What alternative treatment options are available for a patient with a 30-year history of refractory seizures, including infantile spasms, and failed treatments with various antiepileptic medications and a vagus nerve stimulator (VNS)?

Treatment Options for Long-Standing Refractory Epilepsy

For this patient with 30 years of refractory epilepsy who has failed multiple antiepileptic drugs and VNS, the most evidence-based next steps are: (1) epilepsy surgery evaluation if not already done, (2) trial of newer-generation antiepileptic drugs not yet attempted (perampanel, brivaracetam), (3) ketogenic diet, and (4) consideration of immunotherapy if cryptogenic etiology is suspected.

Surgical Evaluation Should Be Priority

• Epilepsy surgery offers the best opportunity for complete seizure freedom in pharmacoresistant epilepsy, even in patients with complicated presentations who may require intracranial EEG monitoring 1
• Patients with refractory epilepsy should be referred to multidisciplinary epilepsy centers for specialized diagnostic testing, as apparent pharmacoresistance can result from misdiagnosis of seizure type, inappropriate medication use, or surgically remediable syndromes 1
• The fact that MRIs show no abnormalities does not exclude surgical candidacy—many patients with non-lesional epilepsy can still benefit from surgical intervention after detailed evaluation including intracranial monitoring 1

Newer Antiepileptic Drug Options

Perampanel

• Perampanel is FDA-approved for partial-onset seizures as adjunctive therapy and has demonstrated efficacy in patients taking 1-2 concomitant AEDs 2
• In clinical trials, 72-86% of patients were taking 2 or more concomitant AEDs, with mean epilepsy duration of approximately 23 years—matching this patient's profile 2
• Dosing starts at 2 mg/day and can be titrated up to 12 mg/day, with no titration period required in clinical studies 2

Brivaracetam

• Brivaracetam showed efficacy in patients with partial-onset seizures not adequately controlled with 1-2 concomitant AEDs, with median baseline frequency of 9 seizures per 28 days and mean epilepsy duration of 23 years 3
• Doses of 100-200 mg/day demonstrated 25.2-25.7% reduction in seizure frequency over placebo 3
• Important caveat: Brivaracetam provided no added benefit when added to levetiracetam, so confirm this patient has not been on levetiracetam recently 3

Non-Pharmacological Interventions

Ketogenic Diet

• The ketogenic diet is an established alternative treatment for patients who are not surgical candidates or unwilling to consider surgery 1
• This should be implemented through a multidisciplinary epilepsy center with appropriate dietary support 1

Neurostimulation Options

• Since the VNS malfunctioned and was not effective, consider alternative neurostimulation approaches including responsive neurostimulation (RNS) or deep brain stimulation (DBS) 1
• These peripheral or central neurostimulation options are available for patients who are not surgical candidates 1

Immunotherapy Consideration

• If no clear etiology has been identified despite 30 years of evaluation, consider cryptogenic new onset refractory status epilepticus (NORSE) or autoimmune/paraneoplastic etiology 4, 5
• Early treatment with immunomodulatory agents is now recommended by experts when autoimmune or paraneoplastic etiology is suspected or no etiology can be identified 4
• This includes consideration of steroids, IVIG, or plasma exchange 5, 6

Critical Pitfalls to Avoid

• Do not assume non-surgical candidacy based solely on normal MRI—specialized evaluation with intracranial monitoring may reveal surgically remediable foci 1
• Verify medication compliance and lifestyle factors before concluding true pharmacoresistance, as apparent pharmacoresistance can result from noncompliance or lifestyle issues 1
• Confirm accurate seizure type diagnosis—misdiagnosis of seizure type or epilepsy syndrome is a common cause of apparent treatment failure 1
• Only a small proportion of patients with refractory epilepsy are referred for expert evaluation, representing a major obstacle to optimal care 1

Multidisciplinary Support

• Even if seizure freedom cannot be achieved, quality of life can be greatly improved through psychological and social support services offered by multidisciplinary epilepsy centers 1
• This is particularly important for a patient who has lived with this condition for 30 years 1