Faculty Bibliography

OBJECTIVE: Cerebellar atrophy has been noted in patients with phenytoin exposure. This finding has been attributed by some investigators to seizures, but by others to phenytoin. Previous studies included patients with mental retardation and convulsive seizures. We undertook a study in a group of nonretarded patients with partial epilepsy to better elucidate the cause of the cerebellar atrophy. DESIGN: Case control study. SETTING: Referral population from an epilepsy center. PATIENTS: Thirty-six patients with partial epilepsy and long-term phenytoin exposure were selected from a consecutive sample of admissions to an epilepsy center. Patients with histories of ethanol abuse, perinatal distress, anoxia, status epilepticus, or neurodegenerative disorders were excluded. Age- and sex-matched controls were selected from a pool of healthy volunteers and patients who had undergone magnetic resonance imaging for complaints of headache and dizziness. INTERVENTIONS: All patients and controls underwent magnetic resonance imaging. MAIN OUTCOME MEASURE: Degree of cerebellar atrophy. RESULTS: The magnetic resonance imaging scans were reviewed in a blind fashion. A rating was assigned to each scan based on the degree of cerebellar atrophy. Cerebellar atrophy was significantly more pronounced in patients than in controls. No correlation was found between cerebellar atrophy and variables reflective of seizure severity or degree of phenytoin exposure. CONCLUSIONS: Cerebellar atrophy may be seen in phenytoin-exposed patients with epilepsy in the absence of generalized tonic-clonic seizures or preexistent brain damage. Whether it is the phenytoin or the seizures that play the primary etiologic role remains unanswered. These factors may be synergistic.

A 25-year-old woman with documented generalized seizures evoked by playing checkers was given a battery of psychological tests as well as a series of cognitive and non-game-related tasks during a session of intensive EEG-video monitoring. Generalized epileptiform discharges during each task, as well as during intervals of checkers playing, were quantified to determine possible triggering factors. Previous reports have discussed the roles of attention, concentration, stress, thinking, and spatial processing in similar cases. Our analysis showed significant activation of the EEG only with tasks involving strategic thinking, i.e., considering a sequence of moves based on evaluating the consequences of previous moves.

This study investigated the use of three-dimensional fast low-angle shot (FLASH) imaging and computer-assisted morphometry for identifying hippocampal changes associated with unilateral temporal lobe seizures. Contiguous 3.1-mm coronal FLASH images were obtained in 28 patients with electroencephalographically verified left (n = 17) or right (n = 11) temporal lobe seizures and 28 age- and sex-matched control subjects. Hippocampal volumes were calculated with the use of a computerized mensuration system developed for detailed morphometric assessment. The results of a multivariate analysis of variance revealed a significant group difference by hemisphere interaction (F = 26.3, p less than .001). Significant reductions in left hippocampal volume (32%, p less than .001) were exhibited in patients with left temporal lobe seizures, and significant reductions in right hippocampal volume (35%, p less than .001) were seen in patients with right temporal lobe seizures. A discriminant analysis with the use of left and right hippocampal volumes classified patients with left temporal lobe seizures with 94% sensitivity and 73% specificity and patients with right temporal lobe seizures with 89% sensitivity and 94% specificity. The results of this study demonstrate that unilateral temporal lobe seizures are accompanied by significant reductions in hippocampal volume ipsilateral to the seizure focus. The use of FLASH imaging and computer-assisted morphometry of the hippocampus appears to provide valuable structural information for confirming the laterality of the electroencephalographic seizure focus.

Remote memory performance was assessed in a carefully matched sample of temporal lobectomy subjects and normal controls. Left temporal lobectomy subjects exhibited a consistent pattern of remote memory disturbance. Right temporal lobectomy subjects performed at the same level as normal controls. The pattern of impairment observed in left temporal lobectomy subjects was characterized by deficits in recall of chronological information from the past decade and extended to deficits in recall in some aspects of factual knowledge. The disorder could not be attributed solely to language deficits and was at least as severe as accompanying deficits in recent memory. These findings suggest that the left medial temporal region may play a significant role in recall of remote information in addition to its role in recent memory functions.

Recent interest in the biological basis of schizophrenia has led to a reexamination of many symptomatic aspects of the disorder in terms of brain-behavioral models. Schizophrenic speech disturbances have traditionally been described in terms of a model of acquired aphasia. We review some of the limitations of this model and provide an alternative model for the study of some characteristics of schizophrenic speech based on neuropsychological theories of frontal lobe dysfunction in schizophrenia. The emphasis is placed on the study of productive errors noted in schizophrenic speech, most notably verbal perseverations. In a study of errors observed during a sample of 15 schizophrenics performance on a confrontation naming test, we were able to reliably identify and classify hierarchic categories of verbal perseverations occurring at both semantic and phonemic levels. These perseverations constituted 20% of the total errors. We argue that these perseverations represent a special case of executive dysfunction resulting from a disturbance of language monitoring mechanisms. We examine the implications of these findings for a hypothesis of schizophrenic speech disturbances in terms of frontal lobe dysfunction and the developmental neuropathological processes involved in the illness.

We examined handedness and cerebral hemispheric asymmetries on computed tomography (CT) scan in a sample of schizophrenic patients who were rated also for the presence or absence of persistent tardive dyskinesia (TD). Patients with TD showed a more standard dominance pattern, with dextral hand preference and normal occipital asymmetry. Anomalous dominance was associated with a marked underrepresentation of TD. Stepwise discriminant analyses indicated that the statistical prediction of TD was enhanced by the inclusion of dominance measures. Schizophrenic patients with strong standard dominance patterns may be more susceptible to developing TD, or conversely, anomalous dominance may confer protection against TD.

On the basis of clinical observation and a developmental theory of cerebral laterality, Geschwind and Galaburda suggested that cerebral arteriovenous malformations (AVMs) are more common in the left hemispheres of male patients. We tested this hypothesis by examining interactions among sex, handedness, and location of lateralized, supratentorial AVMs. Data from 112 cases were analyzed by log-linear procedures. We found that (1) females had a greater proportion of left-hemisphere AVMs, whereas males showed an opposite trend; (2) there were no interactions between sex and handedness; and (3) nondextrals showed a higher proportion of AVMs located in frontal regions, regardless of the hemispheric side of the lesion. Although these findings appear to be inconsistent with the Geschwind-Galaburda hypothesis, the inconsistency may be attributable to the embryonic stage at which this developmental abnormality occurs. In addition, the unexpected findings may also reflect our use of multivariate statistical procedures, which control for interaction effects.

Twenty asymptomatic, HIV-seropositive homosexual men and a control group of 20 seronegative homosexual men were evaluated for evidence of neuropsychological impairment. Two-tailed paired t-tests of group differences revealed that the seropositive patients had significantly lower scores on two of 20 neuropsychological measures. Ten seropositive patients had scores two standard deviations below the sample, compared with three seronegative patients, a significantly different distribution (p = .04). The HIV-infected group exhibited lower mean scores on 17 of 20 variables (binomial probability, p less than .005). The 10 seropositive patients with scores that fell below the cut-off had significantly lower mean T4/T8 ratios than the 10 seropositive patients with scores above the cut-off (p = .02). The data suggest that a subpopulation of HIV-infected adults may exhibit subtle neuropsychological impairment before they develop clinical signs of cognitive deficit or immunosuppression.