Cardiac autonomic dysfunction in drug naı ¨ve hot water epilepsy
A. Meghanaa, T.N. Sathyaprabhaa,*, S. Sinhab, P. Satishchandrab
aDepartment of Neurophysiology, National Institute of Mental Health and Neuroscience (NIMHANS), Bangalore 560 029, India
bDepartment of Neurology, National Institute of Mental Health and Neuroscience (NIMHANS), Bangalore, India
Hot water epilepsy (HWE) is an interesting type of reflex
epilepsy in which a seizure is precipitated by having a bath or
shower with hot water.1–7The condition is also known as ‘water-
immersion epilepsy’ and ‘bathing epilepsy’.8–10Patients affected
with this condition may experience the seizures exclusively
precipitated by those factors. Mani et al. published an epidemio-
logic study from Yelandur, a rural area near the district of Mysore
from the state of Karnataka, India and reported a prevalence rate of
255 per 100,000 for HWE.11The diagnostic scheme proposed by
the International League against Epilepsy (ILAE) in 2001 included
HWE as a type of reflex epilepsy.12It is the second most common
type of reflex epilepsy after photosensitive epilepsy.13
Experimental data suggests that autonomic neural discharge
can be induced by inter-ictal epileptogenic activity.14Previous
studies have shown that autonomic dysfunction plays a major role
in the development of ventricular tachyarrhythmia in patients
with epilepsy and may be related to the high incidence of sudden
death.15Evidence of autonomic dysfunction like variation in heart
rate or in blood pressure and even cardiac arrhythmias has also
been well established in the inter-ictal period.16Other studies have
shown that seizure control with antiepileptic drugs (AEDs) might
help to improve cardiac autonomic impairment in epilepsy
patients.17Incidence of sudden death and autonomic dysfunction
is less in monotherapy than with polytherapy and gradual
withdrawal is more effective than sudden withdrawal of drugs.18
Normal heart rate depends on the balance between sympa-
thetic and parasympathetic systems. HRV is an important non-
invasive tool for the detection of sympatho-vagal balance of the
autonomic nervous system. HRV can be used as a measure of
neuro-cardiac autonomic function. Several studies have documen-
ted that the analysis of time-domain and frequency-domain
measures of HRV reflects sympathetic and parasympathetic
functions.19,20HRV parameters are also suitable as tools for the
quantification of physiologic, pharmacologic and pathologic
changes in the autonomic nervous system.14,20Over the last few
decades, increased emphasis has been placed on these techniques
as measures of cardiovascular autonomic functions. HRV has been
established as a good index of cardio-autonomic regulation.
Several studies have been done in patients with complex,
simple partial and generalized tonic clonic seizures and revealed
autonomic dysfunction in the inter-ictal period.21HRV parameters
have not been used as measure of autonomic function in hot water
reflex epilepsy. Hence in this study, HRV was evaluated to
characterize autonomic function in HWE.
Seizure 21 (2012) 706–710
A R T I C L E
I N F O
Received 7 June 2012
Received in revised form 23 July 2012
Accepted 26 July 2012
Heart rate variability
Hot water epilepsy
A B S T R A C T
Purpose: This study aimed to characterize the role of autonomic nervous system dysfunction in hot water
epilepsy (HWE). Heart rate variability (HRV) has been established as a good index of cardio-autonomic
Methodology: Forty-five patients with HWE (age: 24.6 ? 10.1 years; M:F = 37:8) and 45 age and gender
matched controls (age: 24.17 ? 10.37 years; M:F = 37:8) were studied. Five minutes resting lead II
electrocardiogram (ECG) was obtained (AD instruments) under standard conditions and analyzed for time
and frequency domain HRV parameters using LabChart software.
Result: Patients with hot water epilepsy showed significant increase in LF nu (Low frequency normalized
unit) and LF/HF denoting an interictal increase in sympathetic activity. In addition, reductions were
noted in parasympathetic function [RMSSD (root mean square successive difference of RR intervals), HF
(High frequency) nu and LF/HF].
Conclusion: This study has demonstrated an impaired sympatho-vagal balance characterized by
increased sympathetic activity and reduced parasympathetic activity in patients with HWE. The present
study supports the notion that the hypothalamus is involved in both, the pathogenesis of HWE and
? 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
* Corresponding author. Tel.: +91 80 26995172; fax: +91 80 26564830.
E-mail address: email@example.com (T.N. Sathyaprabha).
Contents lists available at SciVerse ScienceDirect
jou r nal h o mep age: w ww.els evier .co m/lo c ate/ys eiz
1059-1311/$ – see front matter ? 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
M:F = 37:8) were recruited as subjects for this study between
May 2009 and September 2011, from the Neurology outpatients
services of the National Institute for Mental Health and Neurologi-
cal Sciences (NIMHANS), Bangalore, India. Forty-five age and
gender matched healthy volunteers as controls (age: 24.17 ? 10.37
years; M:F = 37:8) were recruited for this study. The study was
approved by the Institutional Ethics Committee (IEC), NIMHANS.
All subjects participated voluntarily and gave their informed
written consent. The diagnosis of HWE was made according to
Revised International League Against Epilepsy (ILAE, 1989) guide-
lines.22Newly diagnosed patients or patients taking intermittent
clobazam treatment were considered as drug naı ¨ve and were
recruited for the study. None of the subjects had a history
suggestive of diabetes, hypertension, cardiac disease, use of drugs
or other comorbidities like head injuries, which are known to
influence the autonomic functions. None of the patients met DSM-
IVR criteria for depression or anxiety.
Details of seizure semiology, age at onset, types and duration of
seizures, provoking factors, bathing habits, and history of febrile
convulsions, family history of non-reflex epilepsy or HWE were
obtained. Inter-ictal scalp EEG was performed in all subjects.
Routine electrocardiogram (ECG) was performed between 9
and 11 AM in the autonomic Laboratory, Department of
Neurophysiology under standardized conditions.23,24ECG was
performed after a minimum gap of 24 h (mean: 168 ? 25.07 h)
from the last seizure. Fifteen minutes resting Lead II ECG was
obtained (AD Instruments), which was analyzed offline for time and
frequency domain HRV parameters using LabChart software. The
recorded ECG signals were conveyed through analog digital
converter (from Power Lab, 16 channel data acquisition system,
AD Instruments, Australia) with a sampling rate of 1024 Hz. An
artifact-free 5-min segment of the ECG was analyzed offline using
LabChart software. This is an automated software program that
permits visual inspection of the raw ECG and breathing signals, so as
to obtain the HRV parameters in time-domain and frequency-
domain, known as ‘linear methods’.
24.6 ? 10.1 years;
2.1. Time-domain analysis
This involves comparing 2 different signals and was analyzed
using descriptive statistical measures. Heart rate fluctuations were
measured using various variables including (a) standard deviation
of RR intervals sensitive to all sources of variation (SDNN); (b) root
mean square successive difference of RR intervals ? (RMSSD); (c)
number of successive NN intervals that vary by more than 50 ms
(NN50); and (d) percentage of NN50 counts which are more
sensitive to the highest frequency component and best predictors
of parasympathetic activity (pNN50).23,24
2.2. Frequency-domain analysis
The non-parametric Fast Fourier Technique (FFT) was per-
formed for frequency-domain parameters. Different components
of FFT with their specific frequency ranges were: (a) total power
(TP) (0–0.4 Hz) which reflects sympathetic and parasympathetic
tone; (b) high frequency (HF) (0.15–0.4 Hz) which is indicative of
parasympathetic tone and respiration; (c) low frequency (LF)
(0.04–0.15 Hz) which indicates sympathetic as well as parasym-
pathetic tone, (d) very low frequency (VLF) (0.003–0.04 Hz) which
indicates thermoregulation, and can be used to calculate LF
normalized unit (LF nu) and HF normalized unit (HF nu) that
represent the relative value of each component in proportion to
the total power minus the VLF component; and (e) LF/HF
which reflects sympathovagal balance and reflects sympathetic
2.3. Data analysis
The data was analyzed using SPSS version 15. After log
transformation independent sample ‘t’ test was used to look for
significant differences in the study parameters between patients
and controls. Significance was assessed at the 5% level. Results of
continuous measurements of HRV and clinical features were
presented as mean ? standard error of mean (SEM) and mean
? standard deviation (SD) respectively.
3.1. Clinical and demographic details
Forty-five subjects (age 24.6 ? 10.15 years; M:F = 37:8) of
HWE and 45 age and gender matched healthy volunteers as
controls (age: 24.17 ? 10.37 years; M:F = 37:8) were studied. The
mean age at onset was 18.7 ? 10.2 years and the duration of illness
was 69.9 ? 13.8 months. All patients had the habit of taking hot
water head bath either every alternate day or at least once in a
week. Thirty percent of the patients experienced 4–6 attacks per
month, 10% experienced 1–2 attacks per month and the remaining
experienced at least one attack every 6–12 months. 58.5% patients
had complex partial seizures without secondary generalization,
generalization. A past history of febrile convulsion was present
in 22%, and a family history of non-reflex epilepsy and HWE was
present in 22% and 26.8% of cases, respectively. Patients with self-
induction experience a feeling of pleasure or euphoria during their
hot water induced seizures, causing them to pour more hot water
over themselves until they manifest with seizure. The phenome-
non of self-induction in HWE is well documented and in this cohort
it was noted in 32.5%.5The majority of the HWE patients (68%)
were drug naı ¨ve while the remaining patients were on intermittent
clobazam. The demographic and clinical data of the subjects are
summarized in Table 1. The EEG was abnormal in 9/45 (20%)
patients. In the majority of patients the abnormalities were located
in the fronto-temporal region on either or both sides. The details of
EEG abnormalities are mentioned in Table 2.
Clinical features and demographic details of hot water epilepsy (HWE) patients.
HWE (n = 45)
Age at evaluation (years)
Age at onset (years)
Duration of illness (months)
Mean number of HWEd
1:1 episodes in relation to hot water head bath (%)a
With secondary generalization (%)
History of Febrile convulsion (%)
Family history of spontaneous seizures (%)
Family history of HWE (%)
Newly diagnosed HWE (%)
Abnormal EEG (%)
24.6 ? 10.1c
18.7 ? 10.2c
69.9 ? 13.8c
19.6 ? 2.36c
5.31 ? 0.42c
a1:1 episodes in relation to hot water head bath, i.e. seizure occur every time
patient have hot water bath.
bPatients with self-induction actually mean that while taking hot water bath
they have a feeling of pleasure and euphoria, making them pour more hot water till
they manifest with seizure.
cValues are expressed in mean ? SD.
dAverage numbers of seizures due to hot water during their life time at the time
A. Meghana et al. / Seizure 21 (2012) 706–710
3.2. Heart rate variability parameters
The mean heart rate was higher in patients with HWE
compared to controls (75 ? 3/min vs 71 ? 2/min) though statisti-
cally not significant. The time-domain parameters of HRV were
significantly reduced in patients with HWE compared to the controls.
SDNN was 42.8 ? 2.1 ms vs 54.4 ? 3.1 ms, p = 0.002; RMSSD was
33.7 ? 2.6 ms vs 72.0 ? 4.1 ms, p = 0.012. The frequency domain
parameters were also altered in patients with HWE. LF nu was
49.3 ? 2.5 vs. 40.1 ? 2.1, p = 0.007; HF nu was 41.2 ? 2.5 vs
49.23 ? 2.3, p = 0.009 and LF/HF was 1.65 ? 0.2 vs 0.97 ? 0.1,
p = 0.004. Results were showing predominant sympathetic over-
activity with reduced parasympathetic activity and sympathovagal
balance tilted toward sympathetic limb. The details are provided in
High variability in heart rate is a marker of a normally
functioning neuro-cardiovascular system. Disturbed cardiac auto-
nomic function might reflect as low heart rate variability, which is
a marker for underlying neuro-cardiovascular diseases.
It has previously been documented that inter-ictal epilepto-
genic activity can induce autonomic disturbance and that cardiac
arrhythmias may be associated with altered autonomic neural
discharges.25The disturbance of the autonomic control of the
heart rate might be one of the causes for the high incidence of
sudden death in epileptic patients.26,27Historically, decreased HF
power as well as RMSSD and pNN50 with increased LF/HF
indicating sympathetic dominance have been documented in
simple and in complex partial seizure.28Several other studies
have showed subtle but definite cardiac autonomic dysfunction in
drug-naı ¨ve and new-onset epilepsy patients.29A previous study of
HRV in patients with newly diagnosed generalized tonic–clonic
seizures reported reduced HF, increased LF and an increased LF/HF
ratio.15However, Ansakorpi et al. showed decreased LF and HF
power especially in temporal lobe epilepsy (TLE), contradicting
the previous studies.30Even, in frontal lobe epilepsy there was
reduced heart rate variability during the inter-ictal period due to
reduced vagal regulation of autonomic cardiac activities.31
Autonomic dysfunction has also been observed in refractory
Effects of AEDs and epilepsy on HRV have been estab-
lished.32–34A study of patients with TLE in which the majority of
the patients were on polytherapy with different AEDs, showed
lower TP and also decreased LF and HF power.33Heart rate and
blood pressure responses were diminished in the group on AEDs,
especially in the subgroup treated with carbamazepine (CBZ).32
Impairment of cardiovascular autonomic functions studied on
those who were on CBZ proved that CBZ increases the risk of
cardio-respiratory changes in susceptible patients.34In this
study, HRV was altered in patients with HWE, who were drug
naı ¨ve. We therefore believe that it is likely that interictal
dysautonomia in patients with HWE is likely to be caused by
interictal epileptic activity.
Autonomic alterations have also been reported in children with
simple and complex partial seizures.28Dutsch et al. showed
increased LF power and LF/HF ratio, decreased HF power in TLE
suggesting disturbance in hypothalamic functionality as well as in
connected areas due to structural microscopic changes in limbic
area.35However, contradicting their observations, Tomson et al.
reported an excess of parasympathetic activity in TLE – either due
to TLE per se or the effects of CBZ treatment.27The present study
shows that patients with hot water induced complex partial
seizures have an increased interictal sympathetic tone. Hot water
epilepsy in TLE patients may also show sympathetic predomi-
nance. In our study, HWE patients were drug naı ¨ve so there was no
possibility of the observed changes being due to antiepileptic
In this study, we explored both time and frequency domains
of HRV in patients of HWE who were drug naı ¨ve. There was
slight increase in heart rate but a significant decrease in SDNN,
RMSSD and pNN50 index in time domain parameters of cases
compared to healthy volunteers. Also, the frequency domain
parameter results, which are more accurate if the analysis is
based on short ECG recordings, showed a very significant
Detailed description of EEG abnormalities and CT scan in patients of hot water epilepsy (HWE).
Type of seizure
Duration of HWE (years)
HWE-CPS with sec. generalization
HWE-CPS with sec. generalization
HWE-CPS with sec. generalization
HWE-CPS with sec. generalization
Left fronto-temporal (T1) spike
Left temporal T5 foci-spike
Bi-temporal T2-5, Rt > Lt
Frontal spike arising from Lt > Rt hemisphere
Independent bilateral fronto-temporal discharge
Bi temporal sharp wave
Left temporal sharp wave
Right frontal lobe discharge
Solitary sharp wave over T4-6
Comparisons of time and frequency domain measures of heart rate variability of hot water epilepsy (HWE) and healthy volunteers.
HWE (n = 45)
Healthy volunteer (n = 45)
SD of RR intervals (SDNN)
Square root of mean of sum of squares of successive differences of RR intervals (RMSSD)
Number of successive NN intervals > 50 ms (NN50)
Total power (TP)
Low frequency power normalized unit (LF nu)
High frequency power normalized unit (HF nu)
42.8 ? 2.1
33.7 ? 2.6
76.7 ? 12.2
21.64 ? 3.6
3380.6 ? 572.1
836.32 ? 119.5
1192.20 ? 277.1
49.3 ? 2.5
41.2 ? 2.5
1.65 ? 0.2
54.4 ? 3.1
72.0 ? 4.1
86.3 ? 9.4
25.89 ? 3.07
3149.1 ? 457.7
756.35 ? 102.83
1205.92 ? 300.20
40.1 ? 2.1
49.23 ? 2.3
0.97 ? 0.1
Values are expressed as mean ? SEM.
A. Meghana et al. / Seizure 21 (2012) 706–710
increased in LF nu and LF/HF which is an indicator of sympatho-
vagal balance, indicating increased sympathetic effects on the
cardiovascular system. There was a significant fall in HF nu but
not in HF power because normalization tends to minimize the
effect on the values of HF components of the changes in total
Hence, both time-domain and frequency-domain
parameters showed increases in sympathetic tone consistent
with an increased risk of cardiac arrhythmias. The relative
predominance of sympathetic over-activity could predispose
patients to the development of ventricular tachyarrhythmias.
Increased parasympathetic activity will have long term effects
on the heart leading to bradycardia and asystole if the seizures
are not well-controlled.36
3.4. Mechanism of HWE and autonomic dysfunction
Kindling phenomena are well established in HWE and have
been shown to be relevant in this condition by animal
experiments.3,37Kindling is likely to stimulate the limbic
Simultaneously, there may be activation of the
prefrontal cortex and anterior cingulate, which are involved in
attention to dangerous or negative stimuli, which ultimately
influence the limbic system (especially the amygdala). This could
lead to an increase in the dendritic growth in the limbic system,
which would lead to even greater limbic stimulation causing an
increase in the excitatory post-synaptic receptors and a decrease
in inhibitory pre-synaptic receptors.39Brain chemistry studies
demonstrate that increased levels of glutamate and decreased
levels of GABA lead to hot water induced seizure.40
Stimulation of the amygdala inhibits the hippocampus which in
turn disinhibits the hypothalamus, hence causing excitation of the
hypothalamus. Predominant sympathetic activity in hot water
epilepsy might be due to stimulation of sympathetic center from
the hypothalamus and amygdala41,42(Fig. 1).
This is the first study in which heart rate variability was
compared between patients with hot water epilepsy and healthy
volunteers. The results reveal a reduced vagal tone during the
inter-ictal period in patients with HWE. Hypothalamic functions,
which play a role in regulating autonomic and thermoregulation,
may be altered in HWE. This study supports an earlier hypothesis
of hypothalamic dysfunction5and a distinctive sympathetic
dysfunction in patients with HWE. This also supports the
hypothesis of a common neuro-anatomical and neuro-physiologi-
cal region for HWE and autonomic dysfunction.
Fig. 1. Schematic diagram showing possible mechanism of autonomic dysfunction in hot water epilepsy (HWE).
A. Meghana et al. / Seizure 21 (2012) 706–710
Conflict of interest Download full-text
We are thankful to Dr. Raju TR (senior professor, Dept. of
Neurophysiology, NIMHANS) for his guidance and valuable
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