The decision to discontinue anti-seizure medication is not one that clinicians make lightly. While some types of seizure can remit, the mechanism of remission is poorly understood. Also, testing whether a patient has really outgrown their epilepsy requires putting a seizure-free patient at risk for relapse, experts said.

Although there is no one-size-fits-all guidance on stopping medication, rates of seizure remission can be estimated with reasonable precision, according to Adam Ostendorf, MD, the medical director of the inpatient epilepsy service at Nationwide Children’s Hospital and a presenter at AES 2023, the annual meeting of the American Epilepsy Society, in Orlando, Fla. But even if seizures are no longer a problem, there may be comorbidities that need ongoing treatment.

Syndrome-Specific Remission

Patients decide to stop therapy for a variety of reasons, many of which are related to age. In children, concerns about cognitive effects of medications on the developing brain may drive the decision to discontinue. In adults, employment and driving risks, reproductive plans, and lifestyle tend to dominate the choice, said Alica Goldman, MD, PhD, a professor of neurology at Baylor College of Medicine, in Houston.

The patient’s specific epilepsy syndrome can provide a lot of information to the care team about their likelihood of remission and whether medication withdrawal could be successful. According to the 2022 guidelines of the International League Against Epilepsy, approximately one-third of pediatric patients fall into one of the specific epilepsy syndromes.

Self-limited epilepsy with centro-temporal spikes, for instance, make up 7% of childhood epilepsies. Although few may develop a more complicated course, most go into remission. Self-limited infantile epilepsy (SeLIE) makes up 9% of childhood epilepsies, and although patients often outgrow the seizures, they may develop paroxysmal dyskinesias. Another syndrome is childhood absence epilepsy (CAE), which includes about 18% of childhood epilepsies. About 60% of these children go into remission.

As for developmental epileptic encephalopathies, two-thirds of patients who have epilepsy with myoclonic?atonic seizures (EMAtS) will experience seizure remission within three years, but behavioral and learning problems may persist. About 30% of all epilepsies in those younger than 3 years fall into the category of the infantile epileptic spasms syndrome (IESS), and only 10% of these patients will go on to have normal development.

Many Factors in Relapse

Even if stopping medication is successful, relapses can occur, sometimes after long periods of remittance. For this reason, epilepsy is only considered resolved if a patient is past the age range for their age-dependent epilepsy syndrome or they remained seizure-free for the last 10 years and off anti-seizure medicines for at least the last five years, according to Dean Naritoku, MD, a professor and the chair of neurology at the University of South Alabama, in Mobile.

A meta-analysis of 10 studies with 1,769 patients (of all ages) found that 46% of patients who withdrew from their medications relapsed. This was true even after long periods of remission: 9% of relapses happened in the final year of follow-up. The median duration of follow-up was 5.3 years (IQR, 3.0-10.0 years; maximum, 23 years).

The analysis found that certain factors predicted a relapse: epilepsy duration before remission, seizure-free interval before medication withdrawal, age at epilepsy onset, history of febrile seizures, number of seizures before remission, absence of a self-limiting epilepsy syndrome, developmental delay and an epileptiform abnormality on EEG before withdrawal. Using these variables, the authors developed a free nomogram to help physicians predict the risk for seizure recurrence.

Dr. Naritoku said the main limitation of studies evaluating long-term seizure freedom is the length of follow-up, typically limited to five years. Thus, the longer term rates of recurrence and remission are poorly understood. It’s possible that the data are not characterizing pediatric relapse accurately since many of these patients are lost to follow-up as they transition to adult care, he said.

Comorbidities

Even if patients do outgrow their epilepsy, any comorbidities may continue. For example, CAE increases the risk for attention deficit/hyperactivity disorder and mood disorders. Patients with SeLIE may have comorbid learning issues, and for patients with EMAtS, learning and behavioral problems may persist after seizures remit.

Often these patients can be lost to follow-up after they stop taking anti-seizure medication, Dr. Ostendorf said. Neurologists and the neurology care team must explain the potential for persistent comorbidities and, once patients are seizure-free, help them transition to the genetic, psychiatric and social support they need, he said.

 

Source: pharmacypracticenews.com, Donavyn Coffey

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