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Methylphenidate: Brain Gain for the Epilepsy Drain

Commentary Cognitive dysfunction in patients with epilepsy is common; it starts early (1) and persists through the patient’s lifetime (2). Previous studies have identified distinct—though likely overlapping—domains of cognitive impairment in patients with epilepsy (3, 4): memory impairments in 24 to 47 percent, attention/executive/speed dysfunction in 29 to 49 percent, and no impairment in only 29 to 47 percent. The etiology is likely multifactorial, with contribution from comorbid psychiatric disorders, medications and surgery, sleep disturbance, and particularly seizures themselves. This phenomenon has been well recognized, and although various strategies have been articulated to minimize its effects (5), specific treatments are lacking. The purpose of the current study by Adams et al. is to determine whether methylphenidate (MPH) improves cognitive performance in adults with epilepsy. It is a conceptually simple double-blind crossover study in which patients were given a single dose of placebo, MPH 10 mg, or MPH 20 mg in random order over the course of three visits occurring 1 week apart. The study included adult patients between the ages 18 and 65 with epilepsy of any cause who had cognitive complaints. Patients with obvious confounders, such as recent neurosurgical procedure, comorbid conditions or medication use that can cause cognitive dysfunction, or contraindication to MPH were excluded. The patients were asked not to take any sedating medications 24 hours prior to the study and were asked to avoid caffeine, nicotine, or food 2 hours prior to the examination. Outcome was assessed by three tests that are relatively standard measures of attention and processing speed. The Symbol Digit Modalities Test (SDMT) involves a simple substitution task in which the patient pairs specific numbers with geometric shapes using a reference table; this is a reliable measure of processing speed. During the Medical College of Georgia Paragraph Memory Test (MCG), patients are read a story of ~300 words after which immediate free recall is scored, thus a test of immediate verbal recall. The Conners Continuous Performance Test 3rd edition (CPT) consists of a 14-minute, 360-item trial during which patients are asked to push the spacebar on a keyboard when any letter except “X” appears. Various measures from this procedure test for inattentiveness and impulsivity. From these tests, the following measures were obtained: the SDMT total correct score, the MCG total score, the CPT d′ Methylphenidate, Cognition, and Epilepsy: A Double-Blind, Placebo-Controlled, Single-Dose Study.