariav Jan 2006 B2
6985771 Fischell et al. Jan 2006 B2
6990377 Gliner et al. Jan 2006 B2
7006859 Osorio et al. Feb 2006 B1
7006872 Gielen et al. Feb 2006 B2
7010351 Firlik et al. Mar 2006 B2
7024247 Gliner et al. Apr 2006 B2
7035684 Lee Apr 2006 B2
7043305 Kenknight et al. May 2006 B2
7047074 Connelly et al. May 2006 B2
7054686 MacDonald May 2006 B2
7054792 Frei et al. May 2006 B2
7058453 Nelson et al. Jun 2006 B2
7068842 Liang et al. Jun 2006 B2
7076288 Skinner Jul 2006 B2
7077810 Lange et al. Jul 2006 B2
7079977 Osorio et al. Jul 2006 B2
7089059 Pless Aug 2006 B1
7104947 Riehl Sep 2006 B2
7110820 Tcheng et al. Sep 2006 B2
7112319 Broderick et al. Sep 2006 B2
7127370 Kelly et al. Oct 2006 B2
7134996 Bardy Nov 2006 B2
7139677 Hively Nov 2006 B2
7146211 Frei et al. Dec 2006 B2
7146217 Firlik et al. Dec 2006 B2
7146218 Esteller et al. Dec 2006 B2
7149572 Frei et al. Dec 2006 B2
7156808 Quy Jan 2007 B2
7156809 Quy Jan 2007 B2
7164941 Misczynski et al. Jan 2007 B2
7167743 Heruth et al. Jan 2007 B2
7167750 Knudson et al. Jan 2007 B2
7174206 Frei et al. Feb 2007 B2
7177678 Osorio et al. Feb 2007 B1
7188053 Nikitin et al. Mar 2007 B2
RE39539 Torch Apr 2007 E
7204833 Osorio et al. Apr 2007 B1
7209786 Brockway et al. Apr 2007 B2
7209787 DiLorenzo Apr 2007 B2
7221981 Gliner May 2007 B2
7228167 Kara et al. Jun 2007 B2
7231254 DiLorenzo Jun 2007 B2
7236830 Gliner Jun 2007 B2
7236831 Firlik et al. Jun 2007 B2
7242983 Frei et al. Jul 2007 B2
7242984 DiLorenzo Jul 2007 B2
7254439 Misczynski et al. Aug 2007 B2
7263467 Sackellares et al. Aug 2007 B2
7274298 Frank Sep 2007 B2
7277758 DiLorenzo Oct 2007 B2
7280867 Frei et al. Oct 2007 B2
7282030 Frei et al. Oct 2007 B2
7289844 Misczynski et al. Oct 2007 B2
7292890 Whitehurst et al. Nov 2007 B2
7295881 Cohen et al. Nov 2007 B2
7299096 Balzer et al. Nov 2007 B2
7302298 Lowry et al. Nov 2007 B2
7304580 Sullivan et al. Dec 2007 B2
7305268 Gliner et al. Dec 2007 B2
7313440 Miesel Dec 2007 B2
7314451 Halperin et al. Jan 2008 B2
7321837 Osorio et al. Jan 2008 B2
7324850 Persen et al. Jan 2008 B2
7324851 DiLorenzo Jan 2008 B1
7330760 Heruth et al. Feb 2008 B2
7346391 Osorio et al. Mar 2008 B1
7353063 Simms Apr 2008 B2
7353064 Gliner et al. Apr 2008 B2
7373199 Sackellares et al. May 2008 B2
7385443 Denison Jun 2008 B1
7389144 Osorio et al. Jun 2008 B1
7389147 Wahlstrand et al. Jun 2008 B2
7395113 Heruth et al. Jul 2008 B2
7395216 Rosenfeld et al. Jul 2008 B2
7401008 Frei et al. Jul 2008 B2
7403820 DiLorenzo Jul 2008 B2
7420472 Tran Sep 2008 B2
7433732 Carney et al. Oct 2008 B1
7437196 Wyler et al. Oct 2008 B2
7447545 Heruth et al. Nov 2008 B2
7454245 Armstrong et al. Nov 2008 B2
7483747 Gliner et al. Jan 2009 B2
7488293 Marcovecchio et al. Feb 2009 B2
7488294 Torch Feb 2009 B2
7491181 Heruth et al. Feb 2009 B2
7494464 Rzesnitzek et al. Feb 2009 B2
7502643 Farringdon et al. Mar 2009 B2
7515054 Torch Apr 2009 B2
7539532 Tran May 2009 B2
7539533 Tran May 2009 B2
7539543 Schiff et al. May 2009 B2
7558622 Tran Jul 2009 B2
7565132 Ben Ayed Jul 2009 B2
7590453 Heruth et al. Sep 2009 B2
7620456 Gliner et al. Nov 2009 B2
7629890 Sullivan et al. Dec 2009 B2
7643655 Liang et al. Jan 2010 B2
7647121 Wahlstrand et al. Jan 2010 B2
7658112 Nakamura Feb 2010 B2
7666151 Sullivan et al. Feb 2010 B2
7714757 Denison et al. May 2010 B2
7717848 Heruth et al. May 2010 B2
RE41376 Torch Jun 2010 E
7733224 Tran Jun 2010 B2
7747318 John et al. Jun 2010 B2
7761145 Virag et al. Jul 2010 B2
7769464 Gerber et al. Aug 2010 B2
7775993 Heruth et al. Aug 2010 B2
7792583 Miesel et al. Sep 2010 B2
7801603 Westlund et al. Sep 2010 B2
7801618 Pless Sep 2010 B2
7801743 Graves et al. Sep 2010 B2
7813802 Tcheng et al. Oct 2010 B2
7822481 Gerber et al. Oct 2010 B2
7827011 DeVaul et al. Nov 2010 B2
7831305 Gliner Nov 2010 B2
7847628 Denison Dec 2010 B2
7866212 Ariav et al. Jan 2011 B2
7899545 John Mar 2011 B2
7935076 Estes et al. May 2011 B2
RE42471 Torch Jun 2011 E
7957809 Bourget et al. Jun 2011 B2
7965833 Meir et al. Jun 2011 B2
7974671 Fujiwara et al. Jul 2011 B2
7996076 Burns et al. Aug 2011 B2
7999857 Bunn et al. Aug 2011 B2
8000789 Denison Aug 2011 B2
8000794 Lozano Aug 2011 B2
8021299 Miesel et al. Sep 2011 B2
8027730 John Sep 2011 B2
8027737 Kokones et al. Sep 2011 B2
8075499 Nathan et al. Dec 2011 B2
8109891 Kramer et al. Feb 2012 B2
10327661 Iasemidis Jun 2019 B1
20010032059 Kelly et al. Oct 2001 A1
20020072782 Osorio et al. Jun 2002 A1
20020082480 Riff et al. Jun 2002 A1
20020099417 Naritoku et al. Jul 2002 A1
20020116030 Rezai Aug 2002 A1
20020151939 Rezai Oct 2002 A1
20020188214 Misczynski et al. Dec 2002 A1
20030040680 Hassert et al. Feb 2003 A1
20030074032 Gliner Apr 2003 A1
20030083716 Nicolelis et al. May 2003 A1
20030083726 Zeijlemaker et al. May 2003 A1
20030125786 Gliner et al. Jul 2003 A1
20030130706 Sheffield et al. Jul 2003 A1
20030144829 Geatz et al. Jul 2003 A1
20030181954 Rezai Sep 2003 A1
20030181958 Dobak, III Sep 2003 A1
20030195588 Fischell et al. Oct 2003 A1
20030208212 Cigaina Nov 2003 A1
20030210147 Humbard Nov 2003 A1
20030212440 Boveja Nov 2003 A1
20030236474 Singh Dec 2003 A1
20030236558 Whitehurst et al. Dec 2003 A1
20040006278 Webb et al. Jan 2004 A1
20040030365 Rubin Feb 2004 A1
20040088024 Firlik et al. May 2004 A1
20040111045 Sullivan et al. Jun 2004 A1
20040122484 Hatlestad et al. Jun 2004 A1
20040122485 Stahmann et al. Jun 2004 A1
20040133119 Osorio et al. Jul 2004 A1
20040138516 Osorio et al. Jul 2004 A1
20040138517 Osorio et al. Jul 2004 A1
20040138647 Osorio et al. Jul 2004 A1
20040138711 Osorio et al. Jul 2004 A1
20040153129 Pless et al. Aug 2004 A1
20040158119 Osorio et al. Aug 2004 A1
20040158165 Yonce et al. Aug 2004 A1
20040172085 Knudson et al. Sep 2004 A1
20040172091 Rezai Sep 2004 A1
20040172094 Cohen et al. Sep 2004 A1
20040176812 Knudson et al. Sep 2004 A1
20040176831 Gliner et al. Sep 2004 A1
20040199212 Fischell et al. Oct 2004 A1
20040225335 Whitehurst et al. Nov 2004 A1
20040249302 Donoghue et al. Dec 2004 A1
20040249416 Yun et al. Dec 2004 A1
20040267152 Pineda Dec 2004 A1
20050004621 Boveja et al. Jan 2005 A1
20050020887 Goldberg Jan 2005 A1
20050021092 Yun et al. Jan 2005 A1
20050021103 DiLorenzo Jan 2005 A1
20050021104 DiLorenzo Jan 2005 A1
20050021105 Firlik et al. Jan 2005 A1
20050021106 Firlik et al. Jan 2005 A1
20050021107 Firlik et al. Jan 2005 A1
20050021118 Genau et al. Jan 2005 A1
20050022606 Partin et al. Feb 2005 A1
20050027284 Lozano et al. Feb 2005 A1
20050033378 Sheffield et al. Feb 2005 A1
20050033379 Lozano et al. Feb 2005 A1
20050038484 Knudson et al. Feb 2005 A1
20050049515 Misczynski et al. Mar 2005 A1
20050049655 Boveja et al. Mar 2005 A1
20050060001 Singhal et al. Mar 2005 A1
20050065562 Rezai Mar 2005 A1
20050065573 Rezai Mar 2005 A1
20050065574 Rezai Mar 2005 A1
20050065575 Dobak Mar 2005 A1
20050070971 Fowler et al. Mar 2005 A1
20050075701 Shafer Apr 2005 A1
20050075702 Shafer Apr 2005 A1
20050101873 Misczynski et al. May 2005 A1
20050107716 Eaton et al. May 2005 A1
20050119703 DiLorenzo Jun 2005 A1
20050124901 Misczynski et al. Jun 2005 A1
20050131467 Boveja Jun 2005 A1
20050131485 Knudson et al. Jun 2005 A1
20050131486 Boveja et al. Jun 2005 A1
20050131493 Boveja et al. Jun 2005 A1
20050143786 Boveja Jun 2005 A1
20050148893 Misczynski et al. Jul 2005 A1
20050148894 Misczynski et al. Jul 2005 A1
20050148895 Misczynski et al. Jul 2005 A1
20050153885 Yun et al. Jul 2005 A1
20050154425 Boveja et al. Jul 2005 A1
20050154426 Boveja et al. Jul 2005 A1
20050165458 Boveja et al. Jul 2005 A1
20050177200 George et al. Aug 2005 A1
20050182389 Laporte et al. Aug 2005 A1
20050187590 Boveja et al. Aug 2005 A1
20050187796 Rosenfeld et al. Aug 2005 A1
20050192644 Boveja et al. Sep 2005 A1
20050197590 Osorio et al. Sep 2005 A1
20050203366 Donoghue et al. Sep 2005 A1
20050245971 Brockway et al. Nov 2005 A1
20050261542 Riehl Nov 2005 A1
20050277998 Tracey et al. Dec 2005 A1
20050283200 Rezai et al. Dec 2005 A1
20050283201 Machado et al. Dec 2005 A1
20050288600 Zhang et al. Dec 2005 A1
20050288760 Machado et al. Dec 2005 A1
20060009815 Boveja et al. Jan 2006 A1
20060018833 Murphy et al. Jan 2006 A1
20060074450 Boveja et al. Apr 2006 A1
20060079936 Boveja et al. Apr 2006 A1
20060094971 Drew May 2006 A1
20060094972 Drew May 2006 A1
20060095081 Zhou et al. May 2006 A1
20060106430 Fowler et al. May 2006 A1
20060111644 Guttag et al. May 2006 A1
20060122525 Shusterman Jun 2006 A1
20060122864 Gottesman et al. Jun 2006 A1
20060135877 Giftakis et al. Jun 2006 A1
20060135881 Giftakis et al. Jun 2006 A1
20060149139 Bonmassar et al. Jul 2006 A1
20060155495 Osorio et al. Jul 2006 A1
20060161459 Rosenfeld et al. Jul 2006 A9
20060167497 Armstrong et al. Jul 2006 A1
20060173493 Armstrong et al. Aug 2006 A1
20060173522 Osorio Aug 2006 A1
20060190056 Fowler et al. Aug 2006 A1
20060195163 Kenknight et al. Aug 2006 A1
20060200206 Firlik et al. Sep 2006 A1
20060212091 Lozano et al. Sep 2006 A1
20060212097 Varadan et al. Sep 2006 A1
20060224067 Giftakis et al. Oct 2006 A1
20060224191 DiLorenzo Oct 2006 A1
20060241697 Libbus et al. Oct 2006 A1
20060241725 Libbus et al. Oct 2006 A1
20060293720 DiLorenzo Dec 2006 A1
20070027486 Armstrong Feb 2007 A1
20070027497 Parnis Feb 2007 A1
20070027498 Maschino et al. Feb 2007 A1
20070027500 Maschino et al. Feb 2007 A1
20070032734 Najafi et al. Feb 2007 A1
20070032834 Gliner et al. Feb 2007 A1
20070043392 Gliner et al. Feb 2007 A1
20070055320 Weinand Mar 2007 A1
20070073150 Gopalsami et al. Mar 2007 A1
20070073355 DiLorenzo Mar 2007 A1
20070088403 Wyler et al. Apr 2007 A1
20070088404 Wyler et al. Apr 2007 A1
20070100278 Frei et al. May 2007 A1
20070100392 Maschino et al. May 2007 A1
20070142862 DiLorenzo Jun 2007 A1
20070142873 Esteller et al. Jun 2007 A1
20070149952 Bland et al. Jun 2007 A1
20070150024 Leyde et al. Jun 2007 A1
20070150025 DiLorenzo et al. Jun 2007 A1
20070156450 Roehm et al. Jul 2007 A1
20070161919 DiLorenzo Jul 2007 A1
20070162086 DiLorenzo Jul 2007 A1
20070167991 DiLorenzo Jul 2007 A1
20070173901 Reeve Jul 2007 A1
20070173902 Maschino et al. Jul 2007 A1
20070179534 Firlik et al. Aug 2007 A1
20070179557 Maschino et al. Aug 2007 A1
20070179558 Gliner et al. Aug 2007 A1
20070208212 DiLorenzo Sep 2007 A1
20070213785 Osorio et al. Sep 2007 A1
20070233192 Craig Oct 2007 A1
20070239210 Libbus et al. Oct 2007 A1
20070242661 Tran Oct 2007 A1
20070244407 Osorio Oct 2007 A1
20070249953 Frei et al. Oct 2007 A1
20070249954 Virag et al. Oct 2007 A1
20070255147 Drew et al. Nov 2007 A1
20070255155 Drew et al. Nov 2007 A1
20070260147 Giftakis et al. Nov 2007 A1
20070260289 Giftakis et al. Nov 2007 A1
20070265536 Giftakis et al. Nov 2007 A1
20070272260 Nikitin et al. Nov 2007 A1
20070282177 Pilz Dec 2007 A1
20070287931 DiLorenzo Dec 2007 A1
20080004904 Tran Jan 2008 A1
20080021341 Harris et al. Jan 2008 A1
20080027347 Harris et al. Jan 2008 A1
20080027348 Harris et al. Jan 2008 A1
20080027515 Harris et al. Jan 2008 A1
20080033502 Harris et al. Feb 2008 A1
20080033503 Fowler et al. Feb 2008 A1
20080033508 Frei et al. Feb 2008 A1
20080046035 Fowler et al. Feb 2008 A1
20080064934 Frei et al. Mar 2008 A1
20080071323 Lowry et al. Mar 2008 A1
20080077028 Schaldach et al. Mar 2008 A1
20080081958 Denison et al. Apr 2008 A1
20080103548 Fowler et al. May 2008 A1
20080114417 Leyde May 2008 A1
20080119900 DiLorenzo May 2008 A1
20080125820 Stahmann et al. May 2008 A1
20080139870 Gliner et al. Jun 2008 A1
20080146890 LeBoeuf et al. Jun 2008 A1
20080146958 Guillory et al. Jun 2008 A1
20080146959 Sheffield et al. Jun 2008 A1
20080161712 Leyde Jul 2008 A1
20080161713 Leyde et al. Jul 2008 A1
20080161879 Firlik et al. Jul 2008 A1
20080161880 Firlik et al. Jul 2008 A1
20080161881 Firlik et al. Jul 2008 A1
20080161882 Firlik et al. Jul 2008 A1
20080183096 Snyder et al. Jul 2008 A1
20080183097 Leyde et al. Jul 2008 A1
20080208013 Zhang et al. Aug 2008 A1
20080208074 Snyder et al. Aug 2008 A1
20080208284 Rezai et al. Aug 2008 A1
20080208781 Snyder Aug 2008 A1
20080234598 Snyder et al. Sep 2008 A1
20080255582 Harris Oct 2008 A1
20080258907 Kalpaxis Oct 2008 A1
20080269579 Schiebler Oct 2008 A1
20080275327 Faarbaek et al. Nov 2008 A1
20080275328 Jones Nov 2008 A1
20080275349 Halperin et al. Nov 2008 A1
20080281376 Gerber et al. Nov 2008 A1
20080281381 Gerber et al. Nov 2008 A1
20080281550 Hogle et al. Nov 2008 A1
20080319281 Aarts Dec 2008 A1
20090030345 Bonnet et al. Jan 2009 A1
20090040052 Cameron et al. Feb 2009 A1
20090054737 Magar et al. Feb 2009 A1
20090054742 Kaminska et al. Feb 2009 A1
20090054795 Misczynski et al. Feb 2009 A1
20090060287 Hyde et al. Mar 2009 A1
20090076350 Bly et al. Mar 2009 A1
20090099624 Kokones et al. Apr 2009 A1
20090099627 Molnar et al. Apr 2009 A1
20090105785 Wei et al. Apr 2009 A1
20090124923 Sackellares et al. May 2009 A1
20090137921 Kramer et al. May 2009 A1
20090227882 Foo Sep 2009 A1
20090227888 Salmi et al. Sep 2009 A1
20090291150 Welsh et al. Nov 2009 A1
20090322540 Richardson et al. Dec 2009 A1
20100010382 Panken Jan 2010 A1
20100010392 Skelton et al. Jan 2010 A1
20100010583 Panken et al. Jan 2010 A1
20100023348 Hardee et al. Jan 2010 A1
20100056878 Partin et al. Mar 2010 A1
20100106217 Colborn Apr 2010 A1
20100109875 Ayon et al. May 2010 A1
20100121214 Giftakis et al. May 2010 A1
20100168603 Himes et al. Jul 2010 A1
20100198289 Kameli Aug 2010 A1
20100217533 Nadkarni et al. Aug 2010 A1
20100223020 Goetz Sep 2010 A1
20100228103 Schecter Sep 2010 A1
20100228314 Goetz Sep 2010 A1
20100268056 Picard et al. Oct 2010 A1
20100274303 Bukhman Oct 2010 A1
20100280336 Giftakis et al. Nov 2010 A1
20100280578 Skelton et al. Nov 2010 A1
20100280579 Denison et al. Nov 2010 A1
20100286567 Wolfe et al. Nov 2010 A1
20100298661 McCombie et al. Nov 2010 A1
20100298742 Perlman et al. Nov 2010 A1
20100305665 Miesel et al. Dec 2010 A1
20100312188 Robertson et al. Dec 2010 A1
20110029044 Hyde et al. Feb 2011 A1
20110040204 Ivorra et al. Feb 2011 A1
20110040546 Gerber et al. Feb 2011 A1
20110060252 Simonsen et al. Mar 2011 A1
20110066062 Banet et al. Mar 2011 A1
20110066081 Goto Mar 2011 A1
20110137372 Makous et al. Jun 2011 A1
20110172545 Grudic et al. Jul 2011 A1
20110230730 Quigg et al. Sep 2011 A1
20110245629 Giftakis et al. Oct 2011 A1
20110251468 Osorio Oct 2011 A1
20110251469 Varadan Oct 2011 A1
20110270117 Warwick et al. Nov 2011 A1
20110270134 Skelton Nov 2011 A1
20110295127 Sandler et al. Dec 2011 A1
20110306845 Osorio Dec 2011 A1
20110306846 Osorio Dec 2011 A1
20110313484 Hincapie Ordonez et al. Dec 2011 A1
20120226108 Osorio Sep 2012 A1
20120271372 Osorio Oct 2012 A1
20120296175 Poh et al. Nov 2012 A1
20130116514 Kroner et al. May 2013 A1
Foreign Referenced Citations (23)
Number Date Country
944411 Apr 2001 EP
1145736 Oct 2001 EP
1486232 Dec 2004 EP
2026870 Jul 1978 GB
2079610 Jul 1978 GB
WO 9302744 Feb 1993 WO
WO 0064336 Nov 2000 WO
WO 20040036377 Apr 2004 WO
WO 20050007120 Jan 2005 WO
WO 20050053788 Jun 2005 WO
WO 20050067599 Jul 2005 WO
WO 20060050144 May 2006 WO
WO 20060122148 Nov 2006 WO
WO 20060134359 Dec 2006 WO
WO 20070066343 Jun 2007 WO
WO 20070072425 Jun 2007 WO
WO 20070124126 Nov 2007 WO
WO 20070124190 Nov 2007 WO
WO 20070124192 Nov 2007 WO
WO 20070142523 Dec 2007 WO
WO 20080045597 Apr 2008 WO
WO 20080054580 May 2008 WO
WO 20110126931 Oct 2011 WO
Non-Patent Literature Citations (63)
Entry
“Heart rate variability: Standards of measurement, physiological interpretation and clinical use”, Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, Circulation, Mar. 1993, vol. 93, Nos. pp. 1043-1065.
Bachman, D. et al., “Effects of Vagal Volleys and Serotonin on Units of Cingulate Cortex in Monkeys”, Brain Research, vol. 130, 1977, pp. 253-269.
Baevskii, R., “Analysis of Heart Rate Variability in Space Medicine”, Human Physiology, vol. 28, No. 2, 2002, pp. 202-213.
Baevsky, R., “Autonomic cardiovascular and respiratory control during prolonged spaceflights aboard the International Space Station”, Journal of Applied Physiological, vol. 103, 2007, pp. 156-161.
Boon, P. et al., “Programmed and Magnet-Induced Vagus Nerve Stimulation for Refractory Epilepsy”, Journal of Clinical Neurophysiology, vol. 18, No. 5, 2001, p. 402-407.
Boon, P. et al., “Vagus Nerve Stimulation for Epilepsy, Clinical Efficacy of Programmed and Magnet Stimulation”, Acta Neurochirurgica Supplement, vol. 79, 2002, pp. 93-98.
Borovikova, L. et al., “Vagus Nerve Stimulation Attenuates the Systemic Inflammatory Response to Endotoxin”, Letters to Nature, vol. 405, May 2000, pp. 458-462.
Brack, K. et al., “Interaction Between Direct Sympathetic and Vagus Nerve Stimulation on Heart Rate in the Isolated Rabbit Heart”, Experimental Physiology, vol. 89, No. 1, 2004, pp. 128-139.
Chakravarthy, N. et al., “Controlling Synchronization in a Neuron-Level Population Model”, International Journal of Neural Systems, vol. 17, No. 2, 2007, pp. 123-138.
Clark, K. et al., “Posttraining Electrical Stimulation of Vagal Afferents with Concomitant Vagal Efferent Inactivation Enhances Memory Storage Processes in the Rat”, Neurobiology of Learning and Memory, vol. 70, Article No. NL983863, 1998, pp. 364-373.
Digenarro, G. et al., “Ictal Heart rate Increase Precedes EEG Discharge in Drug-Resistant Mesial Temporal Lobe Seizures”, Clinical Neurophysiology, vol. 115, No. 5, May 2004, pp. 1169-1177.
Frei, M. et al., “Left Vagus Nerve Stimulation with the Neurocybernetic Prosthesis has Complex Effects on Heart Rate and on its Variability in Humans”, Epilepsia, vol. 42, Nos. 2001, pp. 1007-1016.
George, M. et al., “Vagus Nerve Stimulation: A New Tool for Brain Research and Therapy”, Society of Biological Psychiatry, vol. 47, 2000, pp. 287-295.
Hallowitz, R. et al., “Effects of Vagal Volleys on Units of Intralaminar and Juxtalaminar Thalamic Nuclei in Monkeys”, Brain Research, vol. 130, No. 2, Jul. 1977, pp. 271-286.
Henry, T., “Therapeutic Mechanisms of Vague Name Stimulation”, Neurology, vol. 59 (Supp. 4), Sep. 2002, pp. S3-S14.
Iasemidis, L. et al., “Dynamical Resetting of the Human Brain at Epileptic: Application of Nonlinear Dynamics and Global Optimization Techniques”, IEEE Transactions on Biomedical Engineering, vol. 51, No. 3, Mar. 2004, pp. 493-508.
Iasemidis, L. et al., “Spatiotemporal Transition to Epileptic Seizures: A Nonlinear Dynamical Analysis of Scalp and Intracranial EEG Recordings”, Spatiotemporal Models in Biological and Artificial Systems, IOS Press, 1997, pp. 81-88.
Iasemidis, L., “Epileptic Seizure Prediction and Control”, IEEE Transactions on Biomedical Engineering, vol. 50, No. 5, May 2003, pp. 549-558.
Zijlmans, M. et al., “Heart Rate Changes and ECG Abnormalities During Epileptic Seizures: Prevalence and Definition of an Objective Clinical Sign”, Epilepsia, vol. 43, Nos. 2002, pp. 847-854.
International Search Report for PCT Patent Application No. PCT/US2013/037703, dated Aug. 23, 2013, 12 pages.
Zabara, J., “Neuroinhibition of Xylaine Induced Emesis”, Pharmacology & Toxicology, vol. 63, Aug. 1988, pp. 70-74.
Kautzner, J. et al., “Utility or Snort-Term Heart Rate Variability for Prediction of Sudden Cardiac Death After Acute Myocardial Infarction”, Acta Univ Palacki Olomuc Fac Med., vol. 141, 1998, pp. 69-73.
Koenig, S. et al., “Vagus Nerve Stimulation Improves Severely Impaired Heart Rate Variability in a Patient with Lennox-Gastaut-Syndrome”, Seizure, vol. 17, Issue 5, Jul. 2008, pp. 469-472.
Koo, B., “EEG Changes with Vagus Nerve Stimulation”, Journal of Clinical Neurophysiology, vol. 18, No. 5, Sep. 2001, pp. 434-441.
Krittayaphong, M. et al., “Heart Rate Variability in Patients with Coronary Artery Disease: Differences in Patients with Higher and Lower Depression Scores”, Psychosomatic Medicine, vol. 59, 1997, pp. 231-235.
Leutmezer, F. et al., “Electrocardiographic Changes at the Onset of Epileptic Seizures”, Epilepsia, vol. 44, No. 3, 2003, pp. 348-354.
Lewis, M. et al., “Vagus Nerve Stimulation Decreases Left Ventricular Contractility in Vivo in the Human and Pig Heart”, The Journal of Physiology, vol. 534, No. 2, 2001, pp. 547-552.
Lhatoo, Samden, D. et al., “An Electroclinical Case-Control Study Of Sudden Unexpected Death In Epilepsy,” Annals of Neurology, 68(6): 787-796, Dec. 29, 2010.
Li, M. et al., “Vagal Nerve Stimulation Markedly Improves Long-Term Survival After Chronic Heart Failure in Rats”, Circulation, Jan. 2004, vol. 109, No. 1, pp. 120-124.
Licht, C., “Association Between Major Depressive Disorder and Heart Rate Variability in the Netherlands Study of Depression and Anxiety (NESDA)”, Arch. Gen. Psychiatry, vol. 65, No. 12, Dec. 2008, pp. 1358-1367.
Lockard, J. et al., “Feasibility and safety of vagal stimulation in monkey model”, Epilepsia, vol. 31 (Supp. 2), 1990, pp. S20-S26.
Long, T. et al., “Effectiveness of Heart Rate Seizure Detection Compared to EEG in an Epilepsy Monitoring Unit (EMU)”, Abstract of AES Proceedings, Epilepsia, vol. 40, Supplement 7, 1999, p. 174.
McClintock, P., Can Noise Actually Boost Brain Power, Physics World, Jul. 2002, vol. 15, pp. 20-21.
Mori, T. et al., “Noise-Induced Entrainment and Stochastic Resonance in Human Brain Waves”, Physical Review Letters, vol. 88, No. 21, 2002, pp. 218101-1-2180101-4.
Mormann, F. et al., “Seizure Prediction: The Long and Winding Road”, Brain, vol. 130, 2007, pp. 314-333.
Nouri, M., “Epilepsy and the Autonomic Nervous System”, emedicine, Updated May 5, 2006, http://www.emedicine.com/neuro/toplo658.htm, pp. 1-14.
O'Donovan, C. et al., “Computerized Seizure Detection Based on Heart Rate Changes”, Abstract of AES Proceedings, Epilepsia, vol. 36, Supplement 4, 1995, p. 7.
O'Regan, M. et al., “Abnormalities in Cardiac and Respiratory Function Observed During Seizures in Childhood”, Developmental Medicine & Child Neurology, vol. 47, 2005, pp. 4-9.
Osorio, I. et al., “An Introduction to contingent (Closed-Loop) Brain Electrical Stimulation for Seizure Blockage, to Ultra-Short-Term Clinical Trials, and to Multidimensional Statistical Analysis of Therapeutic Efficacy”, Journal of Clinical Neurophysiology, vol. 18, No. 6, 2001, pp. 533-544.
Osorio, I. et al., “Automated Seizure Abatement in Humans Using Electrical Stimulation”, Annals of Neurology, vol. 57, No. 2, 2005, pp. 258-268.
Osorio, I. et al., “Toward a Quantitative Multivariate Analysis of the Efficacy of Antiseizure Therapies”, Epilepsy & Behavior, vol. 18, No. 4, Aug. 2010, Academic Press, San Diego, CA, pp. 335-343.
Pathwardhan, R. et al., “Control of Refractory Status Epilepticus Precipitated by Anticonvulsant Withdrawal Using Vagal Nerve Stimulation: A Case Report”, Surgical Neurology, Issue 64, Aug. 2005, pp. 170-173.
PCT Search Report and Written Opinion for International application No. PCT/US2011/054287, dated Mar. 12, 2012, 18 pages.
PCT Search Report and Written Opinion for International Application No. PCT/US2012/027639, dated Oct. 4, 2012, 22 pages.
Poddubnaya, E., “Complex Estimation of Adaption Abilities of the Organism in Children Using the Indices of Responsiveness of the Cardiovascular System and Characteristics of EEG”, Neurophysiology, vol. 38, No. 1, 2006, pp. 63-74.
Robinson, S. et al., Heart Rate Variability Changes as Predictor of Response to Vagal Nerve Stimulation Therapy for Epilepsy', Abstract of AES Proceedings, Epilepsia, vol. 40, Supplement 7, 1999, p. 147.
Rugg-Gunn, F. et al., “Cardiac Arrhythmias in Focal Epilepsy: a Prospective Long-Term Study”, Lancet, vol. 364, Dec. 2004, pp. 2212-2219.
Sajadieh, A. et al., “Increased Heart Rate and Reduced Heart-rate Variability and Associated with Subclinical Inflammation in Middle-Aged and Elderly Subjects with No Apparent Heart Disease”, European Heart Journal, vol. 25, 2004, pp. 363-370.
Schernthaner, C. et al., “Autonomic Epilepsy—The Influence of Epileptic Discharges on Heart Rate and Rhythm”, The Middle European Journal of Medicine, vol. 111, No. 10, 1999, pp. 392-401.
Seyal et al., “Postictal Generalized EEG Suppression Is Linked to Seizure-Associated Respiratory Dysfunction but not Postictal Apnea,” Epilepsia, 53(5): 825-831, Mar. 20, 2012.
Zabara, J., “Inhibition of Experimental Seizures in Canines by Repetitive Vagal Stimulation”, Epilepsia, vol. 33, No. 6, 1992, pp. 1005-1012.
Zabara, J., “Neural Control of Circulation I”, The Physiologist, vol. 28, No. 4, Aug. 1985, pp. 273-277.
So, et al., “Postical Central Apnea as a Cause of SUDEP: Evidence From Near-SUDEP Incident,” Epilepsia, 41(11): 1494-1497, Nov. 1, 2000.
Sunderam, S. et al., Vagal and Sciatic Nerve Stimulation Have Complex, Time-Dependent Effects on Chemically-Induced Seizures: A Controlled Study, Brain Research, vol. 918, 2001, pp. 60-66.
Trry, R. et al., “The Implantaple Neurocybernetic Prostnesis System”, Pacing and Clinical Electrophysiology, vol. 14, No. 1, Jan. 1991, pp. 86-93.
Tubbs, R. et al., “Left-Sided Vagus Nerve Stimulation Decreases Intracranial Pressure Without Resultant Bradycardia in the Pig: A Potential Therapeutic Modality for Humans”, Child's Nervous System, vol. 20, No. 5, May 2004, pp. 309-312.
Umetani, M. et al., “Twenty-Four Hour Time Domain Heart Rate Variability and Heart Rate: Relations to Age and Gender Over Nine Decades”, JACC, vol. 31, No. 3, Mar. 1998, pp. 593-601.
Van Elm Pt, W. et al., “A Model of Heart Rate Changes to Detect Seizures in Severe Epilepsy”, Seizure, vol. 15, 2006, pp. 366-375.
Vonck, K. et al., “The Mechanism of Action of Vagus Nerve Stimulation for Refractory Epilepsy—The Current Status”, Journal of Neurophysiology, vol. 18, No. 5, 2001, pp. 394-401.
Weil, S. et al., “Heart Rate Increase in Otherwise Subclinical Seizures is Different in Temporal Versus Extratemporal Seizure Onset: Support for Temporal Lobe Automatic Influence”, Epileptic Disord., vol. 7, Nos. Sep. 2005, pp. 199-204.
Woodbury, J. et al., “Vagal stimulation reduces the severity of maximal electroshock seizures in intact rats: use of a cuff electrode for stimulating and recording”, Pacing and Clinical Electrophysiology, vol. 14, Jan. 1991, pp. 94-107.
Zabara, J. et al., “Neuroinhibition in the regulation of emesis”, Space Life Sciences, vol. 3, Issue 3, Jun. 1972, pp. 282-292.
Office Action on EP Application No. 13721848.3 dated Aug. 13, 2020. 5 pages.
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