Commoner epilepsy syndromes with onset in infancy
| Epilepsy syndromes with generally good prognosis | |
|---|---|
| Benign familial and non-familial infantile seizures | Benign familial neonatal seizures were described in 1964, with eight cases in three generations all developing seizures in the first few days of life but with good long-term prognosis. Similar benign seizures, both familial and non-familial, have been described with onset in later infancy, sometimes referred to as Watanabe–Vigevano syndrome. A number of known chromosomal loci or genetic mutations have been identified.6 7 Associations have been made with paroxysmal choreoathetosis that is variably expressed in these family members.8 9 |
| Benign familial neonatal-infantile seizures | Intermediate features to the conditions described above. Onset of seizures from 2 days to 6 months, and usually resolution by age 12 months. Some cases associated with mutations in the SCN2A gene (neuronal sodium channel, α-2 subunit). |
| Benign infantile seizures associated with mild gastroenteritis | Not formally recognised as an epilepsy syndrome. Probably a situation-related or symptomatic seizure, and although seizures are often clustered and not associated with fever, later seizure recurrence is rare. Common in Japan and other parts of the Far East, and often associated with rotavirus infection. |
| Benign infantile focal epilepsy with midline spikes and waves during sleep | Described by Capovilla and colleagues.9a Onset of seizures between 4 and 30 months, but usually between 12 and 18 months of age. A family history in half of cases. Activity arrest, vacant staring, cyanosis and automatisms. Vertex sharp waves are a normal feature of stage 2 sleep, but these EEG features are distinctive and epileptiform. |
| Benign myoclonic epilepsy of infancy | A rare condition that is commoner in male subjects. The myoclonic attacks have EEG correlates of spike-wave or polyspike-wave discharges—which distinguishes this from benign myoclonus of early infancy—but the interictal EEG is normal. The myoclonus tends to occur in the awake state but not during sleep. |
| Panayiotopoulos syndrome | Peak onset is at 4–5 years old but cases have been described with onset as young as 1 year old. Prominent features are gaze deviation, impaired consciousness, prominent autonomic symptoms and ictal vomiting. |
| Epilepsy syndromes that may be challenging to treat | |
| Early myoclonic encephalopathy | This generally has onset in the neonatal period but can be up to 3 months of age. The myoclonias are often subtle and fragmentary, but there can be more prominent myoclonus, tonic spasms and focal seizures with eye deviation, facial flushing and apnoea. EEG shows a suppression-burst pattern. Often associated with underlying metabolic disorders. |
| Ohtahara syndrome | This generally has onset in the neonatal period but can be up to 3 months of age. Also known as ‘early infantile epileptic encephalopathy’. Tonic seizures associated with suppression-burst pattern on EEG. A rare condition that may evolve into the commoner West syndrome. |
| Epilepsy of infancy with migrating focal seizures | Also known as migrating partial seizures of infancy. Onset usually before 6 months of age and after normal early development. Very frequent, multifocal seizures with onset from both hemispheres independently and often sequentially. These are generally intractable to treatment, though there are some case reports of response to intravenous levetiracetam.10 Developmental regression and a fall in the trajectory of head growth are usual. |
| Gelastic epilepsy associated with hypothalamic hamartoma | Gelastic seizures involve short episodes of, often mirthless, laughter and other variable seizure symptoms. They are strongly association with hypothalamic hamartoma. Age of onset is variable but can be in infancy. Treatment is challenging but gamma-knife radiosurgery can be effective. |
| Dravet syndrome | Onset generally from 3 months and 90% of cases with onset by 7 months of age. Seizures are provoked by intercurrent infection, immunisations or environmental factors that increase body temperature, such as hot baths. The seizures often increase in frequency and duration over time, and often have strongly lateralising features (‘hemiconvulsive seizures’). Subsequent frequent myoclonus, other focal seizures, ataxia and developmental delay or regression. Variable EEG patterns and often photosensitivity. Many associated with mutations in SCN1A gene (α-1 subunit of neuronal sodium channel). There is an increased risk of sudden unexpected death in epilepsy relative to most epilepsy conditions. |
| West syndrome and infantile spasms | The commonest epilepsy syndrome in infancy. A combination of epileptic spasms with the interictal EEG pattern described as hypsarrhythmia is referred to as ‘West syndrome’. The spasms are usually periodic with a frequency of between 5 and 30 s, though sometimes outside this range. Although the truncal and limb flexion spasms are well known, clinical attacks may manifest with extensor limb and/or truncal semiology, or much more subtly with, for example, merely periodic eye deviation. Hypsarrhythmia is less likely in older infants with epileptic spasms, although the ictal EEG patterns are often the same. |
| Doose syndrome of epilepsy with myoclonic-astatic seizures | Onset in late infancy or early childhood. ‘Atonic’ is probably a preferred term to ‘astatic’ since these are seizures with negative myoclonus. Myoclonus, falls, absences and generalised tonic-clonic seizures may all occur, and there is debate about how much the syndrome overlaps with Lennox–Gastaut and Dravet syndromes, though EEG features are generally distinguishable. Prognosis is variable and neurodevelopment good in some cases. |
| Hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome | Peak onset incidence is up to 2 years of age but this seems to be a condition with declining incidence. Prolonged hemiconvulsion (lateralised convulsive status epilepticus) followed by flaccid hemiparesis, then progressive spasticity, and after a seizure-free period of months to several years, focal seizures with variable semiology. |
| Cryptogenic late-onset infantile spasms | Suggested by Eisermann and colleagues as an epilepsy syndrome with features intermediate between West syndrome and Lennox–Gastaut syndrome.11 |
| Lennox–Gastaut syndrome | A combination of seizures—tonic, tonic-clonic, atypical absence and myoclonic—associated with the EEG pattern described as ‘slow spike-wave’ and paroxysmal fast activity in sleep. Onset in late infancy or early childhood. |
| Myoclonic encephalopathy in non-progressive disorders | A less well-known syndrome with absence-type status epilepticus associated with myoclonus and ataxia. There is often a prominent startle response. |
| Progressive myoclonus epilepsies | These generally have onset in later childhood, but it is worth being vigilant for cases of early-onset metabolic diseases such as neuronal ceroid lipofuscinoses. |