Michael R. Sperling

Predictors of outcome after anterior temporal lobectomy Positron emission tomography

We assessed the relationship between temporal lobe metabolism measured quantitatively and qualitatively with PET using [18F]-fluorodeoxyglucose (FDG) and postoperative seizure frequency after anterior temporal lobectomy. Forty-three patients with refractory partial epilepsy had anterior temporal lobectomy and preoperative assessment with PET-FDG. Qualitative PET analysis was performed visually by two blinded observers, and quantitative PET analysis was performed using an anatomic template for six control and six temporal lobe subregions, deriving an asymmetry index for each region. Seizure outcome was assessed 1 year after surgery; patients were classified as being seizure-free or as having persistent seizures. Qualitative data were analyzed using Fishers exact test and the t test, and quantitative data were analyzed using a repeated-measures ANOVA. Thirty-two patients (74%) were seizure-free at follow-up, and 11 had persistent seizures, although most improved. Twenty-nine of 35 patients (83%) with restricted temporal lobe hypometabolism by visual analysis were seizure-free, compared with three of eight patients (37.5%) with normal scans or multilobar hypometabolism. Quantitative analysis revealed that an asymmetry of mesial temporal lobe glucose consumption (uncal region) correlated with improved surgical outcome (p < 0.02). We developed a logistic regression model to predict individual outcome based on the asymmetry in uncal metabolism. Lateral temporal metabolism did not correlate with outcome. We conclude that both visual PET analysis and quantitative PET analysis predict outcome after temporal lobectomy, although quantitative measures offer more precise information.

A noninvasive protocol for anterior temporal lobectomy

We report the results of a protocol for choosing candidates for temporal lobectomy using a standard battery of objective tests without intracranial electrodes. We assigned each test a level of importance, and an algorithm was used to determine whether temporal lobectomy could be performed. Fifty-one patients (total pool, 103 patients) met protocol requirements and had an anterior temporal lobectomy with a mean follow-up of 39.4 months (range, 21 to 64 months), most remaining on anticonvulsant therapy. Eighty percent are seizure free, 12% have <3 seizures per year or only nocturnal seizures, and 8% have >80% reduction in seizure frequency. One-third of patients who failed protocol criteria did not have temporal lobe seizures when studied with intracranial electrodes. We analyzed and modified the algorithm after comparing these patients with others who were poor candidates for temporal lobectomy. We conclude that this protocol is effective and recommend using such an objective algorithm.

Language Before and After Temporal Lobectomy: Specificity of Acute Changes and Relation to Early Risk Factors

Summary: We evaluated language functions in 154 patients with left hemisphere speech dominance undergoing anterior temporal lobectomy (ATL). Measures of phonemic and semantic fluency, confrontation naming, repetition, comprehension, and reading were administered before and 3 weeks postoperatively. Patients were grouped by focus (left, LT; right, RT) and presence of early risk factors for development of seizures (ER, early risk, 5 years; NER, no early risk): (LT‐ER, n = 45; RT‐ER, n = 49; LT‐NER, n = 27; RT‐NER, n = 33). Preoperatively, the LT group showed a selective naming deficit as compared with the RT group. Postoperatively only the LTNER group showed significant overall decline in language. For this group, the change was attributable to a selective decline in naming as compared with other functions. These data indicate that there is a specific risk to naming after dominant ATL for adult temporal lobe epilepsy (TLE) patients with a left hemisphere focus and the absence of an early risk factor for the development of seizures.

Predictors of outcome after anterior temporal lobectomy The intracarotid amobarbital test

The intracarotid amobarbital test (IAT) examines hemispheric memory and language. We set out to determine whether memory performance on the IAT correlated with seizure relief after anterior temporal lobectomy in 117 patients with refractory epilepsy. The IAT assessed recognition memory performance for nine items with correction for false-positive recognitions. We then compared performance of one hemisphere with that of the other, defining a correctly lateralized memory deficit as worse performance when using the hemisphere containing the operated temporal lobe than when using the other hemisphere. The analysis included concurrent factors that might also affect outcome, such as age at first risk for epilepsy, presence or absence of tumor, and Full Scale IQ. A discriminant function analysis demonstrated that patients with a correctly lateralized memory deficit on the IAT had an increased probability of being seizure-free following surgery after controlling for other predictors. The performance of the nonoperated temporal lobe related to outcome, although less strongly. The magnitude of the difference in performance between the two hemispheres and the performance of the operated hemisphere did not relate to outcome. Patients who became seizure-free had an earlier age at first risk than did those with persistent seizures, and tumor presence weakly correlated with postoperative outcome. IQ did not correlate with outcome. We conclude that the IAT predicts seizure relief after anterior temporal lobectomy independent of other known risk factors we examined.

The functional relationship between antidromically evoked field responses of the dentate gyrus and mossy fiber reorganization in temporal lobe epileptic patients.

Field recordings from the dentate granule cell layer of in vitro brain slices of temporal lobe epileptic patients were evoked by antidromic stimulation. Tissue from the same specimen was stained by the Timm-sulfide method to assess the pattern and degree of mossy fiber reorganization into the supragranular layer. A wide range of physiological responses and Timm staining patterns was present across patients. A significant correlation was observed between the abnormality of antidromic responses, reflected by multiple secondary population spikes, and the degree of Timm staining of the supragranular layer. This relationship lends support to the hypothesis that mossy fiber synapses located in the supragranular layer may have functional implications for granule cell excitability in human epileptic tissue.

Acute naming deficits following dominant temporal lobectomy Prediction by age at 1st risk for seizures

Age at 1st risk for seizures may predict anomia following dominant anterior temporal lobectomy. We assessed confrontation naming before and 2 to 3 weeks after surgery in 45 right-handed patients grouped by side of focus and presence or absence of early (≤5 years) risk factors. After left lobectomy, 6 of 10 (60%) patients with no early risks demonstrated significant decline (≥25%) in naming, but none of the patients with early risks showed this decline. After right lobectomy, there was no change. Cerebral representation of naming may be atypical in patients with early risks.

Comparison of mesial versus neocortical onset temporal lobe seizures : neurodiagnostic findings and surgical outcome

Summary: We compared historical features, surface EEG findings, results of intracarotid sodium amobarbital memory testing (IAT), and outcome after anterotemporal lobectomy (ATL) in patients with mesiotemporal lobe seizure onset with those with more diffuse temporal lobe seizure onset (intracranial EEG). Forty‐eight patients evaluated consecutively between July 1985 and October 1991 with both scalp/sphenoidal and intracranial EEG were shown to have seizures originating in one temporal lobe. No patients had temporal lobe tumor or vascular malformation. Thirty‐seven of the 48 patients had seizure onset in the amygdale/hippocampus (amyg/hipp). Eleven of the 48 had either temporal neocortical onset or simultaneous amydhipp and neocortical onset. Patients with mesial onset seizures were more likely to have lateralized memory impairment on I AT (p = 0.05). We noted a trend toward a difference in age of first risk for epilepsy between the two groups (p = 0.09) but not for a difference in any specific risk factor. There were no significant differences in surface EEG interictal findings. Unlike in previous studies, comparison of outcome between the two groups showed no difference in seizure‐free outcome. Sudden unexpected death (SUD) was more frequent in neocortical seizure patients who were not seizure‐free (p < 0.05).

Subcortical Metabolic Alterations in Partial Epilepsy

Summary The function of subcortical nuclei in partial epilepsy was investigated using positron emission tomography (PET) to measure metabolism in the basal ganglia and thalamus. Sixteen patients undergoing surgical evaluation were studied with 18F‐fluorodeoxyglucose (FDG) interictally and had intensive extracranial and intracranial electrophysiologic evaluations. Eight patients had left temporal lobe seizure foci, six had right temporal lobe foci, and two had right posterotemporal or parietal foci. The PET data were analyzed visually and quantitatively, using a multivariate analysis of variance on the quantitative data. Hypometabolism of subcortical nuclei was Present ipsilateral to the cortical seizure focus. Cortical hypometabolism was noted focally in the temporal lobe in patients with left temporal lobe seizure foci, whereas patients with right temporal lobe seizure foci had diffuse hemispheric hypometabolism. We postulate that the subcortical hypometabolism is secondary to decreased efferent activity from temporal lobe structures, in particular amygdala and hippocampus, to subcortical nuclei. Diminished subcortical activity may then lead to defective regulation of cortical excitability in the temporal lobe, increasing the likelihood of seizure development and spread.

Occupational outcome after temporal lobectomy for refractory epilepsy

Article abstract—We evaluated employment after temporal lobectomy for refractory epilepsy in 86 patients (3.5 to 8 years of follow-up). Seventy-three patients qualified for the work force before and after surgery. Unemployment rates declined after surgery (18 patients [25%1 unemployed before surgery, eight patients [11%] unemployed after surgery), and underemployment also tended to diminish. Improvement in occupational status related strongly to the degree of postoperative seizure relief. Seizure-free patients fared better (no unemployment, little underemployment) than patients with some seizure-free years and some years with seizures after surgery, whose high underemployment level persisted. Patients with seizures in each year after surgery fared worst (despite reduced seizure frequency), with increased unemployment after surgery. Age at surgery also influenced vocational outcome in patients who were unemployed before surgery. Historical, educational, cognitive, and behavioral measures did not correlate with vocational outcome. Employment gains came slowly; unemployed patients took up to 6 years to obtain work after surgery. Of 13 students at the time of surgery, 11 have graduated and nine are now employed. We conclude that seizures play a large role in limiting employment, and that by alleviating seizures, temporal lobectomy improves employability in people with refractory epilepsy. Surgery thereby provides benefit to individuals with epilepsy by increasing financial independence and to society by reducing unemployment.

Cardiac rhythm during temporal lobe seizures

We studied the neuroanatomic correlates of ictal tachycardia in 27 seizures from five patients with unilateral temporal lobe epilepsy being evaluated with bilateral temporal lobe depth electrodes and orbitofrontal subdural electrodes. There were 11 complex partial seizures, three simple partial seizures, and 13 subclinical seizures. For all seizures, heart rate (HR) increased in a graded fashion as new cortical regions anywhere in the brain were recruited into the seizure. HR plateaued at the new level despite EEG frequency changes until the next region became involved. Increases in HR did not correlate with increased duration of seizures but rather with volume of brain involved. Restricted amygdaloid seizure activity was generally insufficient to alter HR. We conclude that the amygdala has a limited role in modulating HR during seizures, and ictal tachycardia depends principally on the volume of cerebral structures recruited into a seizure.