Identifying seizures using heart rate decrease

Information

  • Patent Grant
  • 8725239
  • Patent Number
    8,725,239
  • Date Filed
    Monday, April 25, 2011
    14 years ago
  • Date Issued
    Tuesday, May 13, 2014
    11 years ago
Abstract
Methods and systems for detecting a seizure event, including receiving heart beat data versus time for a patient, detecting an increase in the heart rate of a patient from a baseline heart rate to an elevated heart rate, detecting a decrease in heart rate from the elevated heart rate, for a time interval occurring during said decrease in heart rate, determining at least one of a) a rate of decrease in heart rate and b) a rate of change in a rate of decrease in heart rate, and detecting a seizure event in response to determining at least one of a) a rate of decrease in heart rate greater than a threshold rate of decrease, and b) a rate of change in the rate of decrease less than a threshold rate of change in a rate of decrease.
Description
A. CROSS-REFERENCE TO RELATED APPLICATIONS

This application relates to the following commonly assigned co-pending application entitled:


“Identifying Seizures Using Heart Data From Two or More Windows” U.S. patent application 13/093,613, filed Apr. 25, 2011, Reference No. 100.235.


B. BACKGROUND

1. Technical Field of the Present Disclosure


The present disclosure relates generally to the field of seizure identification and more particularly to the field of identifying seizures by monitoring changes in heart rates.


2. Background of the Present Disclosure


Seizures are characterized by abnormal or excessive neural activity in the brain. Seizures may involve loss of consciousness or awareness, and result in falls, uncontrollable convulsions, etc. Significant injuries may result not only from the neuronal activity in the brain but also from the associated loss of motor function from falls or the inability of the patient to perceive and/or respond appropriately to potential danger or harm.


It is desirable to identify a seizure event as quickly as possible after the beginning of the seizure, to allow appropriate responsive action to be taken. Such actions may include sending an alert signal to the patient or a caregiver, taking remedial action such as making the patient and/or the immediate environment safe (e.g., terminating operation of equipment, sitting or lying down, moving away from known hazards), initiating a treatment therapy, etc. Where rapid detection is not possible or feasible, it is still desirable to be able to identify seizures after they have begun to allow a physician and/or caregiver to assess the patient's condition and determine whether existing therapies are effective or require modification and/or additional therapy modalities (for example, changing or adding additional drug therapies or adding a neurostimulation therapy). Seizure detection algorithms have been proposed using a variety of body parameters, including brain waves (e.g., electroencephalogram or EEG signals), heart beats (e.g., electrocardiogram or EKG), and movements (e.g., triaxial accelerometer signals). See, e.g., U.S. Pat. No. 5,928,272 and U.S. application Ser. No. 12/770,562, both of which are hereby incorporated by reference herein.


Detection of seizures using heart data requires that the seizure detection algorithm distinguish—or attempt to distinguish—between pathological changes in the detected heart signal (which may indicate a seizure) and non-pathological changes that may be similar to pathological changes but involve normal physiological functioning. For example, the patient's heart rate may increase both when a seizure event occurs and when the patient exercises, climbs stairs or performs other physiologically demanding acts. In some instances, state changes such as rising from a prone or sitting position to a standing position, such as in rising after a sleep period, may produce cardiac changes similar to seizure events. Thus, seizure detection algorithms must distinguish between changes in heart rate due to a seizure and those due to exertional or positional/postural changes.


Current algorithms fail to provide rapid and accurate detection. There is a need for improved algorithms that can more accurately distinguish between ictal and non-ictal heart rate changes. There is also a need for algorithms that may provide an initial detection to allow early warning or therapeutic intervention, and which allows for continued signal analysis subsequent to the initial detection, and permitting the initial detection to be subsequently confirmed or rejected as a seizure based on the signal data acquired after the initial detection. The present invention addresses limitations associated with existing cardiac-based seizure detection algorithms.


C. SUMMARY

In one respect, disclosed is a method for detecting a seizure event, the method comprising receiving heart beat data versus time for a patient, detecting an increase in the heart rate of a patient from a baseline heart rate to an elevated heart rate, detecting a decrease in heart rate from the elevated heart rate, for a time interval occurring during said decrease in heart rate, determining at least one of a) a rate of decrease in heart rate and b) a rate of change in a rate of decrease in heart rate, and detecting a seizure event in response to determining at least one of a) a rate of decrease in heart rate greater than a threshold rate of decrease, and b) a rate of change in the rate of decrease less than a threshold rate of change in a rate of decrease.


In another respect, disclosed is a system for detecting a seizure event in a patient, the system comprising one or more processors, one or more memory units coupled to the one or more processors, the system being configured to receive data of heart beat versus time, detect an increase in the heart rate from a baseline heart rate to an elevated heart rate, detect a decrease in heart rate from the elevated heart rate, for a time interval occurring during said decrease in heart rate, determine at least one of a) a rate of decrease in heart rate and b) a rate of change in a rate of decrease in heart rate, and detect a seizure event in response to determining at least one of a) that a rate of decrease in heart rate is greater than a threshold rate of decrease, and b) that the rate of change in the rate of decrease is less than a threshold rate of change in a rate of decrease.


In yet another respect, disclosed is a computer program product embodied in a computer-operable medium, the computer program product comprising logic instructions, the logic instructions being effective to process data of heart rate (HR) versus time, and detect an increase in the heart rate of a patient from a baseline heart rate to an elevated heart rate, detect a decrease in heart rate from the elevated heart rate, for a time interval occurring during said decrease in heart rate, determine at least one of a) a rate of decrease in heart rate and b) a rate of change in a rate of decrease in heart rate, and detect a seizure event in response to determining at least one of a) a rate of decrease in heart rate greater than a threshold rate of decrease, and b) a rate of change in the rate of decrease less than a threshold rate of change in a rate of decrease.


In yet another respect, disclosed is a method for detecting a seizure event, the method comprising receiving heart beat data versus time for a patient, determining at least one of a) a rate of decrease in heart rate and b) a rate of change in a rate of decrease in heart rate, and detecting a seizure event in response to determining at least one of a) a rate of decrease in heart rate greater than a threshold rate of decrease, and b) a rate of change in the rate of decrease less than a threshold rate of change in a rate of decrease.


In yet another respect, disclosed is a method for detecting a seizure event, the method comprising receiving heart beat data versus time for a patient, detecting an increase in the heart rate of the patient from a baseline heart rate to an elevated heart rate, detecting a decrease in heart rate from the elevated rate to a first intermediate rate between the elevated rate and the baseline rate, and further detecting a decrease in heart rate to a second intermediate rate between the first intermediate rate and the baseline rate, determining at least one of a) a rate of decrease from said first intermediate rate to said second intermediate rate and b), a rate of change in a rate of decrease in heart rate from said first intermediate rate to said second intermediate rate, and detecting a seizure event in response to determining at least one of a) that the rate of decrease of heart rate from said first intermediate rate to said second intermediate rate is greater than a threshold rate of decrease and b) the rate of change in the rate of decrease from said first intermediate rate to said second intermediate rate is less than a threshold rate of change in a rate of decrease.


Numerous additional embodiments are also possible.





D. BRIEF DESCRIPTION OF THE DRAWINGS

Other objects and advantages of the present disclosure may become apparent upon reading the detailed description and upon reference to the accompanying drawings.



FIG. 1 is a graph illustrating an example of heart rate versus time during a seizure, in accordance with some embodiments.



FIG. 2 is a block diagram illustrating a system for detecting a seizure event using heart beat data, in accordance with some embodiments.



FIG. 3 is a block diagram illustrating an alternative system for detecting a seizure event using heart beat data, in accordance with some embodiments.



FIG. 4 is a diagram illustrating an example of obtaining heart beat data from a subject using electrocardiogram equipment, in accordance with some embodiments.



FIG. 5 is a flow diagram illustrating a method for detecting a seizure event using heart beat data, in accordance with some embodiments.



FIG. 6 is a flow diagram illustrating an alternative method for detecting a seizure event using heart rate data, in accordance with some embodiments.



FIG. 7 is a graph of heart rate versus time during an event such as a seizure that causes an increase from a baseline heart rate to an elevated heart rate followed by a decrease in the heart rate back toward the baseline heart rate, in accordance with some embodiments.





While the present disclosure is subject to various modifications and alternative forms, specific embodiments of the claimed subject matter are shown by way of example in the drawings and the accompanying detailed description. The drawings and detailed description are not intended to limit the presently claimed subject matter to the particular embodiments. This disclosure is instead intended to cover all modifications, equivalents, and alternatives falling within the scope of the presently claimed subject matter.


E. DETAILED DESCRIPTION

One or more embodiments of the present claimed subject matter are described below. It should be noted that these and any other embodiments are exemplary and are intended to be illustrative of the claimed subject matter rather than limiting. While the present claimed subject matter is widely applicable to different types of systems, it is impossible to include all of the possible embodiments and contexts of the present claimed subject matter in this disclosure. Upon reading this disclosure, many alternative embodiments of the presently claimed subject matter will be apparent to persons of ordinary skill in the art.


The various illustrative logical blocks, modules, circuits, and algorithm steps described in connection with the embodiments disclosed here may be implemented as electronic/computer hardware, computer software, or combinations of the two. Various illustrative components, blocks, modules, circuits, and steps are described generally in terms of their functionality. Whether such functionality is implemented as hardware or software, or allocated in varying degrees to hardware and software respectively, may depend upon the particular application and imposed design constraints. The described functionality may be implemented in varying ways for each particular application, but such implementation decisions should not be interpreted as causing a departure from the scope of the presently claimed subject matter.



FIG. 1 is a graph illustrating an example of heart rate versus time during a seizure, in accordance with some embodiments.


Graph 110 shows the rise of a subject's heart rate (HR) from a pre-ictal baseline HR to a peak HR (at point 140) following the onset of a seizure at time S 145. Graph 110 also shows the decrease of a subject's heart rate (HR) from peak HR 140 to a post-ictal baseline HR (at point 150) following the end of a seizure. For some patients, the post-ictal baseline HR may be different from the pre-ictal baseline HR.


Seizures are often characterized by an increase in HR from an initial or baseline HR to an elevated HR, followed by a decrease in HR from the elevated HR back toward the baseline HR. The increase in HR may begin before, at, or shortly after the electrographic or clinical onset of the seizure, and the decrease in HR may begin at the time the seizure ends. The baseline heart rate may be determined as a statistical measure of central tendency of HR during a desired time window, typically a window prior to an increase in HR associated with a seizure or exertional tachycardia. In one nonlimiting example, the baseline HR may be a median, average or similar statistical measure of HR in a 500 second window. In another embodiment, a number-of-beats window may be used instead of a time window. Various forms of weighting may also be employed to determine the baseline HR, such as exponential forgetting.



FIG. 2 is a block diagram illustrating a system for detecting a seizure event using heart beat data, in accordance with some embodiments.


In some embodiments, heart rate data analyzer 210 is configured to receive and analyze heart rate data 225. Heart rate data 225 may be a series of heart rate values at given points in time. The heart rate data may be received in real time or near real time from a subject or the heart rate data may be data that was previously recorded and is being received from a storage device.


In some embodiments, heart rate data analyzer 210 is configured to analyze the data and identify seizure events that the subject may have suffered and/or is currently suffering. Heart rate data analyzer 210 is additionally configured to distinguish seizure events from nonpathologic events that may have similar effects on a subject's HR. The functionality of heart rate data analyzer 210 may be implemented using one or more processors such as processor(s) 215 and one or more memory units coupled to the one or more processors such as memory unit(s) 220.


Heart rate data analyzer 210 may be configured to identify the offset of a seizure by examining the rate and/or profile with which the HR drops during the offset of the seizure as discussed here.


In some embodiments, systems and methods are disclosed for detecting a seizure event by examining data of the heart rate (HR) versus time of a subject. The subject's heart rate may be obtained in real time or near real time using various methods, including well-known electrocardiogram (ECG) processes. In alternative embodiments, previously stored/recorded HR data may be provided to embodiments of the present invention for analysis.


In some embodiments, heart rate data analyzer 210 may identify a seizure by identifying body signal changes associated with the end of the seizure. Existing seizure detection algorithms focus on identifying the beginning of the seizure (i.e., onset of the ictal state from a non-ictal or pre-ictal state), typically as exemplified by a significant change in a body signal, such as an increase in HR from a baseline HR to an elevated HR. Various attempts to distinguish ictal HR increases from non-ictal increases have been made, but prior art approaches have unacceptably high rates of false positives (i.e., detecting non-ictal changes as a seizure) and false negatives (i.e., failure to detect ictal changes).


In contrast to prior art approaches, the present invention involves identifying a seizure by changes associated with the end of a seizure (i.e., the ictal-to-post-ictal transition). Without being bound by theory, it is believed that changes associated with the end of a seizure may provide improved methods of distinguishing between ictal and non-ictal HR changes.


In some embodiments, a seizure may be identified by determining one or more characteristics of a decrease in HR from an elevated HR back towards a baseline HR. More specifically, an episode of elevated heart rate followed by a return towards a baseline rate may be analyzed and classified as a seizure or as a non-seizure event (for example, exertional tachycardia associated with exercise or normal activity).


In one embodiment, a time interval during a decrease in HR from an elevated HR is analyzed to determine one or more of a) a rate of decrease in HR or b) a rate of change of the rate of decrease in HR. The rate of decrease may be determined from actual data or smoothed data (e.g., by fitting a higher order polynomials to one or more segments of actual data). The rate of decrease may be compared to a threshold rate of decrease associated with a seizure event and/or a threshold rate of decrease associated with a non-seizure event. The rate of change in a rate of decrease may be compared to a threshold rate of change of a rate of decrease associated with a seizure event and/or a threshold rate of change of a rate of decrease associated with a non-seizure event. The event may be detected as a seizure event if the rate of decrease from an elevated heart rate back toward a baseline heart rate exceeds a threshold rate of decrease, or if the rate of change of a rate of decrease is less than a threshold rate of change of a rate of decrease.


In some embodiments, the threshold rate of decrease and/or the threshold rate of change of the rate of decrease may be determined from nonpathologic rates of decrease and/or rates of change of rates of decrease from nonpathologic events that also result in patterns of increasing HR followed by decreasing HR. Such nonpathologic events may include, for example, physical exertion during exercising, climbing or descending stairs, walking, or postural changes. In other embodiments, the threshold rate of decrease and/or the threshold rate of change of the rate of decrease may be determined from seizure events. In some embodiments, different thresholds may be established for different types of seizures, e.g., tonic-clonic seizures, complex partial, simple partial, etc. Thresholds may also be established that are patient-specific, i.e., determined from seizure events of the patient, or from aggregated patient data from multiple patients.


In some embodiments, the rate of decrease in HR (which will be referred to here equivalently as heart beat acceleration, HBA, heart rate drop or HRD), may correspond to an instantaneous or time-interval-specific (e.g., a 15-second moving window) slope of a graph of the HR versus time. This slope may be determined at a specific point(s) and/or for specific intervals during the decrease in HR from an elevated heart rate back towards a baseline heart rate. In one embodiment, the peak heart rate during a tachycardia event (i.e., a heart rate increase above a baseline heart rate followed by a decrease toward the baseline rate) and the baseline rate may be used to determine a peak-to-baseline (PTB) value that is useful for performing calculations according to certain embodiments. For a given point along the decreasing HR curve from the peak heart rate, one useful rate of decrease may be determined as the average slope (or average rate of decrease) from the peak to the given point. In other embodiments, short-term rates of decrease may be established for a short-term time window along the decreasing HR curve from peak to baseline. Short-term rates of decrease may be determined for a 5-second or 5-beat window, for example, or from the last two heart beats.


In certain embodiments, particular short-term rates of decrease may be useful to compare to later short-term rates of decrease. It has been appreciated by the present inventor that PTB decreases in heart rate for seizure events and non-seizure events differ qualitatively. In particular, decreases in HR for seizure events tend to maintain a relatively constant rate of decrease during most of the PTB decline. In non-seizure events, by contrast, rates of decrease tend to decline as the HR approaches the baseline HR. Thus, for seizure events the slope of the PTB heart rate curve tends to be relatively straight. The slope of the PTB heart rate curve for non-seizure tachycardia episodes, on the other hand, tends to flatten as the HR approaches the baseline heart rate, resulting in a HR curve that is “upwardly concave” near the baseline for non-seizure events.


Because the differences in HR decline between seizure and non-seizure events is most prominent near the baseline, in some embodiments, rates of decline and/or rates of change of rates of decline are determined at rates below the rate halfway between the peak and the baseline heart rate.


In some embodiments, a seizure end may be identified in response to determining that the HR drop at a specific point during the PTB transition is greater (in absolute value since during a heart rate decrease the slope is negative) than a seizure threshold value. In some embodiments, HRDs during PTB transitions in healthy subjects for nonpathologic events are smaller than HRDs during a corresponding time during a seizure event. The threshold HRD may accordingly be chosen in order to maximize the accuracy of the seizure identification process. Binary classification statistics may be used to maximize the accuracy of the detection by appropriately balancing the sensitivity and specificity of the identification process.


In some embodiments, the HRD (the slope of the HR v. time graph) at a particular point may be computed numerically from the HR v. time data using well-known numerical computation techniques for calculating slope using numerical data.


In some embodiments, average HRDs may be used over one or more intervals for identifying a seizure offset. Intervals may be chosen anywhere between a peak HR and the return towards a baseline HR, the peak HR being the highest HR value reached during the seizure or nonpathologic event, and the baseline HR being the HR of the subject prior to the tachycardia event under consideration (whether pathological or non-pathological). For example, a First Half HRD may be computed for an interval between the peak HR value and the HR that is halfway between the baseline HR and the peak HR. Similarly, a Middle Half HRD may be computed for an interval between the HR that is 25% of the way between the peak HR and the baseline HR and the HR that is 75% of the way between the peak HR and the baseline HR, and a Second Half HRD may be computed for the interval between the HR that is 50% of the distance from peak-to-baseline, and the baseline HR itself. Similarly, a First Third HRD may be computed between the peak HR and the HR that is ⅓ of the way from the peak HR to the baseline HRD, and a Final Third HRD may be computed between the HR that is ⅔ of the way from the peak HR to the baseline HR and the baseline HR itself. Similar intervals may be constructed, and the HRD computed, depending upon the points in the decline from peak to baseline that provides a desirable level of discrimination between seizure and non-seizure events. More generally, in some embodiments, an average HRD over an interval from point A to point B may be computed by dividing the HR change from point A to point B by the time change from point A to point B.


In some embodiments, the offset of a seizure may be identified in response to determining that the First Half HRD and Middle Half HRD are substantially equal. For example, the offset of the seizure may be identified in response to determining that the First Half HRD and the Middle Half HRD are within a certain percentage of each other. It should be noted that other appropriate intervals/average HRDs may be selected and used in various combinations to identify a seizure.


In some embodiments, a seizure may be identified by comparing HRDs at one or more points and/or by comparing average HRDs over one or more intervals to HRDs threshold values. In some embodiments, the threshold HRD values may be determined by examining typical corresponding values of HRDs for seizure and nonpathologic events. For example, a seizure may be identified in response to determining that an average One Third HRD is above a certain threshold, which is determined by examining corresponding One Third HRD values for typical seizures as well as nonpathologic events.


In some embodiments, a general profile of the HR versus time during a seizure offset may be determined and compared to known HR versus time profiles during seizures and nonpathologic events. In some embodiments, a seizure offset may be identified in response to determining that there exists a substantial match between the determined profile and the known seizure profiles, or a substantial dissimilarity between the determined profile and one or more known nonpathologic profiles. In some embodiments, a seizure may be identified in response to determining that a seizure profile is substantially similar to a linear seizure profile and substantially dissimilar to a nonpathologic profile such as an asymptotically decreasing profile (for example, a decreasing exponential profile), a concave decreasing profile, etc.



FIG. 3 is a block diagram illustrating an alternative system for detecting a seizure event using heart beat data, in accordance with some embodiments.


In some embodiments, heart rate data analyzer 310 is configured to receive and analyze heart rate data 325. Heart rate data 325 may be a series of heart rate values at given points in time. The heart rate data may be received in real time or near real time from heart rate detection equipment connected to a subject, such as HR detector 330. HR detector 330, in some embodiments may comprise electrocardiogram equipment, which is configured to couple to a subject's body in order to detect the subject's heart beat.


In some embodiments, heart rate data analyzer 310 is configured to analyze the data and identify seizure events that the subject may have suffered and/or is currently suffering. The functionality of heart rate data analyzer 310 may be implemented using one or more processors such as processor(s) 315 and one or more memory units coupled to the one or more processors such as memory unit(s) 320.


Heart rate data analyzer 310 may be configured to identify the offset of a seizure by examining the rate and generally the profile with which the HR drops during the offset of the seizure as discussed here.


Heart rate data analyzer 310 may also be coupled to human interface input device 335 and human interface output device 340. Human interface input device 335 may be configured to provide a user of the system a means with which to input data into the system and with which to generally control various options. Accordingly, human interface input device 335 may be at least one of a computer keyboard, a touch screen, a microphone, a video camera, etc.


Human interface output device 340 may be configured to provide information to a user of the system visually, audibly, etc. Accordingly, human interface output device 340 may be at least one of a computer display, one or more audio speakers, haptic feedback device, etc. In some embodiments, human interface input device 335 and human interface output device may be combined into a single unit.



FIG. 4 is a diagram illustrating an example of obtaining heart beat data from a subject using electrocardiogram equipment, in accordance with some embodiments.


A particular embodiment of a system for monitoring heart beat data from a subject is shown in the Figure and generally designated 400. System 400 may include, a heart beat sensor 440, a controller 455, and a computer 410.


In some embodiments, heart beat and/or heart rate data may be collected by using an external or implanted heart beat sensor and related electronics (such as heart beat sensor 440), and a controller that may be wirelessly (or via wire) coupled to the sensor for detecting seizure events based upon the patient's heart signal, such as controller 455. In one embodiment, sensor 440 may comprise electrodes in an externally worn patch adhesively applied to a skin surface of patient 485. In some embodiments, sensor 440 may be implanted under the patient's skin. The patch may include electronics for sensing and determining a heart beat signal (e.g., an ECG signal), such as an electrode, an amplifier and associated filters for processing the raw heart beat signal, an A/D converter, a digital signal processor, and in some embodiments, an RF transceiver wirelessly coupled to a separate controller unit, such as controller 455. In some embodiments, the controller unit may be part of the patch electronics.


The controller 455 may implement an algorithm for detection of seizure events based on the heart signal. It may comprise electronics and memory for performing computations of, e.g. HR parameters such as median HR values for the first and second windows, determination of ratios and/or differences of the first and second HR measures, and determination of seizure onset and offset times according to the foregoing disclosure. In some embodiments, the controller 455 may include a display and an input/output device. The controller 455 may comprise part of a handheld computer such as a PDA or smartphone, a cellphone, an iPod® or iPad®, etc.


In the example shown, sensor 440 may be placed on a body surface suitable for detection of heart signals. Electrical signals from the sensing electrodes may be then fed into patch electronics for filtering, amplification and A/D conversion and other preprocessing, and creation of a time-of-beat sequence (e.g., an R-R interval data stream), which may then be transmitted to controller 455. Sensor 440 may be configured to perform various types of processing to the heart rate data, including filtering, determination of R-wave peaks, calculation of R-R intervals, etc. In some embodiments, the patch electronics may include the functions of controller 455, illustrated in FIG. 4 as separate from sesnor 440.


The time-of-beat sequence may be then provided to controller 455 for processing and determination of seizure onset and offset times and related seizure metrics. Controller 455 may be configured to communicate with computer 410. Computer 410 may be located in the same location or computer 410 may be located in a remote location from controller 455. Computer 410 may be configured to further analyze the heart data, store the data, retransmit the data, etc. Computer 410 may comprise a display for displaying information and results to one or more users as well as an input device from which input may be received by the one or more users. In some embodiments, controller 455 may be configured to perform various tasks such as calculating first and second HR measures, HR parameters, comparing HR parameters to appropriate thresholds, and determining of seizure onset and seizure end times, and other seizure metrics.



FIG. 5 is a flow diagram illustrating a method for detecting a seizure event using heart beat data, in accordance with some embodiments.


In some embodiments, the method illustrated in this figure may be performed by one or more of the systems illustrated in FIG. 2, FIG. 3, and FIG. 4.


At block 510, heart beat data versus time for a patient is received.


At block 515, an increase in the heart rate of a patient is detected from a baseline heart rate to an elevated heart rate.


At block 520, a decrease in heart rate is detected from the elevated heart rate.


At block 525, for a time interval occurring during said decrease in heart rate, at least one of a) a rate of decrease in heart rate and b) a rate of change in a rate of decrease in heart rate, is determined.


At block 530, a seizure event is detected in response to determining at least one of a) a rate of decrease in heart rate greater than a threshold rate of decrease, and b) a rate of change in the rate of decrease less than a threshold rate of change in a rate of decrease. In some embodiments, detecting of the seizure event comprises determining the end of a seizure event. The threshold rate of decrease or threshold rate of change of rate of decrease may in some embodiments be selected after examining previous such rates for seizures as well as nonpathologic events.



FIG. 6 is a flow diagram illustrating an alternative method for detecting a seizure event using heart rate data, in accordance with some embodiments.


In some embodiments, the method illustrated in this figure may be performed by one or more of the systems illustrated in FIG. 2, FIG. 3, and FIG. 4.


At block 610, data of heart rate (HR) versus time is provided. In some embodiments, the data may be provided in real time or near real time or the data may be retrieved from storage.


At block 615, an HR drop rate or HRD (which corresponds to a slope of the HR versus time data) is determined at one or more points of the provided data. In some embodiments, instead of an HRD at a single point, an average HRD may be determined over an interval of the HRD versus time data/graph.


At decision 620, a determination is made as to whether the HRD is above a threshold HRD. In some embodiments, the threshold HRD may be chosen by examining previous seizure and nonpathologic HRDs.


If the HRD is not above the threshold HRD, decision 620 branches to the “no” branch, and processing returns to block 610 where additional data is received for processing. On the other hand, if the HRD is above the threshold HRD, decision 620 branches to the “yes” branch, and processing continues at block 625.


At block 625, the examined HRD is indicated as indicative of the end of a seizure, and thus a seizure event is identified. Subsequently, processing returns to block 610 where additional data is provided for processing.



FIG. 7 is a graph of heart rate versus time during an event such as a seizure that causes an increase from a baseline heart rate to an elevated heart rate followed by a decrease in the heart rate back toward the baseline heart rate, in accordance with some embodiments.


Graph 710 shows the rise of a subject's heart rate (HR) from a baseline HR to a peak HR and then the fall of the HR back toward the baseline HR after some time for a typical seizure case and for a non-pathological case. Point ½ HR marks the HR value between the peak HR and the baseline HR, and point ¾ HR marks the HR value that is ¾ of the way from the peak HR to the baseline HR. In the figure, the non-pathological HR drop is indicated by the dotted line.


In some embodiments, in order to determine whether the fall in the HR corresponds to the end of a seizure, the slope of the graph (i.e., HRD) may be computed. In some embodiments, the instantaneous slope may be computed at a point. In alternative embodiments, an average slope may be computed between two points.


For example, the instantaneous slope may be computed at point 725 and corresponding point 730 for the non-pathological case. The two slopes for the typical seizure case and the non-pathological case are illustrated by dashed lines 727 and 732 respectively.


Alternatively, an average slope may be computed between points 725 and 726 and between corresponding points 730 and 731 for the non-pathological case. The two average slopes for the typical seizure case and the non-pathological case are illustrated by dashed lines 728 and 733 respectively.


Regardless of the method used to compute the slope, a seizure may be identified in response to determining that the slope is below (or above in absolute value) a certain threshold value. As seen by the figure, typical seizure cases exhibit slopes that are smaller (or larger in absolute value) when compared to non-pathological cases as indicated by dashed lines representing these slopes.


In alternative embodiments, a seizure may be identified in response to determining that the average HRDs in two intervals is substantially equal. For example, the average HRD may be computed and compared for two intervals by dividing the difference in HR by the difference in time at the beginning and end of the intervals. Then, as discussed here, the seizure is identified in response to determining that the HRDs for the two intervals are substantially equal, or differ by only a threshold slope difference. By comparison, a typical non-pathological case will exhibit a greater difference in the average slope between two different intervals.


Similarly, the concavity of the graph may be computed for a certain interval and compared to certain threshold concavities. As can be seen by the figure, typical seizure cases exhibit concavities that are typically larger compared to the concavities of non-pathological events. In some embodiments, the concavity may be computed by determining the second time derivative of the HR. Thus, a seizure may be identified in response to determining that the concavity (average or at a given point) is higher than a threshold concavity value.


The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present claimed subject matter. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the claimed subject matter. Thus, the present claimed subject matter is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed here.


The benefits and advantages that may be provided by the present claimed subject matter have been described above with regard to specific embodiments. These benefits and advantages, and any elements or limitations that may cause them to occur or to become more pronounced are not to be construed as critical, required, or essential features of any or all of the claims. As used here, the terms “comprises,” “comprising,” or any other variations thereof, are intended to be interpreted as non-exclusively including the elements or limitations which follow those terms. Accordingly, a system, method, or other embodiment that comprises a set of elements is not limited to only those elements and may include other elements not expressly listed or inherent to the claimed embodiment.


While the present claimed subject matter has been described with reference to particular embodiments, it should be understood that the embodiments are illustrative and that the scope of the claimed subject matter is not limited to these embodiments. Many variations, modifications, additions and improvements to the embodiments described above are possible. It is contemplated that these variations, modifications, additions and improvements fall within the scope of the present disclosure as detailed within the following claims.

Claims
  • 1. A method for detecting a seizure event, the method comprising: receiving heart beat data versus time for a patient;detecting an increase in a heart rate of the patient based on the heart rate data from a baseline heart rate to an elevated heart rate;detecting a decrease in heart rate from the elevated heart rate;for a time interval occurring during said decrease in heart rate, determining at least one of a) a rate of change of the decrease in heart rate and b) a rate of change in a rate of decrease in heart rate; anddetermining occurrence of a seizure event in response to the rate of change of the decrease in heart rate satisfying a threshold rate.
  • 2. The method of claim 1, wherein the rate of change of the decrease in heart rate at the time satifies the threshold rate when the rate of change of the decrease in heart rate at the time is greater than the threshold rate, and wherein the threshold rate in based on a non-seizure event.
  • 3. The method of claim 1, further comprising: determining a rate of change of the rate of change of the decrease in her heart rate at the time; andconfirming the occurrence of the seizure event when the rate of change of the rate of change of the decrease in heart rate at the time satisfies a second threshold.
  • 4. The method of claim 3, wherein the second threshold is satisfied when the rate of change in the rate of change of the decrease in heart rate at the time is greater than the second threshold, and wherein the second threshold is based on a non-pathological event.
  • 5. The method of claim 1, further comprising: determining an initial detection of a seizure event based upon the increase in heart rate;determining a profile of the decrease in heart rate;comparing the profile of the decrease in heart rate to a known profile of a seizure event decrease in heart rate; andconfirming the occurrence of the seizure event in response to determining that the profile of the decrease in heart rate is substantially similar to the known profile of the seizure event decrease in heart rate.
  • 6. The method of claim 1, further comprising: determining a profile of the rate of change of decrease in heart rate;comparing the profile of the rate of change of decrease in heart rate to a known profile of a nonpathologic rate of change of decrease in heart rate; andconfirming the detection of the seizure event in response to determining that the profile of the rate of change of decrease in heart rate is substantially dissimilar to the known profile of the nonpathologic rate of change of decrease in heart rate.
  • 7. The method of claim 6, wherein the known profile of the nonpathologic rate of change of decrease in heart rate is at least one of: an asymptotically decreasing profile, an exponentially decreasing profile, or a concave decreasing profile.
  • 8. The method of claim 1, further comprising: determining a first average rate of change of heart rate over a first time interval;determining a second average rate of change of heart rate over a second time interval, wherein the second time interval is different from the first time interval; andconfirming the occurrence of the seizure event in response to determining that the first average rate of change of heart rate is substantially equal to the second average rate of change of heart rate.
  • 9. The method of claim 1, wherein the elevated heart rate is a particular rate of at least one of 10 beats per minute greater than the baseline heart rate or 10 percent greater than the baseline heart rate.
  • 10. A system for detecting a seizure event in a patient, the system comprising: one or more processors; andone or more memory units coupled to the one or more processors;the one or more processors configured to:receive data of heart beat versus time for a patient;detect an increase in a heart rate from a baseline heart rate to an elevated heart rate;detect a decrease in heart rate from the elevated heart rate for a time interval occurring during said decrease in heart rate,determine a first average rate of change of decrease in heart rate over a first time interval;determine a second average rate of change of decrease in heart rate over a second time interval, wherein the second time interval is different from the first time interval; andindicate occurrence of detect a seizure event in response to determining at least one of a) that a rate of decrease in heart rate is greater than a threshold rate of decrease, and b) that the rate of change in the rate of decrease is less than a threshold rate of change in a rate of decrease the first average rate of change of decrease in heart rate being within a particular percentage of the second average rate of change of decrease in heart rate.
  • 11. The system of claim 10, wherein the one or more processors are further comprising to: determine a rate of change in heart rate at a particular time; andconfirm the occurrence of the seizure event when the rate of change in heart rate at the particular time satifies a threshold,comprising a first intermediate heart rate and a second intermediate heart rate, wherein said first intermediate heart rate is a heart rate between said elevated heart rate and said baseline heart rate and occurring during said decrease in heart rate from the elevated heart rate, and wherein said second intermediate heart rate is a heart rate between said first intermediate heart rate and said baseline heart rate and occurring during said decrease in heart rate from the elevated heart rate, wherein the system being configured to identify the seizure event comprises the system being configured to detect the seizure event in response to determining at least one of a) that a rate of decrease in heart rate from said first intermediate heart rate to said second intermediate heart rate is greater than a threshold rate of decrease, and b) that a rate of change in a rate of decrease in heart rate from first intermediate heart rate to said second intermediate heart rate is less than a threshold rate of change in a rate of decrease.
  • 12. The system of claim 10, where the one or more processors are further configured to: determine a profile of the decrease in heart rate;compare the profile of the decrease in heart rate to a known profile of a nonpathological decrease in heart rate; andconfirm the occurrence of the seizure event in response to determining that the profile of the decrease in heart rate is substantially dissimilar to the known profile.
  • 13. The system of claim 10, where the one or more processors are further configured to: determine a profile of the decrease in heart rate;compare the profile of the decrease in heart rate to a known profile of a seizure event decrease in heart rate; andconfirm the occurrence of the seizure event in response to determining that the profile of the decrease in heart rate is substantially similar to the known profile of the seizure event decrease in heart rate.
  • 14. The system of claim 13, wherein the known profile of the seizure event decrease in heart rate is substantially a linearly decreasing profile.
  • 15. The system of claim 10, where the one or more processors are further configured to: determine a rate of change in a rate of a rate of change in heart rate at a particular time; andconfirm the occurrence of the seizure event when the rate of change in the rate of change in heart rate at the particular time satisfies a second threshold,determine a first average decreasing heart rate over a first interval occurring during said decrease in heart rate;determine a second average decreasing heart rate over a second interval occurring during said decrease in heart rate, wherein the second interval is different from the first interval; andconfirm the detection of the seizure event in response to determining that the first average decreasing heart rate is substantially equal to the second average decreasing heart rate.
  • 16. A computer program product embodied in a computer-operable medium, the computer program product comprising logic instructions, the logic instructions executable to: process data of heart rate versus time for a patient to detect an increase in the heart rate of the patient from a baseline heart rate to an elevated heart rate;detect a decrease in heart rate from the elevated heart rate;for a time interval occurring during said decrease in heart rate, determine at least one of a) a rate of decrease in heart rate and b) a rate of change in a rate of decrease in heart rate; andindicate occurrence of a seizure event in response to determining the rate of change in the rate of decrease satisfies a threshold.
  • 17. The product of claim 16, the logic instructions being further executable to: determine a first average heart rate over a first time interval;determine a second average heart rate over a second time interval, wherein the second time interval is different from the first time interval; andreceive heart beat data versus time for a patient;detect an increase in the heart rate of the patient from a baseline heart rate to an elevated heart rate;detect a decrease in heart rate from the elevated rate to a first intermediate rate between the elevated rate and the baseline rate, and furtherdetecting a decrease in heart rate to a second intermediate rate between the first intermediate rate and the baseline rate;determine at least one of a) a rate of decrease from said first intermediate rate to said second intermediate rate and b) a rate of change in a rate of decrease in heart rate from said first intermediate rate to said second intermediate rate; andconfirm the occurrence of the seizure event in response to the first average heart rate being within a particular perecentage of the second average heart rate.
  • 18. The product of claim 16, wherein the elevated heart rate is a rate at least a specified threshold above the baseline heart rate.
  • 19. The product of claim 16, wherein the threshold is satisfied when the rate of change in the rate of decrease is less than the threshold, and wherein the threshold is based on a non-seizure event.
  • 20. The product of claim 16, wherein the baseline heart rate is determined as a statistical measure of central tendency of heart rate during a time window, detect a seizure event based on an increase in heart rate from a baseline heart rate to an intermediate elevated heart rate between the elevated heart rate and the baseline heart rate; anddetect a seizure event in response to determining at least one of that the rate of decrease of heart rate from said first intermediate rate to said second intermediate rate is greater than a threshold rate of decrease and the rate of change in the rate of decrease from said first intermediate rate to said second intermediate rate is less than a threshold rate of change in a rate of decrease comprises confirming said detecting a seizure event based on an increase in heart rate.
US Referenced Citations (562)
Number Name Date Kind
4172459 Hepp Oct 1979 A
4197856 Northrop Apr 1980 A
4291699 Geddes et al. Sep 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, Jr. 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, Jr. 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
5269303 Wernicke et al. Dec 1993 A
5299569 Wernicke et al. Apr 1994 A
5304206 Baker, Jr. et al. Apr 1994 A
5311876 Olsen et al. May 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
5404877 Nolan et al. Apr 1995 A
5425373 Causey, III Jun 1995 A
5513649 Gevins et al. May 1996 A
5522862 Testerman et al. Jun 1996 A
5523742 Simkins et al. Jun 1996 A
5540730 Terry, Jr. et al. Jul 1996 A
5540734 Zabara Jul 1996 A
5571150 Wernicke et al. Nov 1996 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 et al. 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
5743860 Hively et al. Apr 1998 A
5748113 Torch May 1998 A
5792186 Rise Aug 1998 A
5800474 Benabid et al. Sep 1998 A
5807284 Foxlin Sep 1998 A
5808552 Wiley et al. Sep 1998 A
5833709 Rise et al. Nov 1998 A
5853005 Scanlon et al. Dec 1998 A
5871517 Abrams et al. Feb 1999 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, Sr. 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 Osorio 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
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
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
6361507 Foxlin Mar 2002 B1
6361508 Johnson et al. Mar 2002 B1
6366813 DiLorenzo Apr 2002 B1
6366814 Boveja 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, Jr. 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
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
6609025 Barrett et al. Aug 2003 B2
6610713 Tracey Aug 2003 B2
6611715 Boveja Aug 2003 B1
6611783 Kelly, Jr. 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 Boveja 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
6735474 Loeb et al. May 2004 B1
6738671 Christophersom 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 et al. Aug 2005 B2
6934580 Osorio et al. Aug 2005 B1
6934585 Schloss Aug 2005 B1
6944501 Pless Sep 2005 B1
6957107 Rogers Oct 2005 B2
6961618 Osorio et al. Nov 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
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
7104947 Riehl et al. 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 et al. 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
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 Apr 2007 B2
7209787 DiLorenzo Apr 2007 B2
7221981 Gliner May 2007 B2
7228167 Kara 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, Jr. 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
7401008 Frei et al. Jul 2008 B2
7403820 DiLorenzo Jul 2008 B2
7420472 Tran Sep 2008 B2
7433732 Carney et al. Oct 2008 B1
7447545 Heruth et al. Nov 2008 B2
7454245 Armstrong et al. Nov 2008 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 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
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 et al. Aug 2011 B2
8000794 Lozano Aug 2011 B2
8021299 Miesel et al. Sep 2011 B2
8027730 John et al. Sep 2011 B2
8027737 Kokones et al. Sep 2011 B2
8075499 Nathan et al. Dec 2011 B2
8109891 Kramer et al. Feb 2012 B2
20010032059 Kelly et al. Oct 2001 A1
20020072782 Osorio 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 Sep 2003 A1
20030195588 Upton 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 et al. 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
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 et al. 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 et al. 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
20050187590 Boveja 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 Jan 2006 A1
20060018833 Murphy et al. Jan 2006 A1
20060074450 Boveja Apr 2006 A1
20060079936 Boveja Apr 2006 A1
20060094971 Drew May 2006 A1
20060095081 Zhou et al. May 2006 A1
20060106430 Fowler et al. May 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
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 et al. Feb 2007 A1
20070027497 Parnis et al. Feb 2007 A1
20070027498 Maschino et al. Feb 2007 A1
20070027500 Maschino et al. Feb 2007 A1
20070032834 Gliner et al. Feb 2007 A1
20070043392 Gliner et al. Feb 2007 A1
20070055320 Weinand et al. Mar 2007 A1
20070073150 Gopalsami et al. Mar 2007 A1
20070073355 Dilorenzo Mar 2007 A1
20070088403 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
20070150024 Leyde et al. Jun 2007 A1
20070150025 Dilorenzo et al. Jun 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 et al. Oct 2007 A1
20070244407 Osorio Oct 2007 A1
20070249953 Osorio 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
20080004904 Tran et al. Jan 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
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
20080208284 Rezai et al. Aug 2008 A1
20080258907 Kalpaxis Oct 2008 A1
20080269579 Schiebler et al. Oct 2008 A1
20080275327 Faarbaek et al. Nov 2008 A1
20080275328 Jones et al. 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 et al. 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
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
20090137921 Kramer et al. May 2009 A1
20090227882 Foo Sep 2009 A1
20090227888 Salmi Sep 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
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
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 et al. 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
20110251469 Varadan Oct 2011 A1
20110270117 Warwick et al. Nov 2011 A1
20110270134 Skelton et al. Nov 2011 A1
20110295127 Sandler et al. Dec 2011 A1
20110306846 Osorio Dec 2011 A1
20110313484 Hincapie et al. Dec 2011 A1
Foreign Referenced Citations (18)
Number Date Country
1145736 Oct 2001 EP
1486232 Dec 2004 EP
2026870 Feb 1980 GB
2079610 Jan 1982 GB
0064336 Nov 2000 WO
2004036377 Apr 2004 WO
2005007120 Jan 2005 WO
2005053788 Jun 2005 WO
2005067599 Jul 2005 WO
2006050144 May 2006 WO
2006122148 Nov 2006 WO
2007066343 Jun 2007 WO
2007072425 Jun 2007 WO
2007124126 Nov 2007 WO
2007124190 Nov 2007 WO
2007124192 Nov 2007 WO
2007142523 Dec 2007 WO
2008045597 Apr 2008 WO
Non-Patent Literature Citations (65)
Entry
O'Donovan, Cormac et al. “Computerized Seizures Detection Based on Heart Rate Changes”, Epilepsia, vol. 36, Suppl. 4; p. 7, 1995 (1 page).
Robinson, Stephen E. et al. “Heart Rate Variability Changes as Predictor of Response to Vagal Nerve Stimulation Therapy for Epilepsy”, Epilepsia, vol. 40, Suppl. 7, p. 147; 1999 (1 page).
Long,Teresa J. et al. “Effectiveness of Heart Rate Seizures Detection Compared to EEG in an Epilepsy Monitoring Unit (EMU)”, Epilepsia, vol. 40, Suppl. 7, p. 174; 1999 (1 page).
Dimkpa, Uchechukwu “Post-Exercise Heart Rate Recovery; An Index of Cardiovascular Fitness”, Official Research Journal of the American Society of Exercise Physiologists (ASEP), vol. 12, No. 1, pp. 10-23, Feb. 2009 (14 pages).
Hautala, Arto J. et al. “Heart Rate Recovery After Maximal Exercise is Associated with Acetylcholine Receptor M2 (CHRM2) Gene Polymorphism”, American Journal Physiological Society, Circ Physiol 291, pp. H459-H466, Feb. 26, 2006 (8 pages).
Nishime, Erna Obenza et al. “Heart Rate Recovery and Treadmill Exercise Score as Predictors of Mortality in Patients Referred for Exercise ECG”, Journal of American Medical Association, vol. 284, No. 11, pp. 1392-1398, Sep. 20, 2000 (7 pages).
Du, Na et al. “Heart Rate Recovery After Exercise and Neural Regulation of Heart Rate Variability in 30-40 Year Old Female Marathon Runners”, Journal of Sports and Medicine, pp. 9-17, 2005, (9 pages).
International Search Report and Written Opinion received in corresponding PCT Application No. PCT/US2011/061624 from the International Searching Authority dated Feb. 1, 2012, 13 pages.
Van Elmpt, Wouter J.C. et al.; “A Model of Heart Rate Changes to Detect Seizures in Severe Epilepsy”; Seizure, Bailliere Tindall, London, GB; vol. 15, No. 6; Sep. 1, 2006; pp. 366-375.
Smith, P.E.M. et al.; “Profiles of Instant Heart Rate During Partial Seizures”; Electroencephalography and Clinical Neurophysiology, Elsevier; vol. 72, No. 3, Mar. 1, 1989, pp. 207-217.
Bachman, D.,S. 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.M. “Analysis of Heart Rate Variability in Space Medicine;” Human Physiology, vol. 28, No. 2, (2002); pp. 202-213.
Baevsky, R.M., et al.; “Autonomic Cardiovascular and Respiratory Control During Prolonged Spaceflights Aboard the International Space Station;” J. Applied Physiological, vol. 103, (2007) pp. 156-161.
Boon, P., et al.; “Vagus Nerve Stimulation for Epilepsy, Clinical Efficacy of Programmed and Magnet Stimulation;” (2001); pp. 93-98.
Boon, Paul, et al.; “Programmed and Magnet-Induced Vagus Nerve Stimulation for Refractory Epilepsy;” Journal of Clinical Neurophysiology vol. 18 No. 5; (2001); pp. 402-407.
Borovikova, L.V., et al.; “Vagus Nerve Stimulation Attenuates the Systemic Inflammatory Response to Endotoxin;” Letters to Nature; vol. 405; (May 2000); pp. 458-462.
Brack, Kieran E., et al.; “Interaction Between Direct Sympathetic and Vagus Nerve Stimulation on Heart Rate in the Isolated Rabbit Heart;” Experimental Physiology vol. 89, No. 1; 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.B., 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, 364-373 (1998) Art. No. NL983863.
Elmpt, W.J.C., et al.; “A Model of Heart Rate Changes to Detect Seizures in Severe Epilepsy” Seizure vol. 15, (2006) pp. 366-375.
Frei, M.G., 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, No. 8 (2001); pp. 1007-1016.
George, M.S., et al.; “Vagus Nerve Stimulation: A New Tool for Brain Research and Therapy;” Society of Biological Psychiatry vol. 47 (2000) pp. 287-295.
“Heart Rate Variability—Standards of Measurement, Physiological Interpretation, and Clinical Use” Circulation-Electrophysiology vol. 93, No. 5; http://circ.ahajournals.org/cgi/content-nw/full/93/5/1043/F3.
Henry, Thomas R.; “Therapeutic Mechanisms of Vague Name Stimulation;”. Neurology, vol. 59 (Supp 4) (Sep. 2002), pp. S3-S14.
Hallowitz et al., “Effects of Vagal Volleys on Units of Intralaminar and Juxtalaminar Thalamic Nuclei in Monkeys;” Brain Research, vol. 130 (1977), pp. 271-286.
Iasemidis; L.D., et al.; “Dynamical Resetting of the Human Brain at Epilepctic Seizures: Application of Nonlinear Dynamics and Global Optimization Techniques;” IEEE Transactions on Biomedical Engineering, vol. 51, No. 3 (Mar. 2004); pp. 493-506.
Iasemidis; L.D., et al.; “Spatiotemporal Transition to Epileptic Seizures: A Nonlinear Dynamical Analysis of Scalp and Intracranial EEG Recordings;”Spatiotemporal Models in Biological and Artificial Systems; F.L. Silva et al. (Eds.) IOS Press, 1997; pp. 81-88.
Iasemidis, L.D.; “Epileptic Seizure Prediction and Control” IEEE Transactions on Biomedical Engineering, vol. 50, No. 5 (May 2003); pp. 549-558.
Kautzner, J., et al.; “Utility of Short-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.A., et al.; “Vagus Nerve Stimulation Improves Severely Impaired Heart Rate Variability in a Patient with Lennox-Gastaut-Syndrome” Seizure (2007) Article in Press—YSEIZ—1305; pp. 1-4.
Koo, B., “EEG Changes With Vagus Nerve Stimulation” Journal of Clinical Neurophysiology, vol. 18 No. 5 (Sep. 2001); pp. 434-441.
Krittayaphong, M.D., 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.E., 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.
Li, M., et al.; “Vagal Nerve Stimulation Markedly Improves Long-Term Survival After Chronic Heart Failure in Rats;” Circulation (Jan. 2004) pp. 120-124.
Licht, C.M.M.; 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 et al., “Feasibility and Safety of Vagal Stimulation in Monkey Model;” Epilepsia, vol. 31 (Supp. 2) (1990), pp. S20-S26.
McClintock, P., “Can Noise Actually Boost Brain Power” Physics World Jul. 2002; 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. 218101-1-218101-4.
Mormann, F., “Seizure prediction: the long and winding road,” Brain 130 (2007), 314-333.
Nouri, M.D.; “Epilepsy and the Autonomic Nervous System” emedicine (updated May 5, 2006); pp. 1-14; http://www.emedicine.com/neuro/topic658.htm.
O'Regan, M.E., et al.; “Abnormalities in Cardiac and Respiratory Function Observed During Seizures in Childhood” Developmental Medicine & Child Neurlogy, vol. 47 (2005) pp; 4-9.
Pathwardhan, R.V., et al., Control of Refractory status epilepticus precipitated by anticonvulasnt withdrawal using left vagal nerve stimulation: a case report, Surgical Neurology 64 (2005) 170-73.
Poddubnaya, E.P., “Complex Estimation of Adaptation 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.
Rugg-Gunn, F.J., et al.; “Cardiac Arrhythmias in Focal Epilepsy: a Prospective Long-Term Study” www.thelancet.com vol. 364 (2004) pp. 2212-2219.
Sajadieh, a., et al.; “Increased Heart Rate and Reduced Heart-Rte Variability are 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.
Terry et al.; “The Implantable Neurocybernetic Prosthesis System”, Pacing and Clinical Electrophysiology, vol. 14, No. 1 (Jan. 1991), pp. 86-93.
Tubbs, R.S., 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 Original Paper; Springer-Verlag 2004.
Umetani, M.D., et al.; “Twenty-Four Hour Time Domain Heart Rate Variability and Heart Rate: Relations to Age and Gender Over Nince Decades”JACC vol. 31, No. 3; (Mar. 1998); pp. 593-601.
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.
Woodbury, 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.; “Neuroinhibition of Xylaine Induced Emesis” Pharmacology & Toxicology, vol. 63 (1988) pp. 70-74.
Zabara, J. “Inhibition of Experimental Seizures in Canines by Repetivie Vagal Stimulation” Epilepsia vol. 33, No. 6 (1992); pp. 1005-1012.
Zabara, J., et al.; “Neural Control of Circulation I”The Physiologist, vol. 28 No. 4 (1985); 1 page.
Zabara, J., et al.; “Neuroinhibition in the Regulation of Emesis” Space Life Sciences, vol. 3 (1972) pp. 282-292.
Osorio, Ivan 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, pp. 533-544, 2001.
Osorio, Ivan et al., “Automated Seizure Abatement in Humans Using Electrical Stimulation,” Annals of Neurology, vol. 57, No. 2, pp. 258-268, 2005.
Sunderam, Sridhar et al., “Vagal and Sciatic Nerve Stimulation Have Complex, Time-Dependent Effects on Chemically-Induced Seizures: A Controlled Study,” Brain Research, vol. 918, pp. 60-66, 2001.
Weil, Sabine 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, No. 3, Sep. 2005, pp. 199-204.
Digenarro, Giancarlo et al., “Ictal Heart Rate Increase Precedes EEG Discharge in Drug-Resistant Mesial Temporal Lobe Seizures,” Clinical Neurophysiology, No. 115, 2004, pp. 1169-1177.
Zijlmans, Maeike et al., “Heart Rate Changes and ECG Abnormalities During Epileptic Seizures: Prevalence and Definition of an Objective Clinical Sign,” Epilepsia, vol. 43, No. 8, 2002, pp. 847-854.
O'Donovan, Cormac a. et al., “Computerized Seizure Detection Based on Heart Rate Changes,” abstract of AES Proceedings, Epilepsia, vol. 36, Suppl. 4, 1995, p. 7.
Robinson, Stephen E et al., “Heart Rate Variability Changes As Predictor of Response to Vagal Nerve Stimulation Therapy for Epilepsy,” abstract of AES Proceedings, Epilepsia, vol. 40, Suppl. 7, 1999, p. 147.
Long, Teresa J. et al., “Effectiveness of Heart Rate Seizure Detection Compared to EEG in an Epilepsy MoitoringUnit (EMU),” abstract of AES Proceedings, Epilepsia, vol. 40, Suppl. 7, 1999, p. 174.
Related Publications (1)
Number Date Country
20120271181 A1 Oct 2012 US