The relative effects of antiepileptic drugs (AEDs) on cognition are controversial. We compared the cognitive effects of phenobarbital, phenytoin, and valproate in 59 healthy adults using a randomized, double-blind, incomplete-block, crossover design. Cognitive assessments were conducted at baseline, after 1 month on each drug (two AEDs per subject), and at two repeat baselines 11 weeks after each AED treatment. The neuropsychological battery included 12 tests, yielding 22 variables: Choice Reaction Time, P3 Event-Related Potential, Finger Tapping, Lafayette Grooved Pegboard, Selective Reminding Test, Paragraph Memory, Complex Figures, Symbol Digit Modalities Test, Stroop Test, Visual Serial Addition Test, Hopkins Symptom Checklist, and Profile of Mood States. More than one-half of the variables exhibited AED effects when compared with nondrug baselines, and all three AEDs produced some untoward effects. Differential AED effects on cognition were present for approximately one-third of the variables. Phenobarbital produced the worst performance; there was no clinically significant difference between phenytoin and valproate.

We examined Wada memory and neuropsychological memory function in 34 nonlesional patients who underwent anterior temporal lobectomy (ATL) and who were seizure free at 1-year follow-up. Patients who displayed a decline on verbal memory measures that exceeded 1 SD after left ATL had significantly smaller left/right Wada memory asymmetries than left ATL patients without a significant verbal memory decline. When Wada memory asymmetries were used to predict verbal memory decline after left ATL in individual patients, similar statistically significant effects were present. No significant relationship between Wada memory and postoperative memory was present in right ATL patients, and postoperative memory function was not related to Wada memory performance after either left hemisphere or right hemisphere injection alone. We conclude that Wada memory asymmetries provide one measure of the risk to material-specific decline in verbal memory after left ATL.

Summary:Purpose: The cognitive effects of the newer antiepileptic drugs (AEDs) compared with the older standard AEDs are uncertain.Methods: We directly compared the cognitive effects of carbamazepine (CBZ) and gabapentin (GBP) in 35 healthy subjects by using a double-blind, randomized crossover design with two 5-week treatment periods. During each treatment condition, subjects received either GBP, 2,400 mg/day, or CBZ (mean, 731 mg/day) adjusted to a dose to achieve midrange standard therapeutic blood levels (mean, 8.3 Fg/ml). Subjects were tested at the end of each AED treatment period and in four drug-free conditions [two pretreatment baselines and two posttreatment washout periods (1 month after each AED)]. The neuropsychological test battery included 17 measures yielding 31 total variables.Results: Direct comparison of the two AEDs revealed significantly better performance on eight variables for GBP, but none for CBZ. Comparison of CBZ and GBP to the nondrug average revealed significant statistical differences for 15 (48%) of 3 1 the variables. Pairwise follow-up analyses of the 15 variables revealed significantly better performance for nondrug average on 13 variables compared with CBZ, and on four compared with GBP. GBP was better than nondrug average on one variable.Conclusions: Although both CBZ and GBP produced some effects, GBP produced significantly fewer untoward cognitive effects compared with CBZ at the dosages used in this study.

We examined the relationship of Wada memory performance and MRI hippocampal volume measurements to laterality of ultimate seizure localization in 20 patients with complex partial seizures who later underwent temporal lobectomy. Discriminant function analysis employing both Wada memory test asymmetries and hippocampal volume asymmetries correctly classified 100% of the patients into left and right temporal lobe groups. Wada memory asymmetries alone correctly classified 90% of the sample (80% of the sample when the discriminant function included all patients except the one being classified), and hippocampal volume asymmetries alone correctly classified 90% of the patients. A significant correlation was present between Wada memory asymmetries and hippocampal volume asymmetries (r = 0.78), indicating that structural evidence of reduced hippocampal volume has a functional correlate reflected by Wada memory performance. These data suggest that the combination of functional and structural measures is of value in the preoperative evaluation for epilepsy surgery.

We examined the ability of Wada memory testing to predict seizure outcome 1 year following anterior temporal lobectomy. Asymmetry scores for Wada memory performance, using amobarbital doses of 125 mg or less, were calculated for 55 patients under the age of 45 years who had no radiologic evidence of structural lesions other than gliosis. Wada memory asymmetries were significantly greater (p < 0.02) in patients who were seizure free compared with those who continued to experience seizures. Furthermore, patients with Wada memory score asymmetries of at least three objects (maximum = 8) were more likely to be seizure free compared with patients with Wada memory asymmetries less than three (p < 0.01). Of the 36 patients who had Wada memory score asymmetries of at least three objects, 32 (89%) were seizure free. In contrast, of the 19 patients whose Wada memory score asymmetries were less than three, only 12 (63%) were seizure free. These data suggest that Wada memory performance is related to seizure outcome following anterior temporal lobectomy.