Ohtahara syndrome is a rare and severe form of epilepsy that begins in early infancy, frequently within the first ten days of life. It is classified as an early infantile epileptic encephalopathy, a group of disorders where epileptic activity contributes to developmental impairment. This condition is characterized by intractable seizures and significant intellectual disabilities.
Identifying the Symptoms
The primary manifestation of Ohtahara syndrome is seizures, which are often frequent and difficult to control. The most characteristic seizure type is tonic seizures, presenting as a sudden stiffening of the body, arms, or legs, lasting only a few seconds. Infants might also exhibit an upward gaze of the eyes, dilated pupils, and altered breathing during these episodes. Other seizure types can occur, including focal seizures, which involve only one part of the brain, or myoclonic seizures, appearing as sudden jerks or twitches. Beyond seizures, infants with Ohtahara syndrome often display profound mental and physical disabilities, including low muscle tone and abnormal movements.
Underlying Causes
Ohtahara syndrome is caused by severe, underlying issues with the brain’s structure or function. One category involves structural brain abnormalities, malformations that developed during fetal growth. Examples include hemimegalencephaly, where one side of the brain is abnormally large, or focal cortical dysplasia, an area of abnormally formed brain tissue.
Genetic mutations are another cause, with specific genes identified as contributing factors. Mutations in genes such as STXBP1 or ARX can lead to the syndrome. Other genes, including SLC25A22, CDKL5, and KCNQ2, have also been linked to Ohtahara syndrome.
Metabolic disorders, which affect the body’s chemical processes, can also be an underlying cause. Examples include mitochondrial disorders or non-ketotic hyperglycinemia. In some cases, despite extensive investigation, a specific cause for Ohtahara syndrome cannot be identified.
The Diagnostic Process
Confirming a diagnosis of Ohtahara syndrome involves a thorough clinical evaluation alongside specialized tests. The most informative diagnostic tool is the electroencephalogram (EEG), which records the brain’s electrical activity. A characteristic “burst-suppression” pattern on the EEG is a hallmark of Ohtahara syndrome, present in both wakefulness and sleep.
This pattern consists of periods of high-voltage electrical activity, appearing as spikes and polyspikes, alternating with moments of almost no electrical activity, known as suppression. The muscular spasms observed during seizures often coincide with these “bursts” of activity. Magnetic Resonance Imaging (MRI) of the brain is also performed to identify any structural brain abnormalities that might be causing the syndrome.
Genetic testing may be conducted to pinpoint specific gene mutations. These genetic and imaging tests help to understand the underlying reasons for the condition, guiding further management.
Available Treatment Approaches
Treatment for Ohtahara syndrome focuses on managing its manifestations, particularly the frequent and severe seizures, as there is no cure for the underlying condition. The primary approach involves antiepileptic drugs (AEDs), although the seizures are often resistant to medication. Common AEDs tried include phenobarbital, clobazam, clonazepam, and vigabatrin, but their effectiveness can be limited.
The ketogenic diet, a high-fat, low-carbohydrate diet, is another treatment option that has shown some success in reducing seizure frequency. This diet aims to induce a state of ketosis, where the body uses fat for energy instead of carbohydrates, which can have an antiseizure effect. In situations where a focal brain lesion is identified as the cause of the seizures, epilepsy surgery may be considered to improve seizure control.
Long-Term Outlook and Progression
The long-term outlook for infants diagnosed with Ohtahara syndrome is challenging due to the severe underlying brain abnormalities and the difficulty in controlling seizures. Infants often experience profound developmental delays, affecting both their cognitive and motor skills. Many do not reach typical developmental milestones.
The syndrome commonly evolves into other severe epilepsy syndromes as the child ages. Many infants will progress to West syndrome (infantile spasms) within the first few months of life. Subsequently, some of these children may further evolve into Lennox-Gastaut syndrome. Those who survive beyond infancy often live with substantial physical and cognitive disabilities.