Epilepsy & Behavior 28 (2013) S30S39

Contents lists available at SciVerse ScienceDirect

Epilepsy & Behavior

journal homepage: www.elsevier.com/locate/yebeh

Review

Neurophysiology of juvenile myoclonic epilepsy

Anna Serani a, Guido Rubboli b, c, Gian Luigi Gigli a, Michalis Koutroumanidis d, Philippe Gelisse e, f,
a
Center of Sleep Medicine, Neurology Unit, University-Hospital S. Maria della Misericordia, Udine, Italy
b
Neurology Unit, IRCCS Institute of Neurological Sciences, Bologna, Italy
c
Danish Epilepsy Center, Epilepsihospitalet, Dianalund, Denmark
d
Department of Clinical Neurophysiology and Epilepsies, Guy's & St Thomas' NHS Foundation Trust, London, UK
e
Epilepsy Unit, Hpital Gui de Chauliac, Montpellier, France
f
Research Unit Movement Disorders (URMA), Department of Neurobiology, Institute of Functional Genomics, CNRS UMR5203-INSERM U661-UM1, Montpellier, France

a r t i c l e i n f o a b s t r a c t

Article history: Juvenile myclonic epilepsy (JME) can be rmly diagnosed by a careful interview of the patient focusing on the
Accepted 19 November 2012 seizures and by the EEG with the help, if necessary, of long-term video-EEG monitoring using sleep and/or sleep
deprivation. Background activity is normal. The interictal EEG shows diffuse or generalized spike-wave (SW) and
Keywords: polyspike-wave (PSW) discharges. In some patients, non-specic changes or misleading features such as focal
Juvenile myoclonic epilepsy
changes are found. Changes are mostly seen at sleep onset and at awakening. Provoked awakenings are more likely
Myoclonic jerks
EEG
to activate interictal paroxysmal abnormalities than spontaneous awakenings. The presence of a photoparoxysmal
Neurophysiology response with or without myoclonic jerks (MJ) is common (30% of the cases). Myoclonic jerks are associated with a
Sleep discharge of fast, irregular, generalized PSWs that predominate anteriorly. Myoclonic jerks appear to be associated
Sleep deprivation with rhythmic EEG (spike) potentials at around 20 Hz. These frequencies are in the range of movement-related
fast sensorimotor cortex physiological rhythms. The application of jerk-locked averaging technique has provided
ndings consistent with a cortical origin of MJ. Paired TMS (transcranial magnetic stimulation) studies showed
a defective intracortical inhibition, due to impaired GABA-A mediated mechanisms. In this review, we present the
EEG characteristics of JME with particular emphasis on the pathophysiology of MJ and on the role of sleep depriva-
tion on interictal and ictal changes.

This article is part of a supplemental special issue entitled Juvenile Myoclonic Epilepsy: What is it Really?
2012 Elsevier Inc. All rights reserved.

1. Introduction 2. Neurophysiological characteristics during wakefulness

Juvenile myoclonic epilepsy (JME) is the most common type of
idiopathic generalized epilepsy (IGE) and accounts for 26.7% of IGE
and 4.1% of all epilepsies [1]. The EEG discloses a normal background ac-
tivity and typical interictal fast spikewaves (SW) and polyspikewaves
(PSW). Changes are mostly seen at sleep onset and at awakenings
(Fig. 1). In some patients, the EEG remains normal, even during long
recordings. In some patients, non-specic changes or misleading features
such as focal changes are found. The presence of a photoparoxysmal
response during intermittent light stimulation (ILS) is common (30% of
the cases). Electroencephalography remains the most useful assessment
of patients suspected of having JME. In this review, we present the EEG
characteristics of JME with particular emphasis on the pathophysiology
of myoclonic jerks (MJ) and the role of sleep and sleep deprivation on
ictal and interictal changes.
Corresponding author at: Explorations Neurologiques et Epileptologie, Hpital
Gui de Chauliac, 80 avenue Fliche, 34295 Montpellier cedex 05, France. Fax: +33 4 67
33 61 00.
E-mail address: p-gelisse@chu-montpellier.fr (P. Gelisse).
2.1. Background activity
Background activity in IGE is generally reported as being within
normal limits [25]. Genton et al. [6] observed abnormal background
activity in 8% of their cases, always during a period of inadequate
seizure control but all with normal subsequent tracings. Quantitative
EEG (qEEG) analysis of background activity has shown that, in spite of
normal visual analysis of background EEG in patients with JME, there
is an increase in absolute power (AP) of delta, alpha, and beta bands,
which is more evident in frontoparietal regions [7].
2.2. Paroxysmal interictal activity
Electroencephalography features of JME are characterized by PSW,
consisting of slow wave preceded by three or more spikes, often with
fronto-central accentuation [2,6]. Other occasional EEG ndings
include SW at 2.53.5/s (classical pattern) or >3.5/s (fast pattern),
single spikes, and irregular SW complex [8,9]. Classical 3-Hz SW

1525-5050/$ see front matter 2012 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.yebeh.2012.11.042
 A. Serani et al. / Epilepsy & Behavior 28 (2013) S30S39 S31

Fig. 1. 17-year-old woman. EEG (International 1020 electrode system with supplementary anterior/inferior temporal electrodes (TA1, T1, TA2, and T2); right deltoid and left
deltoid). On the left side of the plate, drowsiness with slow eye movements can be seen on the fronto-polar derivations. There is a burst of diffuse spikewaves. The second abstract
was recorded immediately upon awakening. The EEG changes are activated, with generalized polyspikewaves. Right abstract: watching a Japanese cartoon on television triggers a
discharge consisting of polyspikewaves associated with two myoclonic jerks seen on the deltoid muscles.

complexes or 3-Hz PSW complexes, characteristic of typical absence
seizures, occur in approximately 17% of EEGs.
The percentage of EEG with epileptiform abnormalities varies
across studies. Many patients affected by JME may present a normal
EEG pointing out the fact that a normal EEG does not exclude a diag-
nosis of JME. Genton et al. [10] found that routine EEGs were normal
in 27% of cases, misleading or non-specic in 20% and showed typical
changes in 54%. Other studies reported percentages of abnormalities,
consisting of generalized discharges of PSW or SW complex, ranging
between 75% and 85% [11,12].
Focal discharges may also be found among patients with JME
(Fig. 2), leading to an erroneous diagnosis of focal epilepsy. The
percentage of localization-related EEG abnormalities or asymmetrical
changes ranges from 6 to 40%; prolonged recordings offer a better
chance of revealing asymmetrical paroxysms. Aliberti et al. [13]
studied 49 EEGs in 22 patients and found a high prevalence of focal
abnormalities. Focal slow waves, spikes, sharp waves, and focal onset
of the generalized discharges were present in 36.7%. In the series by
Lancman et al. [14], 16.5% of 85 patients presented EEG asymmetries,
switching sides in about 80% of cases. Genton et al. [6] reported,
among a cohort of 85 patients, focal/asymmetrical changes that could
change from one hemisphere to the other during the same recording
in 15%. The same team evaluated the sensitivity of 20-minute standard
EEG in 56 consecutive newly referred patients with JME and found
focal or asymmetrical slow waves in 20% [10]. Later studies reported
percentages of asymmetries of 20.6% [15], 19.7% [16], and 38.1% [17].
Evaluating EEG features of 58 patients with IGE monitored for almost
20 years, Lombroso et al. [18] observed that only 15% of patients with
JME developed focal abnormalities; none of them presented such
ndings in early recordings. Dhanuka et al. [19] found focal discharges
on routine EEG in 6% of patients. Jayalakshmi et al. [20] reported
asymmetric or focal abnormalities in 45.5% of 266 patients with JME
after sleep deprivation (4-hour sleep deprivation in the preceding
24 h; EEG recordings: 20-min sleep followed by 20-min awake or
40-min awake). In addition to generalized and/or focal changes, other
occasional EEG ndings consist of diffuse or intermittent slowing,
associated or not associated with generalized spikes [8,11,17]. These
abnormalities are observed in 611% of patients [12,17].
The paroxysmal EEG discharges of patients with IGE may often show
circadian uctuations. A study performing routine EEG among patients
with JME demonstrated a higher rate of epileptiform discharges in the
morning hours, regardless the awake, asleep, or awakening state [21]
(Fig. 1). Labate et al. [22] reported a signicantly greater rate of detec-
tion of generalized epileptiform abnormalities by performing standard
awake EEG in the morning in comparison with an afternoon session.
Thus, it seems that the distribution of epileptiform discharges follows
the circadian distribution of seizures among patients with JME [23].
Another study found that patients with JME may present an altered
circadian lifestyle, being more active in the evening, thus the denition
of evening types [24]. The authors concluded that the functional
morning impairment of patients with JME may be the consequence
of subclinical epileptic activity. On the contrary, as a consequence
of rigid wake time in the morning for social requirements, it is also
possible that eveningness may result in a chronic sleep deprivation.
In this case, the morning activation of seizures and interictal EEG
abnormalities could be the consequence, at least in part, of a sleep dep-
rivation. Therefore, it is not clear if epileptiform activity in the morning
is the cause or the consequence of impaired vigilance.
Unusual rhythms (wicket spikes, six-hertz spike-and-wave burst)
can be observed in patients with JME like in other patients (Fig. 3).
Wicket patterns or temporal sharp waves are often misinterpreted
as epileptogenic and can lead to an incorrect diagnosis of IGE and
S32 A. Serani et al. / Epilepsy & Behavior 28 (2013) S30S39
Fig. 2. 15-year-old man. Awakening period. Coexistence on the same plate of focal or asymmetrical polyspike-wave/sharp waves (gray area) and generalized spikewaves.
prescription of inappropriate antiepileptic drugs [25]. The morphology
of these paraphysiological elements must be known to avoid a wrong
diagnosis of the type of epilepsy.
2.3. Photosensitivity
Juvenile myclonic epilepsy is the epilepsy syndrome with the closest
relation with photosensitivity. The presence of a photoparoxysmal re-
sponse with or without MJ provoked by ILS is frequent (Figs. 1 and 4).
It is particularly interesting to do ILS during the awakening period. In
170 patients with JME (104 females and 66 males), a photoparoxymal
reaction was found in 38% of cases, higher in females (48%) than in
males (26%) [1].
3. Neurophysiological characteristics during sleep
Routine EEGs may often miss the correct diagnosis due to the
absence of the typical EEG features [17,19,26]. Many EEGs indeed
can be normal, thus the need of performing activating procedures.
One of them, commonly used in the clinical setting, is the recording
of sleep, which may help in conrming the diagnosis when routine
EEGs are normal or non-specic. Billiard [27] found an increase in
epileptic discharges at sleep onset, in light slow sleep among 77 patients
with generalized tonic-clonic seizures. They noted discharges in REM
sleep. In this study, the patients with JME had epileptic discharges at
sleep onset, at sleep arousals, and, sometimes, in REM sleep. Salas
Puig et al. [28] conducted a study using polygraphic tracing of sleep
during a nap period and documented that sleep EEGs were abnormal
in all patients with JME. Indeed, for IGE, the interictal discharges
increase in frequency during sleep and are more frequent than in
wakefulness. On the other hand, in REM sleep, the discharges decrease
or cease. Transitional periods of sleep and arousals are strong activators.
Induced sleep awakenings were stronger activators than spontaneous
awakenings, regardless of the sleep stages at which the awakenings
occurred [29].
Dhanuka et al. [19] studied 15 patients with JME. In all sleep
recordings, generalized epileptiform discharges were found. Discharges
were characterized by spikes, polyspikes, and slow-wave discharges
which were usually frontal predominant. The authors also analyzed
the different distribution of epileptiform abnormalities between sleep
stages. The discharge rate (the number of discharges per hour) was
higher during the transition phase (1 h prior to nal awakening and
in the rst half an hour after awakening) when compared with any
other stage of sleep. The transition from the asleep to awake state
caused an increase in discharge rate, and the transition to slow wave
sleep suppressed the number of discharges. These results show how
 A. Serani et al. / Epilepsy & Behavior 28 (2013) S30S39 S33

Fig. 3. 36-year-old man. EEG (15 mm/s; 10 V/mm; International 1020 electrode system with supplementary anterior/inferior temporal electrodes (TA1, T1, TA2, and T2); right
deltoid and left deltoid). NREM sleep stage II. Arciform waves can be seen over the left temporal region with phase reversal at F7T3 (gray area). Theses waves correspond to wicket
spikes. Wicket spikes do not evoke epileptiform activity. They are considered paraphysiological. At the end of the plate, generalized spikewave.

epileptiform discharges of patients with JME are deactivated by deep
stages of sleep. This suppression of discharges during sleep could
partially explain the lack of JME manifestations during sleep, while
the increase of discharges at the transition from sleep to wake explains
the occurrence of seizures after awakening.
4. Ictal activity
Myoclonic jerks are associated with brief 10- to 27-Hz runs
of spikes followed by irregular slow waves (Figs. 1, 4, and 5). The
number of spikes ranges from 5 to 20 per discharge and correlates
with the intensity rather than the duration of each seizure [30]. The
amplitude of the spikes is progressively increasing and is maximal
over the frontal leads, where it can range from 200 to 300 V. This
polyspike discharge is followed or preceded by brief runs of slow
waves of frequency about 34 Hz, resulting in a PSW complex lasting,
therefore, around 24 s. Polygraphic recordings of EMG activity over
the deltoid muscles may record clinically unseen myoclonias.
Myoclonic jerks occur mostly in the morning soon after awakening
or during intermediate awakenings. Myoclonic jerks may be seen
during REM sleep in patients who exhibit interictal changes during
this sleep stage [29]. Typical absences occur in 1020% of cases
(56/170 cases, 33% in the series of Genton et al. [1]). They are usually
short and according to Panayiotopoulos [32] are different from those
observed in childhood absence and juvenile absence epilepsy. For
this author, they consist of spike/double/treble or polyspikes usually
preceding or superimposed on the slow wave. When a generalized
tonic-clonic seizure is preceded by myoclonic jerks, the EEG shows
bursts of irregular fast PPS prior to onset of the usual pattern of
generalization (Fig. 6).
S34 A. Serani et al. / Epilepsy & Behavior 28 (2013) S30S39
Fig. 4. 16-year-old woman. Arms raised (picture A). Intermittent light stimulation triggers two bursts of polyspikewaves associated with myoclonic jerk (*). The rst myoclonia is
clearly visible on the right deltoid. The second myoclonia (picture B) is more ample.
4.1. Polygraphic ndings and EEGEMG correlations
In patients with JME, epileptic myoclonus usually occurs in brief
irregular bursts, which mainly involve the upper limbs. Myoclonic
jerks, as well as the related EEG polyspikewave complexes, are
assumed to be strictly synchronous bilaterally but not necessarily
symmetrical [33] (Fig. 4). Myoclonic jerks are associated only with
PSW discharges whereas the SW complexes are devoid of any
motor correlate [30,31]. Computerized analysis of the polygraphic
tracings showed that the polyspike component of the PSW complex
consisted of a short train of quasi-rhythmic 16- to 27-Hz spikes
[31] (Fig. 7). These frequencies are in the range of movement-
related fast central rhythm observed in healthy subjects [34] and
similar to those of myoclonus-related EEG activities recorded
from the sensorimotor cortex of patients with symptomatic cerebral
nervous system disorders [35,36]. Observations demonstrating a
facilitation of 20-Hz rhythmic activity by paired TMS (transcranial
magnetic stimulation) in patients with progressive myoclonus
epilepsies further support a relationship between sensorimotor fast
frequencies and abnormal motor function [37]. The application of
jerk-locked averaging technique has provided ndings consistent
with a cortical origin of MJ in JME. In fact, the onset of the EMG
burst recorded on deltoid muscles followed the positive component
of the time-locked EEG spike with a latency of approximately
1011 ms [31], similar to that measured in healthys subjects
between cortical magnetic stimulation and activation of the contra-
lateral deltoid (Fig. 7). The detection of an interhemispheric time
interval of about 10 ms between the positive peak of the averaged
jerk-locked spike recorded on the two hemispheres suggested a
lateralized onset of the EEG transient leading to the MJ; this latency
ts with the time required for interhemispheric propagation through
the transcollosal pathway [35,38]. Analogously, the same latency was
measured between the muscle activation on the two sides of the
body, which was due to the earlier activation of the deltoid contralateral
to the leading EEG peak. These ndings indicate that jerk-related corti-
cal activity in JME occurs from one hemisphere then spreads to the
other, as it has been described in spontaneous and stimulus-induced
myoclonus that characterizes symptomatic or progressive myoclonic
syndromes [35,39]. Recently, a localized onset of EEG epileptic activities,
as well as the involvement of a restricted cortical network during
discharge propagation including frontal and temporal cortices, has
been reported [40].
 A. Serani et al. / Epilepsy & Behavior 28 (2013) S30S39
Fig. 5. 18-year-old man. EEG (15 mm/s; 10 V/mm; International 1020 electrode; right deltoid and left deltoid). After a night sleep recording, spontaneous awakening. A: background
activity with an alpha rhythm. B: polyspikewaves with myoclonic jerks that can be seen on the deltoid muscles.
4.2. Cortical excitability in JME
Although some ndings suggest that the ultimate mechanisms re-
sponsible for ictal MJ in JME are similar to those found in more severe
pathological conditions such as progressive myoclonic epilepsies,
in which myoclonus is primarily due to a neocortical generator, the
study of cortical excitability by means of paired TMS has revealed
interesting differences between the two conditions. Indeed, by de-
livering paired magnetic stimuli at variable interstimulus intervals
(ISI), it is possible to explore early (with ISIs of 15 ms) and late
(with ISIs of 50400 ms) intracortical inhibition, mediated respec-
tively by GABA-A and GABA-B receptors. Present data indicate
that GABA-A-mediated inhibition, with preserved GABA-B-mediated
inhibitory mechanisms, characterizes JME [41,42], whereas in pro-
gressive myoclonic epilepsies, defective GABA-B-mediated inhibitory
processes underlie the abnormal cortical hyperexcitability [37,42]. In
addition, the demonstration that cortical excitability in JME increases
early in the morning might explain the enhanced seizure susceptibili-
ty on awakening of patients with JME [43].
Transcranial magnetic stimulation has also been used to study
cortical excitability in the broader context of IGE, and studies have
demonstrated a lower motor threshold in these patients. Among
patients with IGE, studies in patients with JME conrmed a lack of
cortical inhibition. In patients with JME there were two indications
of abnormality with respect to healthy subjects and to the other
patients with epilepsy: (1) the absence of motor-evoked potential
(MEP) suppression to paired stimulation and (2) a progressive ampli-
tude increase of motor-evoked potentials to the test stimulus alone.
In the two patients with the other form of epilepsy, the pattern of in-
hibition was broadly preserved, even though there was some
difference from the normal prole. The results suggest that the loss
of MEP inhibition can be regarded as a marker of JME [44].
S35
5. Sleep deprivation
5.1. The effect of sleep deprivation
Sleep deprivation (SD) itself may result as an activating factor for
the appearance of paroxysmal activity or seizures even in people
without epilepsy [45,46]. From these observations, SD seemed to be
capable of inuencing ictal or interictal epileptic activity and to be a
powerful activator of seizures in all types of epilepsy. Therefore, it
started being used in clinical settings as an activating procedure on
the occasion of EEG recordings, in patients suspected of having epi-
lepsy, but negative on routine EEG. In a review published in 2000,
Marinig et al. [47] reported that the percentage of EEG with epileptic
activity was higher among sleep recordings after SD. This percentage
was higher than those recordings obtained during waking after SD.
Many variables may inuence the effect of SD on EEG activity,
which include, primarily, the duration and the degree of the SD. The
very rst studies indicated 24-h SD as the most effective procedure.
However, later on, it has been shown that even partial SD can activate
EEG activity [48,49]. The effect of the specic deprivation of one par-
ticular sleep stage has also been studied. The selective deprivation
of NREM sleep showed no effect on generalized discharges, while
selective REM deprivation determined an increase of generalized
discharges [50]. Another factor increasing the diagnostic yield of SD
on EEG is the duration of EEG recordings: prolonged recordings in
fact, offer a better chance of revealing paroxysms.
The most important factor inuencing the effect of SD on the EEG
is the type of epilepsy. Indeed, SD is especially able to activate gener-
alized discharges of IGE. In particular, the most important effect is
seen on awakening epilepsies [5153]. Among those types of epilep-
sies, JME seems to be particularly sensitive to the activating effects of
SD. Indeed, both wake and sleep EEG recorded after sleep deprivation
S36 A. Serani et al. / Epilepsy & Behavior 28 (2013) S30S39

Fig. 6. 38-year-old man. EEG (15 mm/s; 10 V/mm; International 1020 electrode system with supplementary anterior/inferior temporal electrodes (TA1, T1, TP1, TA2, T2, and
TP2). The patient was sleep-deprived, went to sleep at 2 A.M. and was awakened at 6 A.M. A few minutes after awakening, he began having myoclonic jerks. There are bursts of
generalized polyspikes with salvos of myoclonic jerks. At the 8th second, onset of the tonic-clonic seizure with generalized recruiting spikes predominating anteriorly with
rapid superposition of muscular artifacts. It is a typical myoclono-tonico-clonic seizure.

demonstrated an activation of paroxysmal discharges [47]. The activa-
tion after sleep deprivation is seen both in the discharge index and in
the discharge duration [26].
5.2. Sleep dependent mechanism
It has been suggested that the activation after SD might be due to
an increased sleepiness, rather than to a direct activation of discharge
frequency [54]. In a study investigating the effect of SD on spike-wave
discharges in patients with IGE, the highest activation of epileptiform
discharges was seen during supercial sleep following SD. Sleep after
SD determined an increase in SW discharge densities in all vigilance
levels including also the awake state. The highest degree of activation
was observed during supercial sleep stages (NREM1 and NREM2)
[55]. Subsequent studies have analyzed this activating effect of sleep
following SD and hypothesized that the activating effect may be
related to the vigilance uctuations between wake and sleep and to
the dynamic changes of sleep stages, rather than to sleep itself. The
discovery of arousals during sleep allowed a better understanding
of this phenomenon. The American Sleep Disorder Association de-
scribed the arousals as an abrupt shift in EEG frequency, which may
include theta, alpha, and/or frequencies greater than 16 Hz but not
spindles [56,57]. Passouant et al. [58] were the rst to report a rela-
tionship between epileptic discharges and phasic sleep phenomena,
the K-complexes. They observed that patients tend to have bursts of
spikes and spikewaves in association with K-complexes and intro-
duced the term epileptic K-complex. Niedermeyer [59] studied the
association of arousal responses and generalized epileptic discharges
in the context of awakening epilepsy and concluded that arousing
stimuli represent an important mechanism in the precipitation of epileptic
discharges as well as clinical seizures.
Terzano et al. [60] identied and named periodic and physiologic
uctuations of the level of EEG activation of NREM sleep: the cyclic
alternating pattern (CAP). Within these uctuations, two alternating
phases can be distinguished: phase A (CAP A) that reects enhanced
vigilance and can be composed (depending on the sleep stage) of
slower high voltage rhythms, faster lower voltage rhythms, or
mixed patterns including both and phase B (that of reduced arousal)
which consists of low voltage uneventful activity. Cyclic alternating
pattern sequences correspond to periods of sustained sleep instability
as a homeostatic physiologic response to endogenous stimuli. The
number of CAP periods during NREM sleep identies the CAP rate,
a marker of sleep instability. Parrino et al. [61] demonstrated that
the CAP rate is higher in morning sleep after SD due to the outcome
of the two opposite tendencies of high sleep pressure (homeostatic
inuence) and of propensity to wakefulness (circadian inuence).
When studying the relationship between epileptic discharges of pa-
tients with IGE and hypnic microstructure, it has been demonstrated
that the maximal activation of the generalized epileptic paroxysms
occurs during the A phases of CAP [62]. The same relationship was
found among patients with JME [63], suggesting that CAP A is the
window through which epileptiform activity passes more easily,
while CAP B is the phase of increased (rebound) inhibition. A recent
study on 19 patients with JME showed that in the patients with poorly
controlled seizures (but not in those who were either symptom-free
or had only occasional MJ), generalized PSW discharges seem to
 A. Serani et al. / Epilepsy & Behavior 28 (2013) S30S39 S37

Fig. 7. EEGEMG correlations of the polyspike activity of the polyspike wave complex and myoclonic jerks. In the upper panel, the inset indicates a brief polyspike discharge, at a
frequency around 20 Hz, encompassed in a slow wavepolyspike slow wave complex in F3. In the lower panel, the inset is enlarged and EMG leads are included. Each myocolonic
jerk was time-locked to the positive component (arrow) of each spike of the polyspike discharge. The latency between the positive component and the myoclonic burst in the right
deltoid and the latency between myoclonic bursts in the right deltoid and in the right wrist extensor were consistent with propagation along fast conductiong cortico-spinal path-
ways. R: right.
Modied from Panzica et al. [31].

promote transitions from CAP B to CAP A. Results from this study
support the hypothesis that increased epileptic pressure may cause
disruption of the inhibitory mechanisms of phase B, increase the CAP
rate by contributing to more A phases, and thereby foster more epilep-
tiform discharges through the CAP A window. In other words, there
seems to be an epileptic positive feedback with clinical correlates:
increased seizure activity is associated with enhanced intrusion of
spike-wave activity into phase B of CAP sleep, increased CAP rate,
more epileptiform discharges and by implication higher probability
of having more seizures. Increased electrographic awakenings frag-
ment sleep and may independently contribute to the clinical deterio-
ration by impairing sleep quality [64].
The relationship between arousals and epileptiform discharges has
been partly explained by several studies. The mechanism of sleep
spindles is based on the complex relationship of thalamocortical
corticothalamic and nucleus reticularis thalami neurons switching
to bursting-mode during NREM sleep [65,66]. The recognition that
NREM phasic events (sleep spindles) and slow-wave discharges share
the same thalamocortical network strongly supports the activation of
epileptiform discharges during NREM sleep [67,68].
5.3. Direct consequence of sleep deprivation
Sudies have shown that SD increases cortical excitability and de-
creases the threshold [69,70]. The specic effect of sleep deprivation
on cortical excitability has been studied through TMS a safe probe
of neuronal excitability of the primary motor cortex. The single pulse
technique assesses the threshold to stimulation and the silent period.
Then, the paired pulse method allows measurement of the so-called
intracortical (corticocortical) inhibition.
Transcranial magnetic stimulation showed that sleep deprivation is
associated with changes in the balance between inhibition and facilita-
tion in the primary motor cortex of healthy subjects. These changes
might have a link with the background factors of the activating effects
of SD [71]. Similar results were observed by another study on SD,
where a reduction of epileptic threshold, observed in healthy subjects,
was hypothesized to cause a facilitatory inuence upon seizures in
subjects with epilepsy [72]. In a study by Badawy et al. [73], the authors
compared the effect of sleep deprivation between controls and
patients with different forms of epilepsy. An increased cortical excit-
ability seemed to be more prominent in patients with IGE. In particular,
patients with JME also demonstrated an increased paroxysmal activity
following sleep deprivation [74].
6. Conclusion
In clinical practice, MJ associated with PSW complexes are
the main feature of JME. Juvenile myclonic epilepsy can be easily
and rmly diagnosed by careful interview of the patient focusing
on the seizures and by the EEG, with the help, if necessary, of
long-term EEG-video monitoring using sleep and/or sleep deprivation
recordings.
S38 A. Serani et al. / Epilepsy & Behavior 28 (2013) S30S39
Ethical approval
We conrm that we have read the ethical publication guidelines
for this journal and afrm that this report is consistent with those
guidelines.
Conict of interest statement
Dr. Serani and Dr. Gigli declare that there are no conicts of
interest. Dr. Rubboli has received support from implantable device
companies for teaching programs in 2011 and 2012 (Medtronics,
Cyberonics). Dr. Koutroumanidis has received research support,
funding for travel, and speaker honoraria from UCB and funding for
travel from Eisai. He also had a paid consultancy with Eisai. Dr. Gelisse
has received support from pharmaceutical companies for teaching
programs (Sano-Aventis, UCB). Dr. Gelisse was a paid consultant
for Eisai-France in 2011.
References
[1] Genton P, Gelisse P, Thomas P. Juvenile myoclonic epilepsy today: current deni-
tion and limits. In: Schmitz B, Sander T, editors. Juvenile myoclonic epilepsy: the
Janz syndrome. Peterseld and Philadelphia: Wrightson Medical Publishing; 2000.
p. 1132.
[2] Asconape J, Penry JK. Some clinical and EEG aspects of benign juvenile myoclonic
epilepsy. Epilepsia 1984;25:10814.
[3] Delgado-Escueta AV, EnrileBacsal F. Juvenile myoclonic epilepsy of Janz. Neurology
1984;34:28594.
[4] So GM, Thiele EA, Sanger T, Schmid R, Riviello Jr JJ. Eletroencephalogram and
clinical focalities in juvenile myoclonic epilepsy. J Child Neurol 1998;13:5415.
[5] Genton P, Gelisse P. Juvenile myoclonic epilepsy. Arch Neurol 2001;58:148790.
[6] Genton P, Puig XS, Tunon A, Lahoz C, Sanchez MDSG. Juvenile myoclonic epilepsy
and related syndromes: clinical and neurophysiological aspects. In: Malafosse A,
Genton P, Hirsch E, Marescaux C, Broglin D, Bernasconi R, editors. Idiopathic
generalized epilepsies: clinical, experimental and genetic aspects. London, UK:
John Libbey and Company Ltd; 1994. p. 25365.
[7] Santiago-Rodrguez E, Harmony T, Crdenas-Morales L, Hernndez A, Fernndez-
Bouzas A. Analysis of background EEG activity in patients with juvenile myoclonic
epilepsy. Seizure 2008;17:43745.
[8] Grunewald RA, Panayiotopoulos CP. Juvenile myoclonic epilepsya review. Arch
Neurol 1993;50:5948.
[9] Janz D, Durner M. Juvenile myoclonic epilepsy. In: Engel Jr J, Pedley TA, editors.
Epilepsy: a comprehensive textbook. Philadelphia: Lippincott-Raven; 1998.
p. 2389400.
[10] Genton P, Gonzalez Sanchez MS, Saltarelli A, Bureau M, Ch Dravet, Roger J.
Misleading aspects of standard electro-encephalography in JME. Neurophysiol
Clin 1995;25:28390.
[11] Panayiotopoulos CP, Obeid T, Tahan AR. Juvenile myoclonic epilepsy: a 5-year
prospective study. Epilepsia 1994;35:28596.
[12] Baise-Zung C, Guilhoto LM, Grossmann RM. Juvenile myoclonic epilepsy: non-
classic electroencephalographical presentation in adult patients. Eur J Neurol
2006;13:1715.
[13] Aliberti V, Grnewald RA, Panayiotopoulos CP, Chroni E. Focal electroen-
cephalographic abnormalities in juvenile myoclonic epilepsy. Epilepsia 1994;35:
297301.
[14] Lancman ME, Asconap JJ, Penry JK. Clinical and EEG asymmetries in juvenile
myoclonic epilepsy. Epilepsia 1994;35:3026.
[15] Murthy JM, Rao CM, Meena AK. Clinical observations of juvenile myoclonic
epilepsy in 131 patients: a study in South India. Seizure 1998;7:437.
[16] Atakli D, Sozuer D, Atay T, Baybas S, Arpaci B. Misdiagnosis and treatment in juve-
nile myoclonic epilepsy. Seizure 1998;7:636.
[17] Montalenti E, Imperiale D, Rovera A, Bergamasco B, Benna P. Clinical features, EEG
ndings and diagnostic pitfalls in juvenile myoclonic epilepsy: a series of 63 patients.
J Neurol Sci 2001;184:6570.
[18] Lombroso CT. Consistent EEG focalities detected in subjects with primary general-
ized epilepsies monitored for two decades. Epilepsia 1997;38:797812.
[19] Dhanuka AK, Jain BK, Singh D, Maheshwari D. Juvenile myoclonic epilepsy: a
clinical and sleep EEG study. Seizure 2001;10:3748.
[20] Jayalakshmi SS, Srinivasa Rao B, Sailaja S. Focal clinical and electroencephalo-
graphic features in patients with juvenile myoclonic epilepsy. Acta Neurol Scand
2010;122:11523.
[21] Fittipaldi F, Curr A, Fusco L, Ruggieri S, Manfredi M. EEG discharges on awakening: a
marker of idiopathic generalized epilepsy. Neurology 2001;56:1236.
[22] Labate A, Ambrosio R, Gambardella A, Sturniolo M, Pucci F, Quattrone A. Usefulness
of a morning routine EEG recording in patients with juvenile myoclonic epilepsy.
Epilepsy Res 2007;77:1721.
[23] Janz D. Epilepsy with impulsive petit mal (juvenile myoclonic epilepsy). Acta
Neurol Scand 1985;52:44959.
[24] Pung T, Schmitz B. Circadian rhythm and personality prole in juvenile myoclonic
epilepsy. Epilepsia 2006;47:1114.
[25] Crespel A, Velizarova R, Genton P, Coubes P, Glisse P. Wicket spikes misinterpreted
as focal abnormalities in idiopathic generalized epilepsy with prescription of carba-
mazepine leading to paradoxical aggravation. Neurophysiol Clin 2009;39:13942.
[26] Sousa NA, da Silva Sousa P, Garzon E, Sakamoto AC, Braga NI, Yacubian EM. EEG
recording after sleep deprivation in a series of patients with juvenile myoclonic
epilepsy. Arq Neuropsiquiatr 2005;63:3838.
[27] Billiard M. Epilepsies and the sleep-wake cycle. In: Sterman MB, Shouse MN,
Passouant P, editors. Sleep and epilepsy. New York: Academic Press; 1982. p. 26989.
[28] Salas Puig J, Tunon JA, Mateos V, Guisasola LM, Lahoz CH. Janz's juvenile myoclonic
epilepsy: a little known frequent syndrome. Med Clin 1994;103:6849.
[29] Touchon J. Effect of awakening on epileptic activity in primary generalized
myoclonic epilepsy. In: Sterman MB, Shouse MN, Passouant P, editors. Sleep and
epilepsy. New York: Academic Press; 1982. p. 23947.
[30] Janz D, Christian W. Impulsiv - petit mal. Deutsche Zeitschrift fr Nervenheilkunde
1957;176:34686. (English translation by Genton P. In: Malafosse A, Genton P,
Hirsch E, Marescaux C, Broglin D, Bernasconi M, editors. Idiopathic generalized
epilepsies. London: John Libbey; 1994. p. 22951.
[31] Panzica F, Rubboli G, Franceschetti S, et al. Cortical myoclonus in Janz syndrome.
Clin Neurophysiol 2001;112:18039.
[32] Panayiotopoulos CP. A clinical guide to epileptic syndromes and their treatment,
revised 2nd ed. London: Springer Healthcare Ltd; 2010.
[33] Oguni H, Mukahira K, Oguni M, et al. Video-polygraphic analysis of myoclonic
seizures in juvenile myoclonic epilepsy. Epilepsia 1994;35:30716.
[34] Conway BA, Halliday DM, Farmer SF, et al. Synchronization between motor cortex
and spinal motoneuronal pool during the performance of a maintained motor task
in man. J Physiol 1995;489:91724.
[35] Brown P, Day BL, Rothwell JC, Thompson PD, Marsden CD. Intrahemispheric and
interhemispheric spread of cerebral cortical myoclonic activity and its relevance
to epilepsy. Brain 1991;114:233351.
[36] Brown P, Marsden CD. Rhythmic cortical and muscle discharge in cortical myoclonus.
Brain 1996;119:130716.
[37] Valzania F, Strafella AP, Tropeani A, Rubboli G, Nassetti SA, Tassinari CA. Facilitation
of rhythmic events in progressive myoclonus epilepsy: a transcranial magnetic
stimulation study. Clin Neurophysiol 1999;110:1527.
[38] Gotman J. Interhemispheric relations during bilateral spike-and-wave activity.
Epilepsia 1981;22:45366.
[39] Rubboli G, Meletti S, Gardella E, et al. Photic reex myoclonus: a neurophysiological
study in progressive myoclonus epilepsies. Epilepsia 1999;40(Suppl. 4):508.
[40] Holmes MD, Quiring J, Tucker DM. Evidence that juvenile myoclonic epilepsy is a
disorder of frontotemporal corticothalamic networks. Neuroimage 2010;49:8093.
[41] Manganotti P, Bongiovanni LG, Zanette G, Fiaschi A. Early and late intracortical
inhibition in juvenile myoclonic epilepsy. Epilepsia 2000;41:112938.
[42] Badawy R, Macdonell R, Jackson GD, Berkovic SF. Can changes in cortical excitabil-
ity distinguish progressive from juvenile myoclonic epilepsy? Epilepsia 2010;51:
20848.
[43] Badawy RA, Macdonell RA, Jackson GD, Berkovic SF. Why do seizures in generalized
epilepsy often occur in the morning? Neurology 2009;73:21822.
[44] Caramia MD, Gigli G, Iani C, et al. Distinguishing forms of generalized epilepsy
using magnetic brain stimulation. Electroencephalogr Clin Neurophysiol 1996;98:
149.
[45] Rodin EA, Luby ED, Gottlieb JS. The electroencephalogram during prolonged
experimental sleep deprivation. Electroencephalogr Clin Neurophysiol 1962;14:
54451.
[46] Bennett DR, Mattson RH, Ziter FA, Calverley JR, Liske EA, Pratt KL. Sleep deprivation:
neurological and electroencephalographic effects. Aerosp Med 1964;35:88890.
[47] Marinig R, Pauletto G, Dolso P, Valente M, Bergonzi P. Sleep and sleep deprivation
as EEG activating methods. Clin Neurophysiol 2000;111(Suppl. 2):4753.
[48] Ellingson RJ, Wilken K, Bennett DR. Efcacy of sleep deprivation as an activation
procedure in epilepsy patients. J Clin Neurophysiol 1984;1:83101.
[49] Kubicki S, Scheuler W, Wittenbecher H. Short-term sleep EEG recordings after partial
sleep deprivation as a routine procedure in order to uncover epileptic phenomena:
an evaluation of 719 EEG recordings. Epilepsy Res Suppl 1991;2:21730.
[50] Bergonzi P, Mazza S, Mennuni G, Zolo P. Selective sleep deprivation (stage IV) in
epileptic patients with partial seizures. Arch Psicol Neurol Psichiatr 1975;36:3138.
[51] Janz D. Epilepsy and the sleepingwaking cycle. In: Vinken PJ, Bruyn GW,
editors. Handbook of clinical neurology. The epilepsies Amsterdam: Elsevier;
1974. p. 45790.
[52] Halasz P. Sleep, arousal and electroclinical manifestations of generalized epilepsy
with spike and wave pattern. In: Degen R, Niedermeyer E, editors. Epilepsy, sleep
and sleep deprivation. Amsterdam: Elsevier; 1984. p. 97197.
[53] Niedermeyer E. Awakening epilepsy revisited 30 years later. In: Degen R,
Niedermeyer E, editors. Epilepsy, sleep and sleep deprivation. Amsterdam: Elsevier;
1984. p. 8596.
[54] White P, Dyken M, Grant P, Jackson L. Electroencephalographic abnormalities
during sleep as related to the temporal distribution of seizures. Epilepsia 1962;3:
16774.
[55] Halsz P, Filakovsky J, Vargha A, Bagdy G. Effect of sleep deprivation on spike-wave
discharges in idiopathic generalised epilepsy: a 4 24 h continuous long term EEG
monitoring study. Epilepsy Res 2002;51:12332.
[56] EEG arousals: scoring rules and examples: a preliminary report from the Sleep
Disorders Atlas Task Force of the American Sleep Disorders Association. Sleep
1992;15:17384.
[57] Iber C, Ancoli-Israel S, Chesson A, Quan S. For the American Academy of Sleep
Medicine. The AASM manual for the scoring of sleep and associated events: rules,
terminology and technical specications. 1st edition. Westchester, IL: American
Academy of Sleep Medicine; 2007.
 A. Serani et al. / Epilepsy & Behavior 28 (2013) S30S39
[58] Passouant P, Cadilhac J, Labauge R. Rhythmicity of petit mal during sleep,
generalized and localized rhythmic discharges. Rev Neurol (Paris) 1951;84:
65963.
[59] Niedermeyer E. The generalized epilepsies. A clinical electroencephalographic
study. Springeld, Illinois: Charles Thomas; 1972.
[60] Terzano MG, Mancia D, Salati MR, Costani G, Decembrino A, Parrino L. The cyclic
alternating pattern as a physiologic component of normal NREM sleep. Sleep
1985;8:13745.
[61] Parrino L, Staggiari BM, Barusi R, Terzano MG. Effects of prolonged wakefulness
on cyclic alternating pattern (CAP) during sleep recovery at different circadian
phases. J Sleep Res 1993;2:915.
[62] Terzano MG, Parrino L, Anelli S, Halasz P. Modulation of generalized spike and
wave discharges during sleep by cyclical alternating pattern. Epilepsia 1989;30:
77281.
[63] Gigli GL, Calia E, Marciani MG. Sleep microstructure and EEG epileptiform activity
in patients with juvenile myoclonic epilepsy. Epilepsia 1992;33:799804.
[64] Bonakis A, Koutroumanidis M. Epileptic discharges and phasic sleep phenomena
in patients with juvenile myoclonic epilepsy. Epilepsia 2009;50:243445.
[65] Snead III OC. Basic mechanisms of generalized absence seizures. Ann Neurol
1995;37:14657.
[66] Steriade M. Synchronized activities of coupled oscillators in the cerebral cortex
and thalamus at different levels of vigilance. Cereb Cortex 1997;7:583604.
S39
[67] Antoniadis G, Kostopoulos G. Simulation study for the transition from spindles to
spike and wave epileptogenesis. Med Biol Eng Comput 1995;33:2416.
[68] Avoli M, Kostopoulos G. Participation of corticothalamic cells in penicillin-induced
generalized spike and wave discharges. Brain Res 1982;247:15963.
[69] Klingler D, Tragner H, Deisenhammer E. On the nature of the inuence of sleep
deprivation on the EEG. In: Degen R, Niedermeyer E, editors. Epilepsy, sleep and
sleep deprivation. Elsevier: Amsterdam; 1984. p. 3113.
[70] Rodin EA. Sleep deprivation and epileptological implications. In: Degen R, Rodin
EA, editors. Epilepsy, sleep and sleep deprivation. Epilepsy Res, Suppl., 2nd edn
Amerstam: Elsevier Science Publishers BV; 1991. p. 26573.
[71] Civardi C, Boccagni C, Vicentini R, et al. Cortical excitability and sleep deprivation:
a transcranial magnetic stimulation study. J Neurol Neurosurg Psychiatry 2001;71:
80912.
[72] Scalise A, Desiato MT, Gigli GL, et al. Increasing cortical excitability: a possible ex-
planation for the proconvulsant role of sleep deprivation. Sleep 2006;29:15958.
[73] Badawy RA, Curatolo JM, Newton M, Berkovic SF, Macdonell RA. Sleep deprivation
increases cortical excitability in epilepsy: syndrome-specic effects. Neurology
2006;67:101822.
[74] Manganotti P, Bongiovanni LG, Fuggetta G, Zanette G, Fiaschi A. Effects of sleep
deprivation on cortical excitability in patients affected by juvenile myoclonic
epilepsy: a combined transcranial magnetic stimulation and EEG study. J Neurol
Neurosurg Psychiatry 2006;77:5660.