Epilepsy surgery: non-invasive versus invasive focus localization. What is needed from a neuropsychological point of view.

This article discusses the neuropsychological aspects of surgery for epilepsy, and what is needed in EEG evaluation to permit the best use of neuropsychological data to help identify the most promising surgical candidates. Neuropsychological changes after surgery are first discussed, and it is noted that changes in memory are most important with less important fluctuations in intelligence and language and with other areas showing few or no changes. Emotional and psychosocial outcomes of surgery are dependent upon relief from seizures, with substantial relief being essential for improvement to be observed. Finally, it is noted that a combination of EEG and neuropsychological variables results in the best prediction of seizure relief, but reliable EEG data are critical to this effort. Obtaining such data frequently necessitates EEG monitoring, frequently with invasive electrodes. Such information often provides the clearest information and the best chance of assisting patients with epilepsy.

Seizures and adaptive abilities. A case of identical twins.

The effects of seizures on performance were investigated in a pair of identical twins who were concordant for incidence of epilepsy, but who had highly contrasting histories of seizure frequency. An evaluation of abilities focused on intelligence, academic achievement, neuropsychologic functions, and emotional and social adjustments. While both twins showed some disabilities, the twin with the larger number of seizures was less able in every area examined. The results suggest that the greater seizure frequency is related to the lesser abilities.

Unilateral focal preponderance of interictal epileptiform discharges as a predictor of seizure origin.

OBJECTIVE: To test the hypothesis that seizure origin may be predicted from scalp-recorded electroencephalographic interictal epileptiform patterns that occur exclusively or preponderantly over a single focal region. PATIENTS AND METHODS: Fifty-nine of 98 patients (>=16 years old) with intractable epilepsy who underwent sphenoidal/scalp electroencephalographic video monitoring were identified as having interictal epileptiform discharges preponderantly (>=75% of all discharges) or exclusively over a single unilateral region (basal-temporal, midposterior temporal, frontopolar, superior frontal, central). Ictal recordings in 48 patients could be interpreted as demonstrating focal origins, and the ictal findings were compared with the interictal findings. Eleven patients had uninterpretable ictal recordings or no seizures during monitoring and were not further considered. RESULTS: All seizures arose from the expected region in 39 of the 48 patients (Fisher's exact test, P<.001). Interictal discharges occurred exclusively over a single region in 23 of the 48 patients, and all seizures arose from the expected region in 22 of the 23 patients (P<.001). Seventeen patients among this group of 23 had exclusively unilateral basal-temporal discharges, and all seizures arose from the expected side, with the exception of one seizure that arose from the opposite side in one patient, with her other seizure arising from the expected side (P<.001). All seizures arose from the expected region in three patients who exhibited all interictal discharges arising from a single superior frontal region, in two patients with discharges only over a single midposterior temporal region, and in one patient with exclusively unilateral frontopolar discharges. CONCLUSIONS: Interictal discharges that demonstrate a consistent unilateral focal preponderance over a single region, regardless of location, generally predict seizure origin. If the discharges are exclusive to a single region, there is a greater than 95% probability that all recorded seizures will originate from the expected region.

Intellectual impairment as an outcome of status epilepticus.

Mental ability changes following status epilepticus (SE) are explored. With respect to the studies reviewed, it is noted that (1) most dealt with children, (2) few utilized any formal psychologic assessment, (3) most were retrospective, (4) earlier studies tended to disclose greater losses in mental ability than later studies, and (5) most investigators described at least a few adverse changes attributable to SE rather than to underlying neurologic disease. An original prospective study is also reported.

Neuropsychological effects of carbamazepine and phenytoin: a reanalysis.

We previously reported that carbamazepine had fewer adverse neuropsychological effects than phenytoin, but it is now clear that our patients had much higher phenytoin than carbamazepine serum levels. When persons with high initial phenytoin levels were excluded, the statistical significance of all neuropsychological differences between the drugs disappeared.

Relationships between intelligence and electroencephalographic epileptiform activity in adult epileptics.

Intellectual correlates of electroencephalographic epileptiform activity were examined by administering the Wechsler Adult Intelligence Scale to epileptic patients divided into groups on the basis of presence or absence, average rate, and topographic distribution of discharges. The results showed that lower intelligence levels were associated with the presence of discharges, especially when they were generalized rather than focal and when they occurred at an average rate of more than one per minute. An examination of patients having discharges ipsilateral and contralateral to their handedness showed few findings, as did an analysis based on an assessment of strengths and weaknesses within individuals. The results suggest that electroencephalographic epileptiform activity is significantly related to the intellectual functioning of epileptics.

Psychotropic effects of carbamazepine in epilepsy: a double-blind comparison with phenytoin.

The "psychotropic" effects of carbamazepine were evaluated with phenytoin (Dilantin) as reference agent in a counterbalanced, crossover study. Forty adult epileptics were given a series of neuropsychologic tests and the MMPI after 4 months on each agent. Most abilities were much the same with either anticonvulsant, but there were fewer errors with carbamazepine on mental tasks requiring attention and problem solving, and some improvement in emotional status was suggested. The findings were consistent with patient reports of improvement in alertness and mental functioning. These results combine with the excellent anticonvulsant properties of carbamazepine to support its use as an anticonvulsant.

Cognitive and quality of life effects of differing dosages of tiagabine in epilepsy.

Tiagabine blocks the uptake by neurons or glia of synaptically released GABA resulting in prolonged GABAergic activity and decreased likelihood of epileptic seizures. We evaluated the cognitive and quality of life effects of tiagabine in a double-blind, add-on, placebo-controlled, parallel, multicenter, dose-response efficacy study in patients with focal epilepsy whose complex partial seizures were difficult to control. One hundred sixty-two patients provided cognitive and quality of life data for the analyses and received the following treatments: placebo (n = 57), 16 mg/d tiagabine (n = 34), 32 mg/d tiagabine (n = 45), or 56 mg/d tiagabine (n = 26) at a fixed-dose for 12 weeks after a 4-week dose titration period. Eight cognitive tests and three measures of mood and adjustment were administered during the baseline period and again during the double-blind period near the end of treatment (or at the time of dropout). The patient groups were similar at entry into the study. Results showed no clinically important changes with the addition of tiagabine on the test battery. Although this is an encouraging finding, it remains for future investigations to determine the cognitive and behavioral effects of tiagabine either as monotherapy or in relation to other antiepileptic drugs.

Outcome following surgery in patients with bitemporal interictal epileptiform patterns.

We reviewed outcome at least 1 year after temporal lobectomy in 44 patients with bitemporal, independent, interictal epileptiform patterns on EEG. All 44 underwent preoperative intracranial monitoring. Twenty-two (50%) were seizure-free, 14 (32%) had at a least 75% reduction in seizures, and eight (18%) had less than a 75% reduction in seizures. We analyzed age of seizure onset, duration of epilepsy, gender, side of operation, history and clinical findings, findings on MRI, results of intracranial EEG-video monitoring, presence or absence of lateralizing neuropsychological deficits, and pathology of resected tissue to identify factors associated with outcome. Three factors emerged as independently associated with a good outcome: concordance of MRI abnormality and side of operation (p = 0.01), history of febrile seizures (p = 0.04), and 100% lateralization of intracranially recorded ictal onsets to the side of operation (p = 0.05). A seizure-free outcome was much more likely to occur if more than one of these factors was present: with at least two factors co-existing, 83% (15/18) of patients were seizure-free, while only 35% (7/20) were seizure-free with a single factor present (p = 0.0009). Of the six patients without any of the three factors, none were seizure-free. We conclude that it is possible to predict reasonably which patients with bitemporal epileptiform abnormalities will have a good outcome after surgery.

Clorazepate and phenobarbital as antiepileptic drugs: a double-blind study.

The antiepileptic effect of clorazepate when given with phenytoin was compared, in a randomized double-blind crossover study, to the effect of the standard regimen of phenobarbital plus phenytoin in patients with partial seizures. Thirty of 42 subjects preferred the clorazepate-phenytoin regimen (p less than 0.01). The same number of subjects had fewer seizures while taking clorazepate as had fewer seizures while taking phenobarbital. However, subjects had significantly more toxicity, objective and subjective, on the phenobarbital-phenytoin regimen (p less than 0.01 in both cases). In some subjects, increased toxicity due to phenobarbital outweighed better seizure control, so that clorazepate was preferred. As an add-on antiepileptic drug, clorazepate is well tolerated, effective, and preferred by most patients to phenobarbital.

Evaluation of the effects of vigabatrin on cognitive abilities and quality of life in epilepsy.

We evaluated the psychological effects of the antiepilepsy drug vigabatrin in a randomized multicenter double-blind placebo-controlled parallel group study that compared 3 grams oral vigabatrin with placebo as daily add-on therapy in patients with focal epilepsy whose complex partial seizures were difficult to control. Testing at baseline and after 12 weeks of vigabatrin (n = 83) or placebo (n = 85) used eight measures of cognitive abilities and three of mood and adjustment. The vigabatrin and placebo groups were highly similar at entry into the study. At the end of the study, there were no differences between the vigabatrin and placebo groups on any cognitive variable or on any measure of mood and adjustment. Analysis of the results related to relief from seizures demonstrated only chance findings. In a similar manner, there were no relationships between vigabatrin serum levels at the end of the study and changes on measures of abilities and adjustment. Vigabatrin appears to be a useful antiepilepsy drug with little impact upon tests of either cognitive abilities or quality of life.

Carbamazepine--a double-blind comparison with phenytoin.

In a double-blind crossover study, carbamazepine and phenytoin were compared as single anticonvulsants in 47 patients with focal and major generalized seizures. Each drug provided superior seizure control in about half the patients, but significantly fewer patients had objective side effects while taking carbamazepine. Neuropsychologic testing showed improved performance in cognitive function and emotional status of patients while and carbamazepine. No hematotoxic complications arose, but vigilant follow-up is advised. Mean serum level of carbamazepine was 9.3 microng per milliliter with a suggested therapeutic range of 8 to 12 microng per milliliter reached by eventual doses of 16 to 20 mg per kilogram. Carbamazepine offers an independent choice of improved seizure control with a possibility of fewer side effects.

Intrauterine rubella, head size, and intellect.

The assumption that congenital rubella is commonly associated with microcephaly and mental retardation was examined. Among a rubella clinic population of 111 children, 92 children had vision sufficient to allow testing by the Leiter International Scale. The mean IQ for this group was 99.46 (SD, 19.5). Head circumference in this group correlated well with stature but poorly with intellect. The authors conclude that children with intrauterine rubella should be viewed as small children rather than children with small heads and that such children are poorly served if mental subnormality is assumed without careful study.

Effects of antiepileptic drugs on abilities.

The selection of antiepileptic drugs depends not just on efficacy considerations but on psychological side effects, including their effects on abilities. In general, investigations show that antiepileptic drugs have slight to mild adverse effects on abilities. Of the major agents, carbamazepine is frequently associated with fewer of these effects. There are, however, a number of confounding factors which complicate the interpretation of these studies. These include procedures pertaining to subject selection, statistical analysis, seizures, co-medication, test selection, and the use of the active agent versus placebo study design. The importance of each of these factors is briefly discussed, with emphasis on their relevance to interpretation of existing studies.

Neuropsychological aspects of epilepsy.

Brain dysfunction between seizures is common in epilepsy and a systematic assessment of it assists in planning directed programs of remediation. A battery of well-validated neuropsychological tests formulated with the needs of persons with epilepsy in mind can be of particular help in this regard. Increasing impairment in brain functions is shown to be associated with increasing emotional problems. Medical variables pertaining to seizure history include seizure type, cause, age at onset of seizures, duration of disorder, and seizure frequency. An exploration of relationships between these variables and measures of abilities and adjustment reveals a number of findings, some of which are complex. A review of the cognitive effects of antiepileptic drugs shows that the barbiturates have at least slightly greater adverse cognitive and behavioral effects than other drugs including carbamazepine, phenytoin, and sodium valproate. Whether cognitive differences exist among these latter medications is currently in question. Carbamazepine has the best-established favorable psychiatric effect.

Tiagabine versus phenytoin and carbamazepine as add-on therapies: effects on abilities, adjustment, and mood.

The effects of tiagabine (TGB) on abilities and on adjustment and mood are as yet incompletely understood. These effects were compared with those of phenytoin (PHT) and carbamazepine (CBZ) in an add-on study. Patients included in the analysis were adults with uncontrolled partial seizures who at study entry were on CBZ alone (n=153) or on PHT alone (n=124). Of the patients receiving CBZ, 82 were randomized to add-on TGB and 71 were randomized to add-on PHT during the double-blind period. Of the patients receiving PHT, 58 were randomized to add-on TGB and 66 were randomized to add-on CBZ. Eight tests of mental abilities and three of mood and adjustment were given prior to assignment of add-on treatment and after up to 16 weeks of add-on treatment. For the baseline CBZ group, analyses were done to search for differential changes from baseline in the test scores of the add-on TGB and add-on PHT groups, and for the baseline PHT group in the add-on TGB and add-on CBZ groups. In the baseline CBZ group, no differences in test scores were found between PHT and TGB. In the baseline PHT group for the area of abilities, patients treated with TGB had improved verbal fluency, as well as quicker responses on a test of perceptual/motor speed compared with patients treated with CBZ. For the baseline PHT group in the area of adjustment and mood, patients treated with TGB reported less positive mood and more financial concerns compared to patients treated with CBZ. Overall, add-on TGB showed few or no differences in comparison with add-on CBZ and add-on PHT.

Cognitive abilities and adjustment with gabapentin: results of a multisite study.

The cognitive and quality of life effects of gabapentin are not yet well explored. While preliminary work in the area has provided positive findings, a large double-blinded study has been needed to explore this area more thoroughly. From 24 sites in North America, 201 adults were studied who had uncontrolled complex partial seizures with or without secondary generalization. Attempts were made to convert each patient from one or two marketed antiepileptic drugs (AEDs) taken in baseline to gabapentin monotherapy (600, 1200, or 2400 mg/day). Tests of cognitive abilities and adjustment were administered at the end of the 8-week baseline period and at the end of the 26-week double-blind treatment period. Analyses of baseline to treatment period changes were conducted for each dose group in comparison with a reference group of placebo-treated patients from another study. In the area of cognitive functioning, no changes in any of the gabapentin groups were found in comparison with the reference group. In the area of adjustment and mood, however, improvement with gabapentin administration was noted on several variables pertaining to emotional and interpersonal adjustment. These results are consistent with findings from previous studies.

Verbal memory deficits after left temporal lobectomy for epilepsy. Mechanism and intraoperative prediction.

Verbal memory deficits remain a major complication of dominant hemisphere temporal lobectomy for epilepsy. The extent of this deficit was assessed preoperatively and 1 month and 1 year postoperatively with the Wechsler Verbal Memory Scale (WMSV) in 14 adults undergoing left temporal lobectomy. Intraoperative localization of language and verbal memory was also performed by electrical stimulation mapping. The WMSV score decreased an average of 22% at 1 month (13 cases), and 11% at 1 year (10 cases), even though in the majority of cases the medial extent of the resections had been significantly modified as a result of preoperative memory changes in response to intracarotid amobarbital perfusion testing. Memory decline was greater in patients who were not seizure-free, and correlated with the lateral (but not the medial) extent of the resection. The memory deficit could be predicted intraoperatively with 80% accuracy from the relationship of the resection to sites identified by electrical stimulation mapping as essential to naming or input or storage aspects of memory. This technique was applied prospectively in two additional cases with left temporal epileptic foci and complete verbal memory loss with left hemisphere amobarbital inactivation. These resections were tailored to avoid the essential naming and memory sites; the WMSV score increased 1 month postoperatively in both cases. This study identifies a lateral cortical component for verbal memory. Sites essential for that component can be localized intraoperatively with stimulation mapping; when they are spared in a resection, verbal memory deficit following dominant hemisphere temporal lobectomy can be prevented even in high-risk cases.

The role of neuropsychology in the assessment and treatment of persons with epilepsy.

Several areas of current interest in the neuropsychology of epilepsy are briefly reviewed in this article. These include variables pertaining to seizures, seizure history, antiepileptic drugs, and methods of neuropsychological evaluation. It is apparent that epilepsy is a multifaceted area: Psychologists not only can be of great assistance to patients with this condition, but may also learn a great deal from this complex disorder.

Assessment of brain impairment with the Rey Auditory Verbal Learning Test: a comparison with other neuropsychological measures.

In this study the effectiveness of The Rey Auditory Verbal Learning Test (AVLT) at assessing patients with mixed brain impairment was compared with that of a number of other commonly used neuropsychological measures. Subjects were 50 patients with a mixture of medically confirmed neuropathologies, and 50 controls with no evidence of neurological history. Groups were equated for age, education, and sex. The AVLT was administered as pan of a full neuropsychological battery. Results indicated that all seven AVLT recall trials and the total of Trials I-V could significantly differentiate between the two groups (p <.001). The AVLT trial V score performed best (U = 457.5, p <.0001), correctly predicting group membership for 74% of the subjects. This hit-rate was better than any other single test on the Halstead-Reitan or Dodrill batteries, and was surpassed only by the Dodrill Discrimination Index. The potential usefulness of this test as part of a neuropsychological battery is discussed.