Idiopathic and Benign Partial Epilepsies of Childhood

Elaine C. Wirrell

Carol S. Camfield

Peter R. Camfield

The benign and idiopathic partial epilepsies (IPEs) of childhood account for approximately one-fifth of all epilepsies in children and adolescents. IPEs differ in two ways from most other focal epilepsy syndromes. First, IPEs are genetically determined focal disturbances of cerebral activity without any apparent structural abnormality detectable on magnetic resonance imaging (MRI), whereas most focal epilepsies are “lesional,” resulting from a localized area of cortical damage or dysgenesis. Second, most IPEs remit by adolescence, unlike lesional focal epilepsies, which are often refractory.

In a survey of seizure disorders in the southwest of France, the annual incidence of IPEs in children 0 to 15 years of age was estimated to be 8.63 per 100,000 (1), representing one-half of all partial seizures in this age group. The actual incidence of IPE may be higher, however, as many children with partial seizures do not clearly fit into one of the IPE phenotypes and yet have spontaneous remission and no underlying abnormality on neuroimaging. Identification of these epileptic syndromes is paramount to providing these children and their families a favorable prognosis and appropriate management.

Although controversy surrounds their exact clinical boundaries, IPEs of childhood include (2,3):

Age-dependent occurrence—onset generally after 18 months, with specific peak ages for each subtype
Absence of significant anatomic lesions on neuroimaging
Normal neurologic status, with most children intellectually intact and without prior neurologic insult
Favorable long-term outcome, with remission occurring prior to adolescence in most children, even those whose seizures were initially frequent or difficult to control
Possible genetic predisposition—other family members with benign forms of epilepsy that resolved in adolescence
Specific semiology—most seizures are simple partial motor or sensory, although complex partial and secondarily generalized seizures also may be seen; nocturnal occurrence is common and frequency is usually low
Rapid response to antiepileptic medication in most cases
Specific electroencephalographic (EEG) features—spikes of distinctive morphology and variable location superimposed on a normal background, with occasional multifocal sharp waves or brief bursts of generalized spike wave; epileptiform discharges are often activated by sleep

The International League Against Epilepsy (ILAE) currently recognizes two types of IPE in childhood (4): benign childhood epilepsy with centrotemporal spikes (BCECTS) and benign occipital epilepsy (BOE). BOE has been further subdivided into early onset (Panayiotopoulos) and late-onset (Gastaut) types. Other proposed but less well-studied syndromes include benign epilepsy in infancy (BPEI) with complex partial or secondarily generalized seizures (5,6), benign partial epilepsy with affective symptoms (BPEAS) (7, 8, 9, 10), benign partial epilepsy with extreme somatosensory evoked potentials (BPE-ESEP) (11, 12, 13), benign frontal epilepsy (BFE) (14), and benign partial epilepsy of adolescence (BPEA) (15,16). Table 24.1 summarizes the core/classic features of these syndromes.

TABLE 24.1 BENIGN PARTIAL EPILEPSY SYNDROMES

Syndrome	Age of Presentation	Clinical Features	Interictal Electroencephalographic Features	Prognosis
Well-defined syndromes accepted in 1989 ILAE classification
Benign childhood epilepsy with centrotemporal spikes	Range, 3-13 y Peak, 7-8 y	Diurnal or nocturnal simple partial seizures affecting the lower face with numbness, clonic activity, drooling, and/or dysarthria, nocturnal generalized seizure	High-voltage centrotemporal spikes with horizontal dipole, activated with sleep; normal background	Remission by adolescence
Early onset benign occipital epilepsy (Panayiotopoulos type)	Range, 2-8 y Peak, 5 y	Nocturnal seizure with tonic eye deviation, nausea, and vomiting; often prolonged	High-amplitude, repetitive occipital spike and wave, with fixation-off sensitivity Electroencephalogram may be normal or nonspecific	Remission by 1-2 y after onset
Late-onset benign occipital epilepsy (Gastaut type)	Range, 3-16 y Peak, 8 y	Brief diurnal seizures with elementary visual hallucinations, often with migraine-like, postictal headache	As above	5% suffer recurrent seizures in adulthood
Other rare syndromes
Benign partial epilepsy in infancy	Range, 3-10 mo Peak, 4-6 mo	Motion arrest, decreased responsiveness, staring, simple automatisms, mild convulsive movements with possible secondary generalization	Normal- or low-voltage rolandic or vertex spikes in sleep	Remission by age 2 y
Benign partial epilepsy in adolescence	Range, adolescence Peak, 13-14 y	Motor or sensory symptoms, often with jacksonian march; auditory, olfactory, or gustatory symptoms never seen	Normal or nonspecific epileptiform discharge	Infrequent seizures that usually abate soon
Benign frontal epilepsy	Range, 4-8 y	Head version ± trunk turning; fencing posture, sometimes followed by truncal, bipedal, or pelvic movements	Unilateral or bilateral frontal or posterior-frontal foci	May persist into adulthood
Benign partial epilepsy with extreme somatosensory-evoked potentials	Range, 4-6 y	Diurnal partial motor seizures with head and body version	High-voltage spikes in parietal and parasagittal regions evoked by tapping of feet	Resolution by adolescence
Benign partial epilepsy with affective symptoms	Range, 2-9 y	Brief episodes with sudden fear, screaming, autonomic disturbance, automatisms, and altered awareness	Rolandic-like spikes in frontotemporal and parietotemporal regions in wakefulness and sleep	Remission within 1-2 y

BENIGN PARTIAL EPILEPSY SYNDROMES RECOGNIZED BY THE ILAE

Benign Childhood Epilepsy with Centrotemporal Spikes

Although Martinus Rulandus described the first case of rolandic epilepsy in 1597 (17), its specific electrographic and clinical features were recognized only during the past 50 years. In 1952, Gastaut (18) noted that these “pre-rolandic” spikes were unrelated to focal pathology, and 2 years later, Gibbs and coworkers (19) observed that the discharges may occur without clinical seizures. In 1958, Nayrac and Beaussart (20) described the clinical symptoms in 21 patients. The excellent prognosis of this syndrome, compared with the poor outcome in psychomotor epilepsy, was apparent in the early literature (21,22).

Although BCECTS is easily recognized in its “pure” form, atypical features are common and may make a confident diagnosis difficult.

Epidemiology

With an incidence of 6.2 to 21 per 100,000 children age 15 years and younger (23, 24, 25), BCECTS accounts for between 13% and 23% of all childhood epilepsies (23,26)
and approximately two-thirds of all IPEs (27, 28, 29, 30). Onset is between 3 and 13 years, with a peak at 7 to 8 years; BCECTS always resolves by age 16 years (26). Slightly more boys than girls are affected, with a gender ratio of approximately 6:4 (31, 32, 33).

Genetics

The hallmark centrotemporal sharp waves are often found in siblings of children with BCECTS. An autosomal dominant inheritance with an age-specific expression has been suggested (34, 35, 36), but most children with these EEG features never experience clinical seizures, which suggests that development of BCECTS depends on other genetic and environmental factors (37, 38, 39, 40). The first positive evidence for linkage was found on chromosome 15q14, and either the α₇ acetylcholine receptor subunit gene or another closely linked gene may be implicated in pedigrees with BCECTS, but the disorder is genetically heterogeneous (41).

Scheffer and coworkers (42) described a syndrome of autosomal dominant rolandic epilepsy with speech dyspraxia that may also present an opportunity to identify genes involved in BCECTS. This syndrome begins at a mean age of 5.3 years, and its electroclinical manifestations are identical to those of BCECTS, with nocturnal rolandic seizures and centrotemporal spikes with a horizontal dipole. Oromotor and speech dyspraxia are also present, however, and epilepsy and cognitive impairment worsen in subsequent generations.

Pathophysiology

Seizures in BCECTS involve the lower portion of the perirolandic region in the upper sylvian bank. By stimulating this cortical area, Penfield and Rasmussen, according to Lombroso (21), were able to produce symptoms suggestive of BCECTS.

BCECTS most likely represents a “hereditary impairment in brain maturation” (43, 44, 45), and Prince (46) proposed that it may be influenced by out-of-phase developmental timetables for excitation and inhibition. The number of axonal branches and synaptic connections is greater early in development than in the mature animal. Developmental “pruning” of these connections may limit the expression of epilepsy. Younger children may also have hyperexcitable cortical circuits that may be modulated by new or more effective inhibitory connections that appear with maturation. Developmental regulation of voltage-dependent channels may also explain decreased cortical excitability with age.

Clinical Manifestations

Seizures characteristically occur either shortly after falling asleep or before awakening. However, in 15% of patients they happen both in sleep and wakefulness, and in 20% to 30% of patients in the waking state alone (31,32). During wakefulness, simple partial seizures are the rule, with (a) unilateral paresthesias of the tongue, lips, gum, and cheek; (b) unilateral clonic or tonic activity involving the face, lips, and tongue; (c) dysarthria; and (d) drooling (21). Stiffness of the jaw or tongue and a choking sensation are also common. Three types of nocturnal seizures have been described: (a) brief hemifacial seizures with speech arrest and drooling in a conscious state (simple partial seizures); (b) hemifacial seizures, but with loss of consciousness (complex partial seizures), often with gurgling or grunting noises that may terminate with vomiting; and (c) secondarily generalized convulsions (32). Postictal confusion and amnesia are rare (47).

In a small number of cases, Loiseau and Beaussart (48) noted unusual paresthesias or jerking of a single arm or leg, abdominal pain, blindness, or vertigo, which likely reflected seizure foci outside the centrotemporal region, as children with BCECTS may also have interictal sharp waves in other areas. Very young children with BCECTS commonly present with hemiconvulsions instead of the typical facial seizure (32). Rarely, partial motor seizures may change sides without becoming generalized (32).

Seizures are usually infrequent. Loiseau and coworkers (49) reported that 35 (20.8%) of 168 patients suffered a single seizure, and only 10 (5.9%) had very frequent events. Kramer and colleagues (50) described only 13 of 100 patients suffering a single seizure. Very frequent seizures may be more likely in children whose epilepsy begins before 3 years of age (50). Seizures often occur in clusters, followed by long seizure-free intervals. There is no known correlation between severity of the EEG abnormality, seizure frequency, and final outcome (32).

Postictal Todd paresis occurs in 7% to 16% of cases and often suggests a focal onset in patients who present with an apparently primarily generalized seizure (48,51,52).

In most children, seizures last from seconds to several minutes; however, status epilepticus has been described in some children with atypical features (51,52). Temporary oromotor and speech disturbances may be associated with intermittent facial twitching, a disorder that resembles anterior opercular syndrome and correlates with very frequent or continuous spike discharge in the perisylvian region (53, 54, 55, 56, 57). This problem does not always respond to intravenous antiepileptic medication, and long-term use of steroids has sometimes seemed beneficial (53). Eventually, all children recover over 6 months to 8 years. Some are left with mild speech disfluency or minor slowing of tongue or jaw movements, while others are completely normal. Positron emission tomography demonstrated a bilateral increase of glucose metabolism in the opercular regions in one patient with this type of nonconvulsive status (58). Recognition of this unusual presentation as a benign focal epilepsy is important to avoid epilepsy surgery before spontaneous resolution occurs at a later age.

A few children whose initial presentation is typical for BCECTS evolve to “atypical benign partial epilepsy” or
“pseudo-Lennox” syndrome (59, 60, 61, 62, 63). In addition to partial motor seizures, they develop frequent atonic, atypical absence and myoclonic seizures, often with nonconvulsive status epilepticus, as well as cognitive and behavioral disturbances. The sleep electroencephalograms show nearly continuous, bilaterally synchronous spike-and-wave activity. Although these children ultimately have remission of their epilepsy, many are left with varying degrees of mental handicap.

Children with BCECTS usually have an uneventful medical history, although 6% to 10% experience neonatal difficulties (including 3% with neonatal seizures) and 4% to 5% have preceding mild head injuries (32,40). Up to 16% have antecedent febrile seizures, which are likely to be focal or prolonged (40).

The incidence of migraine may be increased in children with BCECTS, although studies have lacked uniformity in migraine diagnosis (64,65). Giroud and colleagues (64) compared four groups of children and found migraine in 62% of 42 children with BCECTS, 34% of 28 children with absence epilepsy, 8% of 38 children with partial epilepsy, and 6% of 30 children with head trauma. Bladin (65) followed up 30 cases of BCECTS, noting that 20 (67%) patients had recurrent headaches during the evolution of seizures and 24 (80%) developed typical migraine after remission of BCECTS. The pathophysiologic link between BCECTS and migraine is unknown.

Figure 24.1 Typical rolandic spikes at C₃ and C₄-T₄.

Electroencephalographic Manifestations

The electroencephalogram shows high-amplitude diphasic spikes or sharp waves with a prominent aftercoming slow wave (Fig. 24.1). Spikes have a characteristic horizontal dipole, with maximal negativity in centrotemporal (inferior rolandic) and positivity in frontal regions (66,67). They frequently cluster and are markedly activated in drowsiness and nonrapid eye movement sleep (Fig. 24.2); approximately 30% of patients show spikes only during sleep (68). The focus is unilateral in 60% of cases and bilateral in 40%, and may be synchronous or asynchronous (32). The location is usually centrotemporal. Legarda and coworkers (69) described two electroclinical subgroups of BCECTS: a
high-central group, with maximum electronegativity at C₃/C₄ and seizures with frequent hand involvement, and a low-central group, with maximum electronegativity at C₅/C₆, ictal drooling, and oromotor involvement.

Atypical locations are frequent, and spikes may shift location on subsequent EEG recordings. On 24-hour electroencephalograms in children with typical BCECTS, Drury and Beydoun (70) found 21% of the patients to have a single focus outside the centrotemporal area. Follow-up recordings showed shifts in foci both toward and away from the centrotemporal area; no clinical differences were found between patients with foci in or outside the centrotemporal zone. Only half of their patients had a horizontal dipole. Wirrell and coworkers (51) also noted atypical spike location in 17% of their patients. Mild background slowing has been observed (47,51), and while generalized spike-and-wave discharge may be present, coexistent absence seizures are rare. With remission, spikes disappear first from the waking record and later from the sleep recording (32).

Few reports of recorded rolandic seizures (Fig. 24.3) exist, but two unique features are noted (32,71, 72, 73, 74, 75). Ictal spike-and-wave discharges may show dipole reversal, with electropositivity in the centrotemporal region and negativity in the frontal area; postictal slowing is not seen.

Figure 24.2 Marked activation of rolandic spikes with sleep.

BCECTS develops in only a small minority of children with typical rolandic spikes or sharp waves on their electroencephalograms. Rolandic discharge was found in 27 of 3726 (0.7%) waking EEG recordings of normal children without a history of seizures (37); if recordings had included sleep, the actual number might have been higher. The percentage of children with rolandic sharp waves who develop clinically apparent seizures is unclear. On the basis of reported incidences of BCECTS and of rolandic EEG discharge in normal children, the risk is probably less than 10%. Therefore, rolandic discharges should be considered most likely an incidental finding in children with other potentially nonepileptic presentations such as staring spells.

Neuropsychological Aspects

A variety of neuropsychological problems have been identified in children with active epilepsy and EEG discharge.
Several early studies noted frequent behavior problems, hyperactivity, inattention, and learning disorders in children with BCECTS, but attributed these difficulties to the social stigma of epilepsy or to side effects of antiepileptic medication (33,49,76). More recent comparisons with normal controls yielded interesting results. On neuropsychological assessments, Croona and colleagues (77) found that children with BCECTS had more problems than matched controls with auditory-verbal memory, learning, and some executive functions, as evidenced by poorer performance on the trailmaking, verbal fluency, and Tower of London tests. No deficits were documented in immediate memory or visuospatial memory and learning. Teachers noted greater difficulty with reading comprehension in the BCECTS group, but not to the degree predicted by the neuropsychological data. In other comparisons with controls, Gunduz and coworkers (78) described more problems in go-no-go testing and language and minor motor deficits, and Baglietto and colleagues (79) documented poorer performance on tests of visuospatial short-term memory, attention, cognitive flexibility, picture naming, verbal fluency, and visuoperceptual and visuomotor coordination. Other uncontrolled studies (80,81) have reported high rates of learning disorders and difficulties with impulsiveness and temperament in children with BCECTS.

Figure 24.3 A-C: Recorded rolandic seizure. A: Start of seizure. B: Ten seconds later. C: End of seizure. (Courtesy of Dr. Mary Connolly, British Columbia Children’s Hospital and University of British Columbia.)

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