CME

Common Pediatric Epilepsy Syndromes Copyrighted material. Not for distribution.

Jun T. Park, MD; Asim M. Shahid, MD; and Adham Jammoul, MD

Abstract
Benign rolandic epilepsy (BRE), childhood idiopathic occipital epilepsy (CIOE), childhood
absence epilepsy (CAE), and juvenile myoclonic epilepsy (JME) are some of the common ep- Jun T. Park, MD, is an Assistant Professor
ilepsy syndromes in the pediatric age group. Among the four, BRE is the most commonly en- of Pediatrics and Neurology, Division of Pe-
countered. BRE remits by age 16 years with many children requiring no treatment. Seizures diatric Epilepsy, Department of Pediatrics,
in CAE also remit at the rate of approximately 80%; whereas, JME is considered a lifelong Rainbow Babies and Children’s Hospital,
Case Western Reserve University School of
condition even with the use of antiepileptic drugs (AEDs). Neonates and infants may also
Medicine. Asim M. Shahid, MD, is an Assis-
present with seizures that are self-limited with no associated psychomotor disturbances.
tant Professor of Pediatrics and Neurology,
Benign familial neonatal convulsions caused by a channelopathy, and inherited in an auto-
Division of Pediatric Epilepsy, Department
somal dominant manner, have a favorable outcome with spontaneous resolution. Benign of Pediatrics, Rainbow Babies and Children’s
idiopathic neonatal seizures, also referred to as “fifth-day fits,” are an example of another ep- Hospital, Case Western Reserve University
ilepsy syndrome in infants that carries a good prognosis. BRE, CIOE, benign familial neonatal School of Medicine. Adham Jammoul, MD,
convulsions, benign idiopathic neonatal seizures, and benign myoclonic epilepsy in infancy is an Epilepsy Fellow, Department of Neu-
are characterized as “benign” idiopathic age-related epilepsies as they have favorable im- rology, Neuroscience Instituite at University
plications, no structural brain abnormality, are sensitive to AEDs, have a high remission rate, Hospitals, Case Western University School
and have no associated psychomotor disturbances. However, sometimes selected patients of Medicine.
may have associated comorbidities such as cognitive and language delay for which the Address correspondence to Jun T. Park,
term “benign” may not be appropriate. [Pediatr Ann. 2015;44(2):e30-e35.] MD, Division of Pediatric Epilepsy, 11100
Euclid Avenue, Mailstop 6009, Cleveland,
OH 44106; email: [email protected].
Disclosure: The authors have no relevant
financial relationships to disclose.
doi: 10.3928/00904481-20150203-09
© Shutterstock

e30 Copyright © SLACK Incorporated

 CME

E
pilepsy syndromes that are sium channel subunit gene KCNQ2, BENIGN MYOCLONIC EPILEPSY IN
commonly encountered by which was previously mapped to the INFANCY
a pediatric clinician are dis- long arm of chromosome 20.3 Benign myoclonic epilepsy in in-
cussed chronologically from the neo- Interictal electroencephalogram fancy (BMEI) is a generalized idio-
natal period to adolescence in this (EEG) may be abnormal but there are pathic epilepsy, characterized by un-
article. Most of these childhood Copyrighted
syn- material.
no characteristic Not forfeatures.
diagnostic distribution.
provoked and/or reflex seizures that
dromes carry a good prognosis—con- Because the seizures resolve spontane- appear between ages 4 months and 3
trary to popular opinion. In fact, sever- ously, treatment is controversial. Phe- years in a previously healthy children.
al may not even necessitate treatment. nobarbital stops the seizures and can As the name of the syndrome im-
The age of onset, nature of seizures, be tapered off after 4 weeks of “sei- plies, myoclonic seizures are the most
and family history may enable the zure freedom.”4 However, epilepsy commonly noted type of seizure in
pediatrician to come to a reasonable develops later in approximately 16% BMEI. The seizures are character-
diagnosis. A pediatrician, in conjunc- of affected newborns. ized by brief generalized myoclonic
tion with the neurologist, may tailor a jerks, correlating with 3-4 Hz gener-
treatment plan that is appropriate for BENIGN IDIOPATHIC NEONATAL alized spike-and-wave discharges on
the child’s situation. Treatment op- SEIZURES EEG.7 Some patients may have reflex
tions are presented in Table 1. Benign idiopathic neonatal seizures seizures, in addition to BMEI, that are
(BINS) occur in otherwise healthy triggered by sudden unexpected visu-
BENIGN FAMILIAL NEONATAL newborns without a family history of al, tactile, or auditory stimuli.7
CONVULSIONS seizures. They are sometimes termed Afebrile generalized tonic-clonic
Benign familial neonatal convul- “fifth-day fits.” Diagnostic criteria in- seizures and simple febrile seizures
sion (BFNC), the first identified cen- clude: (1) infants born after 39 weeks may precede the onset of BMEI.7 In-
tral nervous system channelopathy, is of gestation; (2) Apgar score of 9 or terictal EEG is typically normal in
an autosomal dominant genetic epi- above at 5 minutes of life; (3) the awake and sleep state. The etiology is
lepsy with a high penetrance rate of presence of a seizure-free interval be- unknown; however, it is likely influ-
85%. Seizures usually start within a tween birth and the onset of seizures; enced by genetics.
few days of birth and almost invariably (4) clonic and/or apneic seizures; (5) It has been shown in the long-term
commence by age 2 months.1 Remis- negative workup for etiology; (6) a follow-up that some patients may de-
sion occurs on average by age 6 weeks favorable neurological development; velop other epilepsy syndromes after
(range, 1-6 months).1 and (7) no seizures beyond the neona- a seizure-free period.8 Levetiracetam
The seizures of BFNC are short and tal period.5 As the criteria indicate, the may be the first choice to treat the
occur in clusters. Seizures are charac- diagnosis of BINS is made retrospec- myoclonic seizures in these patients.
terized by apnea, generalized or focal tively and only suspected at the time Valproic acid should be used with cau-
tonic, or clonic convulsions. These of presentation. As such, treatment is tion as fulminant hepatic failure may
newborns have normal psychomotor usually indicated initially. result in a patient with undiagnosed
development during the epilepsy and Seizures typically start on the fifth metabolic disease.
after remission. day of life in half of the patients, but
Diagnosis is suspected in a nor- can range between the first and seventh BENIGN ROLANDIC EPILEPSY OR
mal newborn with spontaneous fo- day of life.5 Seizure semiology is char- BENIGN EPILEPSY WITH CENTRO-
cal or generalized seizures occurring acterized by uni- or bilateral clonus TEMPORAL SPIKES
multiple times a day in the context of and/or apnea with rare tonic seizures. Benign rolandic epilepsy (BRE) (or
positive family history of neonatal sei- Seizures in clusters often occur in in- benign epilepsy with centro-temporal
zures. Further evaluation with genetic creasing frequency, culminating in sta- spikes) is the most common childhood
testing should be done. Genetic muta- tus epilepticus in 82% (63 of 77) of the idiopathic focal epilepsy. The “be-
tions, microdeletions, or duplication patients in one study.5 nign” nature is thought to be due to
involving potassium channel subunits As in BFNC, EEG findings vary the absence of focal neurological defi-
(KCNQ2, KCNQ3) and nicotinic cho- with no certain diagnostic features. cits, sensitivity to antiepileptic drugs
linergic receptor alpha 4 have been Unlike BFNC, etiology is unknown. (AEDs), and spontaneous resolution
2
identified as a cause of BFNC. Muta- Outcome is excellent with low rate of by age 16 years. About 15% of chil-
tions are most often seen in the potas- seizure recurrence.6 dren with epilepsy are affected with

0%$)!42)# !..!,3 s 6OL  .O   e31

 CME

TABLE 1.

Clinical Summary of Childhood Epilepsy Syndromes

Epilepsy Syndromes Age at Onset Typical Clinical Symptoms Cause Prognosis Suggested Treatment
BFNC Copyrighted
Days-2 months material.
Healthy newborn with apnea, Not formutations
Genetic distribution.
Remit PHB or LVT
generalized or focal tonic,
or clonic seizures, and occur
multiple times a day. Positive
family history of neonatal
seizure.
BINS Fifth day of life Healthy newborn with Unknown Remit PHB or LVT
generalized or focal tonic or
clonic seizures and/or apnea
BMEI 4 months-3 years Healthy infant/toddler with Unknown Remit LVT
myoclonic jerks
BRE Adolescent Healthy child with focal Probably geneti- Remit by age 16 LVT or OXC
seizures in the morning that cally influenced years
secondarily generalizes
EBOE 3-6 years Prolonged emesis—mostly Probably geneti- Remit by age 16 LVT or OXC
nocturnal and intact cally influenced years
consciousness
LIOE 8-11 years Visual hallucinations—brief Unknown Excellent LVT or OXC
and frequent. At times,
postictal headache with
migraine features.
CAE 4-10 years Multiple staring episodes Genetically Excellent ETX
influenced remission rate
JME 13-15 years Myoclonic jerks in the Genetically Lifelong VPA, LTG, or LVT
morning influenced
Abbreviations: BFNC, benign familial neonatal convulsions; BINS, benign idiopathic neonatal seizures; BMEI, benign myoclonic epilepsy in infancy; BRE, benign rolandic epilepsy; CAE, childhood
absence epilepsy; EBOE, early-onset benign occipital epilepsy; ETX, ethosuximide; JME, juvenile myoclonic epilepsy; LIOE, late-onset idiopathic occipital epilepsy; LTG, lamotrigine; LVT, levetiracetam;
OXC, oxcarbazepine; PHB, phenobarbital; VPA, valproate.

BRE, usually with onset between ages generalized tonic-clonic (GTC) seizure magnetic resonance imaging is normal
7 and 9 years and before age 13 years. occurs in about half of the children.11 except for incidental findings; therefore,
Seizures are usually 1-3 minutes Uncommonly, long convulsions may neuroimaging is not needed in the pres-
long and status epilepticus is rare. The be followed by Todds’s paresis. Family ence of characteristic history and EEG
cardinal feature of BRE is focal sei- members may hear rhythmic “thump- findings. Very rarely, a patient with a fo-
zures—such that consciousness is intact ing” or “knocking” as the bed shakes cal brain lesion may present in a similar
during the episode in more than half of during the secondary generalized tonic- manner.12
all children. Focal seizures are character- clonic phase. Three-quarters of the sei- No relation can be drawn between the
ized by unilateral facial pulling/twitch- zures occur during non-rapid eye mo- seizure frequency and the frequency of
ing and paresthesia inside the mouth ment (REM) sleep and drowsy state. interictal epileptiform discharges. These
(30% of patients), oropharyngo-laryn- EEG shows a classic pattern consist- discharges also occur in 2%-3% of nor-
geal symptoms (53%), speech arrest ing of central-temporal spikes or poly- mal school-aged children, of whom
(40%), and hypersalivation (30%).9,10 spikes (CTS) uni- or bilaterally often about 8% develop BRE.11 EEG tracings
Patients may try to talk and gesture pur- activated by drowsiness or non-REM normalize later than clinical remission.
posefully during the initial stage of the sleep.9 It is important to note that CTS EEG may continue to be abnormal by
seizure. Speech arrest often occurs due are not specific to BRE, and may occur the time seizures no longer occur. Clini-
to dysarthria. Progression to a secondary in other neurologic conditions. Brain cal genetic studies suggest that the cause

e32 Copyright © SLACK Incorporated

 CME

of BRE is, at least partially, geneti- Prognosis is excellent as in BRE light.17 The clinical course is consid-
cally determined. However, additional with no evidence that long-term prog- ered benign.
acquired or environmental factors may nosis is worse in untreated patients.
contribute to the expression of BRE.13 The majority of patients have less than CHILDHOOD ABSENCE EPILEPSY
Treatment is often not needed. 10 seizures in total, and an AED may Absence seizures are usually brief
Because the seizures are brief,Copyrighted material.
occur not be indicated. 15
Not forofdistribution.
One-tenth chil- in duration (4-20 seconds), but can
mainly during sleep and interfere min- dren with PS have BRE or develop it occur frequently (10 to ≥100 per day)
imally with the daily activities, many later before all seizures remit by ages with abrupt onset/offset associated
clinicians opt not to treat. However, if 15-16 years. As in BRE, the cause is with impaired consciousness. Imme-
the attacks are frequent and become probably genetically determined. diately after the seizure the child re-
generalized, short-term treatment may sumes pre-absence activity. Age of on-
be necessary. With similar seizure Late-Onset Idiopathic Occipital set is 4-10 years with peak incidence at
burden and duration, no difference in Epilepsy 5-6 years. Prevalence is 8%-15% of all
social adjustment was found compar- This is a relatively rare form of pure childhood epilepsies.18
ing children who were treated versus occipital epilepsy, which accounts for Impairment of consciousness as
untreated.12 about 2%-7% of benign childhood fo- characterized by loss of awareness,
The prognosis is invariably excel- cal seizures with the mean age of onset unresponsiveness, and behavioral ar-
lent. Remission occurs within 2-4 between 8 and 11 years.10 rest is an essential feature of childhood
years from onset and before age 16 Seizures are occipital in origin and absence epilepsy (CAE). About two-
years in most instances.9 Seizures primarily manifest as elementary or thirds of these children have associated
disappear regardless of previous drug formed (patients can delineate the na- repeated blinking, lip smacking, pick-
resistance to treatment, which may ture of the object that they “see”) vi- ing/rubbing, head retropulsion, trunk
be present in up to 20% of patients.10 sual hallucinations, sudden blindness, arching, or twitching of the eyelids,
Moreover, development, social adapta- or both. The seizures are brief, fre- eyebrows, or mouth. Some slumping
11,16
tion, and occupation of adults with a quent, and diurnal. These may be of posture can be seen due to decreased
previous history of BRE was found to followed by hemi-sensory, motor signs axial muscle tone, but falls due to ato-
be normal.14 or unresponsiveness. Approximately nia do not occur. Pallor is common, but
one-third of the patients can have se- urinary incontinence is exceptional.18
CHILDHOOD IDIOPATHIC vere postictal, prolonged headache— About one-third of the children have
OCCIPITAL EPILEPSY at times associated with nausea or at least one GTC.19 In 83% of the pa-
Early-Onset Benign Occipital vomiting with additional migrainous tients, seizures are induced by unnatu-
Epilepsy (Panayiotopoulos features.10 In fact, 19% of the patients ral hyperventilation and not associated
Syndrome) have a family history of migraine head- with physiologic hyperventilation.18
10
Panayiotopoulos syndrome (PS) is aches. The headache occurs immedi- Differential diagnosis includes inat-
a benign focal epilepsy that primarily ately or within 10 minutes after visual tention or daydreaming.
occurs between ages 3 and 6 years.11 hallucinations. Consciousness is intact Ictal EEG of CAE is easily recog-
The clinical hallmark of PS is em- during the visual hallucinations or nized. It is characterized by high-am-
esis (70%-80% of seizures).11 The sei- blindness. The majority of the untreat- plitude, bisynchronous, and symmetric
zures are mostly nocturnal and con- ed patients experience visual seizures discharges of rhythmic 3 Hz “spike-
sciousness is retained. The duration of that range in frequency from several and-slow” wave complexes that start
emesis is typically over 6 minutes, with per day to a couple monthly. However, and end abruptly (Figure 1). Interic-
around half lasting over 30 minutes. In seizure propagation to convulsions is tally, paroxysmal activity consisting of
90% of patients, emesis is followed by less frequent. Interictal EEG is nor- fragments of generalized spike-wave
eye deviation or opening (60%-80%), mal; however, unilateral or bilateral, discharges can be seen in up to 92% of
visual hallucinations, and generalized synchronous or asynchronous, spike- patients. EEG abnormalities may per-
or hemi-convulsions.11 Two-thirds oc- wave complexes occur only with the sist into adulthood after resolution of
cur in sleep, during which time the eyes closed. Visual fixation suppresses seizures.
frequency of EEG spikes are also in- the discharges, even in complete dark- Neuropsychological studies have
creased. EEG shows predominantly ness as long as the patient can visually demonstrated that, at the time of diag-
occipital or multifocal spikes.9 fixate on an object, such as a dot of red nosis, these children have behavioral

0%$)!42)# !..!,3 s 6OL  .O   e33

 CME

withdrawal.23 Absence seizures remit

within 2-5 years from the onset. A fa-
vorable prognostic sign is prompt sei-
zure control with an appropriate AED
therapy.
Copyrighted material. Not for distribution.
JUVENILE MYOCLONIC EPILEPSY
Juvenile myoclonic epilepsy
(JME), also a genetically mediated
generalized epilepsy, comprises 5%-
10% of all epilepsy syndromes, and
peaks in early adolescence between
ages 13 and 15 years.19 Multiple sei-
zure types may be present in a patient.
Seizures typically occur after awak-
ening in the mornings. Patients often
Figure 1. Ictal discharges in childhood absence epilepsy showing a 5-year-old patient who stopped complain of suddenly dropping ob-
hyperventilating due to 3 Hz spike-and-wave discharges. She had no memory of the word given to her jects, morning clumsiness, or jitters,
during the induced-absence seizure.
which are, in fact, myoclonic seizures.
Patients have myoclonic jerks
(97%), GTC seizures (79%), absence
seizures (33%), or all three types
(21%).19 Sleep deprivation and fatigue
are the most common precipitating
factors. Other precipitants may be al-
cohol, flashing lights, mental stress,
strong emotions, anxiety, and men-
struation.
Ictal EEG is characterized by a
generalized spike-and-wave pattern at
4-6 Hz that last between 1 and 20 sec-
onds (Figure 2). Interictal EEG may
show generalized spike/polyspike
and wave complexes or focal abnor-
malities (>50% of patients).24 Photic
Figure 2. Interictal discharges in juvenile myoclonic epilepsy showing an 18-year-old female with dif-
stimulation during EEG may induce
fuse polyspikes lasting approximately 1 second with no clinical signs. an electrographic seizure in up to one-
half of patients—termed photoconvul-
disorders in addition to cognitive 25% motrigine. Studies indicate that etho- sive response.19
(17 of 69) and linguistic difficulties suximide is the optimal initial mono- The mechanism and pathophysiol-
43% (29 of 69).20 Cognitive impair- therapy for CAE due to its efficacy ogy of JME are not yet clear. Major
ment, in particular, involves attention in controlling seizure in 70%22 of pa- genes only account for a few cases,
and executive functions21 as well as tients and fewer cognitive side effects. and most cases appear to involve mul-
verbal and visuospatial memory re- However, ethosuximide does not treat tifactorial or complex inheritance.25
gardless of seizure control. Additional convulsions; thus, an add-on therapy Seizures are sensitive to valproate,
studies suggest increased prevalence or an alternative AED needs to be con- rendering at least 80% of patients sei-
of attention-deficit/ hyperactivity dis- sidered in cases where convulsions zure free. Valproate may not be a drug
order in children with CAE.15 coexist. of choice for an adolescent girl due
Seizures usually respond well Prognosis is excellent for remis- to, among other risks, its teratogenic
to ethosuximide, valproate, and la- sion of seizures (56%-84%) and AED effect on the fetus. JME is thought to

e34 Copyright © SLACK Incorporated

 CME

be a lifelong condition as attempts to neonatal and infantile seizures: an autoso- EEG foci. Ann Neurol. 1983;13:642-648.
mal-dominant disorder. Am J Med Genet. 15. Nolan MA, Redobaldo MA, Lah S, et al.
wean AEDs almost-always fails.19 1984;18:455-459. Memory function in childhood epilepsy
5. Plouin P. Benign neonatal convulsions (fa- syndromes. J Paediatr Child Health.
CONCLUSION milial and non-familial). In: Roger J, Dra- 2004;40:20-27.
vet C, Bureau M. Derifuss FE, Wolf P, eds. 16. Auvin S, Pandit F, De Bellecize J, et al. Be-
Pediatricians are often the first to
Epileptic Syndromes in Infancy, Childhood nign myoclonic epilepsy in infants: electro-
encounter children with epilepsyCopyrighted
syn- material. Not for distribution.
and Adolescence. London: John Libbgey clinical features and long-term follow-up
dromes. Being familiar with typical Eurotext; 1985:2-11. of 34 patients. Epilepsia. 2006;47:387-393.
clinical presentations may help triage 6. Miles DK, Holmes GL. Benign neonatal 17. Panayiotopoulos CP. Inhibitory effect of
seizures. J Clin Neurophysiol. 1990;7:369- central vision on occipital lobe seizures.
and manage these patients upon pre- 379. Neurology. 1981;31:1330-1333.
sentation in primary care settings. In 7. Dravet C, Bureau M. The benign myoclonic 18. Sadleir LG, Farrell K, Smith S, et al. Elec-
addition, unnecessary work-up and epilepsy of infancy. Rev Electroencepha- troclinical features of absence seizures in
logr Neurophysiol Clin. 1981;11:438-444. childhood absence epilepsy. Neurology.
morbidities may be avoided. Recogni- 8. Capovilla G, Beccaria F, Gambardella A, 2006;67:413-418.
tion of the benign nature of some of et al. Photosensitive benign myoclonic 19. Panayiotopoulos CP. Obeid T, Tahan AR.
these entities would go a long way in epilepsy in infancy. Epilepsia. 2007;48:96- Juvenile myoclonic epilepsy: a 5-year pro-
100. spective study. Epilepsia. 1994;35:285-
alleviating the fear of families as the
9. Panayiotopoulos CP. Benign childhood par- 296.
term “epilepsy” often conjures up no- tial epilepsies: benign childhood seizure 20. Caplan R, Siddarth P, Stahl L, et al. Child-
tions of lifelong treatment with a sig- susceptibility syndromes [editorial]. J Neu- hood absence epilepsy: behavioral, cogni-
nificant impact on day-to-day life. rol Neurosurg Psychiatr. 1993;56:2-5. tive, and linguistic comorbidities. Epilep-
10. Panayiotopoulos CP. Typical absence sei- sia. 2008;49:1838-1846.
zure and their treatment. Arch Dis Child. 21. Pavone P, Bianchini R, Trifiletti RR, Incor-
REFERENCES 1999;81:351-355. pora G, Pavone A, Parano E. Neuropsycho-
1. Herlenius E, Heron SE, Grinton BE, et al. 11. Panayiotopoulos CP, Michael M. Benign logical assessment in children with absence
SCN2A mutations and benign familial childhood focal epilepsies: assessment epilepsy. Neurology. 2001;56:1047-1051.
neonatal-infantile seizures: the phenotypic of established and newly recognized syn- 22. Matricardi S, Verrotti A, Chiarellil F, et al.
spectrum. Epilepsia. 2007;48:1138-1142. dromes. Brain. 2008;131:2264-2286. Current advances in childhood absence epi-
2. Singh NA, Westenskow P, Charlier C, et 12. Ambrosetto G, Tassinari CA. Antiepileptic lepsy. Pediatr Neurol. 2014;50(3):205-212.
al. KCNQ2 and KCNQ3 potassium chan- drug treatment of benign childhood epi- 23. Callenbach PM, Bouma PA, Geerts AT, et al.
nel genes in benign familial neonatal con- lepsy with rolandic spikes: is it necessary? Long-term outcome of childhood absence
vulsions: Expansion of the functional and Epilepsia. 1990;31:802-805. epilepsy: Dutch study of epilepsy in child-
mutation spectrum. Brain. 2003;126:2726- 13. Vears DF, Tsai MH, Sadleir LG, et al. Clin- hood. Epilepsy Res. 2009;83:249-256.
2737. ical genetic studies in benign childhood 24. Janz D. Epilepsy with impulsive petit mal
3. Biervert C, Steinlein OK. Structural and epilepsy with centrotemporal spikes. Epi- (juvenile myoclonic epilepsy). Acta Neurol
mutational analysis of KCNQ2, the major lepsia. 2012;53:319-324. Scand. 1985;72:449-459.
gene locus for benign familial neonatal 14. Loiseau P, Pestre M, Dartigues JF, et al. 25. Zifkin B, Andermann E, Andermann F.
convulsions. Hum Genet. 1999;104:234- Long-term prognosis in two forms of child- Mechanisms, genetics, and pathogenesis of
240. hood epilepsy: typical absence seizures and juvenile myoclonic epilepsy. Current Opin
4. Zonana J, Silvey K, Strimling B. Familial epilepsy with rolandic (centrotemporal) Neurol. 2005;18:147-153.

0%$)!42)# !..!,3 s 6OL  .O   e35