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Heart rate variability as a biomarker for epilepsy seizure prediction

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Objective: Epilepsy is a neurological disorder that causes seizures of many different types. Recent research has shown that epileptic seizures can be predicted by using the electrocardiogrami instead of the electroencephalogram. In this study, we used the heart rate variability that is generated by the fluctuating balance of sympathetic and parasympathetic nervous systems to predict epileptic seizures. Methods: We studied 11 epilepsy patients to predict the seizure interval. With regar tos the fact that HRV signals are nonstationary, our analysis focused on linear features in the time and frequency domain of HRV signal such as RR Interval (RRI), mean heart rate (HR), high-frequency (HF) (0.15-0.40 Hz) and low-frequency (LF) (0.04-0.15 Hz), as well as LF/HF. Also, quantitative analyses of Poincaré plot features (SD1, SD2, and SD1/SD2 ratio) were performed. HRV signal was divided into intervals of 5 minutes. In each segment linear and nonlinear features were extracted and then the amount of each segment compared to the previous segment using a threshold. Finally, we evaluated the performance of our method using specificity and sensitivity. Results: During seizures, mean HR, LF/HF, and SD2/SD1 ratio significantly increased while RRI significantly decreased. Significant differences between two groups were identified for several HRV features. Therefore, these parameters can be used as a useful feature to discriminate a seizure from a non-seizure The seizure prediction algorithm proposed based on HRV achieved 88.3% sensitivity and 86.2 % specificity. Conclusion: These results indicate that the HRV signal contains valuable information and can be a predictor for epilepsy seizure. Although our results in comparison with EEG ares a little bit weaker, the recording of ECG is much easier and faster than EEG. Also, our finding showed the results of this study are considerably better than recent research based on ECG (Tab. 1, Fig. 10, Ref. 17).
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Indexed and abstracted in Science Citation Index Expanded and in Journal Citation Reports/Science Edition
Bratisl Med J 2017; 118 (1)
3–8
DOI: 10.4149/BLL_2017_001
CLINICAL STUDY
Heart rate variability as a biomarker for epilepsy seizure prediction
Moridani MK, Farhadi H
Department of Biomedical Engineering, Tehran Medical Branch, Islamic Azad University,
Tehran, Iran. m.karimi@gmail.com
ABSTRACT
OBJECTIVE: Epilepsy is a neurological disorder that causes seizures of many different types. Recent research
has shown that epileptic seizures can be predicted by using the electrocardiogrami instead of the electroen-
cephalogram. In this study, we used the heart rate variability that is generated by the uctuating balance of
sympathetic and parasympathetic nervous systems to predict epileptic seizures.
METHODS: We studied 11 epilepsy patients to predict the seizure interval. With regar tos the fact that HRV
signals are nonstationary, our analysis focused on linear features in the time and frequency domain of HRV
signal such as RR Interval (RRI), mean heart rate (HR), high-frequency (HF) (0.15–0.40 Hz) and low-frequency
(LF) (0.04–0.15 Hz), as well as LF/HF. Also, quantitative analyses of Poincaré plot features (SD1, SD2, and
SD1/SD2 ratio) were performed. HRV signal was divided into intervals of 5 minutes. In each segment linear
and nonlinear features were extracted and then the amount of each segment compared to the previous seg-
ment using a threshold. Finally, we evaluated the performance of our method using speci city and sensitivity.
RESULTS: During seizures, mean HR, LF/HF, and SD2/SD1 ratio signi cantly increased while RRI signi cantly
decreased. Signi cant differences between two groups were identi ed for several HRV features. Therefore, these
parameters can be used as a useful feature to discriminate a seizure from a non–seizure The seizure prediction
algorithm proposed based on HRV achieved 88.3% sensitivity and 86.2 % speci city.
CONCLUSION: These results indicate that the HRV signal contains valuable information and can be a predictor
for epilepsy seizure. Although our results in comparison with EEG ares a little bit weaker, the recording of ECG
is much easier and faster than EEG. Also, our nding showed the results of this study are considerably better
than recent research based on ECG (Tab. 1, Fig. 10, Ref. 17). Text in PDF www.elis.sk.
KEY WORDS: epileptic seizure, heart rate variability, linear and non–linear analysis, prediction.
Department of Biomedical Engineering, Tehran Medical Branch, Islamic
Azad University, Tehran, Iran
Address for correspondence: M.K. Moridani, No. 29, Floor 4, Farjam
St., Tehran–Pars, Tehran, Iran.
Postal Code: 1653989618
Phone: +982177874289, Fax: +982188675452
Introduction
Epilepsy refers to chronic disorders and brain dysfunction in
which normal communication between nerve cells in the brain is
disturbed. Seizures are a sudden surge of electrical activity in the
brain. Seizures occur alternately at intervals in the brain. Indeed,
seizures depend on the location of epileptic discharges in the brain
as well as symptoms and type of epileptic seizures. There are dif-
ferent types of seizures, which are associated with various risk
factors for the patients depending on type and severity of epilepsy.
Partial epilepsy is caused by a damage to one side of the brain,
which is divided into two categories: simple partial epilepsy and
simple complex epilepsy. Pure epilepsy lasts less than a minute.
The symptoms depend on the location of epileptic discharges.
Complex epilepsy lasts one to two minutes. Generalized epilepsy
affects both sides of the brain and the affected individual suddenly
becomes unconscious. Sympathetic nervous system dysfunction
occur in epilepsy with febrile seizure. A part of the body shakes
uncontrollably in focal epilepsy, which may spread to other areas of
the body and the whole body may shake uncontrollably. However,
the affected individual does not lose consciousness completely.
An epileptic patient may be affected by two different kinds
of seizures such as unilateral and bilateral seizures depending on
the type of epilepsy. In single seizures, electrical discharge affects
some areas of the brain (cortex), but the affected individual does
not lose consciousness immediately. This type of seizure is called
focal sensory epilepsy. In the bilateral assault, both hemispheres
are simultaneously affected, and the affected individual loses con-
sciousness immediately.
An algorithm that can predict the occurrence of epileptic sei-
zures extremely ensures the patients and their caregivers of prog-
nosis of epileptic seizures to either prevent irreparable damage
to the patients or take necessary measures to reduce the severity
of damages.
Electroencephalogram (EEG) signals are a convenient and
well-known method for examining epileptic seizures. EEG refers
to either super cial (noninvasive) or invasive records of brain
activities. Needle electrodes are implanted in the scalp in the in-
vasive method. Given that the brain is the origin of epileptic sei-
zures recording EEG signal in epileptic patients is problematic and
not easily accessible. Epileptic seizures also affect the autonomic
Bratisl Med J 2017; 118 (1)
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4
nervous system and consequently activities of both sympathetic
and parasympathetic nerves. Thus, the heart is one major organ
affected by epileptic seizures. In this paper, ECG signals were used
to predict epileptic seizures, which can be done more easily and
more quickly. It is expected that the results of ECG recordings do
not differ from the results of EEG signals. Hopefully, ECG signals
can be used as a complementary approach to prediction of epilep-
tic seizures. Finally, a combination of two EEG and ECG signals
can help to improve the results and ef ciency of the algorithm.
Many studies were performed to predict epileptic seizures.
However, EEG signals were used in most of these studies. Mar-
tinerie et al covered 19 seizures in 11 patients in 1998. Density
correlation method was utilized in the recent survey in which sen-
sitivity was reported as 89 % (1).
Le Van Quyen et al used EEG signals to predict 11 epileptic
seizures in 9 patients in 2000. In the above study, similarity index
algorithm was used with 94 % sensitivity (2). Navaro et al used
similarity index method to predict 41 epileptic seizures in 11 pa-
tients in 2002. They obtained sensitivity of 83 % (3). Netoff T et
al used power spectral density method to predict 45 seizures in 9
patients in 2009. They obtained sensitivity of 77.8 % (4).
Yun Park et al used power spectral density method for predic-
tion of 80 seizures in 18 patients in 2011. They obtained sensitivity
of 92.5 % (5). The results of the recent study showed that epileptic
patients are more prone to abnormal heart rhythms not only during
the seizure but also before the seizure (6).
In general, epileptic seizures are associated with an apparent in-
crease in heart rate in most cases. However, arrhythmia occurs, and
heart rate decreases in some cases such as partial epilepsy and gen-
eralized epileptic seizures (7–8). The article is organized as follows.
In the second section, used database and method to predict
seizures with ECG signal processing metrics and evaluation meth-
ods are discussed. In the third section, the results of these meth-
ods are discussed. Discussion and conclusion are presented in the
fourth section. In this section, a summary and comparison of the
proposed approach with previous studied are shown. Work limi-
tations are also discussed. Some recommendations are also given
for future work.
Materials and methods
Heart rate uctuates under the in uence of sympathetic and
parasympathetic nervous systems. Short-term and long-term chang-
es in heart rate re ect the autonomic nervous system function (9).
A typical ECG tracing of the cardiac cycle (heartbeat) consists
of a P wave (atrial depolarization), a QRS complex (ventricular
depolarization), and a T wave (ventricular repolarization and a U
wave. Each wave and the distances between them are related to
different parts of the heart and can be used to assess cardiac health,
but R wave is more signi cant than other waves, which indicates
ventricular contraction or a heartbeat. R–R interval is also called
beat-to-beat or normal-to-normal (NN) interval, which represents
time interval between heart beats (Fig. 1).
A change in cardiac signal during two consecutive beats is
called heart rate variability (10). HRV signal shows different modes
of cardiovascular diseases. Therefore, analysis of heart rate vari-
ability can be used as a tool to monitor changes in the function
of the autonomic nervous system. However, less variable heart
beats show relatively low health. Naturally, heart rate variability
is directly related to individual health and healing. Increased heart
rate variability increases individual health (11).
Studies have shown that correct information on autonomic
nervous system function can be obtained using noninvasive HRV
signal analysis in all brain disorders resulting from sympathetic and
parasympathetic imbalance. HRV signal is a multivariate variable
of cardiovascular systems, which represents dynamic characteris-
tics, short-term and long-term correlations and complexities of the
cardiac signal and autonomous nervous system. Nowadays, there
are different methods for HRV signal processing, which can be
divided into linear and nonlinear methods.
Used database
The data on partial epileptic patients available in Physionet
Database is used in this study (12). Seven patients were examined
in this study. In total, 11 seizures were observed during hospital-
ization of the patients. ECG signals with 200-kHz frequency sam-
pling, 12-bits per sample and 5-mV resolution were digitalized and
recorded in epileptic patients. Seizure interval was speci ed in all
patients and labeled in the database.
Extracting linear and nonlinear features of HRV signal
Changes are calculated with linear statistical methods, which
are divided into time-domain and frequency-domain methods. A
simple calculation is one main advantage of these features. How-
ever, statistical properties depend on the quality of recorded data.
This quality may be affected by environmental noises. In time-
domain method, R–R intervals show, analyze and examine high
frequency changes or short-term changes in which various features
can be extracted as follows: R–R mean interval, standard deviation
of NN intervals (SDNN), Root Mean Square of the Successive Dif-
ferences (RMSSD), the number of differences in consecutive R–R
intervals greater than 50ms (NN50), the ratio obtained by dividing
total number of NN50 intervals to R–R (pNN50). Analysis of heart
rate variability in adults showed that range of HRV signal consists
of three frequencies as follows: low frequency (LF) (0.04–0.1
Hz), high frequency (HF) (0.15–0.4 Hz) and very low frequency
(VLF) (0.0001– 0.04 Hz) (13). Fluctuations in these two compo-
nents represent sympathetic and parasympathetic activity. In the
Fig. 1. ECG signal and R–R intervals.
Moridani MK, Farhadi H. Heart rate variability as a biomarker for epilepsy seizure prediction
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5
frequency-domain method, the ratio of these two components is
used as a measure of the balance of sympathetic and parasympa-
thetic function. In the frequency-domain method, VLF, LF, HF,
LF / HF parameters can be extracted from HRV signal. In fact,
calculated energy is different in various frequency bands (14).
It should be noted that properties of complex systems are
ignored or deleted in linear methods, which cause an additional
error. Physiological systems are fundamentally and inherently
nonlinear. Since standard parameters in HRV only describe lin-
ear and periodic behaviors analysis, more complex and nonlinear
relationship cannot be detected. Recent advances in the theory of
nonlinear dynamics have facilitated signal analysis in nonlinear
living organisms.
Nowadays, nonlinear techniques can describe processes in
living biological organisms.
Poincaré return map is a relatively new technique for analyzing
nonlinear dynamics such as HRV signal. Each point in the graph
is speci ed as n=1, 2, 3,…, k (RRn,RRn+1) where k represents sig-
nal strength (15). Statistically, this mapping graphically displays
the correlation between consecutive R–R intervals. The mapping
gives useful information on short-term and long-term uctuations.
The mapping is shown in Figure 2. SD1 and SD2 parameters are
shown in this diagram. SD1 shows beat-to-beat rapid changes,
which is more related to respiratory sinus arrhythmia. However,
SD2 describes long-term beat-to-beat changes. SD2
SD1 is calculated
to describe the relationship between these components (16). SD1
and SD2 values in Poincare mapping directly depend on statistical
values of standard deviation of heart rate signal and two consecu-
tive intervals of R peaks, which are calculated using equation (1)
where RRn+1 refers to the (n+1)th beat-to-beat interval, RRn repre-
sents to nth beat-to-beat interval and SD denotes standard deviation.
(1)
Prediction algorithm
After recording ECG signals in epileptic patients, R peaks were
detected in these signals using the method proposed by Pan and
Tompkins (17). Then, R–R intervals were calculated, and HRV
signals were organized by identifying the location of the peaks.
Figure 3 shows ECG signal in an epileptic patient recorded in
about 83 minutes and 20 seconds. The patient experienced epileptic
seizures from the 14th minute and 36th second to the 16th minute
and 12th second. In other words, seizures lasted from the 972nd
second to 876th second. Figures 4 and 5, respectively, show ECG
signal in an epileptic patient in a seizure interval and HRV signal
in periods before, during and after the seizure.
Since location and duration of the seizure were speci ed in
available data, HRV signal was divided into time intervals using
Fig. 2. Poincaré return map of RR intervals for a healthy individual
(n = 100).
Fig. 3. ECG signal in an epileptic patient.
Fig. 4. Seizure interval in an epileptic patient.
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window function. Then, linear and nonlinear properties were ex-
tracted in each interval in the signal. Paired t-test was used to de-
tect those features that were signi cantly different in this interval
compared to the previous interval. The detected intervals were
used to predict epileptic seizures. Figure 1 shows a diagram of
the proposed algorithm.
Selecting an optimal threshold
Threshold values with the best optimum sensitivity and the
least prediction error were chosen. In cases where speci city
(predicting non–seizure interval) was acceptable for different
thresholds, the threshold with the lowest prediction error would
be selected. An alarm is given when the desired feature reaches
the threshold. Given that the threshold is different for each patient,
a single threshold is selected for each patient. For example, mean
and variance values of nth window is half the average values of
(n–1)th window. First, speci city and initial sensitivity values were
calculated. Then, sensitivity values and the rate of incorrect pre-
dictions have been computed by changing the threshold. Finally,
the best threshold with the highest speci city and maximum sen-
sitivity and the least prediction error were selected.
Introducing prediction criteria
In this paper, several features were used to predict epileptic
seizures in patients. The goal of all these features lied in achiev-
ing optimum results to obtain complete information on the future
status of patients for nurses and practitioners. Therefore, it is es-
sential to de ne some criteria in this area.
An important criterion is the false positive rate or false-alarm
rate, which shows how much the right time of the epileptic seizure
was predicted in the proposed system or algorithm. In other words,
lower criteria represent the higher ef ciency of the algorithm in the
prediction. The second criteria are prediction of the horizon, which
shows the time of alarm to nurses and practitioners and speci es
how long before the seizure the alarm is given. The greater the
prediction horizon, the greater the ef ciency of the system, so
Fig. 5. HRV signal in epileptic patients before, during and after the
seizure.
Fig. 6. An algorithm to determine a threshold to the prediction of the
future condition of the patient.
Fig. 7. Comparison of R–R Interval and mean heart rate in Poincare
plot in the seizure and non-seizure interval.
Fig. 8. Comparison between low-frequency and high-frequency in
Poincare plot in the seizure and non-seizure interval.
Moridani MK, Farhadi H. Heart rate variability as a biomarker for epilepsy seizure prediction
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7
that nurses and practitioners would have enough time to provide
more facilities and care measures for the patients (Figs 6 – 10).
Statistical test
In general, statistical tests aim to determine criteria for the
feature or features extracted from the signals recorded from the
patients. This paper aimed to examine the features extracted from
HRV signal at different time intervals. Thereby, paired sample t-
test was used to determine changes and distinction in extracted
features at various time intervals. Paired t-test also called before
and after test aimed to compare means in the two groups. The as-
sumption of normality of variables in the two groups should be
observed before the test. There are two observations (observa-
tions close to seizure and intervals far away from the seizure) for
each in this test.
In the output of the test, mean and standard deviation of the
variables are shown to describe the data. Then, the results of cor-
relation between values close to seizure and far away from the
seizure (this part does not affect the interpretation of mean com-
Fig. 9. Comparison between SD1 and SD2 in Poincare plot in the sei-
zure and non-seizure interval.
parison results) are given. Then, the results of mean equality in
the two groups by the mean difference in the two intervals with
zero value are presented. If signi cance values were less than α,
the assumption of equality of means in the two groups would be
rejected at α error level. In this study, the signi cance level was
considered less 0.5.
Evaluation of the performance of the proposed algorithm
To evaluate the performance of the proposed algorithm, we
introduced two criteria, namely, sensitivity and speci city. The
sensitivity (Sn) of seizure detection is the probability that the de-
tection is positive when the HRV segments are with the seizure.
The speci city (Sp) is de ned as the probability that the sei-
zure detection result says a non–seizure segment, when in fact,
they are seizure free. The sensitivity and speci city measures are
given in equation (2). True positive (TP): Sick people correctly
identi ed as sick, False positive (FP): Healthy people incorrectly
identi ed as sick, True negative (TN): Healthy people correctly
identi ed as healthy and False negative (FN): Sick people incor-
rectly identi ed as healthy.
(2)
Results
In order to observe c hanges in cardiac signal of epileptic pa-
tients, linear and nonlinear values mentioned in the previous sec-
tion at following intervals were calculated: ten to ve minutes
before the seizure , from fteen to ten minutes prior to seizure
, from twenty to fteen minutes before the seizure and a distant
interval from the seizure range (two hours before the seizure ).
Table 1 shows a qualitative (statistical) comparison of linear
and nonlinear features using paired t-test and calculated p-value
at two-time intervals ranging from ten to ve minutes before the
seizure and two hours before the seizure. It can be observed that
RRI dropped in moments close to the seizure, but Mean HR,
and SD2
SD1 and signi cantly increased in most intervals compared
to the two hours before the seizure. Since p-values for RRI, Mean
HR, and SD2
SD1 features were less than 0.01, it can be concluded
that these features have acceptable prediction values and can be
regarded as appropriate criteria for predicting the future condi-
tion of the patients.
Also, examining behavioral features extracted at different time
intervals re ects changes in the interval of about 30 minutes before
the seizure but most changes occurred in the interval of 15 min-
utes before the seizure. Therefore, the intervals of 10–15 minutes
and 5–10 minutes before the seizure were more emphasized than
other intervals and HRV signal features were more studied in the
previous intervals than the last intervals (Tab. 1).
Two ratios of SD2
SD1 and SD2
SD1 showed identical behaviors, which
con rmed a signi cant correlation between these two features since
these two indicate parasympathetic and sympathetic activities.
Any increase or decrease in these two features is due to different
Fig. 10. Comparison between low-frequency to high-frequency ratio
and SD2 to SD1 ratio in Poincare plot in the seizure and non-seizure
interval.
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extraction method. Thus, it can be concluded that HRV signal be-
havior before 20–5 minutes interval prior to seizure is suitable for
extraction of the features with regard to comparable intervals in
which maximum changes were observed in the extracted features.
To determine the threshold for the seizure predicting measure-
ment system, the best feature to investigate HRV signal behavior
at various time intervals with signi cant distinction were selected.
These features have been chosen using paired t-test with a p-value
less than 0.01.
The threshold values with the best sensitivity and the least
prediction error have been selected. In cases where acceptable
speci city for different thresholds (predicting noninvasive inter-
val) were obtained, the threshold with the least prediction error has
been determined. An alarm is given when the threshold reaches the
desired feature. Given that the threshold is different for each pa-
tient, a single threshold should be considered for each patient. For
example, mean and variance values of nth window were half the
average values of (n–1)th window. First, initial values of speci c-
ity and sensitivity were calculated. Then, sensitivity value and the
rate of incorrect predictions were determined for other thresholds
by changing the threshold. Finally, the best threshold values with
the maximum speci city and high sensitivity and the least false
predictio rate were selected.
The results generated based on thresholding method show that
it is able to distinguish high and low risk episodes and the seizure
prediction algorithm proposed based on HRV achieved 88.3 %
sensitivity and 86.2 % speci city.
Conclusion
This study analyzed 8 HRV features to predict epileptic sei-
zures from clinical data collected from 7 patients. The analysis re-
sults showed that HRV features, such as mean HR, SD2
SD1 and
changed 5–10 minutes before seizure onset in all seizure episodes.
The possibility of realizing a HRV-based seizure prediction system
was shown through these analyses.
Our data showed that epileptic seizures are associated with
increased heart rate, indicating an increased sympathetic tone
and reduced vagal tone. HRV parameter changes are more dif-
cult to interpret and need further investigation. We credit that
these features are useful biomarkers for clinical use. Now, we are
in the process of working with physicians to nd out more fea-
tures for detection and prediction of epileptic seizures with HRV
signal information.
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Received August 8, 2016.
Accepted October 27, 2016.
Feature type 2 hours before
seizure
10–5 min before
seizure p
RRI (ms)* 885.46±57.64 614.21±43.81 0.008
Mean HR* 73.43±8.58 106.32±13.23 0.006
LF 163.14±19.6 190.09±26.21 0.34
HF 256.28±44.57 177.63±31.72 0.028
LF/HF* 0.64±0.23 1.07±0.56 0.009
SD1 35.56±4.82 39.12±3.08 0.36
SD2 50.44±7.67 65.12±4.19 0.0025
SD2/SD1* 1.33±0.13 1.80±0.22 0.008
Tab. 1. Comparison of linear and non-linear features between 10–5
min and 2 hours before seizure.
... Other works on prediction of epileptic seizures were based only on ECG. In [14], the authors used a set of eight linear and nonlinear features which are: time interval between two successive R peaks (RRi), Mean of heart rate (Mean HR), LF, HF, LF/HF, Poincaré plot standard deviation perpendicular the line of identity (SD1), Poincaré plot standard deviation along the line of identity (SD2) and SD2/SD1 extracted from the data taken from a public database [15] which consists of 11 seizures taken from seven subjects. Besides, using the threshold technique, the authors reported a prediction sensitivity of 86.2%. ...
... However, the proposed approach in [16] achieved a better accuracy than our approach. The authors in [14] did not mention accuracy. The proposed approach also showed a prediction latency much better than both approaches seen in the state of arts. ...
Article
Full-text available
This study presents a new attempt to quantify and predict changes in the ECG signal in the pre-ictal period. In the proposed approach, threshold techniques were applied to the standard deviation of two heart rate variability features (The number of heartbeats per two minutes and approximate entropy) computed to ensure prediction and quantification of the pre-ictal state. We analyzed clinical data taken from two epileptic public databases, Siena scalp EEG and post-ictal heart rate oscillations in partial epilepsy and a local database. By testing the proposed approach on the Siena scalp EEG database, we achieved a sensitivity of 100%, specificity of 95%, and an accuracy of 96.4% whereas using acquisitions from the post-ictal database, we achieved a sensitivity of 100%, specificity of 91% and an accuracy of 94% and using the local database we achieved a sensitivity of 100%, a specificity of 97% and an accuracy of 97.5%. Furthermore, the proposed approach predicted 58.7%, 57.2, and 40% of the seizures before the onset by more than 10 min for the data taken from post-ictal, local and Siena database, respectively. Using the automatic threshold technique, we were able to achieve a sensitivity, specificity, and accuracy of 85%, 81%, 82% using our local database, respectively, whereas using acquisitions take from the Siena scalp EEG database, we achieved a sensitivity of 75%, specificity of 85% and an accuracy of 82%. Besides, using the post-ictal database, we achieved a sensitivity of 90%, a specificity of 83% and an accuracy of 85%.
... Patients' interictal HRV suggests an autonomic balance shift toward sympathetic dominance, which also tends toward further sympathetic overactivity (Myers et al., 2018). In a study of 11 epilepsy patients, HRV was compared from 5-min ECG recordings at 10-5 min and 2 h before seizure onset (Moridani and Farhadi, 2017). Results show that during 5-10 minutes before seizure onset, there were increases of mean HR, LF/HF, and SD2/SD1 (standard deviation of heart rate signals, SD1 shows rapid changes and SD2 describes long-term changes, non-linear analysis in Poincaré plot). ...
... Although Poincaré plot analysis is a non-linear method, SD1 and SD2 determined from Poincaré plots are purely linear. These HRV features can potentially be used to define a threshold to aid in predicting seizures (Moridani and Farhadi, 2017). This was supported by a recent study of 238 temporal lobe seizures from 41 patients where HRV features, including decreased RR and pNN50, helped to identify pre-ictal state in 90% of patients and 41% of seizures (Billeci et al., 2018;Leal et al., 2021). ...
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The heart and brain have bi-directional influences on each other, including autonomic regulation and hemodynamic connections. Heart rate variability (HRV) measures variation in beat-to-beat intervals. New findings about disorganized sinus rhythm (erratic rhythm, quantified as heart rate fragmentation, HRF) are discussed and suggest overestimation of autonomic activities in HRV changes, especially during aging or cardiovascular events. When excluding HRF, HRV is regulated via the central autonomic network (CAN). HRV acts as a proxy of autonomic activity and is associated with executive functions, decision-making, and emotional regulation in our health and wellbeing. Abnormal changes of HRV (e.g., decreased vagal functioning) are observed in various neurological conditions including mild cognitive impairments, dementia, mild traumatic brain injury, migraine, COVID-19, stroke, epilepsy, and psychological conditions (e.g., anxiety, stress, and schizophrenia). Efforts are needed to improve the dynamic and intriguing heart-brain interactions.
... Moreover, they found that the following features in terms of predictability are LF/HF, pNN50, NN50, and RQA ENT. Other works on prediction of epileptic seizures based only on ECG such [15], where the authors used a set of 8 linear and nonlinear features ( which are: RRI, Mean HR, LF, HF, LF/HF, SD1, SD2 and SD2/SD1) extracted from the data taken from a public database ...
... As all the analysis were extracted from the Post-Ictal database, we present in the following table our results: As can be seen in Table 4, our proposed approach achieved a highest value of sensitivity and speci city compared to the other works. However, the proposed approach in [17] achieved a better accuracy than our approach, where the work [15] did not mention his accuracy. Moreover, the proposed approach also showed a prediction latency much better than both approaches seen in the stat of arts. ...
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This study presents a new attempt to quantify and predict changes in the ECG signal in the pre-ictal period. In the proposed approach, threshold techniques were applied to the standard deviation (STD) of two Heart rate variability features (The number of heartbeats per two minutes and approximate entropy) computed to ensure prediction and quantification of the pre-ictal state. We analyzed clinical data taken from two epileptic public databases, Siena Scalp EEG and Post-Ictal Heart Rate Oscillations in Partial Epilepsy and a local database. By testing the proposed approach on the Siena scalp EEG database, we achieved a sensitivity of 100%, specificity of 95%, and an accuracy of 96.4% whereas using acquisitions from the post-Ictal database, we achieved a sensitivity of 100%, specificity of 91% and an accuracy of 94% and using the local database we achieved a sensitivity of 100%, a specificity of 97% and an accuracy of 97.5%. Furthermore, the proposed approach predicted 58.7%, 57.2, and 40% of the seizures before the onset by more than 10 min for the data taken from post-ictal, local and Siena database, respectively. Using the automatic threshold technique, we were able to achieve a sensitivity, specificity, and accuracy of 85%, 81%, 82% using our local database respectively, whereas using acquisitions take from the Siena Scalp EEG database, we achieved a sensitivity of 75%, specificity of 85% and an accuracy of 82%. Besides, using the post-ictal database, we achieved a sensitivity of 90%, a specificity of 83% and an accuracy of 85%.
... In this context, performance is assessed in terms of accuracy and anticipation time. Two studies designed prediction algorithms that ensured an anticipation time of 5 min [69,104], obtaining a maximum sensitivity of about 94% when using an SVM classifier taking multiple HRV features from different domains in input. Improved results are given in [50,74], where it is shown that a seizure can be predicted up to 15 min in advance without degrading the sensitivity levels. ...
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The most critical burden for People with Epilepsy (PwE) is represented by seizures, the unpredictability of which severely impacts quality of life. The design of real-time warning systems that can detect or even predict ictal events would enhance seizure management, leading to high benefits for PwE and their caregivers. In the past, various research works highlighted that seizure onset is anticipated by significant changes in autonomic cardiac control, which can be assessed through heart rate variability (HRV). This manuscript conducted a scoping review of the literature analyzing HRV-based methods for detecting or predicting ictal events. An initial search on the PubMed database returned 402 papers, 72 of which met the inclusion criteria and were included in the review. These results suggest that seizure detection is more accurate in neonatal and pediatric patients due to more significant autonomic modifications during the ictal transitions. In addition, conventional metrics are often incapable of capturing cardiac autonomic variations and should be replaced with more advanced methodologies, considering non-linear HRV features and machine learning tools for processing them. Finally, studies investigating wearable systems for heart monitoring denoted how HRV constitutes an efficient biomarker for seizure detection in patients presenting significant alterations in autonomic cardiac control during ictal events.
... Patients with a history of ES and FDS exhibit chronic and acute seizure-related autonomic disturbances [16,17]. This is particularly evident in people with refractory epilepsy and for SUDEP cases [7,15,[18][19][20][21][22][23][24][25][26][27][28][29]. There are conflicting results as to whether autonomic function differs in people with ES vs. FDS, and surrounding ES vs. FDS [7,15,[28][29][30][31]. ...
Article
Objective: 20-40% of individuals whose seizures are not controlled by anti-seizure medications exhibit manifestations comparable to epileptic seizures (ES), but there are no EEG correlates. These events are called functional or dissociative seizures (FDS). Due to limited access to EEG-monitoring and inconclusive results, we aimed to develop an alternative diagnostic tool that distinguishes ES vs. FDS. We evaluated the temporal evolution of ECG-based measures of autonomic function (heart rate variability, HRV) to determine whether they distinguish ES vs. FDS. Methods: The prospective study includes patients admitted to the University of Rochester Epilepsy Monitoring Unit. Participants are 18-65 years old, without therapies or co-morbidities associated with altered autonomics. A habitual ES or FDS is recorded during admission. HRV analysis is performed to evaluate the temporal changes in autonomic function during the peri‑ictal period (150-minutes each pre-/post-ictal). We determined if autonomic measures distinguish ES vs. FDS. Results: The study includes 53 ES and 46 FDS. Temporal evolution of HR and autonomics significantly differ surrounding ES vs. FDS. The pre-to-post-ictal change (delta) in HR differs surrounding ES vs. FDS, stratified for convulsive and non-convulsive events. Post-ictal HR, total autonomic (SDNN & Total Power), vagal (RMSSD & HF), and baroreflex (LF) function differ for convulsive ES vs. convulsive FDS. HR distinguishes non-convulsive ES vs. non-convulsive FDS with ROC>0.7, sensitivity>70%, but specificity<50%. HR-delta and post-ictal HR, SDNN, RMSSD, LF, HF, and Total Power each distinguish convulsive ES vs. convulsive FDS (ROC, 0.83-0.98). Models with HR-delta and post-ictal HR provide the highest diagnostic accuracy for convulsive ES vs. convulsive FDS: 92% sensitivity, 94% specificity, ROC 0.99). Significance: HR and HRV measures accurately distinguish convulsive, but not non-convulsive, events (ES vs. FDS). Results establish the framework for future studies to apply this diagnostic tool to more heterogeneous populations, and on out-of-hospital recordings, particularly for populations without access to epilepsy monitoring units.
... Epileptic seizures are usually accompanied by an increase in heart rate. However, in some partial and generalized epileptic convulsions, arrhythmia happens, and heart rate falls [5]. ...
Article
Background Drug-resistant epilepsy is one of the most common neurological conditions associated with high mortality and morbidity rates. Aim To assess heart rate variability among drug-resistant epileptic children. Patients and methods This observational cross-sectional case–control study included 60 epileptic children. Cases were assigned into two equal groups: group 1 (drug-resistant group) included children presented with drug-resistant epilepsy and group 2 (control group) included cases with controlled primary epilepsy who achieved sustained seizure freedom for at least 6 months on one antiepileptic drug, matched with the patient group regarding age and sex. All patients were subjected to history taking and clinical and radiological investigations including computed tomography (CT) and/or MRI and electroencephalogram (EEG) monitoring. ECG monitoring was using Holter ECG. Results MRI, EEG, and ECG abnormalities are significantly more common in drug-resistant epilepsy. Interictal tachycardia was the most prevalent abnormality among group I (93.3%). ECG structure was abnormal in 33.3% in group I, in the form of prolonged QTc interval, ST segment abnormalities, P wave dispersion, and T wave alternans. Tachycardia associated with prolonged QTc interval was present in patients with focal or temporal EEG abnormalities, and patients with multifocal EEG abnormalities. Conclusion ECG monitoring is important in drug-resistant epileptic children to detect any autonomic changes occurring in the heart either ictally or interictally. Heart rate is significantly higher and RR interval is significantly shorter ictally than interictally. Careful monitoring of these changes may help in predicting the risk of sudden unexpected death.
... To further improve the prediction accuracy and reliability, data fusion is an effective way; in actual EEG acquisition, simultaneous acquisition of ECG data can meet the requirement of data fusion; in addition, there is increasing evidence that the nervous system plays an important role in regulating cardiac function, and seizure-onset arrhythmias have been shown to be the result of autonomic imbalance induced by seizure activity. Studies have shown that seizures can be predicted using the ECG (Moridani and Farhadi, 2017;Ufongene et al., 2020;Costagliola et al., 2021), so combining the EEG with the ECG signal not only improves the accuracy of seizure prediction, but also allows better detection and understanding of brain-heart interactions for monitoring and treatment of potential arrhythmias. ...
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Epilepsy is the second common neurological disorder after headache, accurate and reliable prediction of seizures is of great clinical value. Most epileptic seizure prediction methods consider only the EEG signal or extract and classify the features of EEG and ECG signals separately, the improvement of prediction performance from multimodal data is not fully considered. In addition, epilepsy data are time-varying, with differences between each episode in a patient, making it difficult for traditional curve-fitting models to achieve high accuracy and reliability. In order to improve the accuracy and reliability of the prediction system, we propose a novel personalized approach based on data fusion and domain adversarial training to predict epileptic seizures using leave-one-out cross-validation, which achieves an average accuracy, sensitivity and specificity of 99.70, 99.76, and 99.61%, respectively, with an average error alarm rate (FAR) of 0.001. Finally, the advantage of this approach is demonstrated by comparison with recent relevant literature. This method will be incorporated into clinical practice to provide personalized reference information for epileptic seizure prediction.
... Recent studies have demonstrated the potential of electrocardiogram (ECG) signals as an alternative or complementary modality for this purpose [14][15][16][17]. This is possible as the alterations in the Autonomic Nervous System (ANS) occur prior to an ictal state, resulting in modified cardiac behavior, and are detectable by monitoring the short-term Heart Rate Variability (HRV) parameters of a patient. ...
Article
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Epilepsy is one of the most common brain diseases, characterized by frequent recurrent seizures or “ictal” states. A patient experiences uncontrollable muscular contractions, inducing loss of mobility and balance, which may result in injury or even death during these ictal states. Extensive investigation is vital to establish a systematic approach for predicting and informing patients about oncoming seizures ahead of time. Most methodologies developed are focused on the detection of abnormalities using mostly electroencephalogram (EEG) recordings. In this regard, research has indicated that certain pre-ictal alterations in the Autonomic Nervous System (ANS) can be detected in patient electrocardiogram (ECG) signals. The latter could potentially provide the basis for a robust seizure prediction approach. The recently proposed ECG-based seizure warning systems utilize machine learning models to classify a patient’s condition. Such approaches require the incorporation of large, diverse, and thoroughly annotated ECG datasets, limiting their application potential. In this work, we investigate anomaly detection models in a patient-specific context with low supervision requirements. Specifically, we consider One-Class SVM (OCSVM), Minimum Covariance Determinant (MCD) Estimator, and Local Outlier Factor (LOF) models to quantify the novelty or abnormality of pre-ictal short-term (2–3 min) Heart Rate Variability (HRV) features of patients, trained on a reference interval considered to contain stable heart rate as the only form of supervision. Our models are evaluated against labels that were either hand-picked or automatically generated (weak labels) by a two-phase clustering procedure for samples of the “Post-Ictal Heart Rate Oscillations in Partial Epilepsy” (PIHROPE) dataset recorded by the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, achieving detection in 9 out of 10 cases, with average AUCs of over 93% across all models and warning times ranging from 6 to 30 min prior to seizure. The proposed anomaly detection and monitoring approach can potentially pave the way for early detection and warning of seizure incidents based on body sensor inputs.
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Approximately 300,000 Americans suffer from epilepsy but no treatment currently exists. A device that could predict a seizure and notify the patient of the impending event or trigger an antiepileptic device would dramatically increase the quality of life for those patients. A patient-specific classification algorithm is proposed to distinguish between preictal and interictal features extracted from EEG recordings. It demonstrates that the classifier based on a Cost-Sensitive Support Vector Machine (CSVM) can distinguish preictal from interictal with a high degree of sensitivity and specificity, when applied to linear features of power spectrum in 9 different frequency bands. The proposed algorithm was applied to EEG recordings of 9 patients in the Freiburg EEG database, totaling 45 seizures and 219-hour-long interictal, and it produced sensitivity of 77.8% (35 of 45 seizures) and the zero false positive rate using 5-minute-long window of preictal via double-cross validation. This approach is advantageous, for it can help an implantable device for seizure prediction consume less power by real-time analysis based on extraction of linear features and by offline optimization, which may be computationally intensive and by real-time analysis.
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Components of heart rate variability have attracted considerable attention in psychology and medicine and have become important dependent measures in psychophysiology and behavioral medicine. Quantification and interpretation of heart rate variability, however, remain complex issues and are fraught with pitfalls. The present report (a) examines the physiological origins and mechanisms of heart rate variability, (b) considers quantitative approaches to measurement, and (c) highlights important caveats in the interpretation of heart rate variability. Summary guidelines for research in this area are outlined, and suggestions and prospects for future developments are considered.
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Epileptic seizures are a principal brain dysfunction with important public health implications, as they affect 0.8% of humans. Many of these patients (20%) are resistant to treatment with drugs. The ability to anticipate the onset of seizures in such cases would permit clinical interventions. The view of chronic focal epilepsy now is that abnormally discharging neurons act as pacemakers to recruit and entrain other normal neurons by loss of inhibition and synchronization into a critical mass. Thus, preictal changes should be detectable during the stages of recruitment. Traditional signal analyses, such as the count of focal spike density, the frequency coherence or spectral analyses are not reliable predictors. Non-linear indicators may undergo consistent changes around seizure onset. Our objective was to follow the transition into seizure by reconstructing intracranial recordings in implanted patients as trajectories in a phase space and then introduce non-linear indicators to characterize them. These indicators take into account the extended spatio-temporal nature of the epileptic recruitment processes and the corresponding physiological events governed by short-term causalities in the time series. We demonstrate that in most cases (17 of 19), seizure onset could be anticipated well in advance (between 2-6 minutes beforehand), and that all subjects seemed to share a similar 'route' towards seizure.
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The transition of brain activity towards an epileptic seizure is still a poorly understood phenomenon. Dynamic changes in brain activity have been detected several minutes before seizure emergence in populations of patients with mesial temporal lobe epilepsy (MTLE), using non-linear analysis of intracranial EEG recordings. Similar detection of a pre-ictal state has been obtained with standard scalp EEG recordings using a modified non-linear method. Here we applied this strategy to the seizures of patients with neocortical partial epilepsy. Results obtained by non-linear similarity analysis of 41 seizures from 11 patients with refractory partial epilepsy originating from various sites of the neocortex showed that (i) a pre-ictal state was detected in 90% of the patients and in 83% of the seizures whatever their location, with a mean anticipation time of 7.5 min; (ii) similar pre-ictal dynamic changes were detected when non-linear analysis methods were applied to either intracranial or scalp EEG recordings; (iii) the recording sites exhibiting these pre-ictal changes were distributed both within the epileptogenic focus and at remote locations; (iv) most pre-ictal dynamic changes were not correlated with linear changes in the frequency spectrum or with changes in the visually inspected EEG and the patients' behaviour. Hypotheses on the neuronal mechanisms underlying the pre-ictal period are discussed. The present results, together with those recently obtained in an MTLE population, suggest that changes in pre-ictal dynamics are a general phenomenon associated with seizure emergence in a wide population of patients with partial epilepsy, wherever the epileptogenic focus is located. The possibility of anticipating the onset of seizures has considerable therapeutic implications.
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The Task Force was established by the Board of the European Society of Cardiology and co-sponsored by the North American Society of Facing and Electrophysiology. It was organised jointly by the Working Groups on Arrhythmias arzd on Computers of Cardiology of the European Society of Cardiology. After exchanges of written views on the subject, the main meeting of a writing core of the Task Force took place on May 8-10. 1994, on Necker Island. Following external reviews, the tent of this report was approved by the Board of the European Society of Cardiology on August 19,1995, and by the Board of the North American Society of Facing and Electrophysiology on October 3, 1995.
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We propose a patient-specific algorithm for seizure prediction using multiple features of spectral power from electroencephalogram (EEG) and support vector machine (SVM) classification. The proposed patient-specific algorithm consists of preprocessing, feature extraction, SVM classification, and postprocessing. Preprocessing removes artifacts of intracranial EEG recordings and they are further preprocessed in bipolar and/or time-differential methods. Features of spectral power of raw, or bipolar and/or time-differential intracranial EEG (iEEG) recordings in nine bands are extracted from a sliding 20-s-long and half-overlapped window. Nine bands are selected based on standard EEG frequency bands, but the wide gamma bands are split into four. Cost-sensitive SVMs are used for classification of preictal and interictal samples, and double cross-validation is used to achieve in-sample optimization and out-of-sample testing. We postprocess SVM classification outputs using the Kalman Filter and it removes sporadic and isolated false alarms. The algorithm has been tested on iEEG of 18 patients of 20 available in the Freiburg EEG database who had three or more seizure events. To investigate the discriminability of the features between preictal and interictal, we use the Kernel Fisher Discriminant analysis. The proposed patient-specific algorithm for seizure prediction has achieved high sensitivity of 97.5% with total 80 seizure events and a low false alarm rate of 0.27 per hour and total false prediction times of 13.0% over a total of 433.2 interictal hours by bipolar preprocessing (92.5% sensitivity, a false positive rate of 0.20 per hour, and false prediction times of 9.5% by time-differential preprocessing). This high prediction rate demonstrates that seizures can be predicted by the patient-specific approach using linear features of spectral power and nonlinear classifiers. Bipolar and/or time-differential preprocessing significantly improves sensitivity and specificity. Spectral powers in high gamma bands are the most discriminating features between preictal and interictal. High sensitivity and specificity are achieved by nonlinear classification of linear features of spectral power. Power changes in certain frequency bands already demonstrated their possibilities for seizure prediction indicators, but we have demonstrated that combining those spectral power features and classifying them in a multivariate approach led to much higher prediction rates. Employing only linear features is advantageous, especially when it comes to an implantable device, because they can be computed rapidly with low power consumption.
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Recent studies have shown that non-linear analysis of intracranial activities can detect a 'pre-ictal phase' preceding the epileptic seizure. Nevertheless, the dynamical nature of the underlying neuronal process and the spatial extension of this pre-ictal phase still remain unknown. In this paper, we address these aspects using a new non-linear measure of dynamic similarity between different parts of intracranial recordings of nine patients with medial temporal lobe epilepsy recorded during transitions to seizure. Our results confirm that non-linear changes in neuronal dynamics allow, in most cases (16 out of 17), a seizure anticipation several minutes in advance. Furthermore, we show that the spatial distribution of pre-ictal changes often involves an extended network projecting beyond the limits of the epileptogenic region. Finally, the pre-ictal phase could frequently (13 out of 17) be characterized with a marked shift toward slower frequencies in upper delta or theta frequency range.