1
Timing of seizure occurrence and response of
medical staff in video-EEG monitoring for
drug-resistant epilepsy
Alief Dhuha, Takehiko Konno, Hidenori Yokota, Keiji Oguro, Eiju Watanabe, Kensuke Kawai
Purpose: The purpose of this study was to determine the optimal duration of long-term video-
EEG monitoring (VEEG) in patients with epilepsy. The response time of medical staff to seizures
was also evaluated from the viewpoint of safety of the monitoring.
Methods: We estimated the optimal duration of VEEG from the seizure onset pattern. We retro-
spectively investigated all VEEG sessions performed in our department during the period between
June 2005 and July 2016. Sessions with no seizures and with only non-epileptic seizures were ex-
cluded. Using 91 sessions from 69 patients, information on the onset time and response time of
medical staff to seizures was collected.
Results: The median duration from the start of VEEG to the first seizure was 2 days. Seventy-seven
percent of first seizures occurred within 3 days of VEEG. The median duration from the first sei-
zure to the third seizure was 2 days. Eighty percent of third seizures occurred within 3 days of the
first seizure. There was no significant diurnal distribution of seizure occurrence. Medical staff did
not respond to 20% of generalized seizures and 69% of focal seizures. The overlooking of general-
ized seizures occurred mainly during the hours of 1-2 pm and 8-9 pm but there was no significant
diurnal pattern in overlooking generalized and focal seizures.
Conclusion:Based on these findings, we suggest that VEEG can be terminated when no seizure
occurs within 4 days after onset. In our VEEG protocol, in which all antiepileptic drugs were dis-
continued before the start of a session, there was no diurnal pattern of seizure occurrence. This is
the first study investigating the diurnal pattern of overlooking seizures by medical staff during
VEEG. Since there was no diurnal pattern to the overlooking, medical staff should pay equal, 24-
hour attention to patients on VEEG.
Corresponding author: Dr. Kensuke Kawai
Department of Neurosurgery, Jichi Medical University, 3311-1 Yakushiji, Simotsuke, Tochigi 329-0498, Japan.
Tel: +81-285-58-7373, Fax: +81-285-44-5147, E-mail: [email protected]
Epilepsy & Seizure Journal of Japan Epilepsy Society
Vol. 9 No.1 (2017) pp. 1-10
Department of Neurosurgery, Jichi Medical University, Simotsuke, Tochigi, Japan
Abstract
Received: January 7, 2017, Accepted: March 4, 2017
Key words: Epilepsy, seizure, video-EEG, long-term monitoring, presurgical evaluation
Original Article
2
Introduction
Video-EEG (VEEG) monitoring is recom-
mended as the gold standard for diagnosis of
epilepsy, classification of seizures/epilepsy,
and pre-surgical evaluation [1–7]. The opti-
mal duration of VEEG monitoring has not
been determined but it was found to be be-
tween 3 to 6 days in most reported studies to
capture more than one seizure [1, 8–10]. The
optimal protocol for VEEG monitoring, in-
cluding the duration of monitoring and time
of discontinuation of anti-epileptic drugs
(AEDs), also has not been determined. Fur-
thermore, occurrence of seizures, particularly
generalized seizures, during VEEG monitor-
ing may cause major adverse events includ-
ing physical injuries and even death from sei-
zures [3, 7, 9, 11–15]. Medical staff plays
important roles in preventing these events
during VEEG monitoring [11]. Our study
aimed to determine the optimal duration of
VEEG monitoring in patients with epilepsy
by retrospectively analyzing the timing and
pattern of seizure occurrence during VEEG
monitoring. From the view point of safety of
the monitoring, the responses of medical staff
to seizures were also evaluated.
Methods Patients and VEEG data
The data for this study were obtained from
a database of digital EEG and movie files
during VEEG monitoring in the Department
of Neurosurgery at Jichi Medical University.
A list of patients who underwent VEEG dur-
ing the period starting from June 2005 was
constructed by the authors (E.W., K.O.,
H.Y.), which included patients’ names, ID
numbers, and presence or absence of im-
portant events (prominent epileptiform dis-
charges, seizures and suspected seizures) dur-
ing VEEG sessions. The corresponding digi-
tal data of VEEG for 2 h which included each
event were available for review. Not all digi-
tal data throughout each session were availa-
ble because of the limited capacity of hard
disks. VEEG monitoring was performed in
patients with drug-resistant epilepsy to deter-
mine indication for surgical treatment and/or
to localize epileptic focus in presurgical
workup. Three patients who had generalized
epilepsy were excluded from this study.
The list included 120 sessions obtained
from 115 patients during a period of more
than 10 years between June 2005 and July
2016. All the corresponding digital data for
each event were reviewed by one of the au-
thors (A.D.) in terms of whether the event
was a true epileptic seizure based upon EEG
and clinical symptoms. In the case of true ep-
ileptic seizures, they were classified into fo-
cal or generalized seizures. The starting and
ending times for each seizure were deter-
mined. Sessions with only psychogenic non-
epileptic seizures (N = 8) and sessions with-
out any seizures (N = 21) were excluded.
Twenty-five seizures were excluded because
the corresponding 2-h digital EEG file or
movie file was missing. Consequently, 91
sessions with 650 true epileptic seizures ob-
tained from 69 patients were analyzed in the
present study. Four patients had two scalp
EEG sessions and one patient had three scalp
EEG sessions. Eighteen patients had one in-
tracranial EEG session and two patients had
two intracranial EEG sessions. All patients
who underwent intracranial EEG sessions had
preceding scalp EEG sessions.
Video-EEG monitoring for drug-resistant epilepsy Alief Dhuha, et al.
3
VEEG monitoring
A single monitoring room equipped with a
128-channel EEG system and a video camera
(Nihon Kohden® 1100, Tokyo, Japan) was
used. A mobile toilet was placed in the room.
Patients had their meals in the room. On the
first day, scalp EEG was prepared using the
international 10-20 system. Sphenoidal elec-
trodes were used when needed (N = 38). For
intracranial studies, subdural electrodes and/
or depth electrodes were used as indicated.
Patients were instructed to push a nurse-call
button or an EEG-marked button when they
had seizures. There was no accompanying
person during monitoring except visitors. A
video feed was streamed for 24 h in the nurs-
es’ station, but it was not continuously moni-
tored by an assigned observer.
In principle, all AEDs were discontinued on
the day before the start of VEEG monitoring,
all of which were resumed immediately after
termination of VEEG. However, in 14 ses-
sions, some AEDs were continued because
the patients had daily seizures even under
AEDs, and these patients were excluded from
the study of the timing of seizures. Recorded
VEEG data were checked twice a day by the
authors (K.O., H.Y. and A.D.). Important
events were marked in the digital data and
were listed up. There were no strict criteria
for terminating the session, but in principle
VEEG was continued until more than 5 sei-
zures were captured or otherwise for 1 week.
There were no strict criteria for resuming
AEDs either, but in principle pre-monitoring
AEDs were resumed when three seizures
were captured for analysis.
Data acquisition and analysis
For the study on the timing of seizures, we
used 571 seizures in 77 sessions from 58 pa-
tients, after excluding 14 sessions in which
AEDs were not discontinued before the start
of VEEG sessions. The starting time of every
seizure was obtained and expressed as the 24-
hour clock time of a given day. The time of
each day was defined as from 00:00 to 24:00,
and not as the time elapsed from the start of
the session. For a given session, the number
of seizures per hour of each day was counted.
The number of days from the start of a ses-
sion to the first seizure and the number of
days from the first seizure to the third seizure
were determined for each session. Then we
counted the number of sessions during which
the first seizure occurred on each day. Simi-
larly, we counted the number of sessions dur-
ing which the third seizure occurred on each
day from the day of the first seizure. Because
11 patients experienced only one or two sei-
zures during monitoring sessions, the latter
analysis was done using 66 sessions from pa-
tients who had three or more seizures.
To test the hypothesis that patients with a
higher seizure frequency had the first seizure
earlier, we analyzed the association between
seizure frequency and the day of the first sei-
zure. The seizure frequency of each session
was calculated by dividing the total number
of seizures during the session by the number
of days of session. Similarly, we tested the
hypothesis that patients with a higher seizure
frequency had the third seizure after a shorter
duration from the first seizure.
To study the diurnal distribution of seizure
occurrence, we used the above-mentioned
data on the total number of seizures per hour
Epilepsy & Seizure Vol. 9 No. 1 (2017)
4
of each day in all 91 sessions. We used two
methods to evaluate the diurnal distribution.
First, we adopted a method that was used in a
previous study [16]. The 24-h day was divid-
ed into four bins. The summated numbers of
seizures in all 91 sessions in the four bins
were compared. Since the effects of inter-
patient differences in seizure frequency and
session length cannot be avoided in this
method, we compared the diurnal rates of sei-
zure occurrence in each patient. For each pa-
tient, we summated the number of seizures in
all sessions for each hour of the day, and de-
termined the rate of seizure occurrence in the
given bins of that day.
Whether any nurse and/or doctor appeared
in the movie during seizure was also checked.
When they were observed on the video, the
seizure was regarded as response positive.
Response negative was defined as when nei-
ther a nurse nor a doctor appeared in the
movie from the start to finish of a seizure.
The diurnal distribution of response to sei-
zures was evaluated. For each time bin, the
summated numbers of response-positive sei-
zures and response-negative seizures were
determined using all session data. The null
hypothesis was that the numbers are equally
distributed in all time bins.
Statistical analysis
Student’s t-test was used for the compari-
son of seizure frequency between the patient
groups in which patients had the first seizure
before and after a given day, and between the
patient groups in which patients had the third
seizure before and after a given number of
days following the first seizure. Repeated
ANOVA was used for the comparison of sei-
zure occurrence during four time bins in 24 h.
The Wilcoxon sign rank test was used for
comparison of seizure occurrence during two
bins in 24 h. IBM® SPSS® 20 was used for
the above-mentioned statistical tests.
Results Patients, VEEG sessions and seizures
We retrospectively analyzed all VEEG ses-
sions in our department for an approximately
10-year period. There were 91 sessions ob-
tained from 69 patients. The median age of
the patients was 31 years (range, 8 to 63
years). Thirty-nine of 69 were males. The
median duration of VEEG sessions was 5
days (range, 1 to 13 days). Six hundred and
fifty seizures were captured in 91 sessions of
the 69 patients. One hundred and seventy-
three were generalized seizures and 477 were
focal seizures. The median number of all sei-
zures in a session was 6 (range, 1 to 38). The
median numbers of generalized and focal sei-
zures were 1 (range, 0 to 22) and 4 (range, 0
to 23), respectively.
Timing of seizure occurrence
Figure 1A demonstrates the day of occur-
rence of the first seizure. The peak number of
first seizures was observed on the second day
and the number gradually decreased thereaf-
ter. The median days from the start of VEEG
to the first seizure was 2 (range, 1 to 10).
Seventy-seven percent of seizures had oc-
curred by the third day. Figure 1B demon-
strates the day of occurrence of the third sei-
zure after the first seizure. The peak number
of the third seizure was again observed on the
second day and the number decreased abrupt-
ly thereafter. The median number of days
from the first seizure to the third seizure was
Alief Dhuha, et al. Video-EEG monitoring for drug-resistant epilepsy
5
2 (range, 1 to 8). Eighty percent of seizures
had occurred by the third day after the first
seizure.
To provide an overview of the association
between the timing of the first seizure and
seizure frequency in a given session, all ses-
sions are plotted in Fig. 2A. The first seizure
tended to occur earlier in sessions with higher
seizure frequencies. To confirm this tenden-
cy, we compared the seizure frequency be-
tween sessions with the first seizure before
and after a given day. We found that seizure
frequency was significantly higher in sessions
with the first seizure occurring before the sec-
ond or third day than in sessions with the first
seizure occurring after those days.
A similar analysis was performed for the
day of occurrence of the third seizure (Fig.
2B). We found that seizure frequency was
significantly higher in sessions with the third
seizure occurring before the second or third
day after the first seizure than in sessions
with the third seizure occurring after those
days.
Epilepsy & Seizure Vol. 9 No. 1 (2017)
Figure 1. Times of occurrence of the fir st seizure and the third seizure. A. Day of occurrence of the fir st seizure. Line graph shows the cumulative percentage of first seizures on each day of monitoring. Bar graph shows the number of first seizures that occurred on each day of monitoring. B. Day of occurrence of the third seizures. Line graph shows the cumulative percentage of third seizures on each day after the first seizure. Bar graph shows the number of third seizures that occurred on each day after the first seizure.
Figure 2. Association between seizure frequency and timing of the fir st seizure (A) and third seizure (B). All sessions were plotted using the days of the first and third seizures (X axis) and mean seizure frequencies per day (Y axis).
A B
A B
6
Diurnal pattern of seizure occurrence
While there were two peaks; between 6 am
and 7 am and between 6 pm and 7 pm, in the
occurrence of focal seizures, there was no
apparent peak in the occurrence of general-
ized seizures (Fig. 3). Reflecting the peaks in
focal seizures, the total number of seizures
demonstrated two peaks in the same hours.
Although seizure occurrence was apparently
higher from midnight to early morning than
during daytime, we did not detect a statisti-
cally significant diurnal pattern of the occur-
rence of total seizures, generalized seizures or
focal seizures.
Response of medical staff
Twenty percent of 173 generalized seizures
and 69% of 477 focal seizures were over-
looked by medical staff. Figure 4A demon-
strates the diurnal distribution of total and
overlooked generalized seizures. Figure 4B
demonstrates the diurnal distribution of the
rate of overlooking generalized seizures.
While there were apparently peaks between 1
pm and 2 pm and between 8 pm and 9 pm,
the rate varied prominently during a 24-h pe-
riod. We did not detect a significant diurnal
pattern in overlooking of generalized sei-
Alief Dhuha, et al. Video-EEG monitoring for drug-resistant epilepsy
Figure 3. Diurnal pattern of seizure occurrence. The summated numbers of seizures of all sessions during each hour are demonstrated. Triangular, cir-cle, and square marks are total number of seizures, number of generalized seizures, and number of focal seizures, respectively. ‘x’ denotes hour x to x+1; for example, hour 0 denotes 0:00 to 1:00.
Figure 4. Diurnal pattern of medical staff re-sponse to generalized seizure. A. The numbers of generalized seizure and overlooked generalized sei-zure during each hour. B. The rate (%) of overlook-ing of generalized seizure during each hour.
A
B
A
B
Figure 5. Diurnal pattern of medical staff re-sponse to focal seizure. A. The numbers of focal seizure and overlooked focal seizure during each hour. B. The rate (%) of overlooking of focal seizure during each hour.
7
zures. The lack of diurnal pattern in over-
looking was clearer for focal seizures (Fig.
5A, B). Again, we did not detect a significant
diurnal pattern in overlooking of focal sei-
zures. Another significant finding was that
the overlooking rates were much higher for
focal seizures than generalized seizures over
24 h.
Discussion The optimal duration of VEEG monitoring
has not been determined but most studies re-
ported between 3 and 6 days to capture more
than one seizure [1, 9, 10]. Capturing one sei-
zure may be enough to rule out non-epileptic
seizures or to make a diagnosis of epilepsy,
but is not regarded sufficient for presurgical
evaluation. Many researchers have recom-
mended that at least three seizures are re-
quired to properly locate the epileptic region
[8, 9, 14, 17, 18]. Therefore, we investigated
the times of occurrence of the first seizure
and third seizure. The occurrence of the first
seizure declined steeply after 5 days. Seventy
-seven percent of first seizures occurred by
the third day. Eighty percent of third seizures
occurred by the third day after the first sei-
zure. Eighty percent of third seizures oc-
curred by the fifth day of VEEG monitoring.
Knowledge of these patterns of occurrence is
useful to avoid meaningless continuation of
VEEG and to save medical resources.
VEEG has been regarded as the gold stand-
ard for diagnosis and classification of epilep-
sy and presurgical evaluation. Therefore,
nearly all previous retrospective studies on
the usefulness or optimal duration of VEEG
monitoring included a variety of patients with
various purposes for performing VEEG [8,
10]. However, inclusion of diverse patients
with various purposes of VEEG may increase
the variability of the time of seizure occur-
rence. Alving and Beniczky [8] reported that
the duration of successful VEEG monitoring
was significantly longer in the presurgical
group (mean: 3.5 days) than in the diagnostic
and classification groups (2.4 and 2.3 days,
respectively). More recently, Hupalo et al.
[10] reported that VEEG should last at least
72 h in patients with refractory epilepsy,
while most of the cases with psychogenic non
-epileptic seizures could be diagnosed after
48 h. A non-uniform regimen of AED dose
reduction or discontinuation during VEEG
monitoring in previous studies also may have
resulted in greater variability of the time of
seizure occurrence [10, 19]. Our study was
unique and strong in that the patient cohort
was considerably uniform because VEEG
was performed solely for presurgical evalua-
tion in patients with drug-resistant partial epi-
lepsy, and AED was discontinued in all pa-
tients one day before the start of VEEG.
To taper or withdraw AEDs before VEEG
monitoring facilitates recording of seizures
sooner or in larger numbers [10, 20]. Our
findings on the association between the time
of occurrence and the frequency of seizures
support this finding. In one study in which
60% of patients had AEDs reduced by half
but none discontinued AEDs totally, only
15% of epileptic seizures occurred within the
first 24 h of long-term VEEG monitoring
(53% and 32% on the second and third day,
respectively) [10]. In contrast, in our study,
seizure occurrence was higher from the be-
ginning of monitoring, considering that we
started VEEG in the afternoon of the first day
Epilepsy & Seizure Vol. 9 No. 1 (2017)
8
and that the first day represented less than 24
h.
Importantly, tapering or withdrawal of
AEDs has been believed to be potentially
dangerous, as it carries a 3% risk of status
epilepticus or cluster seizures [4, 13, 21, 22].
Therefore, most epilepsy centers gradually
taper or partially discontinue AEDs [10, 19].
There were no previous studies in which all
AEDs were discontinued before the VEEG
admission. Interestingly, we and a number of
other authors observed no complications re-
lated to discontinuation or dose reduction of
AEDs [2, 9, 10, 18, 19, 21–25]. However, it
is too early to conclude that we can discontin-
ue all AEDs from our single series of VEEG
monitoring. It is highly probable that frequen-
cy of seizure and risk of status epilepticus are
dependent on pre-VEEG seizure frequency,
semiology of each patient, and medication
regimen. There is also the concern that dis-
continuing all AEDs may increase the epilep-
tic activity of various brain regions too exten-
sively, making it difficult to properly localize
the true epileptic focus to be surgically treat-
ed.
While seizure prevalence associated with
the wake-sleep cycle has been studied exten-
sively, studies on the diurnal pattern of sei-
zure occurrence are limited. Hofstra et al.
[16, 26] reported that more seizures were ob-
served from 11:00 to 17:00, and fewer sei-
zures from 23:00 to 05:00. They suggested
that certain types of seizures have a strong
tendency to occur in a truly diurnal pattern.
However, they tested the diurnal pattern only
by comparing the total number of seizures
from all patients for a 5-year period in four
bins of 24 h. We did not detect any signifi-
cant diurnal pattern by using more extensive
testing applied to a more homogeneous pa-
tient group. Therefore, at least in partial epi-
lepsy, it is unlikely that seizure occurrence
has a clear diurnal pattern.
Our study is the first to examine the diurnal
pattern of overlooking seizures by medical
staff. In our center, there are three meal times
in a day; 7:30 for breakfast, 11:30 for lunch
and 18:30 for dinner. Nurses are busiest at
those times. Interestingly, the peaks of over-
looking seizures did not coincide with those
busiest hours. It is noteworthy that 20% of
generalized seizures and 69% of focal sei-
zures were overlooked by medical staff.
Spanaki et al. [24] reported that focal seizures
had a tendency to be missed by medical staff
during VEEG sessions due to difficulties in
visual detection. Improvement in detection
measures for generalized and focal seizures
may improve the safety of VEEG and save
medical resources by avoiding futilely
lengthy VEEG.
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