Page 252 - ILAE_Lectures_2015

It is becoming increasingly evident that a progressive epileptic encephalopathy may be seen in
association with certain chromosomal abnormalities, most notably ring chromosome 20. These
children present with an early onset apparent focal (frontal) epilepsy. Onset is usually before
six years of age. Seizures are often bizarre in semiology, although suggestive of frontal origin;
they may include seizures with fear, often with visual symptoms, hallucinations and illusions,
generalised tonic, clonic or tonic-clonic seizures, nocturnal tonic seizures or arousals and
recurrent non-convulsive status epilepticus. Cognitive outcome is variable although a plateau
in skills not inevitable.

To what degree is autism related to epileptic regression?

The cognitive plateau and regression seen in association with some of the early epileptic
encephalopathies may show a particular pattern, particularly involving communication skills,
with similarities to children presenting with autism. This is seen in children with infantile
spasms, and also in children with early presentation of seizures associated with right temporal
lobe lesions, especially boys. Conversely, a number of children with classical presentation of
autism have epileptiform abnormalities on EEG (30%) and about 20% suffer from epilepsy.
The question arises as to how much of the epileptiform activity seen on EEG, particularly in
sleep, is related to the autistic regression, and how much this warrants aggressive AED
treatment. To date, there are no studies demonstrating the relationship of epileptiform
abnormalities on EEG to classical autism, or the merits of treatment. Most children showing
a response are those who present with a history of some seizures, and therefore warrant
investigation and treatment from this standpoint. The potential role of AEDs in others needs
further investigation.

Epilepsy as the presentation of a neurodegenerative disorder

A few conditions have epilepsy as a presenting feature (Table 1). The range of disorders that
need to be considered will depend on the age at presentation. In the neonate, metabolic
disorders, particularly non-ketotic hyperglycinaemia, may present with a
clinical/electrophysiological picture suggestive of hypoxic ischaemic encephalopathy, with
very early seizures and a burst-suppression picture on EEG. One may be alerted by the
apparent lack of history of a significant hypoxic insult. Later in the first year, Menkes disease
and biotinidase deficiency may be suggested by the condition of the hair.

Alpers’ disease (also known as progressive neuronal degeneration of childhood – PNDC) is
a rare but well recognised disorder in which progressive epilepsy is seen in association with
liver dysfunction. The condition usually presents in the first two years of life, though may
present at any time during childhood and even into early adult life. It is an autosomal recessive
disease caused by mutation in the gene for the mitochondrial DNA polymerase POLG. It is
likely that many of the reported valproate-associated hepatic failures occurred in individuals
with Alpers’ disease.

Late infantile neuronal ceroid lipofuscinosis (Batten’s disease) presents with initial seizures
in the second year of life, usually including myoclonus with a subtle developmental plateau
that may only later become apparent as regression. Electrical visual studies may lead to
suspicion (with enhanced visual evoked response), and confirmation with white cell enzyme
analysis and genetic studies.

In older children, conditions that may still need to be considered include subacute sclerosing
panencephalitis (SSPE). Progressive behaviour change in association with periodic jerks will
give a clue to this. Wilson’s disease may have associated movement disorder and behaviour