To establish the extent of disease and needs in an individual diagnosed with SCN8A-related epilepsy, the following evaluations are recommended:
- Neurologic examination including:
- Electroencephalogram (EEG), which may provide an assessment of the overall degree of epileptic encephalopathy and seizure type, and
- MRI scan of the brain
- Cognitive & behavioral neuropsychological evaluation
- EKG
- Consultation with a medical geneticist and/or genetic counselor
There are no clear guidelines for treatment. Seizures should be managed by a pediatric neurologist with expertise in epilepsy, familiarity with the pharmacotherapy for this disorder, and differences from other disorders (e.g., Dravet Syndrome). Seizure control is critical because children with SCN8A-related seizure disorder are at risk for sudden unexplained death in epilepsy (SUDEP). In addition, prolonged acute seizures may cause permanent injury [Chipaux et al 2010, Takayanagi et al 2010].
Sodium Channel Blockers
Several studies suggest that patients with SCN8A-related epilepsy respond favorably to the class of antiepileptic drugs (AEDs) that block sodium channels, including phenytoin, valproate, carbamazepine, lacosamide, lamotrigine, rufinamide and oxcarbazepine [
GeneReviews, Hammer et al. 2016]. The effectiveness of sodium channel blockers is consistent with the activating effects of some SCN8A mutations [Wagnon & Meisler 2015]. Most patients are maintained on multiple medications and seizure control is incomplete. One study of four patients reported a positive response to high doses of phenytoin [Boerma et al 2015].
AEDs with Other Mechanisms of Action
Clobazam (0.2-1 mg mg/kg/day), part of the standard of care for epilepsy in Europe, is now approved by the FDA in the US.
Clobazam is FDA approved for the treatment of seizures in Lennox-Gastaut syndrome [Selmer et al 2009].
Phenobarbital
Although effective, phenobarbital is poorly tolerated because of its effects on cognition.
Levetiracetam (Keppra)
Families report an adverse effect of Keppra (unpublished).
Sleep hygiene
As described for Dravet Syndrome, sleep deprivation and illness can exacerbate SCN8A-related seizures; thus, good sleep hygiene should be encouraged. Comorbidity with sleep apnea can also occur frequently in individuals with epilepsy [Malow et al 2000], and can influence seizure control, behavior, and cognition. Polysomnography should be considered if obstructive or central sleep apnea is suspected.
Seizures are not always responsive to conventional AEDs. Anecdotal evidence suggests that the following drugs/treatment modalities may be effective for SCN8A-related seizures:
- Corticosteroids
- Immunoglobulins
- Vagus Nerve Stimulator
- Ketogenic Diet
- Cannabinoids
Non-medical interventions that families have reported to be helpful include the following:
- Having a written emergency department protocol
- Establishing emergency routines for the family
- Assigning a parent on call to lessen the effect on the siblings
- Finding respite care
- Contacting an internet support group
Immunization may trigger a seizure, or in some cases lead to developmental arrest (unpublished data). Therefore it may be advisable to alter immunization schedules. The treating neurologist may also consider increasing the anticonvulsant dose(s) temporarily around the time of the immunization.
Due to the sedating effects of seizure medications and the possibility of respiratory depression (especially with benzodiazepines and barbiturates), parents are advised to take a CPR course. Routine seizure and personal safety counseling is indicated.
Serial neuropsychological evaluation for neurologic, cognitive, and behavioral deterioration is appropriate.
EEG monitoring is appropriate when new or different seizure types are suspected.
Oxygen monitoring and CPAP devices.
Other forms of seizure monitoring (video, special devices).
Families of affected individuals report worsening of seizures with Levetiracetam (Keppra) (Hammer et al. 2016).
Sudden set-backs often occur in this disorder. These may have environmental triggers that are not known.
See
Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
Search
ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions.
Cannabis-derived compounds (including cannabidiol [CBD], tetrahydrocannabinol [THC], and marijuana oils), collectively called “cannabinoids,” have been effective in some cases. This anecdotal evidence has led to more in depth study and randomized clinical trials are now underway. Cannabinoids are bioactive and may have psychotropic and/or systemic side effects. They may have immunosuppressant or anti-inflammatory activity in animal models and thus should be studied carefully in immature humans before widespread use is considered [Rieder et al 2010, Bergamaschi et al 2011].
