Literature Review

Drug-resistant epilepsy needs earlier surgical referral



Most patients with drug-resistant epilepsy should receive a referral for a surgical evaluation as soon as it’s clear their disease is drug resistant, according to expert consensus recommendations from the International League Against Epilepsy (ILAE) published in the journal Epilepsia.

Comprehensive epilepsy care

Such a referral is not ”a commitment to undergo brain surgery,” wrote the authors of the new recommendations study, but surgical evaluations offer patients an opportunity to learn about the range of therapies available to them and to have their diagnosis verified, as well as learning about the cause and type of epilepsy they have, even if they ultimately do not pursue surgery.

”In fact, most patients with drug-resistant epilepsy do not end up undergoing surgery after referral, but still benefit from comprehensive epilepsy care improving quality of life and lowering mortality,” wrote lead author Lara Jehi, MD, professor of neurology and epilepsy specialist at Cleveland Clinic, and her colleagues. “A better characterization of the epilepsy can also help optimize medical therapy and address somatic, cognitive, behavioral, and psychiatric comorbidities.”

Is the diagnosis correct?

They noted that about one-third of patients referred to epilepsy centers with an apparent diagnosis of drug-resistant epilepsy actually have psychogenic nonepileptic seizures (PNES) – not epilepsy – and an early, accurate diagnosis of PNES can ensure they receive psychotherapy, stop taking antiseizure medications, and have better outcomes.

“These recommendations are necessary, as the delay to surgery and the overall underutilization of surgery have not improved much over the last 20 years,” said Selim R. Benbadis, MD, professor of neurology and director of the comprehensive epilepsy program at the University of South Florida and Tampa General Hospital. “Comprehensive epilepsy centers offer more than surgery, including correct and precise diagnosis, drug options, three [Food and Drug Administration]–approved neurostimulation options, and more,” said Dr. Benbadis, who was not involved in the development of these recommendations.

Consensus recommendations

On behalf of the the ILAE’s Surgical Therapies Commission, the authors used the Delphi consensus process to develop expert consensus recommendations on when to refer patients with epilepsy to surgery. They conducted three Delphi rounds on 51 clinical scenarios with 61 epileptologists (38% of participants), epilepsy neurosurgeons (34%), neurologists (23%), neuropsychiatrists (2%), and neuropsychologists (3%) from 28 countries. Most of clinicians focused on adults (39%) or adults and children (41%) while 20% focused only on pediatric epilepsy.

The physicians involved had a median 22 years of practice and represented all six ILAE regions: 30% from North America, 28% from Europe, 18% from Asia/Oceania, 13% from Latin America, 7% from the Eastern Mediterranean, and 4% from Africa.

The result of these rounds were three key recommendations arising from the consensus of experts consulted. First, every patient up to 70 years old who has drug-resistant epilepsy should be offered the option of a surgical evaluation as soon as it’s apparent that they have drug resistance. The option for surgical evaluation should be provided independent of their sex or socioeconomic status and regardless of how long they have had epilepsy, their seizure type, their epilepsy type, localization, and their comorbidities, ”including severe psychiatric comorbidity like psychogenic nonepileptic seizures (PNES) or substance abuse if patients are cooperative with management,” the authors wrote.

”Resective surgery can improve quality of life and cognitive outcomes and is the only treatment demonstrated to improve survival and reverse excess mortality attributed to drug-resistant epilepsy,” the authors wrote. Evidence supports that surgical evaluation is the most cost-effective approach to treating drug-resistant epilepsy, they added. Yet, it still takes about 20 years with epilepsy before an adult patient might be referred, ”and the neurology community remains ambivalent due to ongoing barriers and misconceptions about epilepsy surgery,” they wrote.

The second recommendation is to consider a surgical referral for older patients with drug-resistant epilepsy who have no surgical contraindication. Physicians can also consider a referral for patients of any age who are seizure free while taking one to two antiseizure drugs but who have a brain lesion in the noneloquent cortex.

The third recommendation is not to offer surgery if a patient has an active substance dependency and is not cooperative with management.

“Although there is some evidence that seizure outcomes are no different in individuals with active substance use disorder who have epilepsy surgery, the literature suggests increased perioperative surgical and anesthetic risk in this cohort,” the authors wrote. ”Patients with active substance abuse are more likely to be nonadherent with their seizure medications, and to leave the hospital against medical advice.”

One area where the participants did not reach consensus was regarding whether to refer patients who did not become seizure-free after trying just one “tolerated and appropriately chosen” antiseizure medication. Half (49%) said they would be unlikely to refer or would never refer that patient while 44% said they would likely or always refer them, and 7% weren’t sure.


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