Myoclonic Epilepsy Beginning in Infancy or Early Childhood Treatment & Management

Updated: Oct 02, 2020
  • Author: Michael C Kruer, MD; Chief Editor: Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA  more...
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Approach Considerations

The mainstays of medical therapy for myoclonic epilepsy are valproic acid (sodium valproate), ethosuximide, or benzodiazepines (clonazepam or clobazam). [11] . A number of different antiepileptic medications may be efficacious, although phenobarbital, lamotrigine, vigabatrin, and carbamazepine may worsen the seizures in some cases. [12] Combination therapy with valproic acid and benzodiazepines is often helpful. Stiripentol is indicated for treatment of seizures associated with Dravet syndrome in patients aged 2 years or older who are taking clobazam. There are no clinical data to support the use of stiripentol as monotherapy in Dravet syndrome. [13, 14] The FDA approved a purified formulation of cannabidiol (Epidiolex) in June 2018 for seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) in patients aged 2 years or older.

Adrenocorticotropic hormone (ACTH), steroids, and immunoglobulins have been tried but have not shown conclusive benefit.



Antiepileptic Medication

Patients with benign forms of myoclonic epilepsy often respond well to valproic acid or clonazepam. Either one of the drugs may be started; if both fail independently, they may be combined. The duration of treatment is tailored on an individual basis but is usually approximately 5 years. Second-line medications include ethosuximide, zonisamide, and topiramate.

Treatment for the more severe myoclonic epilepsies is more difficult and similar to the approach used for Lennox-Gastaut syndrome. For example, patients with Dravet syndrome typically have medically refractory epilepsy and often require polytherapy. [15]

A purified formulation of cannabidiol (Epidiolex) is approved for seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex in patients aged 1 year or older. Cannabidiol is a structurally novel anticonvulsant and the exact mechanism by which it produces anticonvulsant effects is unknown. It does not appear to exert its anticonvulsant effects through CB1 receptors, nor through voltage-gated sodium channels.

Approval was based on results from several studies that compared cannabidiol added to conventional AEDs to placebo and the incidence of drop seizures from baseline. An international study of 225 patients with LGS (mean patient age 15 years) were randomized to receive cannabidiol 20 mg/kg/day or 10 mg/kg/day, or placebo over 14 weeks. During the 4-week baseline period, the median number of drop seizures was 85 in all groups combined. The median reduction from baseline in drop-seizure frequency per 28 days during the treatment period was 41.9% in the 20-mg cannabidiol group, 37.2% in the 10-mg group, and 17.2% in the placebo group. During treatment, 30 patients (39%) in the 20-mg group, 26 (36%) in the 10-mg group, and 11 (14%) in the placebo group had at least a 50% reduction from baseline in drop-seizure frequency. The odds ratio (OR) for 20 mg vs placebo was 3.85 (95% CI, 1.75 - 8.47; P < 0.001) and the OR for 10 mg vs placebo was 3.27 (95% CI, 1.47 - 7.26; P = 0.003). [16]

A study (n=171) conducted in 24 clinical sites in the United States, the Netherlands, and Poland showed a median percentage reduction in monthly drop seizure frequency from baseline was 43.9% (IQR -69.6 to -1.9) in the cannabidiol group and 21.8% (IQR -45.7 to 1.7) in the placebo group. The estimated median difference between the treatment groups was -17.21 (p = 0.0135) during the 14-week treatment period. [17]

Fenfluramine (Fintepla) has been reintroduced to the market and is indicated for treatment of seizures associated with Dravet syndrome in patients aged 2 years and older. 

Fenfluramine and its metabolite, norfenfluramine, increase extracellular levels of serotonin through interaction with serotonin transporter proteins, and exhibit agonist activity at serotonin 5HT-2 receptors. The precise mechanism of action for the treatment of seizures associated with Dravet syndrome is unknown. 

Approval was based on data from two phase 3 randomized, double-blind, placebo-controlled trials. When added to existing therapy, fenfluramine significantly reduced the monthly convulsive seizure frequency compared to placebo in study patients whose seizures were not adequately controlled on one or more antiepileptic drugs. Additionally,  most study patients responded to treatment within 3-4 weeks and effects remained consistent over the treatment period. [18, 19]

Go to Antiepileptic Drugs for complete information on this topic.


Dietary Modification and Activity Restrictions

The ketogenic diet may be useful in children with particularly refractory epilepsy. [20] This diet should be instituted carefully, paying particular attention to the possibility of dehydration.

Caution should be used in children with drop attacks, as they may fall and injure themselves. A helmet can be protective. Routine seizure precautions are applicable.


Consultations and Long-Term Monitoring

Patients should be evaluated by a pediatric neurologist. If dysmorphic features are present, a genetic evaluation may be useful.

Serial EEGs often are required to ensure that patients are responding to treatment and that subclinical seizures are not occurring. Typical EEG findings in responsive patients include the disappearance of polyspike and wave activity and other associated epileptiform discharges.