Severe Myoclonic Epilepsy of Infancy

Myoclonic epilepsy of infancy, MEI, benign myoclonic epilepsy in infancy, BMEI, Dravet syndrome, SMEI

Severe myoclonic epilepsy of infancy is a rare seizure disorder that begins in the first year of life in previously healthy babies, characterized by prolonged seizures often triggered by fever and leading to developmental challenges as the child grows.

Table of contents

• What is severe myoclonic epilepsy of infancy?
• What causes this condition?
• Who is affected?
• Signs and symptoms
• How is it diagnosed?
• Treatment options
• What to expect

What is severe myoclonic epilepsy of infancy?

Severe myoclonic epilepsy of infancy, also known as Dravet syndrome, is a serious form of epilepsy that begins in the first year of a child’s life. It is considered a catastrophic form of epilepsy with prolonged seizures that are often triggered by hot temperatures or fever.^[5] The condition affects previously healthy children who were developing normally before the seizures began.^[7]

This condition is different from the milder form called myoclonic epilepsy of infancy (MEI), which has a better outlook. While MEI is a rare, self-limited epileptic syndrome that often resolves within a few years, severe myoclonic epilepsy of infancy is a much more challenging condition that causes ongoing problems throughout life.^[1]

The main characteristic of this disorder is prolonged febrile seizures (seizures triggered by fever) and non-febrile seizures within the first year of life. As the disease progresses, children develop other types of seizures including myoclonic seizures (quick, jerking movements) and partial seizures, along with delays in mental development, difficulty with balance, and clumsiness.^[5]

What causes this condition?

In most cases, severe myoclonic epilepsy of infancy is caused by changes in genes. About 70 to 90 percent of patients have mutations in a gene called SCN1A, which provides instructions for making a protein that helps control electrical signals in the brain.^[5] These mutations result in a protein that does not work properly.

In most cases, these genetic mutations are not inherited from parents. Instead, the mutated gene appears for the first time in a single family member.^[5] This means that parents of an affected child typically do not have the condition themselves.

Who is affected?

Severe myoclonic epilepsy of infancy typically begins before one year of age, with six months being the most common age when seizures start.^[5] The first seizures are usually prolonged convulsions triggered by fever. This condition is rare, but the exact number of affected children is not clearly specified in medical literature.

Signs and symptoms

The condition begins with frequent febrile seizures during the first year of life. These are seizures that occur when a child has a fever.^[5] Sometimes even modest increases in body temperature from activities like physical exercise or a hot bath can trigger seizures in affected children.^[5]

Children with severe myoclonic epilepsy of infancy typically experience several types of symptoms as the condition progresses:

• Prolonged febrile and non-febrile seizures that are difficult to control with medication
• Myoclonic seizures, which are sudden, brief jerking movements of muscles
• Partial seizures affecting only one part of the body
• Delays in language and motor skill development
• Problems with balance and coordination (ataxia)
• Hyperactivity and impulsiveness
• In some cases, behaviors similar to those seen in autism
• Sleep problems including excessive sleepiness and difficulty sleeping
• Difficulty relating to others
• Growth and balance issues
• Chronic infections

The seizures experienced by people with severe myoclonic epilepsy of infancy become worse as the patient ages, and the disease is not very noticeable when symptoms first appear.^[5] The range of severity differs between each person diagnosed with the condition. Children with this disorder require fully committed caregivers who can monitor them closely.^[5]

Any seizure that continues uninterrupted for more than 5 minutes without the child returning to a more normal state of consciousness can lead to a potentially life-threatening condition called status epilepticus.^[5]

How is it diagnosed?

Severe myoclonic epilepsy of infancy is diagnosed clinically, meaning doctors look at the pattern of symptoms and when they occur. Genetic testing is recommended if there is any doubt about the diagnosis.^[5] Testing can identify mutations in the SCN1A gene, which are present in most cases.

Doctors will carefully review the child’s medical history, including family medical history, and ask detailed questions about the seizures. They will perform a physical examination and order diagnostic tests. Common tests include electroencephalography (EEG), which measures electrical activity in the brain, and brain imaging studies such as magnetic resonance imaging (MRI).^[1]

Treatment options

Treatment for severe myoclonic epilepsy of infancy is challenging because the seizures are often resistant to standard anti-epileptic medications. The goal of treatment is to control seizures as much as possible and support the child’s development.^[7]

Several medications may be used, although finding the right combination can be difficult. Commonly used medications include:

• Valproic acid (sodium valproate), often used as a first-line treatment
• Benzodiazepines such as clonazepam or clobazam
• Topiramate, one of the newer anti-epilepsy drugs that has shown promise
• Stiripentol, which is specifically indicated for treatment of seizures in Dravet syndrome in patients aged 2 years or older who are taking clobazam

Some medications should be avoided as they may worsen seizures in patients with this condition. These include phenobarbital, lamotrigine, vigabatrin, and carbamazepine.^[1]

In June 2018, the FDA approved a purified formulation of cannabidiol (Epidiolex) for seizures associated with Dravet syndrome in patients aged 2 years or older. This indication was expanded in July 2022 to include children aged 6 months and older.^[9] The exact mechanism by which cannabidiol works is not fully understood.

In addition to medication, other treatments and approaches may include:

• Avoiding triggers such as hot baths, overheating, and high fevers
• Ensuring adequate sleep and reducing stress
• In some cases, dietary modifications
• Supportive therapies for developmental delays
• Special education services as needed

Children born with a type of brain injury caused by inadequate oxygen or blood flow to the brain may receive hypothermia treatment, which involves cooling the baby’s brain and body by a few degrees immediately after birth for three days. Research shows this treatment may reduce brain injury.^[1]

What to expect

The outlook for children with severe myoclonic epilepsy of infancy is serious. The effects of this disorder do not diminish over time, and most children experience ongoing seizures and developmental challenges.^[5] Cognitive deterioration becomes evident as the condition progresses, along with movement problems and difficulties with balance.^[7]

Children with this condition typically show lagged development of language and motor skills. They often experience cognitive impairment, behavioral disorders, and motor deficits.^[5] Behavioral problems often include hyperactivity and impulsiveness, and in rarer cases, autistic-like behaviors.

The seizures are typically resistant to medication, making them very difficult to control. Patients often require multiple medications throughout their lives. Because of the complexity of care needs, children with severe myoclonic epilepsy of infancy require dedicated caregivers with the ability to monitor them closely.^[5]

Despite these challenges, treatment advances continue to be made. Recent medications and therapies have improved the ability to manage some aspects of the condition, though a cure is not currently available. Early diagnosis and appropriate treatment are important for providing the best possible quality of life for affected children and their families.