Page 245 - ILAE_Lectures_2015

have a trial of pyridoxal phosphate. AEDs are generally ineffective and ketogenic diet has
not been particularly beneficial in this condition.

Late-onset, severe. Dravet syndrome (also known as severe myoclonic epilepsy of infancy,
SMEI) is a rare syndrome with an estimated frequency of one in 40,00015, although it may
turn out to be more common. Otherwise normal infants develop generalised or focal
myoclonic seizures in the first few weeks or months of life; rarely the onset may be as early
as the first week. Infants far more commonly present at 6–9 months of age with isolated but
prolonged and often focal ‘febrile seizures’ or febrile status epilepticus. Myoclonic, tonic-
clonic and partial seizures then develop, often explosively, in the second or third year of life.
The child’s development may stagnate and may even regress, particularly in receptive and
expressive speech and language skills. Around 70–80% of patients with SMEI have a
mutation in the alpha (α) subunit of the first neuronal sodium channel gene (SCN1A) on
chromosome(s) 19 and/or 2 (95% de novo; 5% inherited). Sodium valproate, clonazepam and
stiripentol are probably the more effective anticonvulsants in treating this syndrome.
Topiramate, levetiracetam and the ketogenic diet have also been reported to be helpful.
Importantly, lamotrigine, even in relatively low doses, may significantly exacerbate the
myoclonic seizures – and this observation is often used as a clue in establishing a diagnosis
of SMEI. There is a real danger of inappropriate and excessive ‘polypharmacy’ in treating
children with this epilepsy syndrome with the consequence of significant side effects,
particularly affecting concentration, learning, behaviour and sleep. There are no data to
indicate that the simultaneous use of three AEDs is more effective than two in controlling
seizures. Stiripentol, in association with sodium valproate or clobazam may be particularly
effective in treating most of the seizure types in SMEI. However, its use must be carefully
monitored because of its potential serious side effects on the central nervous system16, mainly
due to its interactions with the other anticonvulsants used to treat this specific epilepsy
syndrome. There is anecdotal evidence that cannabidiol may be an effective treatment for
Dravet syndrome, and clinical trials are currently under way.

Benign17. Benign myoclonic epilepsy in infancy is characterised by brief episodes of
generalised myoclonic seizures which may commence in the first (or more commonly in the
second) year of life in otherwise normal children who frequently have a family history of
epilepsy or febrile seizures. The myoclonic seizures are brief, may be massive and usually
occur on or soon after falling asleep. The only relevant investigation is the EEG, which shows
generalised spike-wave or polyspikes occurring in brief bursts during the early stages of
sleep, and 20% have photosensitivity. Valproate readily controls the infantile myoclonus.
Lamotrigine may be a useful alternative. While it is considered most likely to have a genetic
basis, no genes have been identified to date. In most children, seizures either remit
spontaneously or are relatively easily controlled with anticonvulsants. Febrile seizures occur
in about 10% and generalised tonic-clonic seizures may develop in adolescence.

Ohtahara syndrome

Ohtahara syndrome presents in the first three months of life and is a severe epileptic
encephalopathy. It can be distinguished from EME due to the predominance of tonic seizures
and the relative infrequency of myoclonic seizures. However, like EME it has a poor
prognosis with a drug-resistant epilepsy, severe psychomotor retardation and limited life
expectancy. Structural brain abnormalities are the commonest cause of this epilepsy
syndrome (e.g. hemimegalencephaly, porencephaly, Aicardi syndrome, olivary-dentate
dysplasia, cerebral dysgenesis and focal cortical dysplasia) but genetic mutations (STXBP1
[10–15% of cases], SLC25A22, CDKL5, ARX, SPTAN1, PCDH19, KCNQ2, and SCN2A)
are being increasingly reported. Metabolic aetiologies also occur (mitochondrial disorders,