Epilepsy & Behavior 28 (2013) S81–S86

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Epilepsy & Behavior

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

Review

Management of juvenile myoclonic epilepsy

Arielle Crespel a, b,⁎, Philippe Gelisse a, b, Ronald C. Reed c, Edoardo Ferlazzo d, e, Judith Jerney f,
Bettina Schmitz g, Pierre Genton h
a
Epilepsy Unit, Hôpital Gui de Chauliac, Montpellier, France
b
Research Unit “Movement Disorders” (URMA), Department of Neurobiology, Institute of Functional Genomics, CNRS UMR5203 – INSERM U661 – UM1, Montpellier, France
c
Husson University School of Pharmacy, Bangor, ME, USA
d
Magna Græcia University, Catanzaro, Italy
e
Regional Epilepsy Centre, “Bianchi-Melacrino-Morelli” Hospital, Reggio Calabria, Italy
f
Epilepsy Centre, St. John Hospital, Buda Children's Hospital, Budapest, Hungary
g
Vivantes Humboldt-Klinikum Berlin, Department of Neurology, Stroke Unit, and Center for Epilepsy, Germany
h
Centre Saint Paul-H. Gastaut, Marseille, France

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

Article history: Juvenile myoclonic epilepsy (JME) is a common form of epilepsy and a fairly lifelong disorder that may sig-
Accepted 16 October 2012 nificantly lower a patient's expectations and potential for a full life. Luckily, it is also a highly treatable disor-
der, and up to 85% of patients with JME will enjoy satisfactory seizure control. Among anticonvulsants,
Keywords: valproate still stands out as the most efficacious drug, but may be poorly tolerated by some, and is considered
Juvenile myoclonic epilepsy
unsafe for the fetuses of pregnant women. Alternatives have emerged in recent years, especially
Management
Antiepileptic drugs
levetiracetam, but also topiramate, zonisamide or lamotrigine. In some cases, combination therapy may
Lifestyle be useful or even required. One should not forget the potential aggravation induced not only by some com-
SUDEP monly used anticonvulsants, especially carbamazepine and oxcarbazepine, but also, in some patients, by
lamotrigine. In special settings, older drugs like benzodiazepines and barbiturates may be useful. But the
management of JME should also include intervention in lifestyle, with strict avoidance of sleep deprivation
and the management of copathologies, including the cognitive and psychiatric problems that are often en-
countered. With adequate management, there will only remain a small proportion of patients with
uncontrolled epilepsy and all of its related problems. Juvenile myoclonic epilepsy is a condition in which
the clinician has a fair chance of significantly helping the patient with medication and counseling.

This article is part of a supplemental special issue entitled Juvenile Myoclonic Epilepsy: What is it Really?
© 2013 Elsevier Inc. All rights reserved.

1. Introduction treatment consisting of JME. With treatment of a combination of

Juvenile myoclonic epilepsy (JME) is a treatable epileptic syn-
drome. According to the International League Against Epilepsy, “re-
sponse to appropriate drugs is good” [1]. Juvenile myoclonic epilepsy
has a reputation of being benign. However, Gelisse et al. [2] found
that the seizures of about 15% of patients with JME are drug-
resistant, especially the seizures of those in whom all three seizure
types coexist (myoclonic jerks (MJs), generalized tonic-clonic seizures
(GTCSs), and absence seizures). Independently, the presence of psychi-
atric problems, e.g., personality disorders, was also found as a factor as-
sociated with drug resistance [2]. However, this study was performed at
the end of the 1990s, before the extensive use of levetiracetam (LEV),
topiramate (TPM), lamotrigine (LTG), and zonisamide (ZNS) in the
⁎ Corresponding author at: Explorations Neurologiques et Epileptologie, Hôpital Gui
de Chauliac, 80 avenue Fliche, 34295 Montpellier cedex 05, France. Fax: +33 4 67 33
61 00.
E-mail address: a-crespel@chu-montpellier.fr (A. Crespel).
drugs, the frequency of patients with drug-resistant seizures is probably
lower nowadays. The use of different drug combinations may constitute
a crucial element in the management of patients with refractory JME.
Patients with an abnormal lifestyle, including excessive intake of
alcohol or irregular sleep-wake schedules, are at risk of persisting
seizures. More than in other types of epilepsy, patients with JME
must correct their lifestyle. It was also shown that patients with JME
are at risk of sudden unexpected death in epilepsy (SUDEP). Patients
with JME can die of a cause closely (trauma, drowning, or status
epilepticus) or remotely (e.g., by suicide) related with seizures. Sudden
unexpected death in epilepsy was repeatedly reported in IGE, but IGE
was not considered a major risk. However, uncontrolled epilepsy,
GTCS, lack of compliance, and neurological or mental handicap are risk
factors for SUDEP. All these conditions may be present in JME, and
Genton and Gelisse reported three cases of SUDEP in JME [3]. This is an-
other reason for working with patients to achieve seizure freedom.
In JME, the overall prognosis will remain good with a rational ap-
proach to the choice of drug and by avoiding potential aggravation

1525-5050/$ – see front matter © 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.yebeh.2013.01.001
S82 A. Crespel et al. / Epilepsy & Behavior 28 (2013) S81–S86
by inadequate AEDs. Juvenile myoclonic epilepsy stands out as a phar-
macodependent form of epilepsy. In this review, we discuss some is-
sues surrounding the management of patients with JME: drug
choice, paradoxical aggravation by AEDs, lifestyle, and best treatment
strategies for women of childbearing potential with epilepsy.
2. Choice of antiepileptic drugs
Choice of treatment in JME is based on clinical experience, retro-
spective studies, and prospective open-label trials. But randomized
blinded clinical trials comparing old or new antiepileptic drugs are
clearly lacking. Juvenile myoclonic epilepsy has a particular pharmaco-
logical sensitivity. If some antiepileptic drugs (AEDs) can be used with
success, the potential aggravating effect of others must be kept in mind.
2.1. Valproate
Valproate (VPA) has a very specific efficacy in the treatment of
JME, and this was stressed in the first reports on JME following the
availability of the compound. Valproate quickly became the drug of
choice for the treatment of JME. A few studies used monotherapy of
VPA in patients with JME and showed similar very high rates of total
control of seizures. In North America, high control rates of 90% [4] or
86% [5] were reported in the 1980s, compared with 84.5% in a Europe-
an study by Genton et al. [6]. The superiority of VPA in the treatment of
IGE was clearly demonstrated in the SANAD study [7]. In adults, the
dosage ranges between 1000 and 2000 mg/day. Electroencephalo-
gram abnormalities can persist even if good control is obtained with
VPA, but this persistence of EEG abnormalities does not have a bad
prognostic significance [8]. In the case of initial nonefficacy of VPA in
the treatment of JME, increasing dosage until the occurrence of side ef-
fects does not appear to result in decreased seizure frequency [9].
Valproate is still considered as the first-line treatment in JME in men
and women without childbearing potential.
2.2. Lamotrigine
Open-label studies showed the efficacy of LTG in the treatment
of JME, used in association or not with VPA [10–12]. Nicolson and
Marson studied the efficacy of LTG after VPA failure (side effects or no
efficacy). They observed a remission in 13.6% of the patients but only
for those who had stopped using VPA because of its side effects and
not because of its lack of efficacy [13]. Bodenstein-Sachar et al. found
similar results particularly in patients with JME but without GTCS [14].
Lamotrigine is helpful in treating JME but appears to be less effective
than VPA [7,15]. However, LTG has the potential to aggravate IGE, with
promyoclonic effects which may occur after a long delay [16]. Therefore,
LTG should not be considered as a first-line option compared with VPA,
but it remains useful in younger women because of the potential terato-
genicity of VPA [17], and also in patients with comorbidities like migraine
(with aura) [18] and psychiatric disorders (bipolar depression) [19].
2.3. Levetiracetam
The increasing use of LEV in the treatment of JME is now
well-founded. Since 1996, its efficacy has been shown respectively
against photoparoxysmal responses [20] and myoclonus [21]. Several
open studies demonstrated the specific efficacy of LEV in the treat-
ment of JME with patients who became seizure-free on polytherapy
and monotherapy. In the open study of Labate et al. [22], 8 patients re-
ceived monotherapy, and 13 patients received add-on therapy with
LEV; 62.5% of the patients became seizure-free on monotherapy and
61.5% on add-on therapy. In the monotherapy group, the seizure
frequency decreased more than 50% for one patient, was unchanged
for one, and worsened for one. In the add-on group, the seizure frequen-
cy decreased more than 50% for three patients, was unchanged for one,
and worsened for one; a high dosage of LEV (2000 to 3000 mg/day) was
used. In the long-term open study of Specchio et al. [23], 5 of the 10
newly-diagnosed patients (50%) became seizure-free on monotherapy,
and 11 of the 38 patients with resistant or intolerant seizures (28.5%)
became seizure-free on polytherapy. Thirty-seven percent of patients
had no myoclonias, and 72.9% had no GTCS. They observed a significant
decrease in the number of days with myoclonus and the monthly fre-
quency of GTCS after LEV treatment. The patients received between
1000 and 3000 mg/day of LEV (mean: 2208 mg/day). In a following
study, Specchio et al. [24] studied the effect of LEV on EEG abnormalities
and photoparoxysmal response (PPR) in 48 patients. Electroencephalo-
gram was normalized in 23 patients after LEV treatment. Suppression of
PPR was observed in 13 of the 17 patients with PPR before LEV treat-
ment. When the EEG was normalized, there were significantly more
days without myoclonias compared to patients with unchanged EEG.
A multicenter, randomized, double-blind, placebo-controlled study of
LEV in idiopathic generalized epilepsies was published in 2007 by
Berkovic et al. [25]. Among 164 patients, 54 patients had JME: 24 re-
ceived LEV, while 30 received placebo. They obtained a significantly bet-
ter response in patients on LEV than in patients on placebo. In 2008,
Verotti et al. [26] published an open study on 32 patients with
new-onset JME using LEV treatment as the first monotherapy. At
12 months, all patients were responders with 90.6% of them
seizure-free. Sharpe et al., in their 2008 retrospective study of 32 pa-
tients with JME, showed that 80% of patients were seizure-free after
LEV monotherapy (initial or conversion). They used a dosage between
12 and 50 mg/kg/day [27]. Of the 122 patients with IGE and myoclonias
in whom a first treatment failed, Noachtar et al. gave placebo to 60 and
LEV to 62 [28]. A very significant response to LEV was demonstrated for
myoclonias. The analysis of the two randomized, double-blind,
placebo-controlled studies of Berkovic et al. [25] and Noachtar et al.
[28] by Rosenfeld et al. [29] in 2009 showed a rate of responders of
61% in patients with JME, with 20.8% of them seizure-free. Thus, LEV is
one of the options in the treatment of JME [30] and is an alternative
choice to VPA as a first-line or add-on treatment, especially in women
of childbearing potential. No study comparing VPA and LEV is available.
2.4. Topiramate
Topiramate (TPM) is useful in the treatment of JME. Its efficacy in
add-on therapy was shown in the first studies [31,32]. Biton and
Bourgeois in 2006 [33] made a retrospective analysis of 22 patients
with JME who participated in two prospective, double-blind, add-on
studies of TPM versus placebo in the treatment of IGE and found a re-
duction of GTCSs. In the SANAD study, Marson et al. in 2007 [7] dem-
onstrated the efficacy of TPM in the treatment of IGE. Topiramate was
more efficacious than LTG, but was less tolerated than VPA and LTG.
Levisohn and Holland in 2007 [34] observed that TPM was slightly
more efficacious than VPA in a randomized, open-label study compar-
ing 28 adolescent and adult patients; 19 were on TPM (median dosage
of 250 mg/day) and 9 on VPA (median dosage of 750 mg/day). In
2005, Sousa et al. confirmed the efficacy of TPM against GTCS and
myoclonias in an open study of 15 patients with uncontrolled JME
[35]. But in some patients, TPM may produce neuropsychiatric side ef-
fects (alteration of attention, short-term memory, processing speed,
and verbal fluency) [36] and lead to treatment failure [7]. Neverthe-
less, when it is well tolerated, TPM is a suitable alternative to VPA, par-
ticularly in patients who are overweight or have associated migraine.
2.5. Zonisamide (ZNS)
In 2004, Kothare et al. used zonisamide (ZNS) in 15 patients with JME.
Thirteen patients received ZNS as first monotherapy and 2 as add-on ther-
apy. They reported a good control of seizures, with 80% of responders in
the monotherapy group. Sixty-nine percent of patients were GTCS-free,
62% were seizure-free for myoclonias, and 38% were seizure-free for
 A. Crespel et al. / Epilepsy & Behavior 28 (2013) S81–S86
absences. The daily dose ranged between 200 and 500 mg [37]. A com-
plete resolution of EEG discharges has been observed in a patient with
JME who became seizure-free with ZNS [38]. In a retrospective analysis
of 7 patients with refractory JME, O'Rourke et al. in 2007 showed that
ZNS treatment led to more than 50% reduction of seizure frequency in
83.3% of treated patients for GTCS and in 100% for myoclonias and ab-
sences [39]. Two patients became seizure-free. Marinas et al. in 2009
used ZNS to treat 13 patients with IGE, six of whom had JME. In these
patients with JME, 3 became seizure-free, 2 had no change, and one ex-
perienced side effects and stopped using ZNS [40]. All these retrospec-
tive studies showed good results for treating JME with ZNS, but
prospective controlled studies are clearly missing.
2.6. Other treatments
Before the availability of VPA, phenobarbital (PB) and primidone were
commonly used in the treatment of JME with efficacy in up to 86% of
cases, while a regimen containing predominantly phenytoin (PHT) con-
trolled seizures only in 67% of the patients and left 33% unchanged or
worsened [41]. Other authors described efficacy with acetazolamide
[42], methsuximide [43], and piracetam in the dosage of 3200 mg/day
with sustained antimyoclonic efficacy [44]. Some publications have also
stressed the possibility of adding clonazepam to VPA to improve efficacy
[45]. Recently, lacosamide (LCM) was used in three patients with JME
[46]. Two patients received LCM as monotherapy and one as add-on. A
good effect was observed, but these preliminary data await confirmation.
3. Paradoxical aggravation of JME due to the choice of
inadequate drugs
Juvenile myoclonic epilepsy may be aggravated by AEDs. Kivity and
Rechtman reported that phenytoin (PHT) at high doses is highly toxic
in JME and may clearly exacerbate MJs [47]. Sözüer et al. reported that
PHT exacerbated MJs in four of six patients [48]. Genton et al. reported
that PHT was not very efficacious: among 16 subjects exposed to PHT
alone or in association with other AEDs, seizures in six were aggravat-
ed (38%) including one in monotherapy, two in association with PB,
one in association with VPA, one in association with CBZ and PB, and
one in association with CBZ and VPA [49]. Only two were improved
(12%), whereas 8 (50%) did not notice any change in seizure frequen-
cy. In this study, CBZ aggravated symptoms in nearly 68% of patients
exposed to it, whereas 14% of them have been improved (two in
monotherapy, one in association with VPA, and one in association
with VPA and PB). No effect was seen in the remaining five cases
(one in monotherapy, three in association with VPA, and one in asso-
ciation with PB). Following change of treatment including withdrawal
of PHT and CBZ, all patients who had aggravation were clearly im-
proved by VPA as monotherapy or in association with LTG, PB, or
BZP. Previously, Sözüer et al. had reported aggravation with CBZ in a
series of 19 patients with JME. Sixteen experienced increased MJs
with CBZ monotherapy, and four also experienced absences [48]. In
2000, Osorio et al. observed status epilepticus occurring in 4 patients
with JME refractory to IV benzodiazepines secondary to concurrent
phenytoin or carbamazepine treatment; when PHT or CBZ was with-
drawn and VPA was initiated, seizure control was achieved [50].
Oxcarbazepine (OXC) is a drug chemically related to CBZ.
Oxcarbazepine appears to have a significant potential to aggravate
JME. Gelisse et al. reported a clear aggravation in four patients with
JME: aggravation of MJs in all, increased GTCSs in three, and absence sei-
zures in two [51]. This aggravation followed the prescription of OXC with
a close time relation after its introduction. However, Carignani and Rosso
in 1997 reported a good response with OXC in six patients with JME.
Oxcarbazepine was used at dosages≤45 mg/kg/day. The authors men-
tioned that exacerbation of spike-wave activity and MJs did not occur in
their cases [52]. The main problem with the patients reported by these au-
thors is the lack of characterization of the epilepsy. There is no detail. The
S83
authors mentioned that some patients had hemiclonic or hemitonic sei-
zures at the onset of the disorder, which is a very atypical presentation
for JME, and focal epilepsy cannot be ruled out.
Lamotrigine is a therapeutic option for patients with JME but this
drug can aggravate MJs [53] or GTCSs [54]. Crespel et al. reported de
novo appearance of MJs in juvenile IGE in five women among 93 patients
treated with LTG (5.4%) with a phenotype close to JME at the time of ag-
gravation [16]. Two distinct profiles of aggravation were observed: (1) a
dose-related aggravation of MJs during or at the end of LTG titration that
may respond to LTG dosage reduction by 25 to 50%; and (2) a severe ag-
gravation of MJs occurring several months after LTG titration and evolv-
ing into myoclonic status requiring cessation of LTG.
Status epilepticus has been reported in patients with JME treated
with inappropriate AEDs. Larch et al. reported two cases of myoclonic
status epilepticus (one treated with CBZ and one treated with PHT)
[55]. Thomas et al. reported three cases of myoclonic status epilepticus
and one case of absence status [56]. All were treated with CBZ: two in
monotherapy, 1 in combination with PB and vigabatrin (VGB), and one
in combination with PB and PHT. Potential precipitating factors for the
status were: initiation of CBZ in one case, of VGB in one case, sleep depri-
vation in one case, and an unknown cause in the latter. Vigabatrin is not
considered a good drug for treating JME even if Pedersen et al. have
reported partial efficacy in three of their patients [57]. However, VGB
may aggravate absence epilepsies and is not indicated in IGEs [58].
4. Treatment of status epilepticus
Myoclonic status epilepticus or mixed myoclonic–absence status is
uncommon in JME, often precipitated by sleep deprivation and inade-
quate AEDs or resulting from drug withdrawal (Fig. 1). Such episodes
of status respond well to benzodiazepines [55] or valproate [59].
5. Treatment of JME in women with childbearing potential
Pregnancy is a therapeutic challenge in women with epilepsy, and
the risk/benefit ratio for the mother and fetus must be considered re-
garding the choice of the AED. None of the AEDs can be categorized as
safe during pregnancy. Lamotrigine and levetiracetam seem to be
comparatively safer to use in pregnancy than others [60]. There is a
significant decrease in the plasma concentration during pregnancy in
patients treated with LTG and restoration of prepartum levels after de-
livery. Dosage adjustments may be necessary. Lamotrigine is contra-
indicated while breastfeeding. Valproate (VPA) is associated with an
increased risk of major malformations and has also been associated
with an increased risk of impaired postnatal cognitive development
[61]. It is recommended to avoid VPA during pregnancy or to use it
in monotherapy at low dosages (≤750 mg/day) if GTCSs are difficult
to control with other drugs. For ZNS and TPM (which is FDA Pregnancy
Category D), the available information is relatively sparse. These drugs
should only be given when there is no alternative.
Treatment in women of reproductive age remains a clinical chal-
lenge. Enzyme-inducing drugs can reduce the efficacy of combined
hormonal contraception. Topiramate does not interact with oral con-
traceptives if the daily dose is below 200 mg, but at a higher dose, it
may decrease the efficacy of combined oral contraceptives [62].
Valproate, ZNS, and LTG do not affect hormonal contraception. But
combined oral contraceptives reduce the plasma concentration of
LTG. Women using LTG should be advised that seizure frequency
may increase when initiating this method of contraception.
6. Nonpharmacological approach
6.1. Lifestyle
Lifestyle is a crucial element in the successful management of pa-
tients with JME. Without a good lifestyle, obtaining good control of
S84 A. Crespel et al. / Epilepsy & Behavior 28 (2013) S81–S86

Fig. 1. The EEG (15 mm/s; 10 μV/mm; international 10–20 electrode system with right deltoid and left deltoid) of a 24-year-old woman with juvenile myoclonic epilepsy and bi-
polar disorder. Confusional state 5 days after withdrawal of clonazepam (14 mg/day) and introduction of oxazepam (200 mg/day) followed by catatonic stupor with subtle myoc-
lonus of the face and the arms. Left segment: absence status with continuous activity with bilateral spike–waves and sharp notched theta or delta waves. Right segment: after
treatment with IV clonazepam (1 mg) leading to cessation of the status. The patient was able to speak normally. Note that the EEG did not completely return to normal.

seizures remains difficult. Lifestyle is part of the treatment, and this
point must be particularly discussed with the patient. In spite of ade-
quate treatment, seizures may be precipitated by various stimuli such
as fatigue, sleep deprivation, alcohol intake, and drugs. Patients must
regulate their wake-sleep rhythm in order to have sufficient time of
sleep and the most possible natural awakening. Sleep deprivation
and provoked awakening are two major conditions precipitating sei-
zures. Seizures principally occur within 2 h after awakening (30 min
to 1 h), which is why the patient must have a sufficient time to pre-
pare, must be careful in this period, and must not engage in danger-
ous activities like taking a bath. Alcoholic drinks may be permitted
only in small quantities. Energy drinks should be discouraged in
some patients, especially adolescents consuming a large amount at
night or in combination with alcohol [63]. Low medication adherence
may also be a factor of pseudo-drug resistance. In many countries, pa-
tients with epilepsy can drive if their seizures are controlled. Patients
must be advised not to drive when fatigued, deprived of sleep, and in
the awakening period.
6.2. Photosensitivity
Juvenile myoclonic epilepsy is the epilepsy syndrome with the
closest relation with photosensitivity, both as an EEG phenomenon
and clinically. When flashing lights trigger seizures, some precautions
are necessary such as wearing sunglasses on sunny days when the sun
is reflected on the water or dappled through trees. Nowadays, flat
televisions and flat screens for computers are less provocative than
the old cathode TV tubes. However, the increasing size of screens
as well as the contrast and changing colors of the programs cancel
this positive development, unfortunately [64]. When playing video
games on the TV or computer, it is better to play in a well-lit room
and at maximal possible distance to the screen and not to play
when drowsy and asthenic. In patients suffering clinically from their
photosensitivity, the use of blue lenses can be an interesting
option in those whose photoparoxysmal EEG responses are clearly
suppressed by wearing blue lenses [65]. Patients should be warned
that with the blue lenses, traffic lights are more difficult to discrimi-
nate. Valproate and LEV are both very effective in the treatment of
photosensitivity, and management is therefore similar to the treat-
ment of JME; other drugs do suppress the photosensitivity as well [66].
6.3. Psychotherapy
Juvenile myoclonic epilepsy may be associated with some degree of
social and cognitive dysfunction and some degree of personality disor-
ders. According to Janz and Christian [67], patients with JME have inad-
equate social behavior, emotional instability, and immaturity, which
can lead to social maladjustment, low medication adherence, and inad-
equate lifestyle. Early descriptions were confirmed by studies using
modern psychiatric criteria [68–70]. The presence of psychiatric disor-
ders seems to be a marker of drug resistance [2,70,71]. Their identifica-
tion and treatment should be early since they have a fundamental role
 A. Crespel et al. / Epilepsy & Behavior 28 (2013) S81–S86
in the prognosis. In patients with refractory JME, psychotherapy may
be helpful. Martinović reported that psychotherapy led to seizure free-
dom in 50% of patients with drug-resistant seizures [72]. He investigat-
ed 22 patients with JME with uncontrolled seizures. After a structured
counseling, eight patients became seizure-free. Of the patients who
were not seizure-free, seven had an antistress treatment which resulted
in three becoming seizure-free. Seven had an individual cognitive be-
havioral therapy which resulted in four becoming seizure-free.
6.4. Vagus nerve stimulation
Vagus nerve stimulation (VNS) is an adjunctive treatment in re-
fractory epilepsy. Some authors consider VNS a favorable treatment
option for patients with drug-resistant IGE. Ng and Devinsky reported
that, among 14 patients with IGE, 57.1% achieved a 50% or greater re-
duction in seizure frequency [73]. These authors did not precisely state
how many patients had JME. Kostov et al. reported on 12 patients with
drug-resistant IGE, including seven with JME [74]. Five out of these 7
patients were responders (>50% seizure reduction), with one remaining
on VNS alone with a >75% reduction in GTCSs and a >50% reduction in
typical absence seizures and MJs. These studies are not sufficient for
VNS to qualify as a recommended treatment option in JME.
7. Treatment of JME: the long-term outcome
There are no data showing that JME, once controlled, may have a
fluctuating course with loss of control over time. Lifestyle issues usu-
ally get milder with aging, and factors that might trigger seizures,
such as sleep schedule irregularities, tend to disappear in adulthood.
Recent long-term studies, detailed elsewhere in this volume, have
shown that some patients have a more severe condition that may
pose therapeutic problems over many years, and that some have a
very benign course, with isolated jerks (and those patients can often
do without drug therapy), while the majority will enjoy a fairly mild
course, bordering on long-term, even final remission in some. As a
milder disease is usually found in patients who are in their fourth
decade of life onwards, a reasonable therapeutic compromise is to
maintain treatment in most patients beyond early adulthood,
e.g., with low-dose VPA, with a single evening intake [75].
8. Copathologies
Copathologies can influence the choice of antiepileptic drug by virtue
of the known positive or negative side effects of AEDs. One may thus pre-
fer LTG, TPM, or VPA in the case of migraine or LTG in the case of depres-
sion. In the case of obesity, TPM is an interesting option [30].
Copathologies are conditions that may interfere with prognosis of
JME and must be diagnosed in patients with refractory JME because
they can be aggravating or revealing conditions. Genton et al. reported
one patient with hypothyroidism in whom thyroid replacement ther-
apy quickly led to improvement [6]. Hyperthyroidism has also been
reported as an aggravation factor in JME [76]. Similarly, patients
with well-controlled seizures can relapse with GTCSs when they suffer
from obstructive sleep apnea syndrome due to severe sleep depriva-
tion. Psychiatric disorders are also a factor that can lead to drug resis-
tance or aggravation in patients with well-controlled seizures [2].
9. Conclusion
With proper management, the majority of patients with JME can
have lives much less impacted by seizures. When the epilepsy remains
active in spite of apparently adequate drug choice and management,
the diagnosis of JME must be reviewed, and the lifestyle issues and ad-
herence must be verified.
Several AEDs are useful. Valproate appears to be the first-line treat-
ment option. If VPA is ineffective in controlling seizures in adequate
S85
dosage or is poorly tolerated, other drugs or combination therapy must
be considered. Lamotrigine, levetiracetam, topiramate, zonisamide, and
phenobarbital are other potential options in monotherapy or in combina-
tion with VPA, with LEV as the preferred option for many. Comorbidities
must be considered and treated. Lifestyle remains essential and is an inte-
gral part of JME treatment and can be a true challenge in some patients,
particularly in adolescents. An opinion poll about the popular, modern
therapeutic options in JME was performed among participants of the
2011 Avignon workshop, and its results are detailed elsewhere in this
volume.
Ethical approval
We confirm that we have read the ethical publication guidelines
for this Journal and affirm that this report is consistent with those
guidelines.
Conflict of interest statement
Dr. Crespel has received support from pharmaceutical companies
for teaching programs (Sanofi-Aventis, UCB). Dr. Crespel served as a
board member for Eisai-France.
Dr. Gelisse has received support from pharmaceutical companies
for teaching programs (Sanofi-Aventis, UCB, Psicofarma). He received
a research grant from the French League Against Epilepsy and the
Janssen-Cilag company. He was a paid consultant for Eisai-France in
2011.
Dr. Reed has no conflicts of interest to declare.
Dr. Ferlazzo has received speaker honoraria from Novartis and UCB.
Dr. Jerney has received speaker honoraria from UCB and support
for teaching programs from Eisai.
Dr Schmitz has received research grants and served on advisory
board of Desitin, Eisai, UCB-Pharma, Novartis, Glaxo-Smith-Kline,
Pfizer and Sanofi.
Dr. Genton has received speaker honoraria from Sanofi-Aventis,
UCB, and Eisai.
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