Causes of Myoclonic Seizures in Babies (Dravet Syndrome)

Infantile myoclonic epilepsy is caused by genetic abnormalities in the brain, inborn metabolism errors, and neurogenetic mutations.

Epilepsy is a neurological disorder that causes recurrent seizures. Myoclonic epilepsy is characterized by brief seizures with rapid, uncontrolled muscle jerks. These seizures do not cause loss of consciousness and usually last just a second or two, but a cluster of seizures can occur in a short period.

Epileptic syndromes causing myoclonic seizures usually begin in early childhood and last throughout life, although milder forms may improve with adulthood. Myoclonic epilepsy can occur in isolation or as part of a mixed, generalized epilepsy syndrome.

Causes of myoclonic seizures in babies

Myoclonic seizures result from a sudden burst of abnormal electrical discharge in the brain’s nerve cells (neurons), leading to involuntary muscle contractions. Infantile myoclonic epilepsy is primarily caused by genetic abnormalities in the brain, though the cause is not always identifiable. Causes of childhood myoclonic seizures include:

• Brain malformations
• Inborn metabolism errors
• Neurogenetic mutations

Mutations in the SCN1A gene have been identified as the cause in 80% of cases of Dravet syndrome, a rare, drug-resistant infantile myoclonic seizure disorder.

Infantile myoclonic seizures occur in neurological disorders that include:

• Early infantile epileptic encephalopathies: These are brain disorders which include

• Early myoclonic encephalopathy
• Early infantile epileptic encephalopathy.

Symptoms of myoclonic seizures

Myoclonic seizures usually occur on awakening, and some may be caused by external stimuli such as flashing lights (photic stimuli). Symptoms include:

• Involuntary abrupt muscle jerks in one or both arms and legs, occurring several times a day.
• Head nodding
• Abrupt abduction of arms
• Twitches in eyelids and facial muscles
• Irregular movements in the fingers which lead to dropping things or appearing clumsy

Seizures are more frequent and prolonged in severe forms of myoclonic epilepsy, which are also associated with other forms of generalized seizures, such as in the case of Dravet syndrome. Symptoms of Dravet syndrome may range from mild to severe and include:

• Convulsive seizures that begin before 15 months of age

• Seizures that are prolonged and involve half of the body
• Subsequent seizures that may involve the opposite half of the body
• Temperature changes, like exiting a warm bath, can trigger a seizure
• Myoclonus status epilepticus, a medical emergency condition of continuous seizure, may frequently occur in children with Dravet, especially before age five

Diagnosing myoclonic epilepsy

Accurate diagnosis of the seizure origin is crucial because seizures can occur due to conditions other than epilepsy. Determining if different types of seizure disorders are occurring simultaneously and identifying the distinct epilepsy syndrome are essential for formulating the appropriate treatment. Diagnostic tests include:

• Physical examination or videotaping by caregivers when direct observation is not possible due to the unpredictable nature of the illness
• Electroencephalography (EEG)
• Magnetic resonance imaging (MRI)
• EEG video monitoring
• Lumbar puncture to identify mitochondrial and neurodegenerative disorders
• Genetic testing for SCN1A to establish Dravet syndrome or other genetic mutations in select cases

Treatment for myoclonic epilepsy

There is no cure for myoclonic epilepsy, but antiepileptic drugs (AEDs) can prevent seizures. Many patients with benign forms of myoclonic epilepsy respond well to treatment with AEDs. Severe forms of myoclonic epilepsy are refractory and more difficult to treat, and may require a combination of different therapies.

Treatment options for myoclonic epilepsy

The mainstays of myoclonic epilepsy treatment are antiepileptic and anticonvulsant medications. These drugs prevent seizures by inhibiting neurotransmission of chemical signals between neurons and the resulting electrical discharge.

Lifestyle and dietary modifications can also help manage the condition. In select cases, epilepsy surgeries may be an option.

Antiepileptic drugs

Antiepileptic drugs may be administered alone (monotherapy) or in combination therapy. FDA-approved antiepileptic drugs include:

• Valproic acid (Depakote, Depakene, Depacon, Stavzor): An anticonvulsant used as first-line treatment. Use of valproic acid increases the risk of liver toxicity in children younger than two years.
• Clobazam (Onfi): A benzodiazepine-class drug for adjunctive treatment in Lennox-Gastaut syndrome associated seizures in children two years of age and older.
• Stiripentol (Diacomit): An anticonvulsant medication used with clobazam for seizures associated with Dravet syndrome in children aged two years or older.
• Clonazepam (Klonopin): A benzodiazepine useful in immediate control of seizures but may rapidly lose efficacy.
• Ethosuximide (Zarontin): An anticonvulsant used as an adjunct if valproic acid is not effective as monotherapy.
• Cannabidiol (Epidiolex): A purified form of cannabidiol derived from the cannabis plant, approved for seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex in children aged one year or older. Doctors are unsure of how it works, but cannabidiol consistently showed a 35% to 40% drop in the number of seizures for the Epidiolex groups in several international, controlled clinical trials.

Other antiepileptic medications can control seizures but may worsen them in certain cases:

• Adrenocorticotropic hormone (ACTH)
• Steroids
• Immunoglobulins

Dietary and lifestyle adaptations

Dietary and lifestyle modifications may be beneficial, especially in children with refractory epilepsy:

• Ketogenic diet: An extremely low-carbohydrate, high-fat and protein diet that may be useful in children with epilepsy. Consultation with a pediatrician and, possibly, a nutritionist is necessary before starting a child on this diet. Particular attention must be paid to prevent dehydration with this diet.

Prognosis for myoclonic epilepsy

Children with mild forms of myoclonic epilepsy often respond well to treatment and may even outgrow their epilepsy in adulthood. Prognosis is poor for children with severe forms of epilepsy, such as Dravet syndrome.

Dravet syndrome can lead to cognitive disability ranging from mild to profound. Muscle spasticity appears to worsen during adolescence, leading to a crouched gait. Most patients with Dravet syndrome are reliant on caretakers throughout their lives, though the severity of symptoms may vary. Up to 20% of infants with Dravet syndrome do not survive to adulthood.