Early Infantile Epileptic Encephalopathy (EIEE) or Ohtahara syndrome is a severe and congenital seizure disorder that affects neonates within the first three months of life, and often within the first two weeks.
The clinical features of Ohtahara syndrome consist of weak suckling reflexes, with hypotonia of the muscles, and generalized symmetrical tonic spasms. The characteristic feature is the occurrence of tonic generalized or lateralized seizures. These are seen as stiffening of the muscles of the back, the legs, and the arms. They may occur hundreds of times a day and last for about 10 seconds each. They are symmetrical and may occur singly or in clusters. They are independent of the sleep-wakefulness cycle. They are often fatal.
These spasms may be single but are typically clustered. While each spasm lasts for less than ten 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.
Infants with EIEE may also have partial or myoclonic seizures, and in one of three patients, generalized tonic-clonic seizures, focal seizures, and hemiconvulsions also develop. All types of seizures in EIEE are intractable and show severe progression.
In most of these infants, the hemispheres of the brain are poorly developed or show structural anomalies. In some cases, the symptoms are worsened by the coexistence of metabolic disorders. Pyridoxine deficiencies are especially associated with defects in the metabolism of amino acids, especially homocysteine, as well as of carbohydrates, and lipids. Pyridoxine is also vital for the production of some neurotransmitters, proper immune function, and the synthesis of hemoglobin.
Biotinidase deficiency is an autosomal recessive inborn metabolic error associated with the inability to break down proteins, either ingested or from cells which are being broken down for recycling because of the partial or complete lack of an enzyme needed to degrade biotin. Profound deficiency of the biotinidase enzyme results in seizures, muscular hypotonia, severe defects in vision and hearing, respiratory problems, ataxia of movement and balance, alopecia, and fungal infections with Candida species.
Infants with EIEE show profound mental and physical retardation and often die in infancy or early childhood. The seizures are very difficult to control with any mode of management.