U.S. patent application number 17/098391 was filed with the patent office on 2021-04-29 for seizure detection methods, apparatus, and systems using a wavelet transform maximum modulus algorithm.
The applicant listed for this patent is Alexey Lyubushin, Ivan Osorio, Didier Sornette. Invention is credited to Alexey Lyubushin, Ivan Osorio, Didier Sornette.
Application Number | 20210121081 17/098391 |
Document ID | / |
Family ID | 1000005329166 |
Filed Date | 2021-04-29 |
United States Patent
Application |
20210121081 |
Kind Code |
A1 |
Osorio; Ivan ; et
al. |
April 29, 2021 |
SEIZURE DETECTION METHODS, APPARATUS, AND SYSTEMS USING A WAVELET
TRANSFORM MAXIMUM MODULUS ALGORITHM
Abstract
Methods for detecting a seizure, by use of a wavelet transform
maximum modulus (WTMM) algorithm applied to body data. A
non-transitive, computer-readable storage device for storing data
that when executed by a processor, perform such a method.
Inventors: |
Osorio; Ivan; (Leawood,
KS) ; Lyubushin; Alexey; (Moscow, RU) ;
Sornette; Didier; (Zurich, CH) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Osorio; Ivan
Lyubushin; Alexey
Sornette; Didier |
Leawood
Moscow
Zurich |
KS |
US
RU
CH |
|
|
Family ID: |
1000005329166 |
Appl. No.: |
17/098391 |
Filed: |
November 15, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15377922 |
Dec 13, 2016 |
10835131 |
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17098391 |
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13554367 |
Jul 20, 2012 |
9549677 |
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15377922 |
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15729168 |
Oct 10, 2017 |
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13554367 |
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61547567 |
Oct 14, 2011 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/4836 20130101;
A61B 5/0816 20130101; A61B 5/0205 20130101; A61B 5/1118 20130101;
A61B 5/0833 20130101; A61B 5/726 20130101; A61B 5/165 20130101;
A61B 5/369 20210101; A61B 5/02055 20130101; A61B 5/024 20130101;
A61B 5/16 20130101; A61B 5/14542 20130101; A61B 5/374 20210101;
A61B 5/746 20130101; A61B 5/24 20210101; A61B 5/4094 20130101 |
International
Class: |
A61B 5/0205 20060101
A61B005/0205; A61B 5/16 20060101 A61B005/16; A61B 5/00 20060101
A61B005/00; A61B 5/374 20060101 A61B005/374 |
Claims
1. A non-transitory computer readable program storage unit encoded
with instructions that, when executed by one or more medical
devices, performs a method, comprising: receiving via the one or
more medical devices a time series of a first body signal of a
patient obtained from one or more sensors; determining a sliding
foreground time window and a sliding background time window for the
time series of the first body signal; applying a spectral filter
having a defined power spectral density to each of the sliding
foreground time window and the sliding background time window;
determining a ratio of a spectral power between the sliding
foreground time window and the sliding background time window;
determining a seizure onset in response to a first determination
that the ratio reaches an onset threshold; initiating an electrical
therapy based on the seizure onset determination; determining a
seizure termination in response to a second determination that the
ratio reaches a termination threshold; and wherein the method
further comprises at least one of: determining a seizure occurrence
based on a first output of a STA/LTA algorithm on at least one
second body signal; determining the seizure occurrence based on a
second output of at least one second algorithm on the first body
signal; and determining the seizure occurrence based on a third
output of at least one second algorithm on the at least lease one
second body signal; wherein the second body signal is selected from
an EKG signal, an accelerometer signal, or a signal indicative of a
loss of responsiveness.
2. The non-transitory computer readable program storage unit of
claim 1, including data that when executed by the one or more
medical devices perform the method of claim 1, wherein: a number of
samples in the sliding foreground time window (N.sub.STA) is 16; a
number of samples in the sliding background time window (N.sub.LTA)
is 360; the time of seizure onset (T.sub.onset) corresponds to a
time fulfilling a condition STALTA .function. ( .tau. + N STA / 2 )
.gtoreq. T onset , .times. ##EQU00010## wherein .times.
##EQU00010.2## STALTA .function. ( .tau. ) = t = .tau. - N STA + 1
.tau. .times. X 2 .function. ( t ) / N STA t = .tau. - N LTA + 1
.tau. .times. X 2 .function. ( t ) / N LTA ##EQU00010.3## and .tau.
is a common right-hand end of both the sliding foreground time
window and the sliding background time window; a time of the
seizure termination (T.sub.end) corresponds to a second time
fulfilling a second condition of max
{STALTA(s),.tau.-N.sub.STA.ltoreq.s.ltoreq..tau.}.ltoreq.T.sub.end;
and a filter's spectral density corresponds to a Daubechies wavelet
order 4, level 3.
3. The non-transitory computer readable program storage unit of
claim 1, including data that when executed by the one or more
medical devices perform the method of claim 1, wherein at least one
parameter selected from the sliding foreground time window, the
sliding background time window, the spectral filter, the onset
threshold, or the termination threshold is selected based on at
least one of: a level of safety risk associated with an activity;
at least one of an age, a physical state, or a mental state of the
patient; a length of a window available for a warning; a degree of
circadian and ultradian fluctuations of a patient's seizure
activity; a performance of a detection method as a function of a
patient's sleep/wake cycle or vigilance level; a dependence of a
patient's seizure activity on at least one of a level of
consciousness, a level of cognitive activity, or a level of
physical activity; a site of a seizure origin; or a seizure
type.
4. The non-transitory computer readable program storage unit of
claim 3, including data that when executed by the one or more
medical devices perform the method of claim 3, wherein the method
further comprises adaptively establishing the at least one
parameter.
5. The non-transitory computer readable program storage unit of
claim 1, including data that when executed by one or more medical
devices perform the method of claim 1, wherein the second body
signal comprises at least one of: a measurement of a patient's
heart activity, a measurement of a patient's respiratory activity,
a measurement of a patient's kinetic activity, a measurement of a
patient's brain electrical activity, a measurement of a patient's
oxygen consumption, a measurement of a patient's oxygen saturation,
a measurement of an endocrine activity of the patient, a
measurement of a metabolic activity of the patient, a measurement
of an autonomic activity of the patient, a measurement of a
cognitive activity of the patient, and a measurement of a tissue
stress marker of the patient.
6. The non-transitory computer readable program storage unit of
claim 1, including data that when executed by the one or more
medical devices perform the method of claim 1, wherein the method
further comprises: initiating the electrical therapy by delivering
the electrical therapy for the seizure at a particular time,
wherein at least one of the electrical therapy, the particular
time, or both is based upon the determination of the seizure onset;
determining an efficacy of the electrical therapy; or issuing a
warning for the seizure, wherein the warning is based upon the
determination of the seizure onset.
7. The non-transitory computer readable program storage unit of
claim 1, including data that when executed by the one or more
medical devices perform the method of claim 1, wherein the method
further comprises determining at least one of: a timing of a
delivery of the electrical therapy, a type of the electrical
therapy, at least one parameter of the electrical therapy, a timing
of sending a warning, a type of the warning, a duration of the
warning, or an efficacy index based upon the seizure onset, the
seizure termination, or both.
8. The non-transitory computer readable program storage unit of
claim 1, including data that when executed by the one or more
medical devices perform the method of claim 1, wherein the method
further comprises: determining at least one value selected from a
duration of the seizure, a severity of the seizure, an intensity of
the seizure, an extent of spread of the seizure, an inter-seizure
interval between the seizure and a prior seizure, a patient impact
of the seizure, and a time of the seizure occurrence; and logging
the at least one value in a memory.
9. The non-transitory computer readable program storage unit of
claim 1, including data that when executed by one or more medical
devices perform the method of claim 1, wherein the method further
comprises estimating a degree of nonstationarity of the first body
signal.
10. A non-transitory computer readable program storage unit encoded
with instructions that, when executed by a computer via one or more
processors and computer readable media, perform a method,
comprising: receiving a time series of a first body signal of a
patient; determining at least two sliding adjacent time windows for
the time series of the first body signal comprising a foreground
window and a background window; determining one or more long chains
for the foreground window and the background window based on a
parameter that defines which chains are long; extracting at least
one first long chain from the foreground window and at least one
second long chain from the background window; applying a continuous
wavelet transform to each of the one first long chain and the one
second long chain, to yield a wavelet transform maximum modulus
(WTMM) skeleton for each window; determining a first variance of
the WTMIM skeleton from the foreground window and a second variance
of the WTMM skeleton from the background window; generating a
stepwise approximation of changes in the variances; determining a
seizure onset in response to a determination that an output of the
stepwise approximation of changes in the first variance has reached
an onset threshold; initiating via a therapy device one or more
therapies to treat the seizure onset; and determining a seizure
termination in response to a determination that an output of the
stepwise approximation of changes in the second variance has
reached a termination threshold; wherein the method further
comprises at least one responsive action selected from: delivering
a therapy for said seizure at a particular time, wherein at least
one of said therapy, said particular time, or both is based upon
said determination of said seizure onset; determining an efficacy
of said therapy; or issuing a warning for said seizure, wherein
said warning is based upon a determination of said seizure onset, a
determination of duration of said seizure, a determination of a
type of said seizure, or two to more thereof.
11. The non-transitory computer readable program storage unit of
claim 10, including data that when executed by a processor performs
the method of claim 10, wherein at least one of the delivered
therapy or the issued warning is based at least in part on at least
one of the type of activity engaged in by the patient at the time
of seizure onset, the seizure type, the seizure severity, or the
time elapsed from the last seizure.
12. The non-transitory computer readable program storage unit of
claim 10, including data that when executed by a processor performs
the method of claim 10, wherein the method further comprises
determining at least one of: a time delivery of therapy, a duration
of a therapy, a type of therapy, at least one parameter of the
therapy, a timing of sending a warning, a type of warning, or a
duration of the warning; based upon said seizure onset, said
seizure termination, or both.
13. The non-transitory computer readable program storage unit of
claim 10, including data that when executed by a processor performs
the method of claim 10, wherein the method further comprises:
determining at least one value selected from the duration of said
seizure, the severity of said seizure, the intensity of said
seizure, the extent of spread of said seizure, an inter-seizure
interval between said seizure and a prior seizure, a patient impact
of said seizure, or a time of occurrence of said seizure and
logging said at least one value.
14. A medical device for detecting a seizure onset and a seizure
termination of an epileptic seizure event from a patient body
signal using a multi time-period averaging algorithm, comprising: a
body data processing module for receiving via one or more
processors a body signal of a patient during a first time series
from one or more sensors; and a seizure onset/termination unit
configured to: select a first time window and a second time window
within the first time series; apply a spectral filter having a
predetermined power spectral density to each of the first time
window and the second time window; determine a ratio of a spectral
power between the first time window and the second time window;
determine that the seizure onset has occurred in response to a
first determination that the ratio reaches an onset threshold;
initiating an electrical therapy based on the seizure onset
determination; and determine that the seizure termination has
occurred in response to a second determination that the ratio
reaches a termination threshold; wherein the time window control
module uses parameters selected based on at least one of: a
clinical application of at least one the determination; a level of
safety risk associated with an activity; at least one of an age, a
physical state, or a mental state of the patient; a length of a
window available for a warning; a degree of efficacy of the
electrical therapy and of the electrical therapy's latency; a
degree of a seizure control; a degree of circadian and ultradian
fluctuations of a patient's seizure activity; a performance of the
detection method as a function of a patient's sleep/wake cycle or
vigilance level; a dependence of the patient's seizure activity on
at least one of a level of consciousness, a level of cognitive
activity, or a level of physical activity; a site of seizure
origin; a seizure type, a desired sensitivity of the detection of
the seizure, a desired specificity of the detection of the seizure,
a desired speed of the detection of the seizure, an input provided
by the patient, or an input provided by the one or more
sensors.
15. The medical device of claim 14, wherein the body data
processing module comprises: a body data interface for receiving
the body signal, the body data interface comprising: a buffer to
perform buffering function upon the body signal; an amplifier for
performing an amplification of the body signal; an
analog-to-digital (A/D) converter for converting the body signal
from an analog signal to a digital signal; and a filter for
performing a filtering function upon the body signal; and a body
data memory to store the digital signal.
16. The medical device of claim 15, wherein the seizure
onset/termination unit comprises: a time window control module
capable of selecting the first time window and the second time
window; a spectral filter module for applying the spectral filter
to the first time window and the second time window; a ratio
determination unit for determining the ratio of the spectral power;
and a ratio threshold comparison unit for comparing the ratio of
the spectral power to a first threshold to determine whether the
seizure onset has occurred, and for comparing the ratio of the
spectral power to a second threshold to determine whether the
seizure termination has occurred.
17. The medical device of claim 16, wherein the first time series
body signal comprises at least one of a measurement of a patient's
heart activity, a measurement of a patient's respiratory activity,
a measurement of a patient's kinetic activity, a measurement of a
patient's brain electrical activity, a measurement of a patient's
oxygen consumption, a measurement of a patient's oxygen saturation,
a measurement of an endocrine activity of the patient, a
measurement of a metabolic activity of the patient, a measurement
of an autonomic activity of the patient, a measurement of a
cognitive activity of the patient, or a measurement of a tissue
stress marker of the patient.
Description
BACKGROUND OF THE INVENTION
[0001] The present application claims priority to and is a
Continuation of co-pending U.S. patent application Ser. No.
15/377,922, filed on Dec. 13, 2016, entitled "Seizure Detection
Methods, Apparatus, and Systems Using a Wavelet Transform Maximum
Modulus Algorithm", which claims priority to and is a continuation
of U.S. patent application Ser. No. 13/554,367, filed on Jul. 20,
2012 (Now U.S. Pat. No. 9,549,677), entitled "Seizure Detection
Methods, Apparatus, and Systems Using a Wavelet Transform Maximum
Modulus Algorithm", which claims priority from U.S. provisional
patent application Ser. No. 61/547,567, filed on Oct. 14, 2011,
further the present application claims priority to and is a
Continuation-in-part of co-pending U.S. patent application Ser. No.
15/729,168, filed on Oct. 10, 2017, entitled "Seizure Detection
Methods, Apparatus, and System Using an Autoregression Algorithm",
which are all incorporated herein by reference.
1. FIELD OF THE INVENTION
[0002] The present invention relates generally to the field of
epileptic event detection. More particularly, it concerns epileptic
event detection by use of a wavelet transform maximum modulus
(WTMM) algorithm on a time series of patient body signal data.
2. DESCRIPTION OF RELATED ART
[0003] There have been various advancements in the area of seizure
detection, which remains a fairly subjective endeavor. The task of
automated detection of epileptic seizures is intimately related to
and dependent on the definition of what is a seizure, definition
which to date is subjective and thus inconsistent within and among
experts. The lack of an objective and universal definition not only
complicates the task of validation and comparison of detection
algorithms, but possibly more importantly, the characterization of
the spatio-temporal behavior of seizures and of other dynamical
features required to formulate a comprehensive epilepsy theory.
[0004] The current state of automated seizure detection is, by
extension, a faithful reflection of the power and limitations of
visual analysis, upon which it rests. The subjectivity intrinsic to
expert visual analysis of seizures and its incompleteness (it
cannot quantify or estimate certain signal features, such as power
spectrum) confound the objectivity and reproducibility of results
of signal processing tools used for their automated detection. What
is more, several of the factors, that enter into the determination
of whether or not certain grapho-elements should be classified as a
seizure, are non-explicit ("gestalt-based") and thus difficult to
articulate, formalize and program into algorithms.
[0005] Most, if not all, existing seizure detection algorithms are
structured to operate as expert electroencephalographers. Thus,
seizure detection algorithms that apply expert-based rules are at
once useful and deficient; useful as they are based on a certain
fund of irreplaceable clinical knowledge and deficient as human
analysis biases propagate into their architecture. These cognitive
biases which pervade human decision processes and which have been
the subject of formal inquiry are rooted in common practice
behaviors such as: a) The tendency to rely too heavily on one
feature when making decisions (e.g., if onset is not sudden, it is
unlikely to be a seizure because these are paroxysmal events); b)
To declare objects as equal if they have the same external
properties (e.g., this is a seizure because it is just as
rhythmical as those we score as seizures) or c) Classify phenomena
by relying on the ease with which associations come to mind (e.g.,
this pattern looks just like the seizures we reviewed
yesterday).
[0006] Seizure detection algorithms' discrepant results make
attainment of a unitary or universal seizure definition ostensibly
difficult; the notion that expert cognitive biases are the main if
not only obstacle on the path to "objectivity" is rendered tenuous
by these results. These divergences in objective and reproducible
results may be attributable in part, but not solely, to the
distinctiveness in the architecture and parameters of each
algorithm. The fractal or multi-fractal structures of seizures
accounts at least in part for the differences in results and draws
attention to the so-called "Richardson effect." Richardson
demonstrated that the length of borders between countries (a
natural fractal) is a function of the size of the measurement tool,
increasing without limit as the tool's size is reduced. Mandelbrot,
in his seminal contribution "How long is the coast of Britain,"
stressed the complexities inherent to the Richardson effect, due to
the dependency of particular measurements on the scale of the tool
used to perform them. Although defining seizures as a function of a
detection tool would be acceptable, this approach may be
impracticable when comparisons between, for example, clinical
trials or algorithms are warranted. Another strategy to bring
unification of definitions is to universally adopt the use of one
method, but this would be to the detriment of knowledge mining from
seizure-time series and by extension to clinical epileptology.
[0007] To date, meaningful performance comparisons among myriad
existing algorithms have not been feasible due to lack of a common
and adequate database. However, even if adequate databases were
available, the value of such "comparisons" would be limited by the
absence of a universally accepted definition of what is a
"seizure." The previously noted cognitive biases and
architectural/parametric distinctions among algorithms impede
achievement of consensus and in certain cases even of majority
agreement in classifying particular events as seizures or
non-seizures. Because expert visual analysis provides the
benchmarks (seizure onset and termination times) from which key
metrics (detection latency in reference to electrographic and
clinical onset time ("speed of detection"), sensitivity,
specificity and positive predictive value) are derived, the effects
of cognitive biases propagate beyond the seizure/non-seizure
question into other aspects of the effectiveness of a particular
seizure detection algorithm.
SUMMARY OF THE INVENTION
[0008] In one aspect, the present disclosure relates to a method,
comprising receiving a time series of a first body signal of the
patient; determining at least two sliding adjacent time windows for
said time series of said first body signal comprising a foreground
window and a background window; extracting at least one first long
chain from said foreground window and at least one second long
chain from said background window; applying a continuous wavelet
transform to each of said long chains, to yield a wavelet transform
maximum modulus (WTMM) skeleton for each window; determining a
first variance of the WTMM skeleton from said foreground window and
a second variance of the WTMM skeleton from said background window;
generating a stepwise approximation of changes in said variance;
determining a seizure onset in response to a determination that an
output of the stepwise approximation of changes in said first
variance has reached an onset threshold; and determining a seizure
termination in response to a determination that an output of the
stepwise approximation of changes in said second variance has
reached a termination threshold.
[0009] In one aspect, the present disclosure relates to a
non-transitory computer readable program storage unit encoded with
instructions that, when executed by a computer, perform a method as
described above or herein.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] The invention may be understood by reference to the
following description taken in conjunction with the accompanying
drawings, in which like reference numerals identify like elements,
and in which:
[0011] FIG. 1 illustrates a medical device system for detecting and
classifying seizure events related to epilepsy from sensed body
data processed to extract features indicative of aspects of the
patient's epilepsy condition;
[0012] FIG. 2 illustrates a medical device system, according to an
illustrative embodiment of the present disclosure;
[0013] FIG. 3 provides a stylized diagram of a medical device and
different data acquisition units that may provide output(s) used by
other unit(s) of the medical device, in accordance with one
illustrative embodiment of the present disclosure;
[0014] FIG. 4 provides a stylized diagram of a medical device and
different data acquisition units that may provide output(s) used by
other unit(s) of the medical device, in accordance with one
illustrative embodiment of the present disclosure;
[0015] FIG. 5 provides a stylized diagram of a seizure
onset/termination unit, in accordance with one illustrative
embodiment of the present disclosure;
[0016] FIG. 6 presents WTMM chains constructed from a signal, in
accordance with one illustrative embodiment of the present
disclosure;
[0017] FIG. 7 presents a logarithmic standard deviation of an ECoG
time series and a WTMM-stepwise approximation thereof, in
accordance with one illustrative embodiment of the present
disclosure;
[0018] FIG. 8 illustrates the output of the WTMM algorithm in
reference to an Average Indicator Function (AIF) making use of four
algorithms, including the WTMM algorithm, in accordance with one
illustrative embodiment of the present disclosure;
[0019] FIG. 9 shows a graph of a specificity function for the WTMM
method as a function of time with respect to a validated
algorithm's time of seizure detection, in accordance with one
illustrative embodiment of the present invention;
[0020] FIG. 10 shows a plot of the decimal logarithm of the
dependence of seizure energy on seizure duration, in accordance
with one illustrative embodiment of the present disclosure;
[0021] FIG. 11 shows the empirical "tail" of the conditional
probability distribution functions for: (a) Seizure durations
(minimum duration: 2 sec); and (b) the logarithm of seizure energy
as estimated with four different methods, in accordance with one
illustrative embodiment of the present disclosure;
[0022] FIG. 12 provides a flowchart depiction of a method, in
accordance with one illustrative embodiment of the present
disclosure;
[0023] FIG. 13 shows ECoG before (upper panel) and after
differentiation (lower panel), in accordance with one illustrative
embodiment of the present disclosure; and
[0024] FIG. 14 shows temporal evolution of the decimal logarithm of
the power spectrum of differentiated ECoG.
DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS
[0025] In one aspect, the present disclosure provides several new
seizure detection algorithms that may be applied to one or more
streams of body data. Some of these algorithms rely principally on
power variance for detection of seizures, while others rely mainly
on power spectral shape.
[0026] In another aspect, the present disclosure exploits the
simultaneous application of two or more individual seizure
detection algorithms to derive a probabilistic measure of seizure
activity (PMSA), which may be used to issue detections by majority
or consensus of a plurality of the two or more seizure detection
algorithms, depending on safety factors and others such as
detection speed, sensitivity, specificity or any other performance
measures and the clinical application(s) at hand. Real-time ("on
the run") automated seizure detection provides the only means
through which contingent warning to minimize risk of injury to
patients, delivery of a therapy for control of seizures, or logging
of the date, time of onset and termination and severity may be
performed.
[0027] This disclosure, in one embodiment, provides a wavelet
transform maximum modulus (WTMM) algorithm suitable for use in
epileptic event detection, by operation on a time series of patient
body signal data. Such a WTMM algorithm may be used by itself, as
part of a Probabilistic Measure of Seizure Activity (PMSA), or, by
performing stepwise approximations of the WTMM, as a single
algorithm capable of providing a PMSA.
[0028] More generally, this disclosure: a) draws attention to the
intricacies inherent to the pursuit of a universal seizure
definition even when powerful, well understood signal analysis
methods are utilized to this end; b) identifies this aim as a
multi-objective optimization problem and discusses the advantages
and disadvantages of adopting or rejecting a unitary seizure
definition; c) introduces a Probabilistic Measure of Seizure
Activity to manage this thorny issue.
[0029] Seizure detection belongs to a class of optimization
problems known as "multi-objective" due to the competing nature
between objectives: improvements in specificity of detection
invariably degrade sensitivity, and vice-versa. Attempts to achieve
a universal seizure definition using objective, quantitative means
are likely to be fraught with similar competing objectives. In one
aspect, the present invention involves the application of tools
from the field of multi-objective optimization, among others to
make the problems caused by competing objectives more
tractable.
[0030] Achieving a unitary seizure definition would be difficult,
as consensus among epileptologists as to what grapho-elements are
classifiable as ictal, is rare. In the absence of a universal
definition, issuing seizure warnings for certain cases will be
problematic and unsafe. For example, if a patient with seizures
wishes to operate power equipment or a motor vehicle, the absence
of a universal agreement on when the patient has had a seizure may
preclude any viable way of ensuring, using seizure detection
algorithms that the patient's seizures are under sufficient control
to allow such activities to occur. To manage the difficulties of a
consensus seizure definition, substantive gains are feasible
through steps entailing, for example, the application of advanced
signal analysis tools to ECoG, to hasten the identification of
properties/features that would lead to the probabilistic
discrimination of seizures from non-seizures with worthwhile
sensitivity and specificity for the task at hand. However, to even
have a modicum of success, such an approach should not ignore the
non-stationarity of seizures and, should strike some sort of
balance between supervised (human) and unsupervised
machine-learning) approaches. The resulting multidimensional
parameter space, expected to be broad and intricate, may also
foster discovery of hypothesized (e.g. pre-ictal) brain
sub-states.
[0031] The challenges posed by the attempt to define seizures
unitarily using objective means (distinct from visual analysis) may
be partly related to their fractal properties and understood
through a simplistic analogy to the so-called "Richardson effect".
A revision of the time-honored subjective definition of seizures
may be warranted to further advance epileptology.
[0032] The present inventors propose a Probabilistic Measure of
Seizure Activity (PMSA) as one possible strategy for
characterization of the multi-fractal, non-stationary structure of
seizures, in an attempt to eschew the more substantive limitations
intrinsic to other alternatives.
[0033] The PMSA may make use of "indicator functions" (IFs) denoted
X.sub.algo for each algorithm `algo.` In one embodiment, the PMSA
may also make use of an Average Indicator Function (AIF). In one
embodiment, the AIF is defined as:
AIF(t)=(X.sub.Val(t)+X.sub.r.sub.2(t)+X.sub.STA/LTA(t)+X.sub.WTMM(t))/4
[0034] The subscripts Val, r.sup.2, STA/LTA and WTMM refer to four
different algorithms, particular embodiments of which are described
herein and/or in other related applications. One or more of these
algorithms may be used to detected seizures from one or more body
data streams including, but not limited to, a brain activity (e.g.,
EEG) data stream, a cardiac (e.g., a heartbeat) data stream, and a
kinetic (e.g., body movement as measured by an accelerometer) data
stream.
[0035] "Val" refers to an algorithm for seizure detection using
ECoG data that has been validated by experts without reaching a
universal consensus about its performance (e.g., false positive,
false negative and true positive detections). An "r.sup.2"
algorithm may also be referred to herein as an "r .sup.2,"
"autoregression," or "autoregressive" algorithm. A "STA/LTA"
algorithm refers to an algorithm characterized by the ratio of a
Short-Term Average to a Long-Term Average. A "WTMM" algorithm
refers to a Wavelet Transform Maximum Modulus algorithm.
[0036] For determination of an AIF from the foregoing formula, an
algorithm's IF equals 1 for time intervals (0.5 sec in this
application) "populated" by ictal activity and 0 by inter-ictal
activity. The IF's are used to generate four stepwise time
functions, one for each of: a) a 2.sup.ndorder auto-regressive
model (r.sup.2); b) the Wavelet Transform Maximum Modulus (WTMM);
c) the ratio of short-to-long term averages (STA/LTA) and d) a
Validated algorithm (Val). With these IFs, the AIF is computed (its
values may range between [0-1] with intermediate values of 0.25,
0.5 and 0.75 in this embodiment). (Intermediate AIF values are
functions of the number of algorithms applied to the signal. Since
in this study 4 methods were used and the range of the indicator
function is [0-1], the intermediated values are [0.25, 0.5, 0.75]).
These values [0-1] are estimates of the probability of seizure
occurrence at any given time. In another embodiment, the values of
each algorithm's IF may be weighted differently, and a composite IF
(e.g., a Weighted Indicator Function or WIF) different from the AIF
may be computed.
[0037] Data obtained from one subject undergoing evaluation for
epilepsy surgery with intra-cranial electrodes was selected for
analyses. The ECoG was recorded using electrodes implanted into the
amygdala, pes hippocampus and body of hippocampus bilaterally
through the temporal neocortex and had a duration of 6.9 days
(142'923'853 samples; 239.75 Hz sampling rate).
[0038] For efficient analyses, ECoG signal differentiation was
performed, so as to minimize the non-stationarity present in them.
If Z(t) is raw ECoG, then its difference is X(t)=Z(t)-Z(t-1), where
(t) corresponds to a sample time increment. This linear operation
is exactly invertible and, unlike band-pass filtering or
detrending, does not suppress low frequency fluctuations, but
decreases their overall influence. FIG. 13 illustrates the effect
of this operation on raw ECoG. The differentiated ECoG is less
non-stationary (chiefly at low frequencies) than the
undifferentiated one (x-axis: time in sec.; y-axis: amplitude in
microvolts). FIG. 14 shows a time-frequency map of the evolution of
the power spectra of differentiated ECoG segments (as shown in FIG.
13, bottom panel). The power spectra are estimated within 5 sec
moving windows of length. Six brief seizures appear as marked power
spectrum increases (red and specks of white) in the 10-100 Hz band
(x-axis: time in sec.; y-axis: frequency (Hz); color scale to the
right of main graph).
[0039] Continuous Wavelet Transform Maximum Modulus (WTMM)
[0040] The WTMM technique exploits the large, sudden changes in the
variance of signal features, such as amplitude and frequency that
characterize most epileptic seizures. These features are calculated
within a hierarchy of sequences of short contiguous windows of
equal length and are extracted in the form of chains of continuous
Wavelet Transform Maximum Modulus (WTMM), using a mother wavelet
defined as the 1.sup.st order derivative of the Gaussian function
.about.exp(-t.sup.2). The construction of long chains to form a
WTMM-skeleton is a commonly used method for detecting changes in
the mean value of noisy signals such as edge detection in vision
computer programs. WTMM relies on three parameters: a) The length
of the window used to calculate the sequence of variance values; b)
A parameter a* that defines which WTMM-chains are long and, c) The
threshold .DELTA.U for the stepwise approximation of the
logarithmic variance curve for detecting the onsets and ends of
seizures.
[0041] The Wavelet Transform (WT) may be conceptualized as a
"mathematical microscope" that is well suited to reveal the
hierarchy that governs the spatial distribution of singularities of
multifractal measures. The role of the scaling parameter a* is
similar to that of the magnification setting in a microscope: the
larger the value of a*, the larger the scale of the signal's
structure under investigation. By using wavelets instead of boxes,
the smoothing effect of polynomials that might either mask
singularities or perturb the estimation of their strength (Holder
exponent) is avoided. This approach remedies one of the main
failures of the classical multifractal methods such as the
box-counting algorithms in the case of measures and of the
structure function method in the case of functions. Another
advantage of this method is that the skeleton defined by the WTMM
provides an adaptive space-scale partitioning from which to extract
the singularity spectrum via the Legendre transform of the scaling
exponents (real, positive as well as negative) of some partition
functions defined from the WT skeleton. The person of ordinary
skill in the art is aware of mathematical description and
applications, as well as theoretical treatment, of random
multifractal functions.
[0042] As originally pointed out for the specific purpose of
analyzing the regularity of a function, the redundancy of the WT
may be eliminated by focusing on the WT skeleton defined by its
modulus maxima only. These maxima are defined, at each scale a, as
the local maxima of the set of wavelet transforms over all possible
position x at the fixed scale a of the function f denoted
|T.sub..psi.[f](x,a)|. These WTMM points are disposed on connected
curves in the space-scale (or time-scale) half-plane, called maxima
lines. Let us define L(a.sub.0) as the set of all the maxima lines
that exist at the scale a.sub.0 and which contain maxima at any
scale a<a.sub.0. An important feature of these maxima lines,
when analyzing singular functions, is that there is at least one
maxima line pointing towards each singularity.
[0043] There are almost as many analyzing wavelets as applications
of the continuous WT. A commonly used class of analyzing wavelets
is defined by the successive derivatives of the Gaussian
function:
g ( N ) .function. ( x ) = d N dx N .times. exp .function. ( - x 2
/ 2 ) ( 7 ) ##EQU00001##
[0044] Note that the WT of a signal f(x) with g.sup.(N) (Eq. 7)
takes the following simple expression:
T g ( N ) .function. [ f ] .times. ( x , a ) = 1 a .times. .intg. -
.infin. + .infin. .times. f .function. ( y ) .times. g ( N )
.function. ( ( y - x ) / a ) .times. dy = a N .times. d N dx N
.times. T g ( 0 ) .function. [ f ] .times. ( x , a ) ( 8 )
##EQU00002##
[0045] Equation (8) shows that the WT computed with g.sup.(N) at
scale a is nothing but the N-th derivative of the signal f(x)
smoothed by a dilated version g.sup.(0)(x/a) of the Gaussian
function. This property is at the heart of various applications of
the WT "microscope" as a very efficient multi-scale singularity
tracking technique.
[0046] The algorithm described as follows may be used to construct
the WTMM-skeleton.
[0047] Let Y.sup.(t) be an arbitrary signal and consider the
corresponding smoothed signal obtained by using a scale-dependent
kernel:
c 0 .function. ( t , a ) = .intg. - .infin. + .infin. .times. Y
.function. ( t + av ) .psi. 0 .function. ( v ) .times. dv / .intg.
- .infin. + .infin. .times. .psi. 0 .function. ( v ) .times. dv ( 9
) ##EQU00003##
[0048] where a>0 is a time scale and .psi..sub.0(t) is some
function decaying sufficiently fast on both sides of its single
maximum; further on, .psi..sub.0(t)=exp(-t.sup.2) shall be used.
The wavelet function is defined as:
.psi. n .function. ( t ) = ( - 1 ) n d n .times. .psi. 0 .function.
( t ) dt n .ident. ( - 1 ) n .psi. 0 ( n ) .function. ( t ) ( 10 )
##EQU00004##
[0049] Using integration by part and exploiting the fast decay of
the function .psi..sub.0.sup.(t) at t.+-..infin., the following
formula for the Taylor's coefficients (the n-th derivative of the
smoothed signal, divided by n!) of the smoothed signal is
obtained:
c n .function. ( t , a ) .ident. 1 n ! .times. d n .times. c 0
.function. ( t , a ) dt n = .intg. - .infin. + .infin. .times. Y
.function. ( t + av ) .times. .psi. n .function. ( v ) .times. dv /
a n .times. .intg. - .infin. + .infin. .times. v n .times. .psi. n
.function. ( v ) .times. dv ( 11 ) ##EQU00005##
[0050] Equation (9) is a particular case of formula (11) for
n=0.
[0051] The WTMM-point (t, a) for n.gtoreq.1 is defined as the point
for which |c.sub.n(t,a)| has a local maximum with respect to time t
for a given time scale a. For n=0, the WTMM-points are defined as
points of local extremes (maxima or minima) of the smoothed signal
c.sub.0(t,a) that may be joined to form chains; the set of all
chains creates a WTMM-skeleton of the signal. If .psi..sub.0(t) is
a Gaussian function, then a given WTMM-skeleton chain does not end
when the scale a is decreased. The WTMM-points for the 1.sup.st
order derivative c.sub.1(t,a) indicate time points of the maximum
trend (positive or negative) of the smoothed signal c.sub.0(t,a)
for the given scale. This allows temporal localization of "points"
of large and abrupt changes of the mean value of a noisy signal
such as ECoG; these "points" mark the times when rather long
WTTM-chains begin to grow.
[0052] A stepwise approximation S.sub.Y(t|a*) for the signal Y(t),
is defined as a function which is equal to the sequence of constant
values g.sub.k in the successive intervals t.di-elect
cons.[.tau..sub.k(a*),.tau..sub.k+1(a*)] Here .tau..sub.k(a*) are
the beginnings of the WTMM-chains for c.sub.1(t,a) which exceed the
threshold time scale a* and
g k = t = .tau. k .function. ( a * ) .tau. k + 1 .function. ( a * )
.times. T .function. ( t ) / ( .tau. k + 1 .function. ( a * ) -
.tau. k .function. ( a * ) + 1 ) ( 12 ) ##EQU00006##
[0053] is equal to the mean value of Y(t) within the time interval
[.tau..sub.k(a*),.tau..sub.k+1(a*)]
[0054] For example, consider a signal that is a sum
Y(t)=S.sub.0(t)+.epsilon.(t), t=1, . . . , 2000, where .epsilon.(t)
is a Gaussian white noise with unit standard deviation and
[0055] S.sub.0(t)=0 for t.di-elect cons.[1,250], [751,1250],
[1751,2000];
[0056] S.sub.0(t)=2 for t.di-elect cons.[251,750], [1251,1750].
[0057] The resulting stepwise approximation for this signal using
WTMM-chains is shown in FIG. 6, (noting that for both panels, the
x-axis represents time (in sec)). (a) y-axis: Wavelet Transform
Maximum Modulus-chains constructed using the 1st derivative of the
Gaussian wavelet for the signal S.sub.0(t)+.epsilon.(t) defined by
expression (12) (grey lines in FIG. 3b). The solid lines correspond
to WTMM-chains for negative c.sub.1(t,a) values and the dashed
lines to WTMM-chains for positive c.sub.1(t,a) values. The thin
grey horizontal line indicates the time scale threshold a*=50; (b)
y-axis: The grey lines represent the signal S.sub.0(t)+.epsilon.(t)
(equation (12)), the solid horizontal line is the pure signal
S.sub.0(t) without noise and the dashed horizontal line the
reconstructed signal S.sub.Y(t|a*) using the WTMM method for
a*=50.
[0058] Thus, times of abrupt changes of the mean value of the
signal of interest can be estimated as instants of rather large
steps of the signal S.sub.Y(t|a*) with an appropriate choice of the
time scale threshold a*.
[0059] Seizure Detection with the WTMM-Method
[0060] The WTMM-method of constructing a stepwise approximation
S.sub.Y(t|a*) for an arbitrary signal Y(t) may be applied to the
task of seizure detection. This is suggested from observations of
seizures as intervals of large, abrupt signal variance. Let us
calculate sample estimates of the variance of the normalized ECoG
X(t) within "small" adjacent time intervals of length L and take
the logarithmic values of the standard deviations:
U .function. ( .xi. j ) = 1 2 lg .function. ( V x .function. ( .xi.
j ) ) , .times. V X .function. ( .xi. j ) = 1 L .times. t = .xi. j
- L + 1 .xi. j .times. X 2 .function. ( t ) , .times. .xi. j = j L
, .times. j = 1 , 2 , ( 13 ) ##EQU00007##
[0061] Thus, U(.xi..sub.j) is a time series with a sampling time
interval which is L times larger than the sampling time interval of
the original ECoG. Graphics of U are plotted as a function of the
time position of the right end of these time intervals of length L
and its stepwise approximation S.sub.U(.xi..sub.j|a*) is
constructed, where a* is a scale threshold for the decimal
logarithms of the variance U (FIG. 7) of the ECoG . Specifically,
in FIG. 7, the grey line indicates values of the logarithmic
standard deviation of the time series of ECoG in a rat model (Rat48
increments), estimated within adjacent time intervals of length
L=240. The thick black line is the WTMM-stepwise approximation of
Lg(St.Dev.) with time scale threshold a*=3.
[0062] Seizures onsets and terminations are defined by the
following rule:
.xi..sub.j is onset if
S.sub.U(.xi..sub.j+1|a*)-S.sub.U(.xi..sub.j|a*).gtoreq..DELTA.U
.xi..sub.j is end if
S.sub.U(.xi..sub.j+1|a*)-S.sub.U(.xi..sub.j|a*).gtoreq..DELTA.U
(14)
[0063] The time interval length L, the scale threshold a* for the
decimal logarithms of the variance and the threshold value .DELTA.U
for the logarithm of the variance of the normalized ECoG are this
method's three parameters. In the application shown in FIG. 7, the
chosen parameter values are the following: (L=240, a*=3,
.DELTA.U=0.25). The value of the threshold .DELTA.U determines the
"strength" required to detect ECoG activity that qualifies as
seizures. Given a window L=240 for calculating the sequence of
U(.xi..sub.j) and a sampling rate of 240 Hz, the time resolution of
the WTMM-seizures detection implementation shown in FIG. 7 is 2
s.
[0064] The WTMM and Validated algorithms have been described in
U.S. provisional patent application Ser. No. 61/547,567, filed on
Oct. 14, 2011, which is hereby incorporated by reference herein in
its entirety.
[0065] The total number of detections, their duration and the
percent time spent in seizure over the time series total duration
(6.9 days) are presented in Table 1.
TABLE-US-00001 Validated algorithm WTMM Total number of seizures
with 3184 10795 duration .gtoreq. 2 s. Mean duration, s. 3.8 18.6
Median duration, s. 3.4 6 % time spent in seizure 2 34
[0066] Table 1. Summary statistics obtained by applying two
different detection methods (Validated Algorithm; WTMM). The
minimum duration of seizures was set at 2 s.
[0067] FIG. 8 illustrates the output of the WTMM algorithm in
comparison with an AIF making use of each of the validated
algorithm, and the r2 (AR), STA/LTA and WTMM algorithms.
Specifically, FIG. 8 shows results of applying the WTMM seizure
detection method to a differentiated ECoG (in black; 200 sec/panel)
of a human with pharmaco-resistant epilepsy. The grey boxes
represent the values (right y-axis) of an Average Indicator
Function in the interval [0,1]. Seizures onset and end times
determined by the WTMM algorithm are indicated by vertical lines,
with onset lines shifted upward and end lines, downward. Notice
that the value of the Average Indicator Function is rarely 1, at
onset or termination, indicating all methods do not detect the ECoG
activity as being ictal in nature at those moments. However, with
seizures exceeding certain duration (at least 20 seconds) and
intensity thresholds, they converge to all detect the seizure
event. This indicates that the spectral and other properties of
seizures are not homogeneous at the onset and termination of
seizures, which is consistent with the lack of agreement among
human experts (and algorithms) during onset and termination. Left
y-axis: ECoG amplitude (in .mu.V); excursions above zero correspond
to positive, and below, to negative, polarity.
[0068] Table 2 provides further evidence that, at some point in
time, the majority of seizures detected by the validated algorithm
are also detected by the WTMM method, with WTMM detecting 97% of
seizures. More specifically and by way of example, the value 0.971
in Table 2 means that the WTMM method detections encompass 97.1% of
seizure time intervals detected with the validated method, with the
exception of 1.6 s. that correspond to the delay/lag between them
in detecting seizure onsets (see below for details).
[0069] Time intervals for which the pairwise product X.sub.Val(t)
X.sub.WTMM(t)=1 correspond to seizures detected by both the
validated algorithm and WTMM. Dividing the number of time intervals
when X.sub.Val(t)X.sub.WTMM(t)=1by the number of intervals when
X.sub.Val(t)=1, yields the specificity of the WTMM method with
respect to the validated algorithm. The specificity functions for
the two other methods Spe.sub.r2_Val(.tau.) and
Spe.sub.STA/LTA_Val(.tau.) are identically computed and their
maximum value (dependent on .tau.) may be regarded as the mean
value of the time delay of one method's function with respect to
another for seizure onset and end times. Since the validated
algorithm has an inherent delay of 1 s (the median filter's
foreground window is 2 s) and an additional duration constraint of
0.84 s. is imposed before a detection is issued, its onset and end
times are "delayed" compared to those yielded by the WTMM
method.
[0070] The present inventors discovered that the time differences
are negative for all three algorithms compared to the validated
algorithm; that is, the validated algorithm's detection times lag
behind those given by the other methods. More particularly, the
mean delay of the validated algorithm is 1.6 s with respect to
WTMM. The re-calculated specificity values shifted by .tau. shown
in Table 2 are higher compared to those without shifting.
TABLE-US-00002 Method Spe.sub.Method_Val(0) max .tau. .times.
.times. Spe Method .times. _ .times. Val .function. ( .tau. )
##EQU00008## arg .times. .times. max .tau. .times. .times. Spe
Method .times. _ .times. Val .function. ( .tau. ) ##EQU00009## WTMM
0.823 0.971 -1.6 s
[0071] Table 2. Values of specificity of WTMM calculated with
respect to the validated method and time lag (as defined in the
text) at which the specificity attains its largest value.
[0072] The information in Table 2 is also depicted graphically in
FIG. 9, which illustrates a graph of a specificity function for the
WTMM method as a function of time with respect to the Validated
algorithm's time of seizure detection. Tau (.tau.) zero (x-axis)
corresponds to the time at which Val issues a detection. Negative
.tau. values indicate "late" detections by the validated algorithm
in relation to the WTMM algorithm and positive value the opposite.
As shown, WTMM issues earlier detections than Val. Values of the
lags .tau. corresponding to the maximum and minimum values of the
function are presented under the names argmax and argmin
respectively.
[0073] The present inventors also discovered that only 29.5% of
seizures recognized as such by the WTMM method were also detected
by the validated method, indicating that in its generic form and by
design, the validated algorithm is less sensitive and more specific
for seizure detection than the WTMM algorithm.
[0074] The WTMM method, along with the other methods mentioned
supra, survey different but inter-dependent ECoG signal properties,
thus expanding the breadth and perhaps also the depth of insight
into the spectral "structure" of epileptic seizures in a clinically
relevant manner. The WTMM method is well suited for estimations of
changes in power variance within adjacent "short" time windows. The
WTMM may be implemented in off-line analysis applications given its
relatively high algorithmic complexity. Of course, readily
foreseeable advances in the miniaturization, speed, power, and
energy efficiency of computational devices indicate the WTMM may be
implemented in implantable devices and/or real time
applications.
[0075] Algorithmic and visual expert analysis consensus as to what
grapho-elements define a `seizure` seems to be highly dependent on
when during the course of a `seizure` a decision is made. In this
context, it is noteworthy that AIF frequently reached a value of 1,
indicative of concordance among all detection methods sometime
after seizure onset and before its termination (as determined by
any of the methods), provided said seizures reached a certain
duration (20-30 s.) as discussed in more detail in U.S. provisional
patent application Ser. No. 61/547,567, filed on Oct. 14, 2011. In
short, seizure onsets and terminations may be under certain
conditions universally undefinable by algorithmic or expert visual
analysis. A systematic investigation of the differences in signal
spectral properties between the "preface"/"epilogue" and the "main
body" of seizures was not performed. It is speculated that the
presence of "start-up transients" (in a dynamical sense) and of
temporo-spatial dispersion of the ictal signal (which impacts S/N)
may be most prominent at the onset and termination of seizures.
These and local and global state-dependencies of certain signal
features, account in part for the temporal fluctuations in
algorithmic detection performance that characterize these
results.
[0076] Defining seizure energy as the product of the standard
deviation of the power of ECoG by its duration (in seconds),
reveals that the WTMM algorithm identifies as a continuum seizures
that the validated algorithm detects as clusters of short seizures.
The lack of correspondence between a certain percentage of
detections (2.9% for the WTMM method) and the validated algorithm
may be partially attributed to brief discontinuities in seizure
activity as shown in FIG. 8. This phenomenon ("go-stop-go") appears
to be inherent to seizures (e.g., it is a general feature of
intermittency associated with many dynamical systems). These
discontinuities are also an "artifact" caused by the architecture
of and parameters used in each algorithm. For example, the longer
the foreground window and the higher the order statistical filter
(e.g., median vs. quartile), in the validated algorithm, the higher
the probability that "gaps" in seizure activity will occur.
Clustering of detections is a strategy to manage dynamical or
artifactual ictal "fragmentation," and in this sense the WTMM
algorithm avoids the subjective biases and arbitrariness associated
with human-imposed clustering rules.
[0077] The dependencies of seizure energy (defined as the product
of the standard deviation of the differentiated ECoG signal and
seizure duration, in sec.) on seizure duration, for the set of icti
detected by the WTMM method is depicted in FIG. 10. A subset of
seizures detected by all methods obeys a simple law of
proportionality between energy (y-axis) and duration (x-axis, log
scale, seconds), that is, the longer the seizure, the larger its
energy. However, this relationship is not invariably linear for
other detection algorithms, indicating the presence of interesting
scaling properties of seizure energy.
[0078] FIG. 11 shows the empirical "tail" of the conditional
probability distribution functions for: (a) Seizure durations
(minimum duration: 2 sec); (b) the logarithm of seizure energy as
estimated with the Validated method (dashed) and the Wavelet
Transform Maximum Modulus (solid).
[0079] The conditional probabilities of durations (FIG. 11a) and of
the logarithm of energy of seizures (FIG. 11b) provide additional
support that their properties are partly a function of the method
used for their detection. The validated and STA/LTA algorithms
yield similar durations but different from those of the WTMM and
r.sup.2 methods, which are analogous to each other (FIG. 11a). The
distributions of the logarithm of seizure energies as identified by
each of the methods (FIG. 11b) reveals additional discrepancies as
evidenced by the much narrower and shorter "tail" distribution of
the validated algorithm compared to the others.
[0080] The medical and psycho-socio-economic burden imposed upon
patients, caregivers and health systems by pharmaco-resistant
epilepsies is enormous. Intracranial devices for automated
detection, warning and delivery of therapy, the presently preferred
"line of attack" for an abundance of weighty reasons, would be
insufficient to adequately address said burden at a global scale.
Reliance on signals that while extra-cerebral are under cortical
modulation or control such as cardiac or motor and are altered by
seizures, emerges as a viable research direction with potentially
fruitful clinical applications.
[0081] The greater ease of implementation and lower cost of
automated real-time detection, warning and therapy systems based on
extra-cerebral signals, compared to those requiring intracranial
placement, makes them worthy of investigation.
[0082] Cortical electrical activity has been the primary, if not
sole, source of signals for visual or automated detection and
quantification of seizures in clinical use. The inextricable link
between brain and epilepsy has historically impelled clinical
neuroscientists to leave unexploited the equally inextricable link
between brain and body. The brain-epilepsy link has distracted us
from certain severe limitations (for certain applications) inherent
to the recording of cortical signals from scalp or even directly
from its surface, such as marked cortical signal attenuation and
filtering and limited access to neural sources (only about
one-third of the neocortex is surveyable by scalp electrodes and
subdural electrodes record little activity from the lateral and
bottom walls of sulci). Yet, readily accessible sources that
provide indirect but valuable information about the state of the
brain, particularly during the ictal or postictal state, remain
largely untapped.
[0083] The growing emphasis on widely accessible, cost-effective,
good quality health care in the context of expanding populations,
especially in age-groups above 60 yr. in whom the incidence of
epilepsy is high, and the shrinking financial resources to support
the required infra-structure, pose an enormous challenge to
patients whose seizures are pharmaco-resistant as well as to
epileptologists and functional neurosurgeons. The properly placed
emphasis on implantable intracranial devices for automated seizure
detection, warning and delivery of therapy in patients with
drug-resistant seizures should be viewed in the context that even
if economic resources were unlimited, human resources are starkly
small. Given the number of functional neurosurgeons in the United
States (one source puts the number at 300, of which about 100 work
in epilepsy) is it realistic to pursue exclusively intracranial
devices to address the unmet needs of pharmaco-resistant patients
conservatively estimated (in the US) at 600,000? The deleterious
medical, and psycho-social impact of intractable epilepsy and its
high cost of care, along with the sophisticated human and
technological resources needed to address them, qualifies this, in
these authors opinions, as a public health care problem. Indeed,
scientific advances regardless of their value may not translate
into improved care of epilepsy and lessen its burden, unless
devices are broadly accessible; in short the challenge of
ameliorating the global burden of drug-resistant epilepsies may
exceed scientific and technological ones. If the answer to the
question put forth a few lines above is in the negative
(intracranial devices will not meet the global burden) viable
alternatives must be sought.
[0084] The utilization of certain extra-cerebral signals looms as
one such alternative. Cardiac (e.g., heart rate, EKG morphology)
and motor (speed, direction and force of joint movements) signals
are prime candidates for the following reasons: 1. Structures that
form part of the central autonomic nervous system or are strongly
interconnected with it, are common sites of epileptogenesis (e.g.,
amygdalae-hippocampi); 2. Spread of seizures out of the primary
epileptogenic zone, is prevalent in pharmaco-resistant patients so
that even if the site of origin is not part of the central
autonomic network, invasion of it by ictal activity is quite
common; 3. Partial seizures particularly if complex, are
characterized by either positive (e.g., motor automatisms,
hypermotoric behavior, clonic/myoclonic activity, focal increase in
anti-gravitatory muscle tone) or negative (e.g., motionless, focal
loss of antigravitatory muscle tone) phenomena that are
stereotypical across seizures originating from the same site and
appear relatively early in the course of seizures; 4. Cardiac and
motor signals are highly robust, easily recordable as they do not
require implantable devices or development of ground breaking
technology; EKG, actigraphs, 3-D accelerometers are widely
available commercially and are considerably less costly than those
required for use in the central nervous system (CNS); 5. Signals of
cardiac and motor origin lack the high complexity or large
dimensionality of those generated by the brain's cortex, are
simpler to process and analyze, and, thus, are less computationally
expensive. Ease of computation allows the use of simpler, smaller
devices compared to those required for computation of cortical
signals and as they use less power, battery recharging or
replacements are less frequent; 6. The neurosurgical procedures and
potential associated complications make implantable devices
unappealing to a majority of pharmaco-resistant patients that
responded to a survey.
[0085] Among the numerous extra-cerebral signals usable for seizure
detection, cardiac, have been the most extensively investigated.
Tachycardia is a common manifestation of partial seizures,
occurring in almost 90% of seizures of mesial temporal origin and
precedes electrographic (as determined with scalp electrodes) and
clinical onset in the majority of these seizures. (Tachycardia
invariably occurs in primarily/secondarily generalized tonic-clonic
seizures being higher in magnitude and longer duration than in
partial seizures. Tachycardia with tonic-clonic seizures is
multifactorial: neurogenic, metabolic, and exertional.) From a
cardiac rhythm perspective, the increases in heart rate temporally
correlated with seizures are rarely pathologic, being of sinus
origin; additionally their magnitude is unlikely to compromise
cardiac output in healthy individuals. Ictal tachycardia has a
strong neurogenic component reflective of either an increase in
sympathetic or withdrawal of parasympathetic activity; while
increases in motor activity in reference to the interictal state
would augment its magnitude, tachycardia occurs in subjects in whom
seizures manifest with motionless. Bradycardia also occurs with
seizures, albeit with much lower prevalence than tachycardia; so
called "temporal lobe syncope", denoting the loss of consciousness
(without convulsive activity) during partial seizures is caused by
profound bradycardia.
[0086] In light of the potential to apply cardiac signals, and in
particular of exploiting changes in heart rate (increases or
decreases relative to an interictal baseline) for automated seizure
detection, algorithms are being developed and tested to this end.
In addition to detection and warning of seizures, heart rate
changes may be used to quantify: a) Relative duration defined as
the time said changes spend above or below an interictal reference
value(s); b) Relative intensity corresponding to the area under the
curve or to the product of peak/bottom heart rate and duration (in
sec.); c) Seizure frequency/unit time (e.g., month). The challenge
of this detection modality for ambulatory clinical applications, is
the ubiquitousness of heart rate changes with daily life activities
that may translate into large numbers of false positive detections.
Arousal from sleep, standing up from a recumbent position, climbing
stairs, are but a few of the myriad daily life activities
associated with relative or absolute changes (e.g., increases) in
heart rate. The discriminating power or positive predictive value
(ictal vs. exertional) of this detection modality is currently the
subject of investigation in epilepsy monitoring units. Heart rate,
among other (rate of change/slope; P-QRS-T morphology) markers,
during seizures, are recorded, analyzed and compared to those
associated with protocolized motor activities (e.g., walking on a
treadmill). Preliminary results show that the magnitude of ictal
increases in heart rate is sufficiently large compared to
non-strenous exercises, so as to allow accurate differentiation
and, consequently, detection of certain types of partial seizures.
It would be naive and incorrect to presume that univariate (e.g.,
heart rate changes alone) automated detection of seizures would
yield worthwhile positive predictive power (PPV=number of true
positive detections/total number of detections) in ambulatory
patients. Multivariate-based detection would be required to achieve
satisfactory performance in a sufficiently large number of
patients; ictal (reversible) changes in EKG morphology while less
prevalent than in heart rate, have higher specificity and may
increase considerably speed of detection (e.g., to within 3 heart
beats). Visual analysis of peri-ictal R-R plots, has led to the
discovery of heart rate patterns with characteristic morphology
that are reproducible among seizures sharing a common epileptogenic
zone and appear to be a specific ictal marker. One of these
patterns resembles the letter "M" and indicates heart rate changes
during seizures may not be unidirectional or monotonic: in this
example, heart rate elevation is followed by a return towards its
interictal baseline, which in turn gives way to a second elevation
in rate. These fluctuations may be attributable, in part to the
co-existence of parasympathetic and cholinergic neurons within the
same autonomic nervous system structure; specifically, components
of the central autonomic network such as the Dorsal Medial
Hypothalamus, the Paraventricular Nucleus of the hypothalamus and
the Nucleus Tractus Solitarius have dual cholinergic and
noradrenergic innervation. Heart rate changes are also expected to
be dependent on time of day (circadian), level of consciousness
(awake vs. asleep), patient's fitness level, activity level
(walking vs. jogging), and emotional and cognitive states, as well
as on ingestion of drugs with adrenergic or cholinergic
actions.
[0087] Ictal motor activity (movement amplitude, direction,
velocity and type and number of muscles groups involved) recorded
with actigraphs/3-D accelerometers would enhance specificity of
cardiac-based detection, as it is stereotypical across seizures
originating from the same structure(s). Use of ictal motor
movements to detect seizures independent of heart rate or other
sensors is actively under investigation. For example, a wrist
accelerometer accurately detected seven of eight tonic-clonic
seizures, and nonseizure movements were readily identified by
patients thereby reducing the consequence of false detections. As
wearable technologies advance, so do opportunities for more precise
measurement of complicated seizure-related movements such as
automatisms.
[0088] Respiratory rate is markedly increased (also a neurogenic
phenomenon) during seizures manifesting with tachycardia and its
specificity may be higher than heart rate changes as its magnitude
and pattern differ amply from exertional increases in ventilation.
Electrodermal (e.g. skin resistance, sudomotor) or vocal (e.g.,
non-formed vocalizations) activity, eyelid and ocular movements
(gaze deviation, nystagmus), metabolic (e.g., profound normokalemic
lactic acidosis with convulsions, hormonal (prolactin elevations
with convulsion or certain partial seizures) or tissue stress
(lactic acid, CK) indices may aid in extracerebral seizure
detection.
[0089] Paradoxically, a potentially important hurdle in the path to
adoption of extra-cerebral detection of seizures is the markedly
low sensitivity and other limitations of patient diaries, the
universal "gold" metric or "ground truth" in epileptology. The rate
of automated seizure detection, whether cerebrally or
extra-cerebrally based, will be higher, possibly much higher in
certain cases, than obtainable with diaries as not only clinical,
but also "subclinical" seizures will be logged. This "limitation"
or "inconvenience" that may discourage patients and
epileptologists, is compounded by the absence of simultaneously
recorded cortical activity, since direct proof cannot be furnished
that a change in extra-cerebral indices, was indeed caused by a
seizure. A simple, but powerful means to overcome this hurdle is
through the administration of complex reaction time tests
implementable in real-time, into hand-held devices and triggered by
changes in extra-cerebral signals such as EKG; in a cooperative,
motivated patient, cardiac activity changes in the context of an
abnormal response or failed test will be classified as clinical
seizures, while those with a preserved response as either
subclinical seizures or false positive detections.
[0090] Based on the existing evidence and body or work, it may be
stated that extra-cerebral automated detection, warning, logging of
seizures and delivery of therapy, looms as a useful, cost-effective
and widely accessible option to better manage pharmaco-resistant
epilepsies.
[0091] An embodiment of a medical device adaptable for use in
implementing some aspects of embodiments of the present invention
is provided in FIG. 1. As shown in FIG. 1, a system may involve a
medical device system that senses body signals of the patient--such
as brain or cardiac activity--and analyzes those signals to
identify one or more aspects of the signal that may identify the
occurrence of a seizure. The signal may be processed to extract
(e.g., mathematically by an algorithm that computes certain values
from the raw or partially processed signal) features that may be
used to identify a seizure when compared to the inter-ictal state.
As shown in the right side of FIG. 1, the features may also be
graphically displayed either in real time or subsequent to the
event to enable visual confirmation of the seizure event and gain
additional insight into the seizure (e.g., by identifying a seizure
metric associated with the seizure).
[0092] Turning now to FIG. 2, a block diagram depiction of a
medical device 200 is provided, in accordance with one illustrative
embodiment of the present invention. In some embodiments, the
medical device 200 may be implantable, while in other embodiments
the medical device 200 may be completely external to the body of
the patient.
[0093] The medical device 200 may comprise a controller 210 capable
of controlling various aspects of the operation of the medical
device 200. The controller 210 is capable of receiving internal
data or external data, and in one embodiment, is capable of causing
a stimulation unit (not shown) to generate and deliver an
electrical signal, a drug, cooling, or two or more thereof to one
or more target tissues of the patient's body for treating a medical
condition. For example, the controller 210 may receive manual
instructions from an operator externally, or may cause an
electrical signal to be generated and delivered based on internal
calculations and programming. In other embodiments, the medical
device 200 does not comprise a stimulation unit. In either
embodiment, the controller 210 is capable of affecting
substantially all functions of the medical device 200.
[0094] The controller 210 may comprise various components, such as
a processor 215, a memory 217, etc. The processor 215 may comprise
one or more microcontrollers, microprocessors, etc., capable of
performing various executions of software components. The memory
217 may comprise various memory portions where a number of types of
data (e.g., internal data, external data instructions, software
codes, status data, diagnostic data, etc.) may be stored. The
memory 217 may comprise one or more of random access memory (RAM),
dynamic random access memory (DRAM), electrically erasable
programmable read-only memory (EEPROM), flash memory, etc.
[0095] The medical device 200 may also comprise a power supply 230.
The power supply 230 may comprise a battery, voltage regulators,
capacitors, etc., to provide power for the operation of the medical
device 200, including delivering the therapeutic electrical signal.
The power supply 230 comprises a power source that in some
embodiments may be rechargeable. In other embodiments, a
non-rechargeable power source may be used. The power supply 230
provides power for the operation of the medical device 200,
including electronic operations and the electrical signal
generation and delivery functions. The power supply 230 may
comprise a lithium/thionyl chloride cell or a lithium/carbon
monofluoride (LiCFx) cell if the medical device 200 is implantable,
or may comprise conventional watch or 9V batteries for external
(i.e., non-implantable) embodiments. Other battery types known in
the art of medical devices may also be used.
[0096] The medical device 200 may also comprise a communication
unit 260 capable of facilitating communications between the medical
device 200 and various devices. In particular, the communication
unit 260 is capable of providing transmission and reception of
electronic signals to and from a monitoring unit 270, such as a
handheld computer or PDA that can communicate with the medical
device 200 wirelessly or by cable. The communication unit 260 may
include hardware, software, firmware, or any combination
thereof.
[0097] The medical device 200 may also comprise one or more
sensor(s) 212 coupled via sensor lead(s) 211 to the medical device
200. The sensor(s) 212 are capable of receiving signals related to
a physiological parameter, such as the patient's heart beat, blood
pressure, and/or temperature, and delivering the signals to the
medical device 200. The sensor 212 may also be capable of detecting
kinetic signal associated with a patient's movement. The sensor
212, in one embodiment, may be an accelerometer. The sensor 212, in
another embodiment, may be an inclinometer. In another embodiment,
the sensor 212 may be an actigraph. In one embodiment, the
sensor(s) 212 may be the same as implanted electrode(s) 126, 128.
In other embodiments, the sensor(s) 212 are external structures
that may be placed on the patient's skin, such as over the
patient's heart or elsewhere on the patient's torso. The sensor
212, in one embodiment is a multimodal signal sensor capable of
detecting various autonomic and neurologic signals, including
kinetic signals associated with the patient's movement.
[0098] The seizure onset/termination module 280 is capable of
detecting an epileptic event based upon one or more signals
provided by body data collection module 275. The seizure
onset/termination module 280 can implement one or more algorithms
using the autonomic data and neurologic data in any particular
order, weighting, etc. The seizure onset/termination module 280 may
comprise software module(s) that are capable of performing various
interface functions, filtering functions, etc. In another
embodiment, the seizure onset/termination module 280 may comprise
hardware circuitry that is capable of performing these functions.
In yet another embodiment, the seizure onset/termination module 280
may comprise hardware, firmware, software and/or any combination
thereof.
[0099] The seizure onset/termination unit 280 is capable of
determining an epileptic event by application of a WTMM algorithm
to one or more signals provided by body data collection module 275
and/or seizure onset/termination module 280. The seizure
onset/termination unit 280 may comprise software module(s) that are
capable of performing various interface functions, filtering
functions, etc. In another embodiment, the seizure
onset/termination unit 280 may comprise hardware circuitry that is
capable of performing these functions. In yet another embodiment,
the seizure onset/termination unit 280 may comprise hardware,
firmware, software and/or any combination thereof.
[0100] In addition to components of the medical device 200
described above, a medical device system may comprise a storage
unit to store an indication of at least one of seizure or an
increased risk of a seizure. The storage unit may be the memory 217
of the medical device 200, another storage unit of the medical
device 200, or an external database, such as a local database unit
255 or a remote database unit 250. The medical device 200 may
communicate the indication via the communications unit 260.
Alternatively or in addition to an external database, the medical
device 200 may be adapted to communicate the indication to at least
one of a patient, a caregiver, or a healthcare provider.
[0101] In various embodiments, one or more of the units or modules
described above may be located in a monitoring unit 270 or a remote
device 292, with communications between that unit or module and a
unit or module located in the medical device 200 taking place via
communication unit 260. For example, in one embodiment, one or more
of the body data collection module 275 or the seizure
onset/termination module 280 may be external to the medical device
200, e.g., in a monitoring unit 270. Locating one or more of the
body data collection module 275 or the seizure onset/termination
module 280 outside the medical device 200 may be advantageous if
the calculation(s) is/are computationally intensive, in order to
reduce energy expenditure and heat generation in the medical device
200 or to expedite calculation.
[0102] The monitoring unit 270 may be a device that is capable of
transmitting and receiving data to and from the medical device 200.
In one embodiment, the monitoring unit 270 is a computer system
capable of executing a data-acquisition program. The monitoring
unit 270 may be controlled by a healthcare provider, such as a
physician, at a base station in, for example, a doctor's office. In
alternative embodiments, the monitoring unit 270 may be controlled
by a patient in a system providing less interactive communication
with the medical device 200 than another monitoring unit 270
controlled by a healthcare provider. Whether controlled by the
patient or by a healthcare provider, the monitoring unit 270 may be
a computer, preferably a handheld computer or PDA, but may
alternatively comprise any other device that is capable of
electronic communications and programming, e.g., hand-held computer
system, a PC computer system, a laptop computer system, a server, a
personal digital assistant (PDA), an Apple-based computer system, a
cellular telephone, etc. The monitoring unit 270 may download
various parameters and program software into the medical device 200
for programming the operation of the medical device, and may also
receive and upload various status conditions and other data from
the medical device 200. Communications between the monitoring unit
270 and the communication unit 260 in the medical device 200 may
occur via a wireless or other type of communication, represented
generally by line 277 in FIG. 2. This may occur using, e.g., wand
155 to communicate by RF energy with an implantable signal
generator 110. Alternatively, the wand may be omitted in some
systems, e.g., systems in which the MD 200 is non-implantable, or
implantable systems in which monitoring unit 270 and MD 200 operate
in the MICS bandwidths.
[0103] In one embodiment, the monitoring unit 270 may comprise a
local database unit 255. Optionally or alternatively, the
monitoring unit 270 may also be coupled to a database unit 250,
which may be separate from monitoring unit 270 (e.g., a centralized
database wirelessly linked to a handheld monitoring unit 270). The
database unit 250 and/or the local database unit 255 are capable of
storing various patient data. These data may comprise patient
parameter data acquired from a patient's body, therapy parameter
data, seizure severity data, and/or therapeutic efficacy data. The
database unit 250 and/or the local database unit 255 may comprise
data for a plurality of patients, and may be organized and stored
in a variety of manners, such as in date format, severity of
disease format, etc. The database unit 250 and/or the local
database unit 255 may be relational databases in one embodiment. A
physician may perform various patient management functions (e.g.,
programming parameters for a responsive therapy and/or setting
references for one or more detection parameters) using the
monitoring unit 270, which may include obtaining and/or analyzing
data from the medical device 200 and/or data from the database unit
250 and/or the local database unit 255. The database unit 250
and/or the local database unit 255 may store various patient
data.
[0104] One or more of the blocks illustrated in the block diagram
of the medical device 200 in FIG. 2 may comprise hardware units,
software units, firmware units, or any combination thereof.
Additionally, one or more blocks illustrated in FIG. 2 may be
combined with other blocks, which may represent circuit hardware
units, software algorithms, etc. Additionally, any number of the
circuitry or software units associated with the various blocks
illustrated in FIG. 2 may be combined into a programmable device,
such as a field programmable gate array, an ASIC device, etc.
[0105] Turning now to FIG. 3, a block diagram depiction of an
exemplary implementation of the body data collection module 275 is
shown. The body data collection module 275 may include hardware
(e.g., amplifiers, accelerometers), tools for chemical assays,
optical measuring tools, a body data memory 350 (which may be
independent of memory 117 or part of it) for storing and/or
buffering data. The body data memory 350 may be adapted to store
body data for logging or reporting and/or for future body data
processing and/or statistical analyses. Body data collection module
275 may also include one or more body data interfaces 310 for
input/output (I/O) communications between the body data collection
module 275 and sensors 112. Body data from memory 350 and/or
interface 310 may be provided to one or more body index calculation
unit(s) 355, which may determine one or more body indices.
[0106] In the embodiments of FIG. 3, sensors 112 may be provided as
any of various body data units/modules (e.g., autonomic data
acquisition unit 360, neurological data acquisition unit 370,
endocrine data acquisition unit 373, metabolic data acquisition
unit 374, tissue stress marker data acquisition unit 375, and
physical fitness/integrity determination unit 376) via connection
380. Connection 380 may be a wired connection a wireless
connection, or a combination of the two. Connection 380 may be a
bus-like implementation or may include an individual connection
(not shown) for all or some of the body data units.
[0107] In one embodiment, the autonomic data acquisition unit 360
may include a cardiac data acquisition unit 361 adapted to acquire
a phonocardiogram (PKG), EKG, echocardiography, apexcardiography
and/or the like, a blood pressure acquisition unit 363, a
respiration acquisition unit 364, a blood gases acquisition unit
365, and/or the like. In one embodiment, the neurologic data
acquisition unit 370 may contain a kinetic unit 366 that may
comprise an accelerometer unit 367, an inclinometer unit 368,
and/or the like; the neurologic data acquisition unit 370 may also
contain a responsiveness/awareness unit 369 that may be used to
determine a patient's responsiveness to testing/stimuli and/or a
patient's awareness of their surroundings. Body data collection
module 275 may collect additional data not listed herein, that
would become apparent to one of skill in the art having the benefit
of this disclosure.
[0108] The body data units ([360-370], [373-377]) may be adapted to
collect, acquire, receive/transmit heart beat data, EKG, PKG,
echocardiogram, apexcardiogram, blood pressure, respirations, blood
gases, body acceleration data, body inclination data, EEG/ECoG,
quality of life data, physical fitness data, and/or the like.
[0109] The body data interface(s) 310 may include various
amplifier(s) 320, one or more A/D converters 330 and/or one or more
buffers 340 or other memory (not shown). In one embodiment, the
amplifier(s) 320 may be adapted to boost and condition incoming
and/or outgoing signal strengths for signals such as those to/from
any of the body data acquisition units/modules (e.g., ([360-370],
[373-377])) or signals to/from other units/modules of the MD 100.
The A/D converter(s) 330 may be adapted to convert analog input
signals from the body data unit(s)/module(s) into a digital signal
format for processing by controller 210 (and/or processor 215). A
converted signal may also be stored in a buffer(s) 340, a body data
memory 350, or some other memory internal to the MD 100 (e.g.,
memory 117, FIG. 1) or external to the MD 100 (e.g., monitoring
unit 170, local database unit 155, database unit 150, and remote
device 192). The buffer(s) 340 may be adapted to buffer and/or
store signals received or transmitted by the body data collection
module 275.
[0110] As an illustrative example, in one embodiment, data related
to a patient's respiration may be acquired by respiration unit 364
and sent to MD 100. The body data collection module 275 may receive
the respiration data using body data interface(s) 310. As the data
is received by the body data interface(s) 310, it may be
amplified/conditioned by amplifier(s) 320 and then converted by A/D
converter(s) into a digital form. The digital signal may be
buffered by a buffer(s) 340 before the data signal is transmitted
to other components of the body data collection module 275 (e.g.,
body data memory 350) or other components of the MD 100 (e.g.,
controller 110, processor 115, memory 117, communication unit 160,
or the like). Body data in analog form may be also used in one or
more embodiments.
[0111] Body data collection module 275 may use body data from
memory 350 and/or interface 310 to calculate one or more body
indices in body one or more body index calculation unit(s) 355. A
wide variety of body indices may be determined, including a variety
of autonomic indices such as heart rate, blood pressure,
respiration rate, blood oxygen saturation, neurological indices
such as maximum acceleration, patient position (e.g., standing or
sitting), and other indices derived from body data acquisition
units 360, 370, 373, 374, 375, 376, 377, etc.
[0112] Turning now to FIG. 4, an MD 100 (as described in FIG. 3) is
provided, in accordance with one illustrative embodiment of the
present invention. FIG. 4 depicts the body data acquisition units
similar to those shown in FIG. 3, in accordance with another
embodiment, wherein these unites are included within the MD 100,
rather being externally coupled to the MD 100, as shown in FIG. 3.
In accordance with various embodiments, any number and type of body
data acquisition units may be included within the MD 100, as shown
in FIG. 4, while other body data units may be externally coupled,
as shown in FIG. 3. The body data acquisition units may be coupled
to the body data collection module 275 in a fashion similar to that
described above with respect to FIG. 3, or in any number of
different manners used in coupling intra-medical device modules and
units. The manner by which the body data acquisition units may be
coupled to the body data collection module 275 is not essential to,
and does not limit, embodiments of the instant invention as would
be understood by one of skill in the art having the benefit of this
disclosure. Embodiments of the MD depicted in FIG. 4 may be fully
implantable or may be adapted to be provided in a system that is
external to the patient's body.
[0113] A time series body signal collected by the body data
collection module 275 may comprise at least one of a measurement of
the patient's heart rate, a measurement of the patient's kinetic
activity, a measurement of the patient's brain electrical activity,
a measurement of the patient's oxygen consumption, a measurement of
the patient's work, a measurement of an endocrine activity of the
patient, a measurement of a metabolic activity of the patient, a
measurement of an autonomic activity of the patient, a measurement
of a cognitive activity of the patient, or a measurement of a
tissue stress marker of the patient.
[0114] Turning to FIG. 5, the seizure onset/termination unit 280
depicted in FIG. 2 is shown in greater detail. The seizure
onset/termination unit 280 may comprise a body signal interface 510
adapted to received collected body data from the body data
collection module 275. For example, the seizure onset/termination
unit 280 may be adapted to receive a time series of collected body
data.
[0115] The seizure onset/termination unit 280 may also comprise a
time window control module 520. The time window control module 520
may comprise a foreground window determination module 521, adapted
to determine a sliding time window for the time series body signal
comprising a foreground window; and/or a background window
determination module 522, adapted to determine a sliding time
window for the time series body signal comprising a background
window.
[0116] In other embodiments (not shown), any time window used
herein may be a moving time window, not necessarily a sliding time
window. As used herein, a "sliding" time window moves over
continuous points of a time series and the present (e.g.,
foreground) and past (e.g., background) are contiguous in time, if
not overlapping. For example, if the foreground window is 5 s and
the background 60 s in length, and the current time is 10:00:00 AM,
the temporal location of the foreground window may be
10:00:00-10:00:05 and that of the background, 09:59:00-10:00:00. A
"moving" time window may move over continuous points of the time
series or "jump" over discontinuous points. For example, a moving
window may be chosen from past data that optimizes sensitivity,
specificity, or speed of detection as required by the patient's
prevailing conditions, activities, or time of day, said time being
discontiguous from that of the foreground window. Using the example
cited immediately above, in this example, the foreground window of
5 s at 10:00:00 AM may be compared to a 60 s background recorded 6
hr. earlier (04:00:00-04:01:00). A moving window may also be the
average or median of several windows.
[0117] The seizure onset/termination unit 280 may also comprise a
WTMM unit 530. The WTMM unit 530 may be adapted to apply a WTMM
skeleton to at least one long chain extracted from the windowed
signals using a continuous wavelet transform.
[0118] The parameters of the WTMM may comprise at least one window
length of 1 second, a scale for selecting chain length of 3, and a
variance increment of 0.25.
[0119] The parameters of the WTMM model may be selected based on at
least one of a clinical application of said detection; a level of
safety risk associated with an activity; at least one of an age,
physical state, or mental state of the patient; a length of a
window available for warning; a degree of efficacy of therapy and
of its latency; a degree of seizure control; a degree of circadian
and ultradian fluctuations of said patient's seizure activity; a
performance of the detection method as a function of the patient's
sleep/wake cycle or vigilance level; a dependence of the patient's
seizure activity on at least one of a level of consciousness, a
level of cognitive activity, or a level of physical activity; the
site of seizure origin; a seizure type suffered by said patient; a
desired sensitivity of detection of a seizure, a desired
specificity of detection of a seizure, a desired speed of detection
of a seizure, an input provided by the patient, or an input
provided by a sensor.
[0120] In various embodiments, the selected parameters may reflect
the degree of certainty of detections desired by the patient, a
caregiver, a medical professional, or two or more thereof. Such
person(s) are expected to have biases regarding their desire for
certainty of detection, and variation in their risk-proneness
and/or aversion to risk. Thus, in one embodiment, the patient,
caregiver, and/or medical professional may be allowed to change
(within certain limits and for certain activities only, if desired)
the sensitivity, specificity, and/or speed of detection of the
algorithms.
[0121] The seizure onset/termination unit 280 may also comprise a
variance determination unit 540. The variance determination unit
540 may be adapted to determine a variance of the output of the
WTMM unit 530 based upon the WTMM skeleton.
[0122] The seizure onset/termination unit 280 may also comprise a
stepwise approximation unit 550. The stepwise approximation unit
550 may be adapted to generate a stepwise approximation of the
changes in variance of the windowed signal as analyzed by the WTMM
unit 530 and/or the variance determination unit 540.
[0123] The seizure onset/termination unit 280 may also comprise a
seizure onset determination module 560. The seizure onset
determination module 560 may be configured to determine an onset of
a seizure in response to a determination that an output of the
stepwise approximation of the changes in variance in the foreground
window has reached an onset threshold.
[0124] The seizure onset/termination unit 280 may also comprise a
seizure termination determination module 570. The seizure
termination determination module 570 may be adapted to determine a
termination of a seizure in response to a determination that an
output of the stepwise approximation of the changes in variance in
the background window has reached a termination threshold.
[0125] Turning to FIG. 12, a flowchart depiction of a method for
detecting an onset and a termination of an epileptic event from a
patient body signal is shown. A time series body signal of a
patient may be received at 1210. Sliding first and second time
windows for the time series body signal may be determined at 1220.
The determination at 1220 may comprise determining a foreground
window at 1225 and/or determining a background window at 1227. A
WTMM operation may be performed at 1230 to each of the sliding
adjacent time windows. The performance at 1230 may comprise
constructing at 1232 a WTMM skeleton, determining at 1234 a
variance of the output of the construction, and/or constructing at
1236 a stepwise approximation of change in the variance.
[0126] An onset of a seizure may be determined at 1240 based on the
stepwise approximation and/or the variance. A termination of a
seizure may be determined at 1250 based on the stepwise
approximation and/or the variance.
[0127] Optionally, the method depicted in FIG. 12 may comprise
other activities. The method may further involve delivering a
therapy for the seizure at a particular time at 1270, wherein at
least one of the therapy, the particular time, or both may be based
upon the determination of the seizure onset.
[0128] Alternatively or in addition, the method may further involve
determining at 1280 an efficacy of the therapy.
[0129] Alternatively or in addition, the method may further involve
issuing at 1285 a warning for the seizure, wherein the warning may
be based upon the determination of the seizure onset.
[0130] In one embodiment, at least one of the delivered therapy or
the issued warning is based at least in part on at least one of the
type of activity engaged in by the patient at the time of seizure
onset, the seizure type, the seizure severity, or the time elapsed
from the last seizure.
[0131] Alternatively or in addition, the method may further involve
determining at 1290 at least one of a timing of delivery of
therapy, a type of therapy, at least one parameter of the therapy,
a timing of sending a warning, a type of warning, a duration of the
warning, or an efficacy of said therapy, based upon a timing of
said determination of said seizure onset, said determination of
said seizure termination, or both.
[0132] Alternatively or in addition, the method may further involve
determining at 1295 at least one value selected from the duration
of the epileptic event, the severity of the epileptic event, the
intensity of the epileptic event, the extent of spread of the
epileptic event, an inter-seizure interval between the epileptic
event and a prior epileptic event, a patient impact of the
epileptic event, or a time of occurrence of the epileptic event.
The method may further comprise logging at 1296 the at least one
value.
[0133] A method, such as that depicted in FIG. 12, may be
implemented by a non-transitory computer readable program storage
unit encoded with instructions that, when executed by a computer,
perform the method.
[0134] An activity, such as walking, swimming, driving, etc., may
be allowed or terminated, a warning may be issued or not issued, or
a therapy may be delivered or not delivered, based on the
determination of seizure onset, seizure termination, or both,
either from a WTMM algorithm alone or a PMSA value calculated at
least in part from an indicator function derived from the WTMM
algorithm.
[0135] An "efficacy index" may be used herein to refer to any
quantification of an efficacious result of a therapy. In one
example, if a patient's seizures typically present an increase in
heart rate from a resting rate of 80 beats per minute (BPM) to a
peak ictal heart rate of 160 BPM, and upon administering a therapy
to the patient, the patient's peak ictal heart rate is 110 BPM,
this result may be quantified as an efficacy index of 50 (on a
scale of non-therapy peak ictal heart rate--peak ictal heart rate
after therapy), 0.625 (50 BPM reduction from peak ictal heart
rate/80 BPM increase from resting rate to peak ictal heart rate in
the absence of therapy), etc.
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