AUTHOR AND EDITOR INFORMATION

Section 1 of 7  

• Authors and Editors
• Introduction
• Benign Epilepsies in the Neonatal Period
• Benign Epilepsies in Infancy
• Benign Generalized Epilepsies in Childhood and Adolescence
• Benign Partial Epilepsies of Childhood
• References

INTRODUCTION

Section 2 of 7  

• Authors and Editors
• Introduction
• Benign Epilepsies in the Neonatal Period
• Benign Epilepsies in Infancy
• Benign Generalized Epilepsies in Childhood and Adolescence
• Benign Partial Epilepsies of Childhood
• References

Epilepsy is defined as 2 or more unprovoked seizures. The various types of epilepsy differ in many aspects, including (1) age of onset, (2) semiology, (3) EEG findings, and (4) outcome. In 1987, Freeman et al reported that most children with generalized tonic-clonic (GTC) seizures have a "benign developmental disorder" that reduces their seizure threshold and will be outgrown. This disorder has been termed benign childhood epilepsy and is thought to be secondary to CNS immaturity.

In this article the term benign epilepsy is used to refer to a group of pediatric epileptic disorders in which remission and lack of significant neurologic sequelae are expected in the vast majority of patients. These disorders are idiopathic, occur in otherwise healthy children, and have (with rare exceptions) a strong genetic component. They include both generalized epilepsies and partial epilepsies. These epilepsies are presented according to the age of onset, starting from the neonatal period.

For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education article Epilepsy.

BENIGN EPILEPSIES IN THE NEONATAL PERIOD

Section 3 of 7  

• Authors and Editors
• Introduction
• Benign Epilepsies in the Neonatal Period
• Benign Epilepsies in Infancy
• Benign Generalized Epilepsies in Childhood and Adolescence
• Benign Partial Epilepsies of Childhood
• References

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

Benign familial neonatal convulsions

Epidemiology

In a study from Finland, the point prevalence of active epilepsy was found to be 3.93 per 1000 in children aged 0-15 years; almost 1% of the patients had BFNC. 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 often are multifocal clonic, followed in frequency by focal clonic. In most cases, seizures are associated with cyanosis due to apnea. Generalized tonic seizures occur less commonly. Seizures may be precipitated by feeding.

Electroencephalography

BFNC have been proven to be epileptic by electroclinical correlation. The following variable patterns are reported in interictal EEG: (1) normal, (2) discontinuous, (3) focal or multifocal sharp waves or epileptiform patterns, and (4) theta pointu alternant. The reported ictal EEG may show either focal or generalized patterns. Recordings of focal ictal patterns have led some authors to question the appropriateness of the current international classification of BFNC as generalized seizures. The suggestion has been made that expression of a generalized seizure may be asymmetrical, probably because the immaturity of the corpus callosum or other related structures prevents synchronization. The electroclinical events occurring in BFNC can occur in other types of neonatal seizures.

Genetics

BFNC is inherited as an autosomal dominant disorder, although autosomal recessive mode of inheritance has been reported. The condition was first linked to a gene locus on chromosome arm 20q. However, genetic heterogeneity was suggested (and later established) after identification of another gene locus on chromosome band 8q24. Approximately 80% of BFNC pedigrees are due to a genetic defect on 20q13.3. In 1998, the genes responsible for BFNC were identified as voltage-gated potassium channel genes (KCNQ2 on chromosome arm 20q and KCNQ3 on chromosome arm 8q). 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.

Treatment

Phenobarbital is the most commonly used drug for treatment of BFNC; it usually is effective in about 75% of patients. Valproic acid and phenytoin also have been tried in some patients.

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 as 40%. Risk of subsequent epilepsy is not restricted to BFNC linked to chromosome arm 20q. Psychomotor development is usually normal. In 1993, Ronnen et al reported that 7% of patients had learning disabilities or mild cognitive impairments.

Some authors prefer the term familial neonatal convulsions without the adjective benign. 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 be counseled regarding the increased risk of subsequent seizures.

Benign idiopathic neonatal convulsions

BINC represents 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 recent study of epilepsy and epilepsy syndromes in children, BINC represented 1% of epilepsies in children younger than 16 years.

The following criteria must be present for diagnosis:

• Normal pregnancy and delivery
• Birth after 39 weeks of gestation
• Birth Apgar score greater than 8
• Seizure-free interval between birth and seizure onset
• Seizure onset on days 4-6 of life (This is the onset in 80% of cases.)
• Normal neurologic state before and between seizures (at least at the beginning of seizures)
• Clonic and/or apneic seizures (never tonic)
• Normal findings on biological and radiological examinations
• Interictal EEG with theta pointu alternant pattern
  • This pattern occurs in 60% of cases.
  • The EEG findings may be normal or moderately altered but never of paroxysmal, inactive, or low-voltage type.
• Brief seizures lasting 1-3 minutes

Because of the timing of occurrence, these seizures were referred to initially as fifth day fits. However, this term probably represents a misnomer and should be avoided. The etiology is unknown; however, cerebrospinal fluid zinc concentration has been reported to be low in some cases. The diagnosis remains one of exclusion, and other etiologies (eg, metabolic, infectious, structural) must be sought. BINC carries a favorable outcome, with only a few patients reported to have transitory psychomotor retardation until the age of 1 year, febrile or afebrile convulsions, or EEG spikes with no clinical seizures. Risk of late epilepsy is 0.5%.

The following are differences between BFNC and BINC:

• Family history is common in BFNC but rare (about 2%) in BINC.
• BFNC occurs earlier (days 2-3) than BINC (days 4-5).
• Persistence of convulsions is longer in BFNC.
• Occurrence of epilepsy is more frequent in BFNC.

BENIGN EPILEPSIES IN INFANCY

Section 4 of 7  

• Authors and Editors
• Introduction
• Benign Epilepsies in the Neonatal Period
• Benign Epilepsies in Infancy
• Benign Generalized Epilepsies in Childhood and Adolescence
• Benign Partial Epilepsies of Childhood
• References

Benign epilepsies that occur during infancy include (1) benign myoclonic epilepsy of infancy (BMEI), (2) benign partial epilepsy with complex partial seizures, and (3) benign infantile familial convulsions. The first 2 are discussed here.

Benign myoclonic epilepsy of infancy

Of all the myoclonic epilepsies, BMEI (also known as benign infantile myoclonic epilepsy) is distinguished by its appearance early in life and its favorable prognosis. This belongs to the group of primary generalized epilepsies and is probably the equivalent of juvenile myoclonic epilepsy. Since its first description by Dravet and Bureau in 1981, many other cases have been described.

Epidemiology

In 2005, Dravet and Bureau made an updated review of BMEI, in which they mention 120 cases. The syndrome occurs in 7% of children with myoclonus and 2% of epileptic children aged 1-36 months; 0.39 of epilepsies that begin in the first 6 years of life are BMEI. The male-to-female ratio is about 2:1. Age of onset is usually between 4 months and 3 years. However, as reported by Rossi et al in 1997, later onset up to 4 years and 8 months is possible.

Genetics

The genetics is unknown. In 78 cases, family history of febrile seizures was present in 17% and history 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 outward movements 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 mild forms (eg, eye closure). Episodes are brief, lasting 1-3 seconds. Less commonly, episodes may be repeated up to 10 seconds, especially in older children. They do not occur in clusters and are not favored by awakening, 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.

In a subgroup of patients, myoclonic jerks may be triggered by tactile or sudden acoustic stimuli, referred to as reflex BMEI. These may or may not be associated with spontaneous jerking. Although some authors have tried to distinguish between reflex BMEI and the classic form, Dravet and Bureau did not think such a distinction is necessary in their 1996 article.

Electroencephalography

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

Treatment

Seizures usually are controlled easily by sodium valproate monotherapy. If seizures are not controlled, other proposed medications include benzodiazepines (ie, clobazam, nitrazepam, clonazepam) or ethosuximide. Phenobarbital has also been tried.

Evolution and prognosis

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

The psychological evolution of the patients is less favorable than 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, such as Mangano et al in a 2005 article that described 7 cases, have indicated high incidence of neuropsychological and intellectual disorders. The earlier age of onset may be one of the main factors associated with less favorable outcome. Other factors may involve delay in treatment or the efficacy of drugs.

Differential diagnosis

Clinical features as well as the associated EEG findings help differentiate BMEI from both nonepileptic conditions and other epileptic syndromes.

The following are nonepileptic conditions that may be mistaken for BMEI:

• Physiologic myoclonus
• Benign nonepileptic myoclonus
• Hyperekplexia (startle disease)
• Shuddering attacks

Epileptic syndromes that may resemble BMEI include the following:

• West syndrome
• Severe myoclonic epilepsy in infancy
• Early onset Lennox-Gastaut syndrome
• Myoclonic-astatic epilepsy (Doose syndrome)

Benign partial epilepsy with complex partial seizures

Described by Watanabe et al in 1987, these seizures often occur in clusters and are manifested in the following ways:

• Arrested motion
• Staring spells
• Decreased responsiveness
• Automatisms with mild convulsive movements

Features of this condition include the following:

• Family history of benign seizures (often)
• Normal development prior to onset
• Onset at 3-10 months usually (ranges to 20 mo)
• No underlying disorders
• Normal findings on interictal EEGs
• Good response to treatment
• Normal developmental outcome

BENIGN GENERALIZED EPILEPSIES IN CHILDHOOD AND ADOLESCENCE

Section 5 of 7  

• Authors and Editors
• Introduction
• Benign Epilepsies in the Neonatal Period
• Benign Epilepsies in Infancy
• Benign Generalized Epilepsies in Childhood and Adolescence
• Benign Partial Epilepsies of Childhood
• References

These include generalized as well as partial epilepsies. The generalized epilepsies discussed are limited to childhood absence epilepsy (CAE), which is also called pyknolepsy, and juvenile absence epilepsy (JAE), also known as epilepsy with nonpyknoleptic absences or epilepsy with spanioleptic absences. The benign partial epilepsies include benign partial epilepsy of childhood with centrotemporal spikes, benign occipital epilepsy, and benign epilepsy with affective symptoms.

Childhood absence epilepsy

Epidemiology

Annual incidence has been estimated at 1-8 per 100,000 in children aged 0-15 years, comprising 8% 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.

Genetics

A positive family history of epilepsy is present in about one third of patients. Febrile convulsions occur. Although an autosomal dominant pattern of inheritance with age-dependent penetrance has been suggested, a multifactorial pattern that involves both genetic and environmental factors is more likely. One form of childhood absence epilepsy, designated ECA1, has been linked to chromosome band 8q24. In 1998, Fong et al reported this linkage in a patient with CAE with tonic-clonic seizures. Another form, ECA2, in which patients have absence and febrile seizures, is caused by mutation in the GABRG2 gene on band 5q31.1. This was described by Wallace et al in 2001 in a large family from Australia. In 2006, Maljevic et al reported a de novo mutation in GABRA1 in a patient with childhood absence epilepsy.

A third form, ECA3, is caused by a mutation of the chloride channel gene CLCN2 on band 3q26. In a 2003 article, Haug et al identified mutations in this gene associated with the most common types of idiopathic generalized epilepsies. Also in 2003, Chen et al reported mutations in the T-type voltage-gated calcium channel gene CACNA1H, coding for the alpha-1 H calcium channel recently named Cav3.2. Mutations were present in 14 of 118 patients but not in 230 controls.

Other variants in the CACNA1H gene were identified in childhood absence epilepsy, suggesting that this gene is an important susceptibility gene in this epilepsy syndrome in the Chinese Han population, as reported by Liang et al in 2006. Recent characterization of the Cav3.2 mutations and their functional gating effects were also described by Khosravani et al in 2004 and 2005 and by Peloquin et al in 2006. In 2003, Audenaert et al reported a mutation in the sodium channel gene SCN1B in a family with febrile seizures plus early-onset absence epilepsy.

Seizure characteristics

Absence seizures are the initial seizures that occur in developmentally normal children. Seizures are brief, most commonly lasting 5-10 seconds (or 5-30 s, depending upon study). Seizures start and end suddenly, frequently occurring 10-100 times a day. Seizures occur spontaneously but may be precipitated by multiple factors, including emotional, intellectual, or metabolic (eg, hypoglycemia, hyperventilation). Absence status occurs in 10% of cases.

The main feature of absence seizures is loss of responsiveness with cessation of ongoing activity. Depending on the associated symptoms, 6 types of absence seizures can be identified: (1) simple absence manifesting only as impaired consciousness (10%), (2) absence with mild clonic components usually involving the eyelids (50%), (3) absence with atonic components resulting in gradual lowering of the head or arms (20%), (4) absence with tonic components (rotating the eyes upwards), (5) absence with automatisms that are either perseverative (ie, the patient persists in what he is doing) or de novo such as lip smacking or swallowing (60%), and (6) absence with autonomic components (eg, pupillary dilatation, flushing, tachycardia).

Electroencephalography

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

Prognosis and evolution

Prognostic parameters need to include both 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 GTC seizures later in the course of the epilepsy. Absence seizures persist in about 6% of cases (although less frequent). GTC seizures develop in about 40%. They are infrequent, easily controlled, and generally occur 5-10 years after the onset of absences. Juvenile myoclonic epilepsy (JME) is reported to occur in 44% of patients who do not have remission of their seizures. Problems with cognition, social adaptation, or behavior are not uncommon. Such difficulties may occur in one third of patients.

Differential diagnosis

CAE must be differentiated from the following:

• Absence seizures with late adolescent onset
• Symptomatic absence epilepsy (eg, Sturge-Weber syndrome, lipidosis, brain tumors, and moyamoya disease [Kikuta, 2006])
• Epilepsy with other seizure types preceding absences (implying a worse prognosis)
• Myoclonic absences
• Absence seizures associated with an unusual EEG pattern

Treatment

Both ethosuximide and valproate suppress absence seizures in more than 80% of patients. Valproate has the advantage of also controlling GTC seizures. For refractory seizures, both medications can be used in combination. Lamotrigine may also be effective as monotherapy. According to a Cochrane Database review of the use of ethosuximide, sodium valproate, and lamotrigine in absence seizures (Posner, 2005), evidence was insufficient to recommend a specific medication as a best choice for clinical practice. Levetiracetam (Di Bonaventura, 2005) and zonisamide (Wilfong, 2005) may also be effective. Acetazolamide and benzodiazepines, especially clonazepam, are other options. These alternate medications are useful for absence status.

Juvenile absence epilepsy

Epidemiology

The epidemiology has not been well studied, but JAE is less common than CAE. It is reported to represent 2.4% of epilepsies in children aged 0-15 years, compared to 12.1% for CAE. 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 JAE; the frequency appears to resemble that in CAE. One study suggested that allelic variants of the kainate-selective glutamate receptor GluR5 gene (GRIK1) on chromosome sub-band 21q22.1 contribute a major genetic determinant to the pathogenesis of JAE-related phenotypes.

Clinical features

As in CAE, children with JAE usually are neurologically normal. Absence seizures occur in all cases. Compared to CAE, however, absence seizures in JAE have the following features:

• Relative infrequency with only a few episodes daily
• Longer duration with a mean of 16 ± 7 seconds
• Less impairment of consciousness
• 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. Myoclonic seizures occur in about 15% of patients.

Electroencephalography

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

Treatment 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 (Di Bonaventura, 2005) for resistant cases. Treatment choices include (1) lamotrigine (either as monotherapy or in combination with valproate), (2) ethosuximide in combination with valproate, or (3) acetazolamide in combination with valproate. The long-term evolution has not been well established, but the prognosis is worse than that of CAE.

BENIGN PARTIAL EPILEPSIES OF CHILDHOOD

Section 6 of 7  

• Authors and Editors
• Introduction
• Benign Epilepsies in the Neonatal Period
• Benign Epilepsies in Infancy
• Benign Generalized Epilepsies in Childhood and Adolescence
• Benign Partial Epilepsies of Childhood
• References

Benign epilepsy of childhood with centrotemporal spikes

Definition

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

Epidemiology

BECCT is the most common epilepsy syndrome in childhood. In Connecticut, USA, it represents 9.6% of all epilepsies in children aged 0-15 years. However, BECCT and its variants may represent 20-25% of epilepsy cases diagnosed in those 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 than 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 is 6:4. In a 1998 publication, Kramer found no gender difference in incidence.

Clinical manifestations of seizures

The syndrome is termed rolandic epilepsy because of the characteristic features of partial seizures involving the region around the lower portion of the central gyrus of Rolando.

Common characteristic features include the following:

• Unilateral somatosensory involvement, mostly of the tongue (occasionally of the inner cheeks, lips, gums, or even a single tooth)
• Speech arrest
• Preservation of consciousness in most cases
• Pooling of saliva
• Tonic or tonic-clonic spread to face

Less often, sensory spread to the face or arms occurs; very rarely, a typical jacksonian march occurs. Other features include (1) absence of psychic symptoms, (2) rarity of complex automatisms, and (3) absence of amnesia and postictal confusion states.

BECCT is associated with the following 3 types of nocturnal seizures:

• Typical brief hemifacial seizures associated with speech arrest, drooling, and preservation of consciousness (identical to diurnal seizures)
• Seizures similar to those described above but with gurgling/grunting noises, loss of consciousness, and terminating in vomiting (at times)
• Generalized convulsions (often secondarily generalized)

Although the somatosensory aura is common, it often is missed because the child is young and the symptoms usually occur at night. The expression of seizures appears to be age dependent. In older children, pure hemifacial seizures are more common, whereas in younger children hemispheric and generalized convulsions are more frequent.

Seizures can occur during the day or night, although in most children seizures occur most often during sleep. Seizures occur only during sleep in 51-80%, during both sleep and wakefulness in 5-40%, and only during wakefulness in 0-32% of cases.

Frequency of seizures is usually low. Approximately 10-13% of patients have only a single seizure during the entire course, regardless of AED therapy; 66% have infrequent seizures; and 20% have frequent seizures (sometimes multiple seizures per day).

Occurrence of seizures in clusters is common. Duration of seizures is usually quite brief, ranging from 3-60 minutes; diurnal seizures tend to be shorter, especially the sensory ones. However, associated status epilepticus may be resistant to standard AEDs. One case manifested as an anterior operculum syndrome. Status epilepticus may occur in as many as 11% of patients. Postictal paralysis may occur in 7-21%.

Other clinical features

Headache and migraine occur commonly in patients with BECCT. In one series, recurrent headache was present in 67% of patients with BECCT upon presentation, and up to 80% had migraine reported on follow-up care. A case-controlled study, however, found no significant difference in migraine incidence between cases and controls. Febrile seizure history is not uncommon in BECCT.

Neuropsychological assessment

Children with BECCT usually show normal development and intelligence and have normal neurologic examination findings. Considering its prevalence, BECCT may be present in developmentally or neurologically abnormal children. The presence of developmental abnormality does not rule out the diagnosis of BECCT nor does it necessarily worsen the prognosis. Behavioral and learning problems do occur.

Children with BECCT may have problems with visuomotor skills, visuospatial memory and skills, language, and attention; neuropsychological abnormalities usually are transient. A recent study by Connolly et al in 2006 found that the quality of life in children with BECCT, as measured, may be compromised. The compromise, which affects domains such as competence and psychosocial function, may be related to a cognitive variable and the emotional impact of the child's epilepsy on 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 with BECCT. One study reported that at least 1 close relative had a temporal spike or SW discharge in up to 30% of the families. In another study, 15% of siblings of probands had seizures and rolandic discharges, whereas 19% had rolandic discharges alone.

Centrotemporal sharp and spike activity on EEG has been proposed to be an autosomal dominant trait with age-dependent penetrance. Only 12% of affected individuals have even had a seizure. Penetrance 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 trait develops epilepsy depends on a variety of inherited factors. Therefore, BECCT is inherited multifactorially rather than in an autosomal dominant fashion.

Some individuals with benign neonatal seizures later developed BECCT. Linkage studies failed to establish a relationship between BECCT and BFNC. Two loci previously thought to be linked with BECCT, the human leukocyte antigen (HLA) region on chromosome arm 6p and the fragile X site, have been excluded. In a 1998 study, Neubauer et al found evidence for linkage of BECCT to a region on chromosome band 15q14. In 1995, a new autosomal dominant syndrome was characterized by rolandic epilepsy, oral and speech dyspraxia, and cognitive dysfunction, with electroclinical features that resembled BECCT. Clinical anticipation was found in the family described in the study, suggesting that the genetic mechanism could be an expansion of an unstable triplet repeat.

Pathophysiology

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

Electroencephalography

EEG findings in BECCT are distinctive. The typical interictal EEG shows centrotemporal spikes or SW, which are either unifocal or bifocal. The spikes are usually slow, high voltage, and diphasic. 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 in frequency 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 in as many as 30% of patients. Obtain a sleep recording if BECCT is suspected on clinical grounds when the awake EEG is not revealing. Spike discharges are not altered significantly by photic stimulation 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 the spikes.

Typically, the centrotemporal spikes have a horizontal dipole with maximal electronegativity in the centrotemporal region and electropositivity in the frontal region. This suggests that the spikes are 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 clinical seizures 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 the discharge in association with the benign rolandic epilepsy. Insistence on a centrotemporal location for the EEG may lead to a misclassification of the type of epilepsy. The term benign focal epilepsy of childhood also has been used, and when the discharge is located in the centrotemporal region, it is called benign focal epilepsy of childhood with a centrotemporal (or rolandic) location.

Differential diagnosis

Benign rolandic epilepsy must be differentiated from the following:

• Rolandic spikes and no seizures (often with behavior problems, headaches, or autonomic dysfunction)
• Rolandic spikes and a history of antecedent brain damage, cerebral palsy, or active local pathology
• Central spikes occurring commonly in Rett syndrome and fragile X syndrome
• Malignant rolandic epilepsy
• Psychomotor seizures and evolving temporal lobe epilepsy
• The aphasia-convulsion (Landau-Kleffner) syndrome and massive midtemporal spikes

Investigations

If the patient has the typical clinical history and EEG findings and has normal findings on neurologic examination, further workup is not indicated. However, in the presence of atypical features or abnormal examination findings, MRI is indicated.

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.

Treatment

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 are comfortable with this approach. One study found that seizure frequency and duration and prevalence of active epilepsy were no different between treated and untreated patients with BECCT.

If treatment is indicated, carbamazepine is often the first medication to be tried, and seizures usually are well controlled. Once-a-day administration may be the only regimen needed to control seizures. Other reported effective AEDs include phenobarbital, phenytoin, valproic acid, clonazepam, clobazam, gabapentin, and sulthiame.

Although most patients respond to a low dose of a single drug, a few have seizures that are highly 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 be discontinued 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 achieve remission by adolescence. This includes patients whose seizures have been drug resistant. A recent meta-analysis study on the course of BECCT found that 50% of patients were in remission by age 6 years; by age 18 years, 99.8% of the patients were in remission. Rarely, BECCT can relapse in adulthood; about 2% of patients in BECCT remission experience other seizure types.

Benign partial epilepsy of childhood with occipital paroxysms

Definition

The understanding of the syndrome of benign partial epilepsy with occipital paroxysms (also called benign occipital epilepsy of childhood [BOE]) has evolved significantly with time. The syndrome as first described by Gastaut was initially the only childhood occipital epilepsy syndrome 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, migrainous headaches. The EEG findings include paroxysms of rhythmic occipital and posterior temporal spikes when the eyes are closed.

However, this concept was challenged by Panayiotopoulos 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 as early-onset childhood epilepsy with occipital spikes (Panayiotopoulos type). This is also called Panayiotopoulos syndrome. This was confirmed by many authors, including Panayiotopoulos, Caraballo et al, and Lada et al. This was found to be a much more common syndrome compared to the first recognized one, which is now known as late-onset childhood epilepsy with occipital spikes (Gastaut type).

According to a recent consensus conference (Ferrie, 2006), Panayiotopoulos syndrome is defined as "a benign age-related focal seizure disorder occurring in early and mid childhood. It is characterized by seizures, often prolonged, with predominantly autonomic symptoms, and by an EEG that shows shifting and/or multiple foci, often with occipital predominance." The group of international researchers in the conference concluded that the syndrome should be classified as an autonomic epilepsy rather than an occipital epilepsy.

Epidemiology

BOE is less common than BECCT. Prevalence depends on selection criteria. The Panayiotopoulos syndrome is much more common than the late-onset Gastaut-type. As noted by Panayiotopoulos in 4 independent studies of 607 patients, the prevalence of Panayiotopoulos syndrome was found to be 2.4 times lower than that of rolandic epilepsy. This means that around 6% of children with seizures have Panayiotopoulos syndrome, with the assumption 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 1-12 years. The Gastaut type of childhood occipital epilepsy is estimated to comprise 2-10% of benign childhood partial seizures. The mean age of onset is 8 years, with a range of 3-15 years. Both sexes seem to be affected with equal frequency in both syndromes, although this is not reported consistently.

Clinical features

In Panayiotopoulos syndrome, seizures comprise an unusual constellation of autonomic, mainly emetic, 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 also flushing and cyanosis. Pupillary 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. Brief apnea and irregular or heavy breathing is reported to occur in 7% of cases. Ictal cardiorespiratory arrest has also been reported. Headache and cephalic auras that may be autonomic manifestations may occur, particularly at onset.

More conventional symptoms may follow, including confusion or unresponsiveness, eyes and head deviation to one side (60%), wide opening of eyes without deviation, speech arrest, hemifacial spasms, and visual symptoms or hallucinations (6-9%). The seizures may end with hemiconvulsions, often with jacksonian march (19%) or generalized convulsions (21%). Ictal syncope or a syncopelike episode has been reported to occur in one fifth of cases. These manifest as 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 status epilepticus is rare (2%). One third of patients have a single seizure only. About half have 2-5 seizures. 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 the commonest 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 in the course of the seizure. Nonvisual ictal symptoms include adversive (versive) seizure manifested 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 with automatisms, 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, throbbing headache 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 present in 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 about more than a third and of migraines in about 20% has been reported in patients with late-onset childhood epilepsy with occipital spikes (Gastaut type). In Panayiotopoulos syndrome, reported family history of epilepsy ranged from none to 30% and febrile seizure from 17-25%.

Electroencephalography

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 occipital and adjacent head regions. These could be unilateral or bilateral, synchronous or asynchronous. Discharges can occur singly or in trains of 1-3 Hz and usually are attenuated by eye 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 darkness. Response to hyperventilation or photic stimulation is variable. Generalized spike-and-wave discharges, multiple spike-and-wave discharges, or central temporal or frontal spikes have been reported. Ictal EEG shows sudden occipital discharges.

The interictal EEG in Panayiotopoulos syndrome commonly reveals functional, mainly multifocal, high-amplitude sharp and slow wave complexes, with great variability at various electrode locations. All brain regions are involved, although the posterior predominate. About one third of patients never show occipital spikes. Some authors (Panayiotopoulos, 2004; Ferrie, 2006) have argued not to equate Panayiotopoulos syndrome with occipital epilepsy. In a 2003 study of EEG changes involving 76 children with Panayiotopoulos syndrome, Ohtsu et al found that occipital EEG spike focus was most frequently seen in children aged 2-5 years. Frontopolar and occipital spike pattern was seen in seizures of later age of onset.

Differential diagnosis

Occipital spikes, like other focal spikes, can exist without clinical epilepsy. They can also be noted in children with visual impairment.

BOE should be differentiated from other symptomatic forms of occipital lobe seizures due to underlying pathology (eg, atrophic, neoplastic, degenerative). Examples include the following:

• Sturge-Weber syndrome
• Epilepsy with bilateral occipital calcification
• Late infantile neuronal ceroid lipofuscinosis
• Hematoma
• Tuberous sclerosis
• Cortical dysplastic tumors
• Inflammatory processes
• Mitochondrial encephalomyopathies

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

BOE should be differentiated from other forms of primary partial epilepsy (eg, BECCT).

Migraines and epileptic syndromes can be confused and often coexist.

Treatment

Carbamazepine may be the drug of choice, although almost all of the classic anticonvulsants (eg, phenobarbital, valproate, benzodiazepines) are effective.

In Panayiotopoulos syndrome, education about the nature and prognosis of the syndrome is the cornerstone of correct management. Regular antiepileptic drug treatment is probably most appropriately reserved for those children in whom seizures are unusually frequent or distressing or are otherwise significantly interfering in the life of the child. Prolonged seizures may be treated with rescue benzodiazepines. No evidence indicates that any particular antiepileptic drug is more efficacious than any other (Ferrie, 2006). Although many authors recommend carbamazepine as drug of choice, on rare occasions this medication worsens seizures (Kikumoto, 2006).

Prognosis

Prognosis is usually good but is more favorable with Panayiotopoulos syndrome, which is considered as a remarkably benign condition despite high incidence of autonomic status epilepticus. Seizure frequency as noted above is very low. Seizure remission usually occurs within 1-2 years of seizure onset and occasionally up to 8 years as reported in a 2000 series by Caraballo. 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 (Gastaut type), remission can occur in 50-60%, 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 in whom affective symptoms (predominantly fear) were the major clinical features. The children were aged 7-17 years.

Clinical data

Age of onset ranged from 2-9 years with no sexual predilection. The predominant feature of the seizures was sudden terror or fright manifested by screaming, yelling, calling the mother, or clinging to her. The terrorized expression was associated sometimes with chewing, swallowing, 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 mean duration of the events was 1-2 minutes. Postictal lethargy was associated with the events. No tonic, atonic, or tonic-clonic seizures were reported.

Genetics

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

Electroencephalography

The background activity was normal. Seventy-three percent had slow spike or slow waves involving the frontotemporal and parietotemporal areas of one or both hemispheres. Other abnormalities included unilateral rhythmic frontotemporal or parietotemporal SW and brief bursts of generalized spike waves (alone, or in association with the above-mentioned abnormalities).

Prognosis

The course appeared to be benign; 3 patients never received treatment. Twenty-one responded to antiepileptic medications (usually carbamazepine or phenobarbital). In 2 cases, infrequent seizures persisted for months or years despite treatment but ultimately disappeared.

REFERENCES

Section 7 of 7

• Authors and Editors
• Introduction
• Benign Epilepsies in the Neonatal Period
• Benign Epilepsies in Infancy
• Benign Generalized Epilepsies in Childhood and Adolescence
• Benign Partial Epilepsies of Childhood
• References

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