Authors: Katherine Xiong, MD; Courtney J. Wusthoff, MD, MS
Division of Child Neurology, Stanford University

Reviewed: February 2022

SUMMARY

Ohtahara syndrome (OS) is a rare form of epilepsy that occurs in infants. It is also sometimes called:

• Early infantile epileptic encephalopathy (EIEE)
• EEIE with burst suppression pattern (EIEE-BS)

OS is one of a group of developmental epileptic encephalopathies (DEEs). DEEs are epilepsy syndromes that impact development at an early age. Children with Ohtahara syndrome typically develop seizures within the first weeks or months of life. These seizures can be hard to control. Children with OS also have developmental delays.

Ohtahara syndrome can have different kinds of causes:

• Structural abnormalities. Most often, OS is caused by differences in how the brain has developed before birth.
• Metabolic disorders. This is a less common cause of OS.
• Genetic mutations. This is a less common cause of OS.

Disorder Overview

SIGNS AND SYMPTOMS

Children with Ohtahara syndrome have two primary symptoms:

• Seizures
• Developmental delays

Seizures

Timing 

Children with Ohtahara syndrome develop frequent seizures within the first 3 months of life. They most commonly appear within the first 2 weeks after birth.  

Severity 

These seizures can be very difficult to control. They often require several antiseizure medications. 

Types of Seizures 

OS is associated with several different types of seizures.  

An EEG or long-term video EEG monitoring is often very helpful to: 

• Identify all the seizure types taking place  
• Identify the frequency of the seizures 
• Decide if an episode is a seizure or not 

Tonic seizures are the most common type of seizure in those with OS. Tonic seizures are also known as tonic spasms. They usually last only a few seconds. They may: 

• Look like stiffening of the arms and/or legs 
• Affect one or both sides of the body 
• Occur alone or in clusters 
• Occur when a baby is awake or asleep 

Other types of seizures that can occur in OS include: 

• Focal seizures. Focal seizures start in one area of the brain. They can cause abnormal movements in just one part of the body. 
• Atonic seizures. Atonic seizures are also called “drop attacks.” They cause children to suddenly lose muscle tone. This causes them to go limp. 
• Myoclonic seizures. This involves brief, shock-like jerks of a muscle or group of muscles. 
• Generalized tonic-clonic seizures. These are also called “grand mal” seizures. They affect both halves of the brain. They begin with a sudden loss of alertness. This is followed by muscle stiffness and jerking movements. 

Development

Infants with Ohtahara syndrome have developmental delays. This can be the result of the underlying cause of their condition in combination with ongoing seizures. They often do not reach milestones at the same age as other infants. They may also have abnormal results on a neurological exam. For instance, they may be:

• Less active
• Less alert
• Prone to low muscle tone (hypotonia)

Developmental symptoms may be present before seizures start. However, they can worsen as the seizures increase.

CAUSES

Ohtahara syndrome can have several different causes.

• Brain malformations. Most cases of OS are due to abnormal brain development. These abnormalities can be:
  • Diffuse. Affecting both sides of the brain. Most infants have diffuse brain abnormalities.
  • Focal. Affecting only one area of the brain. This is less common.
• Genetic mutations. Genetic mutations can cause OS. This is because genetic differences can impact brain development or function.
• Metabolic disorders. Metabolic disorders can cause OS. They can impact how the body and brain use energy. This can lead to abnormal brain function and seizures.

Sometimes no clear cause is found, even after exams and testing. Cases in which there is no known cause are called idiopathic cases.

LABORATORY INVESTIGATIONS

TREATMENT AND THERAPIES

Several treatments can be used to treat OS. The treatments are focused on controlling the seizures caused by OS.

OUTLOOK

There is no cure for Ohtahara syndrome. Treatment focuses on controlling seizures as much as possible and supporting development. Even with treatment, most children with OS will have seizures throughout their lifetime. Further, these seizures will be difficult to control.

Many children will have different types of seizures when they are older than they did when they were younger. Some will progress to having additional epilepsy syndromes, such as:

• Infantile spasms
• Lennox-Gastaut syndrome

Some children will experience significant complications from OS or from its underlying cause. These children may die within the first two years of life.

Children who survive into childhood typically have severe physical and cognitive disabilities. They usually require a lot of assistance to perform the tasks of daily life. They may need help with eating or dressing. They may benefit from:

• Special educational support
• Physical and occupational therapy
• Speech and language therapy

Research 

ClinicalTrials.gov for Ohtahara Syndrome (birth to 17 years)
These are clinical trials that are recruiting or will be recruiting. Updates are made daily, so you are encouraged to check back frequently.

ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted around the world. This is a resource provided by the U.S. National Library of Medicine (NLM), which is an institute within the National Institutes of Health (NIH). Listing a study does not mean it has been evaluated by the U.S. Federal Government. Please read the NLM disclaimer for details.  

Before participating in a study, you are encouraged to talk to your health care provider and learn about the risks and potential benefits. 

The information in the CNF Child Neurology Disorder Directory is not intended to provide diagnosis, treatment, or medical advice and should not be considered a substitute for advice from a healthcare professional. Content provided is for informational purposes only.  CNF is not responsible for actions taken based on the information included on this webpage. Please consult with a physician or other healthcare professional regarding any medical or health related diagnosis or treatment options. 

References:

1. Gürsoy S, Erçal D. Diagnostic Approach to Genetic Causes of Early-Onset Epileptic Encephalopathy. J Child Neurol. 2016 Mar 1;31(4):523–32. https://doi.org/10.1177/0883073815599262

2. Beal JC, Cherian K, Moshe SL. Early-Onset Epileptic Encephalopathies: Ohtahara Syndrome and Early Myoclonic Encephalopathy. Pediatric Neurology. 2012 Nov 1;47(5):317–23. https://doi.org/10.1016/j.pediatrneurol.2012.06.002

3. Ohtahara Syndrome [Internet]. Epilepsy Foundation. [cited 2021 Oct 4]. Available from: https://www.epilepsy.com/learn/types-epilepsy-syndromes/ohtahara-syndrome

4. Ohtahara Syndrome Information Page | National Institute of Neurological Disorders and Stroke [Internet]. [cited 2021 Oct 4]. Available from: https://www.ninds.nih.gov/Disorders/All-Disorders/Ohtahara-Syndrome-Information-Page

5. Pavone P, Spalice A, Polizzi A, Parisi P, Ruggieri M. Ohtahara syndrome with emphasis on recent genetic discovery. Brain and Development. 2012 Jun 1;34(6):459–68. https://doi.org/10.1016/j.braindev.2011.09.004

6. Yamamoto H, Okumura A, Fukuda M. Epilepsies and epileptic syndromes starting in the neonatal period. Brain and Development. 2011 Mar;33(3):213–20. https://doi.org/10.1016/j.braindev.2010.10.009