Ohtahara syndrome

Synonyms

3

Overview

Ohtahara syndrome (OS, also known as Early Infantile Epileptic Encephalopathy with Burst-Suppression ,EIEE), is a progressive epileptic encephalopathy. The syndrome is outwardly characterized by tonic spasms and partial seizures, and receives its more elaborate name from the pattern of burst activity on an electroencephalogram (EEG). It is an extremely debilitating progressive neurological disorder, involving intractable seizures and severe mental retardation. No single cause has been identified, although in many cases structural brain damage is present.

It is named for the Japanese neurologist Shunsuke Ohtahara (1930–2013), who identified it in 1976.

Symptoms

Ohtahara syndrome is rare and the earliest-appearing age-related epileptic encephalopathy, with seizure onset occurring within the first three months of life, and often in the first ten days. Many, but not all, cases of OS evolve into other seizure disorders, namely West syndrome and Lennox-Gastaut syndrome.

The primary outward manifestation of OS is seizures, usually presenting as tonic seizures (a generalized seizure involving a sudden stiffening of the limbs). Other seizure types that may occur include partial seizures, clusters of infantile spasms, and, rarely, myoclonic seizures. In addition to seizures, children with OS exhibit profound mental and physical retardation.

Clinically, OS is characterized by a “burst suppression” pattern on an EEG. This pattern involves high voltage spike wave discharge followed by little brain wave activity.

Causes

No single cause of OS has been identified. In most cases, there is severe atrophy of both hemispheres of the brain. Less often, the root of the disorder is an underlying metabolic syndrome. Although it was initially published that no genetic connection had been established, several genes have since associated with Ohtahara syndrome. It can be associated with mutations in ARX, CDKL5, SLC25A22, STXBP1, SPTAN1, KCNQ2, ARHGEF9, PCDH19, PNKP, SCN2A, PLCB1, SCN8A, and likely others.

Diagnosis

Electroencephalogram (EEG) shows evidence of abnormal discharges or spikes and waves alternating with periods of flatness. This type of record is referred to as suppression-burst. All infants are neurologically very abnormal. Often they are very floppy and excessively sleepy. With time they may develop stiffness (spasticity) in the limbs.

Prognosis

Infants with Ohtahara Syndrome make very little developmental progress. They remain totally dependent on others and often feed poorly. They often die within the first two years of life because of repeated chest infections. Those who do survive will be severely disabled.

Treatment

Treatment outlook is poor. Anticonvulsant drugs and glucocorticoid steroids may be used to try to control the seizures, but their effectiveness is limited. Most therapies are related to symptoms and day-to-day living.

When the cause of the seizures is a malformation of either the left or right hemisphere of the brain then a surgical procedure, a functional hemispherectomy, can significantly improve the developmental outcome of the child and even completely stop the seizures