M. E. Nichols

Comparative cognitive effects of phenobarbital, phenytoin, and valproate in healthy adults.

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. NEUROLOGY 1995;45: 1494-1499

Wada memory testing and hippocampal volume measurements in the evaluation for temporal lobectomy.

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.

Differential Cognitive Effects of Carbamazepine and Gabapentin

Summary: Purpose: The cognitive effects of the newer antiepileptic drugs (AEDs) compared with the older standard AEDs are uncertain.

Wada memory asymmetries predict verbal memory decline after anterior temporal lobectomy

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.

Wada memory performance predicts seizure outcome following anterior temporal lobectomy

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.

Anosognosia and asomatognosia during intracarotid amobarbital inactivation.

Background: Anosognosia (i.e., denial of hemiparesis) and asomatognosia (i.e., inability to recognize the affected limb as one’s own) occur more frequently with right cerebral lesions. However, the incidence, relative recovery, and underlying mechanisms remain unclear. Methods: Anosognosia and asomatognosia were examined in 62 patients undergoing the intracarotid amobarbital procedure as part of their preoperative evaluation for epilepsy surgery. Additional questions were asked in the last 32 patients studied. Results: During inactivation of the non–language-dominant cerebral hemisphere, 88% of the 62 patients were unaware of their paralysis, and 82% could not recognize their own hand at some point. Only 3% did not exhibit anosognosia or asomatognosia. In general, asomatognosia resolved earlier than anosognosia. When patients could not recognize their hand, they uniformly thought that it was someone else’s hand. Dissociations in awareness were seen in the second series of 32 patients. Although 23 patients (72%) thought that both arms were in the air, 31% pointed to the correct position of the paralyzed arm on the table. Despite the inability of 24 of 32 patients (75%) to recognize their own hand, 21% of these patients were aware that their arm was weak, and 38% had correctly located their paralyzed arm on the angiography table. Conclusions: Anosognosia and asomatognosia are both common during acute dysfunction of the non–language-dominant cerebral hemisphere. Dissociations of perception of location, weakness, and ownership of the affected limb are frequent, as are misperceptions of location and body part identity. The dissociations suggest that multiple mechanisms are involved.

Preliminary Findings of High-Dose Thiamine in Dementia of Alzheimer's Type:

Thiamine is important not only in the metabolism of acetylcholine but also in its release from the presynaptic neuron. Pathologic, clinical, and biochemical data suggest that thiamine deficiency is detrimental to the cholinergic system and that thiamine-dependent enzymes may be altered in Alzheimers disease. Two previous studies reported contradictory results in patients with dementia of Alzheimers type treated with 3 g/day of thiamine. In the present study, we examined the effects of 3 to 8 g/day thiamine administered orally. Our results suggest that thiamine at these pharmacologic dosages may have a mild beneficial effect in dementia of Alzheimers type. The mechanism of the observed effect is unknown, but the findings warrant further investigation, not only for their therapeutic implications but for their possible etiologic clues. In addition, the results suggest long-term carry-over effects that should be considered in the design of future studies.

Cerebral lateralization: Relationship of language and ideomotor praxis

Objective: To determine the relationship of language lateralization and hand preference to praxis performance following left and right hemispheric amobarbital-induced inactivations. Background: Patients who are aphasic from left cerebral dysfunction also frequently exhibit ideomotor apraxia in which they make temporal, spatial, and postural errors of learned skilled movements. However, hemispheric lateralization of the systems mediating ideomotor praxis in patients with atypical cerebral language dominance (i.e., bilateral or right hemispheric language function) remains uncertain. Methods: Subjects included 90 patients with intractable seizures who were undergoing the intracarotid amobarbital procedure (IAP) as part of their preoperative evaluation for epilepsy surgery. Hand preference was determined by the Benton Handedness Questionnaire. Praxis was assessed by the subject’s performance when pantomiming the use of four pictured tools. Results: During left IAP, patients with typical language dominance made more ideomotor apraxic errors than did patients with atypical language dominance. During right IAP, patients with atypical language dominance made more ideomotor apraxic errors than did patients with typical language dominance. Overall, patients with atypical language dominance made fewer ideomotor apraxic errors than did patients with typical language dominance. These relationships were present irrespective of hand preference. Conclusions: Language dominance is more closely associated with the laterality of temporal and spatial movement representations (i.e., ideomotor praxis dominance) than is hand preference. Patients with atypical language dominance exhibit more bilateral cerebral distribution of both language and praxis function.

The role of cholinergic systems in visuospatial processing and memory

Few studies have specifically addressed the cholinergic role in visuospatial memory. In the present study, we employed a randomized double-blind repeated measures design to investigate the effects of scopolamine on Judgement of Line Orientation (JLO) and two distinct visuospatial memory tasks. Complex Figures (CF) is a test of drawn reproduction similar to the Rey complex figure. The Spatial Array Memory Test (SAMT) is a two-dimensional free-recall visuospatial test which minimizes constructive skills and allows sensitive measurement of placement errors. Scopolamine impaired performance on JLO and CF. However, no effects of scopolamine on SAMT were apparent even though the SAMT is sensitive to aging and right temporal-lobe lesions. Selective effects of scopolamine on focused versus distributed attention may account for these differential results.

Neuropsychological effects of antiepileptic drugs: a current perspective.

Summary: Epilepsy has widespread direct and indirect effects on the patients quality of life. These patients generally have neuropsychological impairments that lower their educational and occupational levels of achievement, and many have additional emotional and/or behavioral disorders. Multiple factors underlie the cognitive changes associated with epilepsy, including the effect of antiepileptic drug (AED) therapy itself. Although it is recognized that the beneficial results of reduced seizure frequency may compensate at least in part for detrimental cognitive AED side effects, polypharmacy and higher AED blood levels can shift this balance. Further, there is much debate concerning the existence and clinical importance of differential AED cognitive side effects. While all the. major AEDs can produce cognitive side effects, more recent research indicates that the magnitude of these effects may not be clinically significant with monotherapy within standard therapeutic range. The impact of AED differential cognitive side effects on the patients quality of life is only beginning to be appreciated as research focuses on this important aspect of patient management. The information gained from such investigations will influence not only current therapeutic decisions, but also the development of future anticonvulsants.