(Early Infantile Epileptic Encephalopathy)

  • Encountered before 3 months of age.
  • Usually first seizure, in retrospect could be felt in the womb of a mother during pregnancy or during the first 10 days of the infant’s life.
  • Boys and girls are equally affected.
  • Typically newborns or infants will have tonic spasms and partial (focal) seizures that do not respond to anti-seizure medication.
  • Many cases are caused by a brain malformation, metabolic disorder or genetic mutations.
  • EEG is the most important test to diagnose OS.

What is Ohtahara Syndrome?

Ohtahara Syndrome (OS) is a rare epilepsy syndrome seen in neonates/infants. It is also known as early infantile epileptic encephalopathy or early infantile epileptic encephalopathy with burst suppression pattern.

It is usually diagnosed before age 3 months, but in retrospect the first seizure could be felt towards the last trimester (when the baby is in the mother’s womb) or is seen during the first 10 days of life.  Motor and cognitive problems can be seen in a baby that can get progressively worse. Ohtahara syndrome can affect both boys and girls.

What types of seizures are seen in Ohtahara Syndrome?

Many seizure types may occur, but tonic seizures (stiffening of the arms or legs) that lasts seconds are seen most often. The tonic seizures can occur singly or in clusters. About 1 out of 3 infants with OS may develop other seizure types, such as partial or focal seizures (start in one area of the brain), atonic, myoclonic or generalized tonic clonic seizures.  Infants with OS may also develop infantile spasms.

What causes Ohtahara Syndrome?

Though the cause can’t be found in some cases of OS, possible causes may include brain malformations, metabolic disorders and certain gene mutations. It is common for infants with OS to have part or all of the cerebral hemispheres (the two sides of the brain) not develop fully. Changes in the brainstem may also be seen. 

Gene mutations refer to changes in a gene or group of genes that may affect how the gene affects brain development or function. Some genes that have been associated with OS include ARX, CDKL5, SLC25A22, STXBP1, SPTAN1, KCNQ2, ARHGEF9, PCDH19, PNKP, SCN2A, PLCB1, SCN8A, ST3GAL3, TBC1D24, and BRAT1.

How is Ohtahara Syndrome diagnosed? 

Diagnosing a baby with OS is based on clinical features (what signs or symptoms the baby has) and EEG findings. The EEG is the most important test in making a diagnosis of OS. The EEG in babies not treated with medications is very abnormal with a burst suppression pattern (high amplitude spikes followed by little brain activity or flattening of the brain waves). These changes can be seen during sleep and when the infant is awake.

Ohtahara EEG

An MRI is helpful to look for structural changes in the brain that could cause OS. MRIs could be normal initially, but follow up MRIs can show atrophy (shrinkage) of the brain. Sometimes the MRI may be abnormal and the neurologist will determine if the abnormality is the cause of the OS.

Blood work will also be done to look for possible metabolic or genetic problems.

How is Ohtahara Syndrome treated?

Anti-seizure medications are routinely used, but seizures with OS are usually difficult to control. Medications that are often tried include clobazam (Onfi), clonazepam (Klonopin), vigabatrin (Sabril), topiramate (Topamax), zonisamide (Zonegran), Phenobarbital, valproate, or felbamate (Felbatol).

Steroid therapy with ACTH or prednisone has been helpful in some children.

Epilepsy surgery may be an option in children with seizures starting in one area or involving one side of the brain. In these situations, a focal resection (removal of one area) or a hemispherectomy (removing most of one side of the brain) may be considered.

Devices or dietary therapy: A vagus nerve stimulator or the ketogenic diet may also be considered when medicines don’t work well.

Correcting metabolic problems: Sometimes a metabolic disorder that affects how the brain works may lead to OS. While these currently can’t be reversed, sometimes treating the underlying disorder can help.

What is the outlook for persons with Ohtahara Syndrome?

The outlook for children with OS may be grim. Many children progress to have infantile spasms (West Syndrome) or Lennox-Gastaut Syndrome (LGS).  Some children with OS may die within the first 2 years of life. Those who survive are typically left with severe physical and cognitive disabilities.

Hope for children with Ohtahara Syndrome relies on the medical and research community understanding more about the causes and what treatment may work best in OS.

The Rare Epilepsy Network (REN) helps connect families with research in these areas.

Authored by: Elaine Kiriakopoulos MD, MSc, Drug Resistant and Rare Epilepsies Editor, and Angel W. Hernandez-Mulero MD, Pediatrics Editor on 3/2015