What Causes 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 a type of epilepsy characterized by brief seizures with rapid, uncontrolled muscle jerks. Myoclonic 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 that cause myoclonic seizures usually begin in early childhood, and last throughout life, though milder forms may improve with adulthood. Myoclonic epilepsy can occur in isolation, or as part of a mixed, generalized epilepsy syndrome.

Myoclonic seizures are the result of a sudden burst of abnormal electrical discharge in the brain’s nerve cells (neurons), which leads 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 the following:

• Brain malformations
• Inborn metabolism errors
• Neurogenetic mutations

Mutations in the SCN1A gene have been identified to be the cause in 80% 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.
• Myoclonic epilepsy occurring as part of a mixed generalized epilepsy syndrome: This includes
  • Doose syndrome (myoclonic-atonic epilepsy)
  • Dravet syndrome (severe myoclonic epilepsy of infancy [SMEI])
  • Lennox-Gastaut syndrome
• Nonprogressive myoclonic epilepsies: This group of disorders include
  • Benign neonatal myoclonic epilepsy
  • Familial myoclonic epilepsy
  • Autosomal dominant cortical myoclonus and epilepsy
• Progressive myoclonic epilepsies: In these myoclonic epilepsies, seizures occur with certain stimuli or actions, because of underlying neurodegenerative disorders which include
  • Unverricht-Lundborg disease
  • Lafora body disease
  • Myoclonic epilepsy with ragged red fibers (MERRF)
  • Neuronal ceroid lipofuscinoses
  • Sialidosis
  • Dentate-rubral-pallidoluysian atrophy (DRPLA)
  • Alpers syndrome (POLG1 mutations)

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

• Involuntary abrupt muscle jerks in one or both arms and legs, which typically occur several times a day.
• Head nodding
• Abrupt abduction of arms
• Twitches in eyelids and facial muscles
• Irregular movements in the fingers which make patients drop things or appear clumsy.

Seizures are more frequent and get prolonged in severe forms of myoclonic epilepsy, which are also associated with other forms of generalized seizures, 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 are prolonged and involve half of the body
  • Subsequent seizures may involve the opposite half of the body
  • Temperature changes, like exiting a warm bath, can bring on a seizure
  • Myoclonus status epilepticus, a medical emergency condition of continuous seizure, may happen often in children with Dravet, especially before age five
• Developmental cognitive and physical delays resulting from seizures
• Changes in eating and appetite
• Crouched gait and compromised balance as the child grows older

In epilepsies such as Doose syndrome and Lennox-Gastaut syndrome, children may have drop seizures which cause sudden loss of muscle strength, making them collapse. Cognitive development may also be delayed or impaired.

Correct diagnosis of the seizure origin is of prime importance, because seizures can also occur due to many conditions other than epilepsy. Ascertaining if different types of seizure disorders are co-occurring, and identification of the distinct epilepsy syndrome are essential to formulate 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

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

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

Lifestyle and dietary modifications may also help in managing the condition. Epilepsy surgeries may be an option in a few select cases.

Antiepileptic drugs

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

• Valproic acid (Depakote, Depakene, Depacon, Stavzor): An anticonvulsant used as first-line treatment. Use of valproic acid has increased risk of liver toxicity in children younger than two years.
• Clobazam (Onfi): A benzodiazepine class of drug for adjunctive treatment in Lennox-Gastaut syndrome associated seizures in children two years of 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 lose efficacy rapidly.
• Ethosuximide (Zarontin): An anticonvulsant used as an adjunct if valproic acid is not effective as a 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 don’t know 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.
• Fenfluramine (Fintepla): A serotonin agonist (booster) for seizures associated with Dravet syndrome in children aged two years or older.

Other antiepileptic medications that are used in controlling seizures but may worsen seizures in some cases include:

• Phenobarbital
• Lamotrigine
• Vigabatrin
• Carbamazepine

Other medications that have been tried but have not shown conclusive benefits include:

• Adrenocorticotropic hormone (ACTH)
• Steroids
• Immunoglobulins

Dietary and lifestyle adaptations

Dietary and lifestyle modifications may be of benefit, particularly in children with refractory epilepsy:

• Ketogenic diet: A diet that is extremely low in carbohydrates and high in fats and protein, may be useful in children with epilepsy.
  • Pediatrician and maybe a nutritionist should be consulted before starting a child on this diet.
  • Particular attention must be paid to prevent dehydration with this diet.
• Protection from injury: Taking routine seizure precautions prevents injuries during seizures. A helmet may be protective in children with drop seizures, as they may fall and injure themselves.
• Long-term monitoring: Regular consultations with a pediatric neurologist, along with EEGs to evaluate the patient’s response to treatment is important for effective long-term epilepsy management.

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

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