Ohtahara Syndrome - Causes, Symptoms and Treatment

Introduction:

Epilepsy is a central nervous system disorder (neurological disorder) that causes abnormal brain activity, which leads to seizures, unusual behavior, or loss of consciousness. Anyone can develop epilepsy; males and females are both affected equally. Ohtahara syndrome is one of the rare types of epilepsy that begins during the infancy stage. Children with this condition experience seizures as well as developmental problems.

What Is Ohtahara Syndrome?

Ohtahara syndrome is one among a group of developmental epileptic encephalopathies (DEEs), a rare epilepsy syndrome primarily seen in infants. Ohtahara syndrome is also known as early infantile epileptic encephalopathy (EIEE) or early infantile epileptic encephalopathy with burst suppression pattern (EIEE-BS). Children with this syndrome start to have seizures early in the first few weeks or months of life (mainly before three years). These seizures are hard to control and cause developmental delays.

What Are the Causes of Ohtahara Syndrome?

Ohrahara syndrome can occur due to various causes, such as:

• Brain Malformations - Ohtahara syndrome occurs primarily due to abnormal brain development. The abnormalities include:

  1. Diffuse - Most common, affecting both sides of the brain.

  2. Focal - Less common, affecting only one area of the brain.

• Genetic Mutations - Genetic mutation is another reason causing Ohtahara syndrome due to abnormal development or function of the brain.

• Metabolic Disorders - Metabolic disorders can lead to Ohtahara syndrome as they impact the usage of energy by the body and brain, resulting in abnormal brain function and seizures.

• Idiopathic Cases - These are those cases in which no apparent cause of Ohtahara syndrome is found, even after conducting multiple tests and examinations.

What Are the Signs and Symptoms of Ohtahara?

Children with Ohtahara syndrome show two primary symptoms:

• Seizures.

• Developmental delays.

1. Seizures -

• Timing - Children with Ohtahara syndrome develop seizures within the first three months of their life. Usually, the symptoms appear within the first two weeks after birth.

• The Severity of Seizures - These seizures are difficult to control and often require treatment with the help of antiseizure medications.

• Types of seizures involved - Ohtahara syndrome is associated with many different types of seizures. An EEG (electroencephalogram) or long-term video EEG (electroencephalogram) monitoring is often helpful to:

• Identify all the types of seizures taking place in this syndrome.

• Identify the frequency of the seizures.

• Decide if an episode is a seizure or not.

The most common seizure in this syndrome is tonic, also known as tonic spasms, which usually last for a few seconds. The tonic seizure involves the following signs such as:

• Stiffening of arms and legs.

• It can affect one or both sides of the body.

• It can occur when a baby is awake or asleep.

Other types of seizures that can occur in Ohtahara syndrome include:

1. Focal Seizure - Focal seizures only affect a specific part of the brain and cause abnormal movement in that part.

2. Atonic Seizures - This type of seizure causes the sudden loss of muscle tone in children and is also known as drop attacks.

3. Myoclonic Seizures - This involves shock-like jerks of the muscle or group of muscles.

4. Generalized Tonic-Clonic or Grand Mal Seizures - Affect both halves of the brain and cause sudden loss of alertness followed by muscle stiffness and jerking movements.

5. Infantile Spasms: This involves sudden neck, arms, or leg movements that may last for only one second.

2. Developmental Delays -

Some developmental delays related to this syndrome can result from the underlying condition in combination with ongoing seizures. The infants affected with this syndrome do not reach the exact growth milestone compared to the other infants of the same age. Some of the signs or symptoms seen in these infants are as follows:

• Less active or less alert.

• Prone to low muscle tone (hypotonia).

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

How Is This Syndrome Diagnosed?

Ohtahara syndrome can be diagnosed by considering multiple factors such as a history of seizures and developmental problems in children, physical examination, EEG (electroencephalogram), and other brain imaging tests.

• Physical Examination:

Examining young infants can be challenging; only specialists can review their physical condition. Children in this condition can have somewhat stiff or floppy muscles. They also have abnormal reflexes and might not be able to follow the moving object with their eyes.

• Diagnostic Tests:

Several diagnostic tests that may be used in Ohtahara syndrome include:

1. Electroencephalogram (EEG) - An electroencephalogram (EEG) is a non-invasive test that determines brain wave activity. In this test, metal discs are placed on the scalp of a child, which detect brain wave activity on a computer screen. The EEG pattern in Ohtahara syndrome is seen as a burst suppression pattern.

2. Brain Imaging Tests - These tests involve magnetic resonance imaging (MRI) and computed tomography (CT), which create images of the structure of the brain. The underdeveloped areas of the brain or altered brain structure can be accessed in these imaging tests.

Other Laboratory Tests:

Along with the above-mentioned tests, some of the additional tests can also be advised by the doctor, such as:

• Genetic Tests: Three common types of genetic tests that help diagnose Ohtahara syndrome are :

• Chromosomal Microarrays - A technology used for the detection of clinically-significant microdeletions or duplications, with high sensitivity for submicroscopic aberrations.

• Epilepsy Genetic Panels - This test involves the analysis of the most common genes associated with epilepsy.

• Whole Exome Sequencing - A type of genetic sequencing used to understand the symptoms and cause of the disease.

What Is the Treatment for Ohtahara Syndrome?

There are several treatment options available to manage Ohtahara syndrome. The treatment can help reduce the frequency and severity of the seizures, but they are ineffective in managing developmental conditions. Some of the treatment options include:

1. Anti-Epileptic Drugs (AED) - Some of the medicine used for the treatment of epilepsy are Topamax (Topiramate), Zonegran (Zonisamide), Sabril (Vigabatrin), Felbatol (Felbamate), and others. The medicine can be given as an injection or in liquid form as the babies will not be able to swallow it.

2. Steroid Treatment - The high-dose steroids such as Adrenocorticotropic hormone (ACTH) or Methylprednisolone can also be used to treat Ohtahara syndrome.

3. Ketogenic Diet - This diet is high in fats and low in protein and carbohydrates. It helps in the prevention of seizures through a metabolic process called ketosis.

4. Transcranial Stimulation - Another technique known as high-definition transcranial direct current stimulation (HD-tDCS) is used to administer electrical stimulation to the brain using electrodes.

5. Epilepsy Surgery - In some cases, epilepsy can be treated with surgery which involves removing the affected part of the brain to prevent the spread of chaotic nerve activity.

6. Physical and Cognitive Therapy - In mild cases of Ohtahara syndrome, the therapy can help maximize their ability to walk, talk, learn, and interact with others.

7. Palliative Care - This type of care involves comfort and pain control which helps in patients with a short life expectancy or who are dealing with significant disabilities.

Conclusion:

Ohtahara syndrome is a rare disorder, and there is no cure for Ohtahara syndrome; treatment mainly focuses on controlling seizures and supporting their development. And in some cases, even after treatment, the patient may have seizures throughout their lifetime. This grave condition requires proper diagnosis and critical care for the affected child.