Table 4.

Treatment of Manifestations in Individuals with SCN8A-Related Epilepsy and/or Neurodevelopmental Disorders

Manifestation/ConcernTreatmentConsiderations/Other
Epilepsy
  • Standardized treatment w/ASM by experienced neurologist
  • Counsel on SUDEP risk & monitoring for seizures, particularly in persons at higher risk, incl those w/SCN8A-DEE & those w/generalized tonic-clonic seizures &/or nighttime seizures.
  • Many ASMs may be effective; studies suggest that persons w/focal epilepsy phenotypes (SCN8A-DEE, SCN8A-mild/modDEE, SCN8A-SeLFIE) respond favorably to sodium channel blockers (e.g., phenytoin, valproate, carbamazepine, lacosamide, lamotrigine, rufinamide, & oxcarbazepine). 1 Other classes of ASM may also be useful.
  • The effectiveness of sodium channel blockers is consistent w/activating effects of SCN8A pathogenic GoF variants. 2 1 study of 4 persons reported positive response to high doses of phenytoin. 3
  • Many affected persons are maintained on multiple ASMs w/incomplete seizure control. Vigorous attempts to control seizures w/drug polytherapy are warranted, as children w/DEE are at risk for SUDEP as well as prolonged acute seizures that may cause permanent injury. 4
  • Levetiracetam (Keppra®) has been reported by several families to be ineffective or occasionally assoc w/worsening seizures, encephalopathy, &/or developmental regression. 5 However, some may respond favorably, regardless of phenotype.
  • Education of parents/caregivers 6
Other treatments incl corticosteroids, immunoglobulins, vagus nerve stimulation, ketogenic diet, & cannabinoidsWhen seizures are not responsive to standard ASMs, these drugs / treatment modalities may be effective based on anecdotal data.
Developmental delay /
Intellectual disability 		See Developmental Delay / Intellectual Disability Management Issues.
Poor weight gain /
Failure to thrive
  • Feeding therapy
  • Gastrostomy tube placement may be required for persistent feeding issues.
Low threshold for clinical feeding eval &/or radiographic swallowing study when showing clinical signs or symptoms of dysphagia
Constipation Eval & treatment by GI specialist
Sleep
  • Eval by sleep &/or ENT specialist for any sleep issues incl sleep apnea
  • Polysomnography should be considered if obstructive or central sleep apnea is suspected.
  • Sleep deprivation & illness can exacerbate SCN8A-related seizures; thus, good sleep hygiene should be encouraged. Comorbidity w/sleep apnea can also occur frequently in persons w/epilepsy, 7 & can influence seizure control, behavior, & cognition.
  • Because of ↑ risk of SUDEP, some families use oxygen monitoring during sleep.
Aspiration pneumonia
  • Swallow eval
  • Eval by pulmonary & GI
Aspiration pneumonia occurs more commonly in SCN8A-DEE.
Respiratory insufficiency/failure Respiratory support incl respiratory therapy, supplemental oxygen, positive airway pressure, & ventilatory supportRespiratory insufficiency/failure can occur in SCN8A-DEE.
Family/Community
  • Ensure appropriate social work involvement to connect families w/local resources, respite, & support.
  • Coordinate care to manage multiple subspecialty appointments, equipment, medications, & supplies.
  • Ongoing assessment of need for palliative care involvement &/or home nursing
  • Consider involvement in adaptive sports or Special Olympics.

ASM = anti-seizure medication; GoF = gain of function; SCN8A-DEE = SCN8A-related developmental and epileptic encephalopathy; SCN8A-mild/modDEE = SCN8A-related mild-to-moderate developmental and epileptic encephalopathy; SCN8A-SeLFIE = SCN8A-related self-limited familial infantile epilepsy; SUDEP = sudden unexpected death in epilepsy

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Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see Epilepsy Foundation Toolbox.

7.

From: SCN8A-Related Epilepsy and/or Neurodevelopmental Disorders

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