Can We Predict Pharmacoresistant Epilepsy?
Can We Predict Pharmacoresistant Epilepsy?
Abstract & Commentary
By Padmaja Kandula, MD, Assistant Professor of Neurology and Neuroscience, Comprehensive Epilepsy Center, Weill Cornell Medical College. Dr. Kandula reports no financial relationships relevant to this field of study.
Synopsis: In this long-term, population-based patient series, the authors explore the natural course of drug-resistant epilepsy and explore whether remission can be predicted by clinical features.
Source: Sillanpaa M, et al. Is incident drug-resistance of childhood-onset epilepsy reversible? A long-term follow-up study. Brain 2012;135:2256-2262.
Drug-resistant epilepsy affects nearly a third of epilepsy patients and is defined as failure of two or more maximally tolerated, adequately chosen, anti-epileptic agents. The recommended clinical practice (2003 American Academy of Neurology Practice Parameter) is to consider referral for potential epilepsy surgery in pharmacoresistant epilepsy. However, the literature is scarce regarding the natural history of incident (new-onset) drug-resistant epilepsy. In this observational, population-based study, the authors aim to answer two questions, mainly the proportion of patients with drug-resistant epilepsy that become seizure free and the clinical features that predict seizure freedom.
Children under the age of 16 who met International League Against Epilepsy criteria for epilepsy (two or more unprovoked seizures) within the catchment area of University of Turku, Finland, up until the year 1964 were study eligible. Further inclusion criteria were well-documented and adequate anti-epileptic regimen trials, drug resistance (failure of one or two appropriate drugs used singly or in combination without seizure remission at the 2-year mark), and at least 10-year follow-up from time of epilepsy onset.
One hundred two patients ultimately met study criteria. Outcome variables, including time to and duration of seizure remission, were defined as the following: 1-year remission ever, 2-year remission ever, 2-year terminal remission, 5-year remission ever, or 5-year terminal remission. Terminal remission was the remission at the end of follow up. Remote symptomatic epilepsy was defined as major neurological impairment or history of major neurologic insult.
Of the 102 patients, 98 had focal seizures (68 symptomatic and 30 idiopathic/cryptogenic), one had generalized convulsive seizures, and three had unclassified seizures. At the conclusion of the 40.5 year median follow-up, 82% of patients entered one or more 1-year remissions, 79% one or more 2-year remissions, 69% one or more 5-year remissions, and 51% with 5-year terminal remission. On multivariate analysis, only idiopathic/cryptogenic seizure etiology proved to be a significant predictor of seizure freedom.
Commentary
Based on the results of this long-term study, the patients with the highest likelihood to enter terminal remission were those with idiopathic (no apparent cause) or cryptogenic epilepsy and those who have been seizure-free after incident drug-resistant epilepsy for at least 2 years. Although the advantage of this study is a very long median follow-up period, the concept that symptomatic epilepsy is often medically refractory is not new information. A large observational study by Semah et al in 1998 revealed that only a quarter of patients with structural lesions eventually became seizure-free.1 On the other hand, the study has significant limitations largely due to the historical time frame in which the patients were initially studied. The two main limitations include the absence of MRI data (based on 1960s recruitment period) as well as limited FDA-approved anti-epileptic drug regimens. Overall, the study reinforces the need to consider early surgery in pharmacoresistant epilepsy, particularly in surgically amenable syndromes.
Reference
1. Semah F, et al. Is the underlying cause of epilepsy a major prognostic factor for recurrence? Neurology 1998;51:1256-1262.
In this long-term, population-based patient series, the authors explore the natural course of drug-resistant epilepsy and explore whether remission can be predicted by clinical features.Subscribe Now for Access
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