Ohtahara Syndrome (OS)
Ohtahara Syndrome (OS), also known as Early Infantile Epileptic Encephalopathy with Burst-Suppression (EIEE), is a rare and devastating epileptic encephalopathy of the neonatal period. The ILAE classifies it as a developmental and epileptic encephalopathy, emphasising that the underlying cause, combined with the epileptic activity, leads to severe developmental impairment.
Presentation and Clinical Features
Age of Onset: OS is one of the earliest occurring epileptic encephalopathies, with seizures beginning in the first days or weeks of life.
Seizure Types: The most common seizure type is a tonic spasm, which is a brief stiffening or arching of the body, lasting up to 10 seconds. These spasms are often seen in clusters during sleep. Other seizure types, such as focal motor seizures and myoclonic jerks, may also be present. The seizures are typically frequent and intractable, meaning they are highly resistant to medication.
Aetiology: A majority of cases have an identifiable cause. These can be structural brain abnormalities, such as cortical dysplasia or brain malformations, genetic mutations (e.g., STXBP1, KCNQ2, CDKL5, ARX), or metabolic disorders.
Developmental Outcome: The prognosis for development is poor. Children with OS have severe psychomotor delay from the very beginning. They often have profound developmental regression, particularly in motor skills and cognition, and may develop acquired microcephaly.
Syndromic Evolution: A significant number of infants with OS will evolve into another epileptic encephalopathy, most commonly West Syndrome (infantile spasms) around 3 to 6 months of age, and later into Lennox-Gastaut Syndrome.
Investigations
EEG: The key to diagnosing OS is the characteristic EEG pattern known as “burst-suppression.” This pattern is seen during both wakefulness and sleep and consists of periods of high-voltage spike or polyspike-and-wave discharges (“bursts”) alternating with periods of low-voltage or flat activity (“suppression”).
Neuroimaging: A brain MRI is essential to identify any underlying structural brain abnormalities.
Genetic and Metabolic Testing: Genetic testing (e.g., whole exome sequencing or specific gene panels) and metabolic screening should be performed to identify an underlying cause, as this can have implications for prognosis and treatment.
Management and Prognosis
Treatment: The seizures in OS are notoriously difficult to control.
Medication: First-line treatments often include Levetiracetam, Vigabatrin, and Clobazam. These medications may provide some seizure reduction, but complete control is rare.
Aetiology-Specific Treatment: If an underlying metabolic disorder is identified, specific treatments may be available. For structural brain lesions, surgical intervention, such as focal resection or callosotomy, may be considered.
Symptomatic and Supportive Care: Management often focuses on supportive care, including feeding support (e.g., gastrostomy tube), physiotherapy for low muscle tone and spasticity, and respiratory care due to the high risk of aspiration pneumonia.
Prognosis: The prognosis is grim. The combination of intractable seizures and severe developmental impairment often leads to profound disability and a high mortality rate, with most children not surviving beyond early childhood.