Page 64 - ILAE_Lectures_2015

Doose syndrome is considered a genetic generalised epilepsy but it often acts as an epileptic
encephalopathy. Children with congenital hemiplegia due to middle cerebral artery infarcts
may develop a severe epilepsy but more usually the epilepsy is mild. Dravet syndrome (one
of the most severe of all childhood severe epilepsies) is a chanellopathy.

Severe epilepsy syndromes of the neonatal period

There are two well described epileptic encephalopathies in this age group. They share some
common features.

Ohtahara syndrome (also known as early infantile epileptic encephalopathy)
This is a rare epilepsy syndrome usually presenting in the first few days or weeks of life, but
sometimes as late as three months of age. Clinically it is characterised by the occurrence of
tonic seizures which can be generalised and symmetrical or lateralised. These tend to be very
frequent (often hundreds a day), occur both during awake and sleep and can be single or occur
in clusters (similar to infantile spasms). Other seizure types include focal motor seizures and
hemi- or generalised tonic-clonic seizures. Myoclonic seizures are not characteristic. The
EEG shows a burst-suppression pattern both during awake and sleep (Figure 1). Bursts,
usually lasting 26 seconds, consist of high amplitude slow waves intermixed with spikes.
These alternate with periods of suppression, usually lasting for 35 seconds, during which
the EEG is flat or nearly flat. Tonic seizures can occur during the bursts or can be associated
with periods of desynchronisation or ‘accentuation’ of the burst-suppression pattern.

Ohtahara syndrome is commonly caused by severe cerebral malformations, such as
hemimegalencephaly, diffuse migrational disorders, porencephaly, Aicardi syndrome, etc.
The prognosis is very poor. Half of infants affected are said to die within weeks or months of
its onset. The remainder are left with severe learning difficulties and often with motor
impairments (cerebral palsy). Survivors often show an evolution to West syndrome and this
may subsequently evolve to Lennox-Gastaut syndrome. This observation lead to the concept
of the age-related encephalopathies.

Treatment with antiepileptic drugs (AEDs) is usually ineffective. ACTH has been used,
usually without effect.

Early myoclonic encephalopathy
This is a also a rare neonatal epilepsy syndrome often presenting very shortly after birth and
nearly always within the first few weeks of life. It is characterised by erratic or fragmentary
myoclonus consisting of myoclonias affecting the face and limbs which shift from one part
of the body in a random and asynchronous manner. They may be single or repetitive and are
usually very frequent, if not near continuous. Massive axial myoclonic jerks may also occur.
Other seizure types seen include: focal seizures, often subtle and manifested with, for
example, eye deviations or autonomic symptoms; tonic seizures; and epileptic spasms
(usually later in the evolution of the disorder). The EEG shows a burst-suppression pattern
(Figure 1), often more apparent in sleep than when awake. The myoclonias do not usually
have an EEG correlate.

Early myoclonic encephalopathy is often caused by inborn errors of metabolism, such as
amino and organic acidurias, disorders of purine metabolism and peroxisomal disorders.
Detailed metabolic studies are mandatory. These should include CSF studies for glycine to
exclude non-ketotic hyperglycinaemia. Not surprisingly, autosomal recessive inheritance is
often apparent. Structural brain defects, except for the development of diffuse atrophy, are
not expected. Unless a treatable metabolic disorder is found no effective treatment exists.
There is a very high mortality in the early weeks and months of life and survivors are left
with severe physical and mental impairments.