The incidence of early infantile epileptic encephalopathy is between 1 in 50 ,000 and 1 in 100,000. This condition, also called Ohtahara syndrome, sets in within the first year of life and most commonly within the first three months. A large number of babies are diagnosed within two weeks after birth.
The clinical features consist of weak suckling reflexes, hypotonia of the muscles, and generalized symmetrical tonic spasms. These may be single or clustered, and their duration may be up to 10 seconds. They may occur hundreds of times in a single day and are not affected by sleep or wakefulness. In one of three patients, generalized tonic-clonic seizures, focal seizures, and hemiconvulsions also develop. Mortality in infancy is high, and among the survivors, severe mental and motor disability is common. Death is due to pneumonia or other complications in a number of cases.
Ohtahara syndrome may convert into West syndrome within 2-6 months after birth, in about 75% of cases. Among these, 12% go on to develop the Lennox-Gastaut syndrome. The change is typically shown by changes in the EEG pattern. While EIEE is diagnosed by a suppression-burst pattern, West syndrome is typically accompanied by hypsarrhythmia, and when Lennox-Gastaut develops, a slow spike wave pattern sets in. These three are thought to possibly be brain reactions to the same type of exogenous stimulus which change with brain age, rather than three different conditions.
Electroencephalography (EEG) is a test in which the electrical activity of the brain is mapped. In Ohtahara syndrome, the EEG shows a unique suppression-burst pattern, which describes a sequence of spikes and polyspikes at high amplitude, in regular alternation with periods of low-voltage electrical activity or electrical suppression. The muscular spasms occur at the time of the bursts. The EEG confirms the lack of any relationship between the pattern and the sleep-wake cycle.
In some cases, the baby has coexistent or underlying metabolic or structural disease. Metabolic conditions that can cause EIEE include cytochrome C oxidase deficiency and carnitine palmitoyltransferase II deficiency. Structural brain disease includes porencephaly or hemimegalencephaly, sometimes of genetic origin.
In some patients, the EIEE is found in association with mutations of the ARX, CDKL5, SL 25A22 and STXBP1 genes. These may cause dysfunction of the brain neurons or anatomical maldevelopment of the brain cells which can be picked up on cranial MRI. Neuroimaging is thus generally performed once this diagnosis is reached.
The diagnosis of Ohtahara syndrome is made on the basis of the clinical picture and the typical suppression burst electroencephalogram pattern. Brainstem evoked potentials are not definitively abnormal and may therefore not be very important in the diagnosis.
Other conditions which must be distinguished from EIEE include early myoclonic encephalopathy, West syndrome and other illnesses which are associated with early onset encephalopathy and epilepsy. Prenatal diagnosis can be carried out if a family member has EIEE with a genetic component.
Genetic counseling is important because most cases of EIEE are sporadic, and parents of affected children may be reassured as to the low risk of further children having this condition. Autosomal recessive inheritance has been observed in only a few cases.