Epilepsy syndromes in children

Epilepsy THEME Epilepsy syndromes in children BACKGROUND Understanding the common childhood epilepsy syndromes is valuable when approaching the diagnosis and management of a child presenting with seizures. OBJECTIVE This article discusses the common epilepsy syndromes in children and provides a guide to appropriate investigation and management of these syndromes. DISCUSSION A careful history and examination, supported by an electroencephalogram, are the cornerstones of epilepsy syndrome diagnosis. This, in turn, guides the need for further investigation such as magnetic resonance imaging, optimisation of therapy and prognostic counselling. Understanding the implications of a specific syndrome diagnosis helps support families who are frequently overwhelmed by a diagnosis of epilepsy in their child. Patrick W Carney BSc, BMed, is a neurology registrar, Austin Health, Melbourne, Victoria. patrick.carney@ austin.org.au Michael A Prowse MBBS, FRACGP, is a general practitioner, Berwick, Victoria. Epilepsy is defined as more than one unprovoked seizure 1 and is essentially a clinical diagnosis based on an eye witness account of the attacks. When a child or adolescent presents with their first seizure, a detailed history should be sought for other seizure types that may not have previously been appreciated (Table 1, 2). For example, an adolescent presenting with their first generalised tonic-clonic seizure (GTCS) may have had subtle absence or myoclonic seizures; diagnosis of these seizure types is critical to diagnosis of the specific epilepsy syndrome. An electroencephalogram (EEG) provides supporting evidence for diagnosis of a specific epilepsy syndrome; if a routine EEG is normal, a sleep deprived study should be considered. In individuals with focal epilepsy not classified as idiopathic partial epilepsy, magnetic resonance imaging (MRI) should be performed. Investigations may be initiated by a general practitioner, but more sophisticated syndrome diagnosis would usually be made by a paediatrician or neurologist. Classification of the epilepsies The International League Against Epilepsy (ILAE) classifies epilepsy syndromes as: idiopathic epilepsy develops in an otherwise normal child, and symptomatic epilepsy occurs in the setting of a known or suspected abnormality of the central nervous system (Table 3). 2,3 For example, a child with developmental delay has symptomatic epilepsy, as does an individual with hippocampal sclerosis. The epilepsies are further subdivided into: generalised seizures arise from both hemispheres simultaneously, and partial (or focal) epilepsy which begins in one part of the brain and may secondarily generalise. Generalised epilepsies Idiopathic generalised epilepsies Absence seizures are the hallmark of childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE) (Table 3). Typical absence seizures, or staring spells, have an abrupt onset without warning and rapid offset with resumption of previous activities (Table 1, 2). The events are brief, lasting less than 20 seconds, and awareness is impaired. Other features may include mild clonic, myoclonic, atonic or tonic movements, and oral and manual automatisms. 4,5 Ingrid E Scheffer PhD, FRACP, is Professor and paediatric neurologist, Departments of Medicine and Paediatrics, The University of Melbourne, Austin Health and Royal Children s Hospital, Melbourne, Victoria. Reprinted from Australian Family Physician Vol. 34, No. 12, December 2005 4 1009

Table 1. Common generalised seizure types Seizure type Clinical features Postictal Duration Usual epilepsy syndrome Absence Abrupt onset of staring with cessation of motor activity Abrupt return to normal <30 seconds CAE, JAE Myoclonic Brief contraction of muscle/muscle groups either singularly or repetitively Abrupt return to normal <5 seconds IGE, Lennox- Gastaut, progressive, myoclonus epilepsies Tonic-clonic seizure May begin with a cry or fall to the ground followed by tonic flexion. This is followed by a clonic phase involving symmetrical movement of all limbs. Autonomic features are common as are incontinence and tongue biting Drowsiness may be prolonged with recovery taking minutes to hours. Postictal confusion and agitation is common Usually <5 minutes May be generalised from onset, secondarily generalised with focal onset or occur due to an acute metabolic disturbance. Associated with a broad range of epilepsies including IGE and SGE Tonic Tonic extension of all limbs with semiflexed arms (bear hug). Patients often fall backward 10 seconds SGE especially the Lennox-Gastaut syndrome Atonic Classic drop attacks with sudden loss of postural tone Few seconds SGE including Lennox- Gastaut syndrome Table 2. Common partial (focal) seizure types Location Temporal Frontal Occipital Clinical features Aura may involve epigastric sensation, olfactory or gustatory hallucinations, autonomic features, dysmnestic changes such as déjà vu followed by loss of awareness and automatisms involving the mouth or upper limbs. Duration 30 300 seconds with a brief period of postictal confusion May be hyperkinetic with motor automatisms or an asymmetric tonic seizure depending on the location in the frontal cortex; may be incontinent Visual symptoms including hallucinations, field defects, and flashing lights; may vomit Childhood absence epilepsy Childhood absence epilepsy begins between 3 and 12 years of age with peak onset at 6 years. Absence seizures occur frequently, often 20 times per day, 5 and adversely affect school performance. Absence seizures may be triggered by stress, fatigue, and hyperventilation. The EEG shows bilaterally synchronous 3 Hz spike and wave discharges (generalised spike wave [GSW]) on a normal background. Trains of 3 Hz GSW correlate with a clinical absence seizure on EEG; hyperventilation is used to trigger GSW and absence seizures during an EEG (Figure 1). Childhood absence epilepsy may be accompanied by GTCS, which tend to occur later in adolescence. Seizures resolve in 60% of children by mid adolescence. 4,5 Juvenile absence epilepsy Juvenile absence epilepsy differs from CAE not only because of a later age of onset (after the age of 10 years and occasionally as late as 20 years), but also because of the seizure pattern. Absence seizures are less frequent, perhaps once per week, and less 1010 3Reprinted from Australian Family Physician Vol. 34, No. 12, December 2005

severe impairment of awareness may occur. Other seizure types, such as GTCS, are more common. The EEG shows faster GSW, usually at 3.5 4.0 Hz and occasionally faster, and generalised polyspike wave is often seen. 6 Juvenile myoclonic epilepsy Juvenile myoclonic epilepsy (JME) accounts for up to a quarter of idiopathic generalised epilepsies (IGE). Onset is in adolescence (8 20 years of age) and is characterised by isolated myoclonic seizures, especially after awakening (see Case study 1). Other seizure types are common including GTCS in up to 80% of patients and absence seizures in 30%. Seizures often occur following sleep deprivation, fatigue and alcohol use. 8 The EEG shows 4 6 Hz polyspike wave and photosensitivity is common; occurring in more than 30% of individuals. 7 Treatment of IGE Valproate is the drug of first choice for IGE. 8 Although generally well tolerated, common side effects include weight gain and fatigue. Another concern for teenage girls is teratogenesis, as valproate is associated with an increased incidence of neural tube defects. Contraceptive advice should be provided and specialist advice sought before conception. Lamotrigine is an effective second line agent, especially in combination with valproate. The principal side effect of lamotrigine is rash, which is more likely when on valproate cotherapy. Therefore, lamotrigine should be started at a low dose and slowly increased over several months. Other medications include topiramate, clobazam and clonazepam. 9,10 Symptomatic generalised epilepsies The symptomatic generalised epilepsies are characterised by multiple seizure types and other neurological deficits including intellectual disability. Table 3. ILAE classification of epilepsy syndromes 2 Generalised Idiopathic generalised epilepsy syndromes with age related onset (in order of age) Benign neonatal convulsions sporadic and familial forms Childhood absence epilepsy Juvenile absence epilepsy Juvenile myoclonic epilepsy Epilepsy with generalised tonic-clonic seizures alone Symptomatic generalised epilepsies (in order of age) West syndrome Lennox-Gastaut syndrome Epilepsy with myoclonic-astatic seizures Focal/partial seizure disorders Idiopathic focal epilepsies Benign epilepsy with centro-temporal spikes Childhood epilepsy with occipital paroxysms Symptomatic focal epilepsies Temporal lobe epilepsy Frontal lobe epilepsy Parietal lobe epilepsy Occipital lobe epilepsy Epilepsies or syndromes undetermined as to whether focal or generalised Neonatal seizures Dravet syndrome (severe myoclonic epilepsy of infancy Epileptic-aphasia syndromes Special syndromes Febrile seizures Isolated seizures or isolated status epilepticus Acute symptomatic seizures (associated with acute metabolic or toxic event) West syndrome West syndrome usually begins at 6 months of age (range 3 12 months years) and is sometimes mistaken for infantile colic. The baby has clusters of epileptic spasms, developmental arrest or regression. The EEG shows hypsarrhythmia with continuous multifocal epileptiform activity. Cerebral malformations are an important cause but often no aetiology is apparent. Seizures generally respond to corticosteroid treatment, which should be initiated as early as possible. 11 Figure 1. EEG showing typical 3 Hz generalised spike and wave associated with childhood absence epilepsy Reprinted from Australian Family Physician Vol. 34, No. 12, December 2005 4 1011

Lennox-Gastaut syndrome Lennox-Gastaut syndrome (LGS) begins between 1 and 8 years of age; 20% of infants with West syndrome evolve to LGS. 12 The key seizure type is the tonic seizure but atonic drop attacks, atypical absence, GTCS and myoclonic seizures may also occur. The EEG shows slow 1.0 2.5 Hz sharp and slow activity that can be virtually continuous. 13 Lennox-Gastaut syndrome has many aetiologies including cortical malformations, tuberous sclerosis and acquired causes such as trauma. Lennox-Gastaut syndrome accounts for up to 10% of childhood epilepsy. Lennox-Gastaut syndrome children have variable intellect, however most commonly display intellectual disability. Cognition may be normal before development of the syndrome, however few maintain normal intellect with frequent poorly controlled seizures. 12,13 Treatment is difficult, but the combination of valproate and lamotrigine is the most effective regimen. 10 Partial seizure disorders A partial, or focal seizure arises in one part of the cerebral cortex and may generalise to involve the entire brain. 14 Clinical features of partial seizures reflect the cortical origin of the seizure (Table 2). Seizures may arise from normal brain tissue or specific lesions. Advances in imaging have highlighted the importance of cortical developmental malformations in focal epilepsies. 15 If a child has focal epilepsy (focal features clinically or on EEG) not falling into the recognised idiopathic partial epilepsy syndromes, then a MRI brain scan is indicated to exclude a structural lesion. A computerised tomography (CT) scan is rarely useful. Idiopathic partial epilepsies Benign epilepsy with centro-temporal spikes Benign epilepsy with centro-temporal spikes (BECTS), also known as benign rolandic epilepsy or benign focal epilepsy of childhood, is the most common childhood epilepsy syndrome. 16,17 Nocturnal seizures begin at 3 13 years of age and stop by 16 years of age. Seizures occur shortly after falling asleep or just before awakening. It is worth asking the child if he/she experiences a warning, or aura, of perioral or gum paraesthesia. Other common features include speech arrest, drooling, and tonic or clonic involvement of the face or upper limb. Alternatively parents may be alerted by gurgling or grunting noises, and find their child having a secondarily GTCS. The EEG shows a spike over the rolandic or centro-temporal area. 2 If not present Case study 1 Chloe Chloe, 15 years of age, partied late into the night. At 6 am her mother found her in the middle of a 2 minute generalised tonic-clonic seizure. When asked specifically, Chloe admitted to noticing sudden jerks of her arms when eating her cereal at breakfast time she had even dropped her grandmother s antique butter dish. Her sleep deprived EEG showed fast generalised polyspike-wave activity with photosensitivity. Chloe s myoclonic seizures and convulsions were fully controlled with valproate 200 mg twice per day. The diagnosis of epilepsy and its implications were discussed with Chloe and her parents. Chloe has juvenile myoclonic epilepsy, which means that although she may require long term treatment, her epilepsy should be well controlled with the appropriate medication. It was emphasised that sleep deprivation and fatigue were potent triggers of seizures, even with medication compliance. This is often an issue for adolescents, but strategies such as having a nap in the afternoon before a late night, and limiting alcohol to one drink per night lessens the risk. Another issue is compliance and it is important for adolescents to take responsibility for this as they become independent. The appropriate age depends on the adolescent. Often they become more interested in compliance when they wish to sit for their driver learner s permit. For Chloe s epilepsy syndrome, she requires 3 months without seizures to drive a vehicle. Chloe presented again at the age of 18 years following a generalised tonic-clonic seizure, the first in over 2 years. She said that she had been having some late nights, as she had just finished her final exams, and was not taking her medications as reliably. She also stated that she was worried about the effects of her medication and what effect they would have on a baby if she were to fall pregnant. Chloe was told that it would be best to plan a pregnancy and talk to her doctors well in advance. Some antiepileptic drugs are not safe in pregnancy, so this needs to be carefully planned with specialist consultation. Chloe was encouraged to become more adherent so that she could continue to drive a vehicle. Case study 2 Jack Jack, 8 years of age, awakens half an hour after falling asleep with tingling in his tongue and gums. He finds himself unable to speak and is drooling. He alerts his parents by banging on the wall and they find him having a secondarily generalised tonic-clonic seizure. Jack had an EEG performed the following day which showed frequent right centrotemporal spikes when drowsy. Jack s parents were worried about him going on medication but equally worried about the risks of further seizures. They also asked whether he needed a brain scan to rule out a brain tumour. His parents were told that Jack s seizures were a common, benign form of childhood epilepsy called benign childhood epilepsy with centro-temporal spikes (BECTS). Medication would generally be considered after three seizures as many children with this syndrome only have 1 2 seizures and never require treatment. In view of Jack s typical clinical history and EEG pattern, the diagnosis could be made with relative certainty and a scan would not be required. Jack s parents were initially distressed with the diagnosis of epilepsy and required reassurance and a detailed explanation of the excellent prognosis of BECTS. Jack had no further seizures and never required medication. Reprinted from Australian Family Physician Vol. 34, No. 12, December 2005 4 1013

awake, the rolandic spike is brought out in sleep, so a sleep deprived EEG may help (see Case study 2). Benign epilepsy with centro-temporal spikes has an excellent prognosis even in patients with frequent seizures. Controversy surrounds the neuropsychological findings in children with BECTS with some studies suggesting mild limitations in memory and phonologic skills while others show no difficulties. 16 Overall, intellectual and language ability is consistent with peers. No treatment is required for the first few seizures but if seizures are frequent, carbamazepine or valproate should be considered. The decision to start treatment needs to be balanced between the risks of medication side effects and the social and learning implications of untreated seizures. 17 Benign occipital epilepsies of childhood The benign occipital epilepsies of childhood comprise early and late onset syndromes with overlapping age ranges of onset between 3 14 years; they generally resolve by the mid teens. 18 The early Panayiotopoulos syndrome is characterised by rare prolonged nocturnal attacks with eye deviation, vomiting and autonomic features. The later Gastaut syndrome has frequent, brief, elementary visual auras, prominent headache and transient visual impairment. The EEG in both syndromes shows interictal occipital rhythmic activity brought out by eye closure. Symptomatic occipital epilepsy may present similarly so MRI of the brain is indicated to exclude an occipital malformation. 19,20 Symptomatic partial epilepsies Temporal lobe epilepsy Temporal lobe epilepsy (TLE) is the most common form of refractory partial epilepsy in children and adults. 21 Temporal lobe auras comprise olfactory or gustatory hallucinations or perceptual phenomena such as déjà vu. Seizures typically consist of staring spells with psychomotor arrest with loss of awareness and automatisms involving the perioral region or upper limbs. Seizures last 30 seconds to a few minutes, with postictal confusion, drowsiness and headache. Features that differentiate temporal lobe seizures from absence seizures include an aura, duration and postictal changes. The most common aetiology of refractory TLE is hippocampal sclerosis, 21 often associated with a history of prolonged febrile seizures. 22 Management may require more than one drug to achieve seizure control. Where seizures persist, epilepsy surgery should be considered with appropriate evaluation by a comprehensive epilepsy program. When indicated for hippocampal sclerosis, anterior temporal lobectomy is successful in at least 60% of patients who are rendered seizure free or experience a substantial reduction in seizure frequency. 23 Conclusion A range of epilepsy syndromes develop in childhood and adolescence. Accurately identifying the seizure type and correlating this with the EEG findings provides important prognostic and management information for families with a child with epilepsy. Many childhood epilepsy syndromes are readily treated and have an excellent prognosis. Accurate and early diagnosis may ameliorate the psychosocial impact of these disorders on children and their families. Conflict of interest: none declared. References 1. Fisher RS, Boas W, Blume W, Elger C, Genton P, Lee P, Engel J. 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