benign childhood epilepsy

8/6/2019 Benign Childhood Epilepsy

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Benign Childhood Epilepsyy Author: Ahmad K Kaddurah, MD; Chief Editor: Amy Kao, MD

Overview

Epilepsy is defined as 2 or more unprovoked seizures. The various types of epilepsy differ inmany aspects, including (1) age of onset, (2) semiology, (3) EEG findings, and (4) outcome. In1987, Freeman et al reported that most children with generalized tonic-clonic seizures have a

benign developmental disorder that reduces their seizure threshold and will be outgrown. [1] Thisdisorder has been termed benign childhood epilepsy and is thought to be secondary to centralnervous system (CNS) immaturity.In this article, the term benign epilepsy is used to refer to a group of pediatric epileptic disordersin which remission and lack of significant neurologic sequelae are expected in the vast majorityof patients. These disorders are idiopathic, occur in otherwise healthy children, and have (withrare exceptions) a strong genetic component. They include generalized epilepsies and partialepilepsies. These epilepsies are presented according to the age of onset, starting from theneonatal period.

Benign epilepsies in the neonatal period

Although the prognosis of neonatal convulsions remains poor, benign neonatal convulsions aredifferentiated by their generally good prognosis. Two syndromes in which no metabolic,hypoxic-ischemic, or structural etiology is apparent are benign familial neonatal convulsions and

benign idiopathic neonatal convulsions. (Regarding the former syndrome, some authors prefer toidentify it by the term familial neonatal convulsions, dispensing with the adjective benign .)

Benign generalized epilepsies in childhood and adolescence

These include generalized, as well as partial, epilepsies. The generalized epilepsies discussed arelimited to childhood absence epilepsy, which is also called pyknolepsy, and juvenile absenceepilepsy, also known as epilepsy with nonpyknoleptic absences or epilepsy with spaniolepticabsences.The benign partial epilepsies include benign partial epilepsy of childhood with centrotemporal

spikes, benign occipital epilepsy, and benign epilepsy with affective symptoms.Go to Epilepsy and Seizures for a general overview, and see the following articles for information on these specific disorders:

y First Pediatric Seizure y Benign Neonatal Convulsions y Neonatal Seizures


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y Pediatric Status Epilepticus y My oclonic Epileps y Beginning in Infanc y or Earl y Childhood y Juvenile My oclonic Epileps y y EEG in Common Epileps y Syndromes y Generalized Epilepsies on EEG

Benign Familial Neonatal Convulsions

Epidemiology

In a study from Finland, the point prevalence of active epilepsy was found to be 3.93 per 1000 inchildren aged 0-15 years; almost 1% of the patients had benign familial neonatal convulsions.Based on reports of 77 cases, boys constituted the majority (43 boys and 34 girls).

Clinical characteristics

Seizures occur in otherwise healthy neonates. Onset is usually in the first week of life; in 80% of patients, onset is on day 2 or 3 of life. However, seizures can occur any time in the neonatal period until age 3 months. Seizures may occur during sleep or wakefulness, frequency is 3-6 per day, and duration is brief (commonly 2-60 s). Seizure types vary; however, seizures most oftenare multifocal clonic, followed in frequency by focal clonic. In most cases, seizures areassociated with cyanosis due to apnea. Generalized tonic seizures occur less commonly. Seizuresmay be precipitated by feeding.

Electroencephalography

Benign familial neonatal convulsions have been proven to be epileptic by electroclinicalcorrelation. The following variable patterns are reported in interictal encephalography: (1)normal, (2) discontinuous, (3) focal or multifocal sharp waves or epileptiform patterns, and (4)theta pointu alternant.The reported ictal electroencephalogram (EEG) may show either focal or generalized patterns.Recordings of focal ictal patterns have led some authors to question the appropriateness of thecurrent international classification of benign familial neonatal convulsions as generalizedseizures. The suggestion has been made that expression of a generalized seizure may beasymmetrical, probably because the immaturity of the corpus callosum or other related structures

prevents synchronization. The electroclinical events occurring in benign familial neonatalconvulsions can occur in other types of neonatal seizures.

Genetics

Benign familial neonatal convulsion is inherited as an autosomal dominant disorder, althoughautosomal recessive mode of inheritance has been reported. The condition was first linked to a


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gene locus on arm 20q. However, genetic heterogeneity was suggested (and later established)after identification of another gene locus on band 8q24. Approximately 80% of benign familialneonatal convulsion pedigrees are due to a genetic defect on 20q13.3.In 1998, the genes responsible for benign familial neonatal convulsions were identified asvoltage-gated potassium-channel genes ( KCNQ2 on chromosome arm 20q and KCNQ3 on arm8q).

No correlation between the type of mutations involving KCNQ2 and KCNQ3 and the severity of the phenotype has been found. The potassium-channel currents may have significance in other epilepsies, because one of the antiepileptic drugs, retigabine, activates these currents.

T reatment

P henobarbital is the most commonly used drug for treatment of benign familial neonatalconvulsions; it is effective in about 75% of patients. Valproic acid and phenytoin also have beentried in some patients.Although prolonged therapy with antiepileptic drugs (AEDs) after the first few months of life

probably is not warranted, patients (when of appropriate age) and their parents should becounseled regarding the increased risk of subsequent seizures.

Prognosis

Most authors report a favorable prognosis. In a study of 69 affected individuals, seizures stopped by 6 weeks in 68% of cases. The reported range of prevalence of subsequent epilepsy is 11-22%;however, incidence of subsequent seizures after the first year of life is reported to be as high as40%. Risk of subsequent epilepsy is not restricted to benign familial neonatal convulsions linkedto arm 20q.P sychomotor development is usually normal. Ronen et al reported that 7% of patients hadlearning disabilities or mild cognitive impairments. [2]

Go to Benign Neonatal Convulsions for complete information on this topic.

Benign Idiopathic Neonatal Convulsions

Benign idiopathic neonatal convulsions represent about 4% of neonatal convulsions. However,the literature reports a significant discrepancy regarding the existence (ignored) and incidence

(up to 38% of convulsions in neonates) of this syndrome.In a study of epilepsy and epilepsy syndromes in children, benign idiopathic neonatalconvulsions represented 1% of epilepsies in children younger than 16 years.The following criteria must be present for diagnosis:

y Normal pregnanc y and deliver y y Birth after 39 weeks gestation


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y Birth Apgar score greater than 8y Seizure-free interval between birth and seizure onsety Seizure onset on da ys 4-6 of life (This is the onset in 80% of cases.)y Normal neurologic state before and between seizures (at least at the beginning of seizures)y Clonic and/or apneic seizures (never tonic)y Normal findings on biological and radiological examinationsy Brief seizures lasting 1-3 minutesy Interictal EEG with theta pointu alternant pattern

Regarding the last item above, the theta pointu alternant pattern occurs in 60% of cases. TheEEG findings may be normal or moderately altered but never of paroxysmal, inactive, or low-voltage type.Because of the timing of occurrence, these seizures were referred to initially as fifth-day fits.However, this term probably is a misnomer and should be avoided. The etiology is unknown;however, cerebrospinal fluid zinc concentration has been reported to be low in some cases. Thediagnosis remains one of exclusion, and other etiologies (eg, metabolic, infectious, structural)must be sought.Mutations in the genes responsible for benign familial neonatal convulsions could possibly befound in sporadic cases. This was suggested by Ishii et al when they reported a mutation in KCNQ2 gene in a girl with nonfamilial benign convulsions. [3] Mutations in the same gene werealso reported in 4 other patients. [4]

Benign idiopathic neonatal convulsions carry a favorable outcome, with only a few patientsreported to have transitory psychomotor retardation until the age of 1 year, febrile or afebrileconvulsions, or EEG spikes with no clinical seizures. Risk of late epilepsy is 0.5%.

The following are differences between benign familial neonatal convulsions and benignidiopathic neonatal convulsions:

y Family histor y is common in benign familial neonatal convulsions but rare (about 2%) in benignidiopathic neonatal convulsions

y Benign familial neonatal convulsions occurs earlier (da ys 2-3) than benign idiopathic neonatalconvulsions (da ys 4-5)

y Persistence of convulsions is longer in benign familial neonatal convulsionsy O ccurrence of epileps y is more frequent in benign familial neonatal convulsions

Go to Benign Neonatal Convulsions for complete information on this topic.

Benign Epilepsies in Infancy

Benign myoclonic epilepsy of infancy

Of all the myoclonic epilepsies, benign myoclonic epilepsy of infancy (also known as benigninfantile myoclonic epilepsy) is distinguished by its appearance early in life and its favorable


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prognosis. This belongs to the group of primary generalized epilepsies and is probably theequivalent of juvenile myoclonic epilepsy. Since its first description by Dravet and Bureau in1981, many other cases have been described.Go to Myoclonic Epilepsy Beginning in Infancy or Early Childhood and Juvenile MyoclonicEpilepsy for complete information on these topics.

Epidemiology

In a review of benign myoclonic epilepsy of infancy, [5] Dravet and Bureau found that thesyndrome occurs in 7% of children with myoclonus and in 2% of epileptic children aged 1-36months; 0.39 of epilepsies that begin in the first 6 years of life are benign myoclonic epilepsy of infancy. The male-to-female ratio is about 2:1. Age of onset is usually between 4 months and 3years. [5] However, as reported by Rossi et al, later onset up to 4 years and 8 months is possible. [6]

Genetics

The genetics is unknown. In 78 cases, family history of febrile seizures was present in 17% andhistory of epilepsy was noted in 27%.

Clinical symptoms

Generalized myoclonic seizures occur in otherwise healthy infants, some of whom (about 25%)have a history of isolated febrile convulsions.Myoclonia involves the axis of the body and limbs, causing head drops, upward and/or outwardmovements of the upper limbs with flexing in the lower limbs, and possible rolling of the eyes.Seizures vary in intensity from severe forms (eg, causing the child to fall suddenly) to mildforms (eg, eye closure).Episodes are brief, lasting 1-3 seconds. Less commonly, episodes may be repeated up to 10seconds, especially in older children. They do not occur in clusters and are not favored byawakening, but rather by drowsiness. Alertness may be slightly reduced with repeated seizures.The seizures are not associated with other seizure types such as absence or tonic seizures.


Findings on interictal waking EEG usually are normal for age. Spontaneous spike-wave (SW)discharges are rare. Almost all SW and polyspike-wave ( P SW) discharges have some form of clinical expression.Drowsiness and early stages of sleep activate generalized SW. During light sleep, they almostalways are accompanied by myoclonus. The discharges gradually disappear during slow-wavesleep, as does the myoclonus.Clinical and EEG photosensitivity are present in one third of patients. Ictal EEG recordings showgeneralized fast SW or P SW accompanying the myoclonus.


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In a study of 22 patients with benign myoclonic epilepsy of infancy, Darra et al reported that theictal EEG discharges were often focal, being limited to the rolandic and vertex regions, andconcluded that seizures are rarely truly generalized. [7]

T reatment

Seizures usually are controlled easily by sodium valproate monotherapy. If seizures are notcontrolled, other proposed medications include benzodiazepines (ie, clobazam, nitrazepam,clonazepam) and ethosuximide. P henobarbital has also been tried.

Evolution and prognosis

The seizure outcome is favorable. The myoclonias have disappeared in all reported patients whowere monitored. In most patients, they lasted less than a year, with the longest duration being upto 6 years and 4 months. On long-term follow-up, 18% of patients had other seizure types, with

some having rare generalized tonic-clonic seizures .The psychological evolution of the patients is less favorable than is the clinical evolution of seizures. In 1996, Dravet and Bureau noted that the psychological outcome was normal in 83%of 69 cases in whom the outcome was precisely known. However, this outcome is controversial.Some authors have indicated that a high incidence of neuropsychological and intellectualdisorders occur in patients with benign myoclonic epilepsy of infancy. [8] In a report by Darra et alon 22 patients, 2 had significant cognitive impairment, and 3 had a significant learningimpairment at follow-up. [7] The earlier age of onset may be one of the main factors associatedwith less favorable outcome. Other factors may involve delay in treatment or the efficacy of drugs.

Differential diagnosis in benign myoclonic epilepsy of infancy

Clinical features, as well as the associated EEG findings, help to differentiate benign myoclonicepilepsy of infancy from nonepileptic conditions and other epileptic syndromes.The following are nonepileptic conditions that may be mistaken for benign myoclonic epilepsyof infancy:

y Physiologic m yoclonusy Benign nonepileptic m yoclonusy H yperekplexia (startle disease)y Shuddering attacks

Epileptic syndromes that may resemble benign myoclonic epilepsy of infancy include thefollowing:

y W est s yndrome


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y Severe m yoclonic epileps y in infanc y y Early onset Lennox-Gastaut s yndrome y My oclonic-astatic epileps y (Doose s yndrome)

Reflex benign myoclonic epilepsy of infancy

In a subgroup of patients, myoclonic jerks may be triggered by tactile or sudden acoustic stimuli,referred to as reflex benign myoclonic epilepsy of infancy. These may or may not be associatedwith spontaneous jerking. Although some authors have tried to distinguish between reflex benignmyoclonic epilepsy of infancy and the classic form, Dravet and Bureau did not think such adistinction was necessary in their 1996 article.

Benign partial epilepsy with complex partial seizures

Described by Watanabe et al, [9]complex partial seizures often occur in clusters and are

manifested in the following ways:

y Arrested motiony Staring spellsy Decreased responsivenessy Automatisms with mild convulsive movements

Features of benign partial epilepsy with complex partial seizures include the following:

y Family histor y of benign seizures (often)y Normal development prior to onsety O nset usuall y at age 3-10 months (ranges to 20 mo)y No underl ying disordersy Normal findings on interictal EEGsy Good response to treatmenty Normal developmental outcome

Childhood Absence Epilepsy

Epidemiology

Annual incidence has been estimated at 1-8 per 100,000 in children aged 0-15 years, making up8% of epilepsy cases in school-aged children (probable). Girls represent 60-76% of patients.Onset ranges from ages 3-13 years, with a peak at ages 6-7 years.Also see Absence Seizures .


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y Absence with automatisms that are either perseverative (ie, the patient persists in what he isdoing) or de novo, such as lip smacking or swallowing (60%)

y Absence with autonomic components (eg, pupillar y dilatation, flushing, tach ycardia)


The background is usually normal, although mild abnormalities may be accepted. Interictalsingle or brief bilateral SW discharges are frequent. These are more abundant during nonrapideye movement (REM) sleep.During the ictal period, absence seizures are associated with bilaterally synchronous andsymmetrical SW discharges that begin abruptly and synchronously in both hemispheres but endless abruptly. The SW discharges occur at a frequency of 3 Hz, may slow to 2-2.5 Hz toward theend, and have the highest amplitude in the frontocentral regions.

Prognosis and evolution

P rognostic parameters need to include the seizure and the psychosocial prognosis. The reported percentage of patients who become seizure free varies widely, ranging from 33-79.3%.The longer the follow-up, the smaller the percentage of patients whose seizures are controlled;many patients develop generalized tonic-clonic seizures later in the course of the epilepsy.Absence seizures persist in about 6% of cases (although they become less frequent). Generalizedtonic-clonic seizures develop in about 40% of patients. They are infrequent, easily controlled,and generally occur 5-10 years after the onset of absences.Juvenile myoclonic epilepsy is reported to occur in 44% of patients who do not have remissionof their seizures.P roblems with cognition, social adaptation, or behavior are not uncommon. Such difficulties mayoccur in one third of patients.Caplan et al, reporting on 69 patients with childhood absence epilepsy and 103 age- and gender-matched children, found that in patients with childhood absence epilepsy, 25% had subtlecognitive deficits; 43% had linguistic difficulties; 61% had a psychiatric diagnosis, particularlyattention deficit hyperactivity disorder (ADHD) and anxiety disorders; and 30% had clinicallyrelevant child behavior checklist (CBCL) broad band scores. [20]

Differential diagnosis

Childhood absence epilepsy must be differentiated from the following conditions:

y Absence seizures with late adolescent onsety Symptomatic absence epileps y (eg, Sturge- W eber s yndrome , lipidosis, brain tumors, and

mo yamo ya disease [21] )y Epileps y with other seizure t ypes preceding absences (impl ying a worse prognosis)y My oclonic absences


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y Absence seizures associated with an unusual EEG pattern

T reatment

Ethosuximide and valproate each suppress absence seizures in more than 80% of patients.

Valproate has the advantage of also controlling generalized tonic-clonic seizures. For refractoryseizures, both medications can be used in combination. Lamotrigine may also be effective asmonotherapy. According to a Cochrane Database review of the use of ethosuximide, sodiumvalproate, and lamotrigine in absence seizures, [22] evidence was insufficient to recommend aspecific medication as a best choice for clinical practice. Levetiracetam [23, 24] and zonisamide [25]

may also be effective. Acetazolamide and benzodiazepines, especially clonazepam, are other options. These alternate medications are useful for absence status.In a double-blind, randomized, controlled trial, Glauser et al compared the efficacy of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed absence seizuresand found that ethosuximide and valproic acid were more effective than lamotrigine for thetreatment of newly diagnosed absence seizures. [26]

Children in the study were randomly assigned to treatment with ethosuximide ( n =156),lamotrigine ( n =149), or valproic acid ( n =148). After 16 weeks of therapy, the freedom-from-failure rates for ethosuximide and valproic acid were similar (53% and 58%) and were higher than the rate for lamotrigine (29%).

Juvenile Absence Epilepsy

Epidemiology

The epidemiology has not been well studied, but juvenile absence epilepsy is less common thanchildhood absence epilepsy. It is reported to represent 2.4% of epilepsies in children aged 0-15years, compared with 12.1% for childhood absence epilepsy. Age of onset is 7-16 years with a

peak age of 10-12 years. The sexes are affected with equal frequency.

Genetics

Incidence of epilepsy is increased in families of patients with juvenile absence epilepsy; thefrequency appears to resemble that in childhood absence epilepsy. One study suggested thatallelic variants of the kainate-selective glutamate receptor GluR5 gene ( GRI K 1 ) on chromosomesubband 21q22.1 contribute a major genetic determinant to the pathogenesis of juvenile absenceepilepsyrelated phenotypes.


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Clinical features

As in childhood absence epilepsy, children with juvenile absence epilepsy usually areneurologically normal. Absence seizures occur in all cases. Compared with childhood absenceepilepsy, however, absence seizures in juvenile absence epilepsy have the following features:

y R elative infrequenc y, with onl y a few episodes dail y y Longer duration, with a mean of 16 7 secondsy Less impairment of consciousnessy Less retropulsive in movements

Absence status is relatively common. A tonic-clonic seizure can be the presenting feature,occurring shortly after awakening. This type of seizure occurs in 80% of patients. Myoclonicseizures occur in about 15% of patients.


Background is usually normal. Characteristic features are the ictal and interictal generalizedsymmetrical spike-and-wave discharges with frontal accentuation. The SW frequency usually isa fast SW at 3.5-4 Hz and can be precipitated easily by sleep withdrawal and by hyperventilation.P hotosensitivity is unusual.

T reatment and prognosis

Valproate is the drug of choice, because it controls absences and the other associated seizure

types in about 80% of cases. Levetiracetam may be effective.[23, 24]

Treatment choices include (1)lamotrigine (either as monotherapy or in combination with valproate), (2) ethosuximide incombination with valproate, or (3) acetazolamide in combination with valproate. The long-termevolution has not been well established, but the prognosis is worse than that of childhoodabsence epilepsy.

Benign Epilepsy of Childhood With Centrotemporal Spikes

A benign partial epilepsy of childhood, this condition, benign epilepsy of childhood withcentrotemporal spikes (BECCT), is defined within the International League Against Epilepsy(ILAE) classification scheme as an idiopathic age- and localization-related epileptic syndromewith a combination of clinical and EEG characteristics used for diagnosis.This epileptic syndrome is characterized by brief, simple partial and hemifacial motor seizureswith associated somatosensory symptoms, which have a tendency to evolve into generalizedtonic-clonic seizures. EEG shows high-voltage centrotemporal spikes often followed by a slowwave. BECCT is also known as lingual epilepsy, sylvian seizures, benign centrotemporalepilepsy, and benign rolandic epilepsy.


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If the patient has the typical clinical history and EEG findings and has normal findings onneurologic examination, further workup is not indicated. However, in the presence of atypicalfeatures or abnormal examination findings, the use of magnetic resonance imaging (MRI) isindicated.Benign rolandic epilepsy has been reported to occur in the presence of CNS pathology. However,in most of these reported instances, the BECCT was probably coincidental.

Epidemiology

BECCT is the most common epilepsy syndrome in childhood. In Connecticut, USA, it represents9.6% of all epilepsies in children aged 0-15 years. However, BECCT and its variants mayrepresent 20-25% of epilepsy cases diagnosed in patients aged 5-15 years.Studies from other countries show that BECCT accounts for 6.5-16% of all childhood epilepsy.In a study from India, however, it represented only 1.6% of epilepsies in children younger thanage 16 years. In a study from Italy, epilepsies with rolandic foci accounted for up to 23.9% of epilepsies in children aged 4-15 years.Reported incidence of seizures with central temporal spikes ranges from 10.7-21 per 100,000.Age of onset ranges from 2-13 years but usually is between 4 and 11 years, and frequency of onset peaks at 5-9 years. The disorder occurs more commonly in boys; the boy-to-girl ratio is6:4. A study by Kramer et al found no gender difference in incidence. [27]

Clinical manifestations of seizures

The syndrome is termed rolandic epilepsy because of the characteristic features of partialseizures involving the region around the lower portion of the central gyrus of Rolando.Common characteristic features include the following:

y U nilateral somatosensor y involvement, mostl y of the tongue (occasionall y of the inner cheeks,lips, gums, or even a single tooth)

y Speech arresty Preservation of consciousness in most casesy Pooling of salivay Tonic or tonic-clonic spread to face

Less often, sensory spread to the face or arms occurs; very rarely, a typical jacksonian marchoccurs. Other features include (1) absence of psychic symptoms, (2) rarity of complexautomatisms, and (3) absence of amnesia and postictal confusion states.BECCT is associated with the following 3 types of nocturnal seizures:

y Typical brief hemifacial seizures associated with speech arrest, drooling, and preservation of consciousness (identical to diurnal seizures)


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evaluated, indicated that attention systems are impaired in children with active centrotemporalspikes. The impairments resolve upon EEG remission. [28]

A study by Connolly et al found that the quality of life in children with BECCT may becompromised. [29] The compromise, which affects domains such as competence and psychosocialfunction, may be related to a cognitive variable and the emotional impact of the child's epilepsyon the parent.

No evidence exists to suggest that BECCT causes neurologic or behavioral abnormalities.

Genetics

BECCT is considered to be of genetic origin. Some patients have significant family history of epilepsy or centrotemporal spikes, although the exact frequencies vary, with a range of 9-59%.Isolated EEG abnormalities (including rolandic spikes) are common in families of patients withBECCT. One study reported that at least 1 close relative had a temporal spike or SW discharge inup to 30% of the families. In another study, 15% of siblings of probands had seizures androlandic discharges, whereas 19% had rolandic discharges alone.Centrotemporal sharp and spike activity on EEG has been proposed to be an autosomal dominanttrait with age-dependent penetrance. Only 12% of affected individuals have even had a seizure.P enetrance is low during the first 5 years of life, approximates 50% between ages 5 and 15 years,and then drops off to a low value after age 20 years. Whether a given child with the EEG traitdevelops epilepsy depends on a variety of inherited factors. Therefore, BECCT is inheritedmultifactorially rather than in an autosomal dominant fashion.Some individuals with benign neonatal seizures have later developed BECCT. Linkage studiesfailed to establish a relationship between BECCT and benign familial neonatal convulsions. Two

loci previously thought to be linked with BECCT, the human leukocyte antigen (HLA) region onarm 6p and the fragile X site, have been excluded.In a study, Neubauer et al found evidence for linkage of BECCT to a region on band 15q14. [30]

In 1995, a new autosomal dominant syndrome was characterized by rolandic epilepsy, oral andspeech dyspraxia, and cognitive dysfunction, with electroclinical features that resembledBECCT. Clinical anticipation was found in the family described in the study, suggesting that thegenetic mechanism could be an expansion of an unstable triplet repeat.

Etiology

BECCT arises from the lower portion of the central gyrus of Rolando. Because BECCT is agedependent, has a strong genetic predisposition and an excellent prognosis, and occurs instructurally normal brains, it most likely represents hereditary brain maturation.Many children with the EEG trait never develop seizures. Whether a child develops seizuresdepends on many factors, which may be hereditary. There may be an inhibitory factor that iscapable of preventing seizures but can be broken through by external or internal elements.


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EEG findings in BECCT are distinctive. The typical interictal EEG shows centrotemporal spikesor SW, which are either unifocal or bifocal. The spikes are usually slow, high voltage, anddiphasic. Typical findings include a negative SW with a blunted peak preceded by a small

positive wave and followed by a prominent positive wave with amplitude frequently up to 50%of the preceding negative SW.When the SWs are unilateral, they are always synchronous in the central and midtemporal areas,although sometimes of different amplitudes. When bilaterally asynchronous, the spikes vary infrequency and amplitude from side to side. They can occur singly or in clusters. In about 40% of

patients, the spikes are bilateral on initial or subsequent EEG records.Sleep and drowsiness activate the spikes. Centrotemporal spikes are present only during sleep inas many as 30% of patients. Obtain a sleep recording if BECCT is suspected on clinical groundswhen the awake EEG is not revealing. Spike discharges are not altered significantly by photicstimulation or hyperventilation.Rolandic spikes usually occur on a normal background. When the spikes occur frequently,however, a focal pseudoslowing occurs that is secondary to the slow-wave component of thespikes.Typically, the centrotemporal spikes have a horizontal dipole, with maximal electronegativity inthe centrotemporal region and electropositivity in the frontal region. This suggests that the spikesare the result of a generator located in the lower rolandic region where the zero potential exists

between the frontal positivity and centrotemporal negativity.Rolandic discharges having the same dipole field can be seen in children without clinicalseizures and in children with epilepsy who do not have typical benign rolandic seizures. The

spikes included with BECCT may be located in many areas other than the typical central-midtemporal areas.The morphology of the spikes (rather than the location) is the distinctive factor in identifying thedischarge in association with the benign rolandic epilepsy. Insistence on a centrotemporallocation for the EEG may lead to a misclassification of the type of epilepsy. The term benignfocal epilepsy of childhood also has been used, and when the discharge is located in thecentrotemporal region, it is called benign focal epilepsy of childhood with a centrotemporal (or rolandic) location.


Benign rolandic epilepsy must be differentiated from the following:

y R olandic spikes and no seizures (often with behavior problems, headaches, or autonomicdysfunction)

y R olandic spikes and a histor y of antecedent brain damage, cerebral pals y, or active localpatholog y


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y Central spikes occurring commonl y in R ett s yndrome and fragile X s yndromey M alignant rolandic epileps y y Psychomotor seizures and evolving temporal lobe epileps y y The aphasia-convulsion (Landau-Kleffner) s yndrome and massive midtemporal spikes

T reatment

In view of the benign nature of the condition, intensive therapy is unnecessary. In the case of infrequent nocturnal partial seizures, withholding AEDs is reasonable if the child and family arecomfortable with this approach.One study found that in treated patients with BECCT, the frequency and duration seizures andthe prevalence of active epilepsy were no different from those in untreated patients with thesyndrome.If treatment is indicated, carbamazepine is often the first medication to be tried, and seizuresusually are well controlled. Once-a-day administration may be the only regimen needed tocontrol seizures. Other reportedly effective AEDs include phenobarbital, phenytoin, valproicacid, clonazepam, clobazam, gabapentin, and sulthiame. Levetiracetam may also be effective andwell tolerated. [31]

Although most patients respond to a low dose of a single drug, a few have seizures that arehighly drug resistant. No correlation is known between resistance to AEDs and final outcome.Duration of treatment may be shorter in some cases than epilepsy in general, and AEDs may bediscontinued successfully in patients with normal EEG findings who have been seizure free for more than 2 years.

Prognosis

By general consensus, the prognosis of BECCT is excellent, as almost all patients achieveremission by adolescence. This includes patients whose seizures have been drug resistant.A meta-analysis study on the course of BECCT found that 50% of patients were in remission byage 6 years; by age 18 years, 99.8% of the patients were in remission. Rarely, BECCT canrelapse in adulthood; about 2% of patients in BECCT remission experience other seizure types.

Benign Partial Epilepsy of Childhood With Occipital Paroxysms

The understanding of the syndrome of benign partial epilepsy with occipital paroxysms (alsocalled benign occipital epilepsy of childhood) has evolved significantly with time. Thesyndrome, as first described by Gastaut, was initially the only childhood occipital epilepsysyndrome recognized by ILAE. It is characterized by seizures that start with visual symptoms,which often are followed by hemiclonic seizures or automatisms and, in some cases, migrainousheadaches. The EEG findings include paroxysms of rhythmic occipital and posterior temporalspikes when the eyes are closed.


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However, this concept was challenged by P anayiotopoulos in 1989, when he described an early-onset syndrome characterized mainly by ictal vomiting, head and eye deviation, and, sometimes,

prolonged periods of loss of awareness. The syndrome was later incorporated into the ILAE asearly-onset childhood epilepsy with occipital spikes ( P anayiotopoulos type). This is also calledP anayiotopoulos syndrome. This was confirmed by many authors, including P anayiotopoulos,Caraballo et al, [32] and Lada et al. [33] This was found to be a much more common syndrome thanthe first recognized one, which is now known as late-onset childhood epilepsy with occipitalspikes (Gastaut type).According to a consensus conference, [34] P anayiotopoulos syndrome is defined as "a benign age-related focal seizure disorder occurring in early and mid childhood. It is characterized byseizures, often prolonged, with predominantly autonomic symptoms, and by an EEG that showsshifting and/or multiple foci, often with occipital predominance." The group of internationalresearchers in the conference concluded that the syndrome should be classified as an autonomicepilepsy rather than as an occipital epilepsy.

Epidemiology

Benign occipital epilepsy of childhood is less common than BECCT. P revalence depends onselection criteria. The P anayiotopoulos syndrome is much more common than the late-onsetGastaut-type.As noted by P anayiotopoulos in 4 independent studies of 607 patients, the prevalence of P anayiotopoulos syndrome was found to be 2.4 times lower than that of rolandic epilepsy. Thismeans that around 6% of children with seizures have P anayiotopoulos syndrome, with theassumption of 15% prevalence of rolandic epilepsy.

Age of onset is 3-6 years in 80% of patients, with a mean age of 5 years and a range of 1-12years. The Gastaut type of childhood occipital epilepsy is estimated to make up 2-10% of benignchildhood partial seizures. The mean age of onset is 8 years, with a range of 3-15 years. Bothsexes seem to be affected with equal frequency in both syndromes, although this is not reportedconsistently.

Clinical features

In P anayiotopoulos syndrome, seizures make up an unusual constellation of autonomic, mainlyemetic, symptoms, often with unilateral deviation of eyes and other, more conventional,

symptoms. Seizures are nocturnal in about two thirds of patients. The full emetic triad (ie,nausea, retching, vomiting) culminates in vomiting in 74% of seizures.Other autonomic symptoms may occur, including color change (especially pallor), but alsoflushing and cyanosis. P upillary changes, particularly mydriasis, also may occur. Less often,miosis, hypersalivation, and bladder incontinence occur. Even less often, bowel incontinence,abnormal intestinal motility, and cardiorespiratory and thermoregulatory alterations are reported.


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Brief apnea and irregular or heavy breathing is reported to occur in 7% of cases. Ictalcardiorespiratory arrest has also been reported. Headache and cephalic auras that may beautonomic manifestations may occur, particularly at onset.More conventional symptoms may follow, including confusion or unresponsiveness, eye andhead deviation to one side (60%), wide opening of the eyes without deviation, speech arrest,hemifacial spasms, and visual symptoms or hallucinations (6-9%). The seizures may end withhemiconvulsions, often with jacksonian march (19%) or generalized convulsions (21%). Ictalsyncope or a syncopelike episode has been reported to occur in one fifth of cases. These manifestas the child becoming unresponsive and flaccid.Typically, the seizures are infrequent but long; 44% have seizures lasting 30 minutes or more,consisting of autonomic status epilepticus. Hemiconvulsive or generalized convulsive statusepilepticus is rare (2%). One third of patients have a single seizure only. About half have 2-5seizures. Only 5% have more than 10 seizures.In late-onset childhood epilepsy with occipital spikes (Gastaut type), clinical semiology is

complex and is characterized by ictal and postictal symptoms. Visual symptoms include (1)transient, partial, or complete loss of vision, (2) elementary or complex visual hallucinations, and(3) visual illusions (eg, micropsia, metamorphosis). Elementary visual hallucinations are thecommonest and most characteristic ictal symptoms. These consist of small, multicolored, circular

patterns that often appear in the periphery of a visual field, becoming larger and multiplying inthe course of the seizure. Nonvisual ictal symptoms include adversive (versive) seizuremanifested as tonic deviation of head and eyes. These are the most common of the ictal motor

phenomena.Other motor seizures include (1) hemiclonic convulsions, (2) complex partial seizures withautomatisms, and (3) generalized clonic seizures. Other ictal manifestations include dysphasia

and dysesthesia. Seizures are commonly diurnal and usually frequent. They are typically short,lasting seconds to less than 3 minutes. Other symptoms include postictal, diffuse, throbbingheadache in about half of the patients and vomiting in about 10%. Ictal headache, mainly orbital,is rare.Typically, children with both syndromes have normal findings on neurologic examinations.However, as with BECCT, neurologic abnormalities or developmental disorders may be presentin a small number of children. This was affected by the selection criteria of the authors.

Genetics

Reported numbers regarding family history are affected by selection criteria. A family history of seizures in approximately more than a third of cases and of migraines in about 20% of cases has

been reported in patients with late-onset childhood epilepsy with occipital spikes (Gastaut type).In P anayiotopoulos syndrome, reported family history of epilepsy ranged from none to 30% of

patients and febrile seizure from 17-25% of patients.


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In the late-onset Gastaut type, the interictal EEG shows normal background and distinct paroxysms of spikes, spike-and-wave, or SW with high amplitude typically over the occipitaland adjacent head regions. These could be unilateral or bilateral and synchronous or

asynchronous. Discharges can occur singly or in trains of 1-3 Hz and usually are attenuated byeye opening and occur again with eye closure.The occipital paroxysms are actually induced by elimination of visual fixation and central vision(fixation-off sensitivity) rather than by darkness. Response to hyperventilation or photicstimulation is variable. Generalized spike-and-wave discharges, multiple spike-and-wavedischarges, or central temporal or frontal spikes have been reported. Ictal EEGs show suddenoccipital discharges.The interictal EEG in P anayiotopoulos syndrome commonly reveals functional, mainlymultifocal, high-amplitude sharp- and slow-wave complexes, with great variability at variouselectrode locations. All brain regions are involved, although the posterior predominate. Aboutone third of patients never show occipital spikes.Some authors have argued not to equate P anayiotopoulos syndrome with occipital epilepsy. [34, 35]

In a study of EEG changes involving 76 children with P anayiotopoulos syndrome, Ohtsu et alfound that occipital EEG spike focus was most frequently seen in children aged 2-5 years. [36]

Frontopolar and occipital spike pattern was seen in seizures of later age of onset.


Occipital spikes, like other focal spikes, can exist without clinical epilepsy. They can also be

noted in children with visual impairment.Benign occipital epilepsy of childhood should be differentiated from other symptomatic forms of occipital lobe seizures due to underlying pathology (eg, atrophic, neoplastic, degenerative).Examples include the following:

y Sturge- W eber s yndromey Epileps y with bilateral occipital calcificationy Late infantile neuronal ceroid lipofuscinosisy H ematomay Tuberous sclerosisy

Cortical d ysplastic tumorsy Inflammator y processesy M itochondrial encephalom yopathies

Careful neurologic examination, developmental history, and brain imaging are necessary toverify or rule out the existence of benign primary occipital epilepsy.


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Benign occipital epilepsy of childhood should be differentiated from other forms of primary partial epilepsy (eg, BECCT).Migraines and epileptic syndromes can be confused and often coexist.

T reatment

Carbamazepine may be the drug of choice, although almost all of the classic anticonvulsants (eg, phenobarbital, valproate, benzodiazepines) are effective.In P anayiotopoulos syndrome, education about the nature and prognosis of the syndrome is thecornerstone of correct management. Regular antiepileptic drug treatment is probably mostappropriately reserved for those children in whom seizures are unusually frequent or distressingor are otherwise significantly interfering in the life of the child.P rolonged seizures may be treated with rescue benzodiazepines. No evidence indicates that any

particular antiepileptic drug is more efficacious than any other. [34] Although many authorsrecommend carbamazepine as drug of choice, on rare occasions this medication worsensseizures. [37]

Prognosis

P rognosis is usually good but is more favorable with P anayiotopoulos syndrome, which isconsidered as a remarkably benign condition despite high incidence of autonomic statusepilepticus. Seizure frequency, as noted above, is very low. Seizure remission usually occurswithin 1-2 years of seizure onset and occasionally up to 8 years, as reported in a series byCaraballo. [32] Some patients may develop other seizure types, mostly age-related seizures, such as

benign rolandic seizures. In the late-onset childhood epilepsy with occipital spikes (Gastauttype), remission can occur in 50-60% of cases, often within 2-5 years of onset.

Benign Epilepsy With Affective Symptoms (Benign Psychomotor Epilepsy)

In 1995, Della Bernardina et al described a group of 26 children with complex partial seizures inwhom affective symptoms (predominantly fear) were the major clinical features. The childrenwere aged 7-17 years.

Epidemiology

Age of onset in the study ranged from 2-9 years, with no sexual predilection.

Clinical data

The predominant feature of the seizures in the Bernardina study was sudden terror or fright in the patient, manifested by screaming or yelling or by the patient calling for or clinging to his or her mother. The patients terrorized expression was associated sometimes with chewing, swallowing,


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distressed laughter, arrest of speech, salivation, moaning, or autonomic manifestations (eg, pallor, sweating, abdominal pain).Associated changes in awareness occurred with no complete loss of consciousness. The meanduration of the events was 1-2 minutes. P ostictal lethargy was associated with the events. Notonic, atonic, or tonic-clonic seizures were reported.

Genetics

Family history is positive in 38% of cases. Five of the 26 children in the Bernardina study had ahistory of febrile seizures.


In the Bernardina study, the background activity was normal. Seventy-three percent of the patients had slow spike or slow waves involving the frontotemporal and parietotemporal areas of

1 or both hemispheres. Other abnormalities included unilateral rhythmic frontotemporal or parietotemporal SW and brief bursts of generalized spike waves (alone or in association with theabove-mentioned abnormalities).

Prognosis

In the study, the course of the syndrome appeared to be benign; 3 patients never receivedtreatment. Twenty-one patients responded to antiepileptic medications (usually carbamazepine or

phenobarbital). In 2 cases, infrequent seizures persisted for months or years despite treatment, but ultimately disappeared.

benign childhood epilepsy

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