Thomas R. Henry

Presurgical evaluation for partial epilepsy : relative contributions of chronic depth-electrode recordings versus FDG-PET and scalp-sphenoidal ictal EEG

One hundred fifty-three patients with medically refractory partial epilepsy underwent chronic stereotactic depth-electrode EEG (SEEG) evaluations after being studied by positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) and scalp-sphenoidal EEG telemetry. We carried out retrospective standardized reviews of local cerebral metabolism and scalp-sphenoidal ictal onsets to determine when SEEG recordings revealed additional useful information. FDG-PET localization was misleading in only 3 patients with temporal lobe SEEG ictal onsets for whom extratemporal or contralateral hypometabolism could be attributed to obvious nonepileptic structural defects. Two patients with predominantly temporal hypometabolism may have had frontal epileptogenic regions, but ultimate localization remains uncertain. Scalp-sphenoidal ictal onsets were misleading in 5 patients. For 37 patients with congruent focal scalp-sphenoidal ictal onsets and temporal hypo-metabolic zones, SEEG recordings never demonstrated extratemporal or contralateral epileptogenic regions; however, 3 of these patients had nondiagnostic SEEG evaluations. The results of subsequent subdural grid recordings indicated that at least 1 of these patients may have been denied beneficial surgery as a result of an equivocal SEEG evaluation. Weighing risks and benefits, it is concluded that anterior temporal lobectomy is justified without chronic intracranial recording when specific criteria for focal scalp-sphenoidal ictal EEG onsets are met, localized hypometabolism predominantly involves the same temporal lobe, and no other conflicting information has been obtained from additional tests of focal functional deficit, structural imaging, or seizure semiology.

Ictal localization of temporal lobe seizures with scalp/sphenoidal recordings

We assessed the reliability and accuracy of scalp/sphenoidal recordings for ictal localization by retrospectively analyzing 706 noninvasive ictal recordings from 110 patients who subsequently underwent stereoencephalographic evaluation. Strictly defined unilateral temporal/sphenoidal ictal patterns correctly predicted findings of depth electrode examination in 82 to 94% of cases. These strictly defined predictive patterns could be detected with excellent interrater reliability. The patterns are misleading in only a minority of cases, but cannot be used in isolation for definite ictal localization.

In vivo cerebral metabolism and central benzodiazepine‐receptor binding in temporal lobe epilepsy

Positron emission tomography measured interictal cerebral glucose metabolism with [18F]fluorodeoxyglucose and central benzodiazepine-receptor binding with [11C]flumazenil in 10 mesial temporal lobe epilepsy (TLE) patients and in normal subjects. Eight TLE patients had mesial temporal, lateral temporal, and thalamic hypometabolism ipsilateral to EEG ictal onsets, with additional extratemporal hypometabolism in four. One had unilateral anterior mesial temporal hypometabolism only, and one had normal metabolism. Each patient had decreased benzodiazepine-receptor binding in the ipsilateral anterior mesial temporal region, without neocortical changes. Thus, interictal metabolic dysfunction is variable and usually extensive in TLE, whereas decreased central benzodiazepine-receptor density is more restricted to mesial temporal areas. Metabolic patterns in TLE may reflect diaschisis, while benzodiazepine-receptor changes may reflect localized neuronal and synaptic loss that is specific to the epileptogenic zone. [11C]Flumazenil imaging maybe useful in presurgical evaluation of refractory complex partial seizures.

Quantifying interictal metabolic activity in human temporal lobe epilepsy

The majority of patients with complex partial seizures of unilateral temporal lobe origin have interictal temporal hypometabolism on [18F]fluorodeoxyglucose positron emission tomography (FDG PET) studies. Often, this hypometabolism extends to ipsilateral extratemporal sites. The use of accurately quantified metabolic data has been limited by the absence of an equally reliable method of anatomical analysis of PET images. We developed a standardized method for visual placement of anatomically configured regions of interest on FDG PET studies, which is particularly adapted to the widespread, asymmetric, and often severe interictal metabolic alterations of temporal lobe epilepsy. This method was applied by a single investigator, who was blind to the identity of subjects, to 10 normal control and 25 interictal temporal lobe epilepsy studies. All subjects had normal brain anatomical volumes on structural neuroimaging studies. The results demonstrate ipsilateral thalamic and temporal lobe involvement in the interictal hypometabolism of unilateral temporal lobe epilepsy. Ipsilateral frontal, parietal, and basal ganglial metabolism is also reduced, although not as markedly as is temporal and thalamic metabolism.

Interictal cerebral metabolism in partial epilepsies of neocortical origin

We performed interictal [18F]fluorodeoxyglucose positron emission tomography (FDG PET) in 24 patients with partial epilepsy of neocortical origin. Two-thirds of patients had regions of hypometabolism. The zone of intracranially recorded electrographic ictal onset was always located in a region of hypometabolism, in those with hypometabolism. Hypometabolic regions in partial epilepsies of neocortical origin were usually associated with structural imaging abnormalities. Regional hypometabolism occasionally occurred without localizing ictal scalp EEG and cerebral magnetic resonance imaging findings, however. FDG PET may be useful in directing placement of intracranial electrodes for presurgical evaluation of refractory neocortical seizures.

Focal Cerebral Magnetic Resonance Changes Associated with Partial Status Epilepticus

Summary: We report 2 patients with transient abnormalities on magnetic resonance imaging (MRI) associated with partial status epilepticus (SE). A man with a 4‐month history of partial seizures had complex partial SE for 9 days, with left temporal maximum on ictal EEG. Left temporal lobe T2 signal was increased on MRI during SE, but cerebral MRI was normal 9 weeks later. A woman with “cryptogenic” temporal lobe epilepsy for 16 years had complex partial SE for 1 week, with right temporal maximum on ictal EEG. T2 Signal was increased over the entire right temporal lobe, extending into the insula, without mass effect, on MRI 1 month after SE ended. Repeat MRI 1 month later showed marked decrease in volume of increased T2 intensity, without gadolinium enhancement, but with mild mass effect over the right anteroinferomesial temporal areas. A gemistocytic astrocytoma was resected. Focal cerebral MRI abnormalities consistent with cerebral edema may be due to partial SE but also may indicate underlying glioma, even in long‐standing partial epilepsy. Focal structural imaging changes consistent with neoplasm should be followed to full resolution after partial SE.

Temporal lobe central benzodiazepine binding in unilateral mesial temporal lobe epilepsy

Article abstract—PET-demonstrated decreases in [11C]flumazenil binding occur in anterior mesial temporal structures on the side of epileptogenesis in unilateral mesial temporal lobe epilepsy. We performed quantitative autoradiog-raphy on anterior mesial and lateral temporal specimens from 11 subjects with unilateral mesial temporal lobe epilepsy and six neurologically normal controls to identify the predominant in vitro correlates of the decreased [11C]flumazenil binding. In anterior mesial temporal regions exhibiting the greatest neuronal cell loss, decreases in agonist and antagonist binding to type 1 and 2 (central) benzodiazepine binding sites were highly correlated with neuronal cell counts. Cell loss and decreased binding were particularly prominent in the lateral portion of hippocampal region CA1, adjacent to CA2. Lateral temporal central benzodiazepine binding was diffusely increased, achieving statistical significance in cortical laminae V and VI. These findings suggest that the predominant source of PET-demonstrated decreases in [11C]flumazenil binding in mesial temporal epilepsy is hippocampal sclerosis, rather than down-regulation of central benzodiazepine binding sites on surviving hippocampal neurons.

Serial Cognitive Testing in Temporal Lobe Epilepsy: Longitudinal Changes with Medical and Surgical Therapies

Summary: Cognitive testing was repeated at intervals ranging from 1 to 8 years in 47 adult patients with temporal lobe epilepsy (TLE). Each patient underwent standardized batteries, including the Wechsler Adult Intelligence Scale, Revised (WAIS‐R), and Wechsler Memory Scale (WMS). Both surgically treated and nonsurgical patients were examined. The nonsurgical group underwent serial testing for clinical indications, usually for complaints of memory dysfunction. Longitudinal testing could not verify any mean deterioration of intellect or memory in this group; variance over time was similar to test‐retest norms in healthy controls. WAIS‐R scores before and after resection in the surgical group were similar to our serial WAIS‐R data in nonsurgical patients. When we divided surgical patients according to side of epileptogenesis, we noted the expected differences in verbal and visual memory. Right‐sided surgery patients improved significantly in Full‐scale IQ (FSIQ) and tended to improve in logical memory on postoperative testing. Patients undergoing left resections had no retest improvement and tended to show decrease in several measures of verbal memory. Our findings should stimulate continued investigation into the natural history of lateralized memory and intellectual function in epilepsy, particularly to clarify longterm cognitive outcome in nonsurgical patients.

Asymmetric hypsarrhythmia : clinical electroencephalographic and radiological findings

Summary: Twenty‐six children (16 boys and 10 girls) with hypsarrhythmia and infantile spasms (IS) were studied at the University of Michigan EEG Laboratory in a 4‐year period. Six (2 boys, 4 girls), had asymmetric hypsarrhythmia with a preponderance of both slowing and epileptic form activity over one hemisphere. All 6 had the symptomatic form of IS, 4 with dysplastic conditions, 1 with porencephaly from a cerebral infarct, and 1 with hypoxic‐ischemic encephalopathy. Five children had focal abnormalities on either physical examination or imaging studies. Four had the highest amplitude slowing and most epileptiform activity ipsilateral to the lesion, in 1, it was contralateral. Asymmetric hypsarrhythmia constituted 23% of cases with hypsarrhythmia examined at our EEG laboratory. The significant success in surgical therapy for some children with IS indicates the importance of identifying focal hemispheric abnormalities even if they are not apparent clinically. EEG may suggest focal changes not detected clinically or radiologically.

Muscarinic Receptor Loss and Preservation of Presynaptic Cholinergic Terminals in Hippocampal Sclerosis

Summary: Purpose: Prior single‐photon emission tomography studies showed losses of muscarinic acetylcholine receptor (MAChR) binding in patients with refractory mesial temporal lobe epilepsy. Experimental animal studies demonstrated transient losses of MAChR due to electrically induced seizures originating in the amygdala. However, the relations between cholinergic synaptic markers, seizures, and underlying neuro‐pathology in human temporal lobe epilepsy are unknow. We tested the hypotheses that human brain MAChR changes are attributable to hippocampal sclerosis (HS), and that HS resembles axon‐sparing lesions in experimental animal models.