Severe myoclonic epilepsy of infancy (smei)

Other names

Dravet syndrome

Pathophysiology

Severe myoclonic epilepsy of infancy (SMEI) is an epilepsy syndrome that begins in infancy or early childhood and can include a spectrum of symptoms ranging from mild to severe.

Signs and symptoms

Children with Dravet syndrome initially show focal (confined to one area) or generalized (throughout the brain) convulsive seizures that start before 15 months of age (often before age one). These initial seizures are often prolonged and involve half of the body, with subsequent seizures that may switch to the other side of the body. These initial seizures are frequently provoked by seizures or exposure to increased temperatures or temperature changes, such as getting out of a bath. Other seizure types emerge after 12 months of age and can be quite varied. Status epilepticus – a state of continuous seizure requiring emergency medical care – may occur frequently in these children, particularly in the first five years of life.

Progression

Children with Dravet syndrome typically have normal development in the first fews years of life. As seizures increase, the pace of acquiring skills slows and children start to lag in development behind their peers. Other symptoms can begin throughout childhood with changes in eating, appetitie, balance, and a crouched gait (walking).

Cause

In at least 80 percent of cases, Dravet syndrome is caused by defects in a gene required for the proper function of brain cells. Mutations in the SCN1A gene (a gene that encodes as a sodium channel, a part of the cell membrane involved in nervous system function) are the primary causes of Dravet syndrome. Borderline SMEI (SMEB) and another type of infant-onset epilepsy called generalized epilepsy with febrile seizures plus (GEFS+) but which is much less severe, are caused by defects in the same gene. Dravet syndrome is a lifelong condition.

Treatment

Seizures in Dravet syndrome are difficult to control, but can be reduced by anticonvulsant drugs. A ketogenic diet, high in fats and low in carbohydrates, also may be beneficial. Some anticonvulsant medications that bind to sodium channels (such as oxcarbazepine, carbamazepine, phenytoin, and lamotrigine) should not be used on a daily basis as they may exacerbate seizures.

In June 2018 the U.S. Food and Drug Administration approved cannabidiol (Epidolex, derived from marijuana) for the treatment of seizures associated with Dravet syndrome for people ages 2 and older.  The drug contains only small amount of the psychoactive element in marijuana and does not induce euphoria associated with the drug. This is the first FDA-approved drug for Dravet syndrome.

Prognosis

As children with Dravet syndrome get older, their decline in cognitive function stabilizes. The degree of intellectual disability varies widely from mild to profound, yet most teenages and adults with Dravet syndrome are dependent on caregivers. Gait abnormalities seem to worsen during adolescence. Seizures tend to decrease in number and duration with age. Individuals with Dravet syndrome have a higher risk than the general population for sudden, unexpected death but that risk is still low.