Faculty Bibliography

We determined how localization of simple partial seizures (SPS) correlated with localization of complex partial seizure (CPS) in scalp/sphenoidal EEG and assessed prognosis after temporal lobe resective surgery in patients with an ictal correlate of SPS in scalp/sphenoidal EEG recordings. EEGs were recorded with the 10-20 system of electrode placement and supplemented with sphenoidal electrodes. Between 1985 and 1992, 183 patients with temporal lobe epilepsy (TLE) reported an aura (SPS) during inpatient monitoring; all were eligible for inclusion in our study. The EEGs during SPS showed ictal changes in 51 patients (28%, 117 SPS). Forty-four patients had unilateral temporal interictal spikes (IIS), and SPS and CPS always arose from the same region. Seven patients had bitemporal interictal spikes; SPS colocalized with CPS in 4 patients (57%), SPS were contralateral to CPS in 2 patients, and 1 patient had bilateral independent CPS but unilateral SPS. SPS accompanied by EEG ictal changes conveyed a favorable prognosis in patients who underwent epilepsy surgery. Scalp/sphenoidal recorded IIS but were less reliable in identifying the location of CPS onset in patients with bitemporal spikes

Neuronal cell distributions were measured for anterior and posterior locations in the hippocampi of epilepsy patients who were seizure-free after temporal lobectomy. Patients were divided into two groups, those with an early risk factor, defined as a neurologic insult occurring in the first 4 years of life, and those with no early risk factor. Early-risk patients had lower hilar cell densities, lower granule cell densities, and fewer granule cells per millimeter, a measured related to total granule cell number, than to early risk patients. Moreover, each risk group had different anteroposterior density gradients for granule cells and hilar cells. These differences in cell distribution may arise from different patterns of cell loss of cell migration in the dentate gyrus during development. In the early-risk group, there was also a distinction between patients with a history of febrile convulsions without CNS infection and patients with a history of meningitis or encephalitis. These two subgroups had similar numbers of granule cells, However, the meningitis/encephalitis subgroup exhibited a wider granule cell layer, suggesting that the granule cell layer was more dispersed. Our results support the hypothesis of a predominantly anterior hippocampal insult in temporal lobe epilepsy (TLE). In nonepileptic hippocampus, the ratio of putatively excitatory granule neurons to putatively inhibitory hilar neurons is highest in the anterior hippocampus. This ratio may explain in part why the anterior hippocampus is more prone to cell loss and seizures

This study compared the efficacy and tolerability of vigabatrin 3/day as add-on therapy with that of placebo in patients with focal epilepsy whose complex partial seizures were difficult to control with established antiepilepsy drug therapy. We enrolled 203 patients; 182 (90 placebo; 92 vigabatrin) received drug therapy under double-blind conditions. We increased the daily dosage to 2.5 g/day during a 4-week titration segment and maintained it at 3 g/day during the 12-week maintenance segment. By analyses we found a statistically significant lower frequency of seizures (complex seizures plus partial seizures secondarily generalized) at the end of the study for patients receiving vigabatrin than for those receiving placebo. The median monthly frequency was reduced by three seizures per 28 days in the placebo group (baseline, 8.3; end of study, 7.5) (p = 0.0002). Therapeutic success (a 50% reduction from baseline in mean monthly seizure frequency) was attained in 40 of the vigabatrin patients (43%) compared with 17 of those treated with placebo (19%) (p < 0.001). Vigabatrin significantly increased the mean number of seizure-free days per 28 days (2.2 days) compared with placebo (0.5 days) (p = 0.0024). Mean trough serum vigabatrin concentration during therapy was 8.6 +/- 7.7 micrograms/ml. The oral clearance of vigabatrin was determined to be 7.8 L/hr, and the elimination half-life was 8.4 hours. No clinically important changes in MRI, evoked potential, or other laboratory tests were noted during vigabatrin treatment. The results of this study indicate that 3 g/day vigabatrin is more effective than placebo as add-on therapy. Vigabatrin was well tolerated, compliance was high with twice-daily administration, and therapy did not result in clinically relevant drug interactions

A number of new antiepileptic drugs (AEDs), including topiramate (TPM), felbamate (FBM), and gabapentin (GBP), are approved or believed to be close to approval for marketing in the United States. Key efficacy findings for these AEDs in refractory partial epilepsy were reviewed. Large and significant drug-placebo differences were observed with TPM in two large dose-finding trials conducted in the United States. The minimal effective dose of TPM in the population studied was determined to be approximately 200 mg/day, and doses above 600 mg/day produced good efficacy but little incremental benefit versus the lower dosages for the overall study population. FBM is active in partial epilepsy, although seizure reduction is less marked and drug interactions complicate the findings. GBP is also active in this population, but only the 1,800 mg/day dosage was significantly better than placebo with respect to percent responders. It may be useful to explore higher dosage ranges for both FBM and GBP if they can be well tolerated

Functional magnetic resonance imaging (fMRI) with susceptibility-based contrast was used to detect focal changes in cerebral blood flow and metabolism in a patient with focal epilepsy. The patient presented with frequent partial motor seizures involving his right lower face that spread to produce speech arrest and occasionally right arm jerking. Consciousness was never impaired during these events. A multislice echoplanar technique was used to acquire 16 contiguous axial slices every 4 seconds for 11 minutes. Although no overt seizures were observed or reported by the patient during the scanning, a time series analysis of the functional data revealed focal signal-intensity changes in the posterior left frontal lobe, which correlated well both in duration and spatial localization with ictal activity subsequently recorded by invasive electrophysiological monitoring. The spatial localization of fMRI was more accurate than electroencephalography recorded from a subdural grid in predicting the site of successful surgical therapy. These results illustrate the potential of functional MRI for localizing seizure foci with high spatial and temporal resolution. Such studies can be readily combined with high-resolution anatomical imaging, task-activation studies, and other magnetic resonance techniques

We report 2 patients in whom visual interpretation of interictal positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) suggested false lateralization of an epileptic focus. PET scans were interpreted as showing diffuse left temporal lobe hypometabolism in 1 patient and lateral temporal hypometabolism in the other. However, seizures began in the right mesial temporal lobe in both patients, and both responded favorably to right temporal lobectomy. In 1 patient, the intracranial EEG showed continuous asymptomatic subclinical seizure activity emanating from the right amygdala. These limbic discharges probably caused unrecognized right temporal lobe hypermetabolism. In the other case, quantitative analysis of metabolic rates showed conflicting mesial and lateral metabolic indexes. Frequent mesial interictal discharges might have increased lateral temporal metabolism. We conclude that asymptomatic epileptiform activity may alter temporal lobe metabolism and that quantitative PET analysis helps clarify contradictory visual PET interpretations