The effects of guanfacine on working memory performance in patients with localization-related epilepsy and healthy controls.

OBJECTIVES: Previous research has demonstrated that alpha2 agonists improve working memory performances in healthy individuals and in primates with prefrontal lesions. We conducted this study to determine whether the alpha2 agonist, guanfacine, could improve working memory performances in patients with frontal lobe epilepsy (FLE) and/or in those with focal epilepsy outside the frontal lobes (ie, temporal lobe epilepsy [TLE]). METHODS: Fourteen patients with FLE, 13 patients with TLE, and 10 healthy controls completed immediate and delayed match-to-sample tasks before and after ingestion of 2 to 3 mg of guanfacine. RESULTS: All 3 groups showed an increase in accuracy on the delayed match-to-sample task, but not the immediate match-to-sample task, following administration of guanfacine. Inspection of the group means revealed somewhat greater benefits for the control and FLE groups relative to the TLE group. Increased accuracy was not associated with slower performances in any group, suggesting that the cognitive benefits of guanfacine did not occur at the expense of increased sedation. CONCLUSIONS: These data suggest that guanfacine improves working memory in patients with FLE and may be a viable treatment for attenuating such deficits in this patient population.

Hippocampal cell loss in posttraumatic human epilepsy.

PURPOSE: We performed this study to determine whether significant head trauma in human adults can result in hippocampal cell loss, particularly in hilar (polymorph) and CA3 neurons, similar to that observed in animal models of traumatic brain injury. We examined the incidence of hippocampal pathology and its relation to temporal neocortical pathology, neuronal reorganization, and other variables. METHODS: Twenty-one of 200 sequential temporal lobectomies had only trauma as a risk factor for epilepsy. Tissue specimens from temporal neocortex and hippocampus were stained with glial fibrillary acidic protein (GFAP) and hematoxylin and eosin (H&E). Eleven hippocampal specimens had additional analysis of neuronal distributions by using cresyl violet and immunolabeling of a neuron-specific nuclear protein. RESULTS: The median age at onset of trauma was 19 years, the median time between trauma and onset of seizures was 2 years, and the median epilepsy duration was 16 years. The length of the latent period was inversely related to the age at the time of trauma (r=0.75; Spearman). The neocortex showed gliosis in all specimens, with hemosiderosis (n=8) or heterotopias (n=6) in some, a distribution differing from chance (p=0.02; Fisher). Hippocampal neuronal loss was found in 94% of specimens, and all of these had cell loss in the polymorph (hilar) region of the dentate gyrus. Hilar cell loss ranged from mild, when cell loss was confined to the hilus, to severe, when cell loss extended into CA3 and CA1. Some degree of mossy fiber sprouting was found in the dentate gyrus of all 10 specimens in which it was evaluated. Granule cell dispersion (n=4) was seen only in specimens with moderate to severe neuronal loss. CONCLUSIONS: Neocortical pathology was universally present after trauma. Neuronal loss in the hilar region was the most consistent finding in the hippocampal formation, similar to that found in the fluid-percussion model of traumatic head injury. These findings support the idea that head trauma can induce hippocampal epilepsy in humans in the absence of other known risk factors.

The relationship of regional frontal hypometabolism to executive function: a resting fluorodeoxyglucose PET study of patients with epilepsy and healthy controls.

Executive dysfunction is common in patients with frontal lobe damage and may depend on the location of pathology within the frontal lobes. However, it is unclear how specific brain regions contribute to different aspects of executive functioning. Eighteen patients with frontal lobe epilepsy, 10 patients with juvenile myoclonic epilepsy, and 14 controls completed a series of tests that measure a broad range of executive functions. Resting fluorodeoxyglucose positron emission tomography scans were collected and regional cerebral rates of glucose uptake values were regressed on test scores. Results revealed that frontal lobe metabolic values were strong predictors of executive functioning in patients with epilepsy, but not in healthy controls. However, nonfrontal regions also contributed unique variance on several measures, suggesting that (1) a network of frontal and nonfrontal regions subserve many executive functions and (2) resting hypometabolism can be a useful predictor of executive dysfunction in patients with epilepsy.

Occipital hypometabolism demonstrated by positron emission tomography after temporal lobectomy for refractory epilepsy.

BACKGROUND: Epilepsy surgery involves well-planned discrete injury to the brain and may create visual deficits. This study seeks to evaluate the indirect effects of temporal lobectomy on brain metabolism by correlating visual field defects and glucose metabolism in the visual cortex of patients before and after undergoing epilepsy surgery. METHODS: A retrospective survey of 11 patients who had undergone temporal lobectomy for refractory epilepsy in a single institution from 1986 to 1989, and who had pre-lobectomy and post-lobectomy visual field examinations and F-18 2-fluorodeoxyglucose positron emission tomography (FDG-PET) as part of a standard comprehensive epilepsy surgery evaluation. The PET images were analyzed to provide a correlation with the visual field defects that developed after the temporal lobectomy. RESULTS: Occipital hypometabolism in the absence of structural lesions of the occipital lobe was noted in seven patients with contralateral visual field defects and in one of four patients without a visual field defect. FDG-PET studies in three patients repeated for as long as 20 months after lobectomy showed no significant change in the occipital hypometabolism pattern. CONCLUSIONS: Although the occipital cortex was not directly injured during temporal lobectomy, the resulting hypometabolism correlates with the clinical findings of visual field defects. The hypometabolism may be due to deafferentation after interruption of the optic pathways and appears to be persistent.

Pathogenesis of clinical signs in recessive ataxia with saccadic intrusions.

We describe a family of Slovenian descent with progressive ataxia, corticospinal signs, axonal sensorimotor neuropathy, and disruption of visual fixation by saccadic intrusions. Chromosome mapping indicated a mutation on 1p36, and this recessive disorder has been designated spinocerebellar ataxia with saccadic intrusions. Affected patients showed overshooting horizontal saccades, macrosaccadic oscillations, and increased velocity of larger saccades; other eye movements were normal. Slowed conduction in axons that are selectively vulnerable to the molecular defect could explain both the sensorimotor neuropathy and the saccadic disorder, which would be caused by delayed feedback control because of slow conduction in cerebellar parallel fibers.

The use of 2-deoxy-2-[18F]fluoro-D-glucose (FDG-PET) positron emission tomography in the routine diagnosis of epilepsy.

PURPOSE: Positron emission tomography with 2-deoxy fluoroglucose positron emission tomography (18-FDG-PET) is widely used in the pre-surgical evaluation of subjects with epilepsy, but little is known of its usefulness in a non-surgical population. PROCEDURES: We analyzed the sensitivity of PET as a diagnostic tool in a large unselected population of epilepsy subjects. Pre-surgical and non-surgical portions of this population were individually assessed as well. The relationship of PET abnormalities to other neurodiagnostic tests was examined. Statistical assessment relied primarily on contingency tables (chi-square tests), with ANOVA or non-parametric assessment used as necessary. RESULTS: While PET was more likely to identify areas of decreased metabolism in the surgical population than in the non-surgical populations, it nevertheless found a significant number of abnormalities in the total population and in the non-surgical group alone. Even in groups in which the clinical diagnosis was unknown, abnormalities were found 40% of the time. PET was useful as an exclusionary diagnostic tool for non-epileptic seizures (NES) and primary generalized epilepsies (PGE) with sensitivity, specificity, and accuracy > 90%. The PET was somewhat more sensitive than magnetic resonance imaging (MRI) in finding abnormalities in the total population, but was less sensitive than electroencephalography (EEG). CONCLUSION: PET may be a useful diagnostic tool in the general epilepsy population even when a definitive clinical diagnosis is not suggested by other modalities.

Rapid Quantitative Analysis of Individual (18)FDG-PET Scans.

To evaluate an objective, quantitative, semi-automatic method of single (18)FDG-PET scan analysis. Scans of 60 normal controls was compared to scans from individuals with known pathology using two methods of visual analysis and Statistical Parametric Mapping with two different smoothing filters. We analyzed the sensitivity, specificity, and accuracy of each technique and evaluated the agreement between the four methods using a kappa statistic. When corrected for false positives, which were due to anatomical distortions, all techniques had a sensitivity and accuracy of 0.5 to 0.6. Specificity was highest, 1.0, using SPM with a 16 mm smoothing filter, followed by visual analyses. Good agreement between all techniques was found. A computerized expert which makes use of a normal data base and SPM to analyze single (18)FDG-PET scans can aid in the routine interpretation of scans and provide rapid, quantification of abnormalities for research or clinical purposes.