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Background Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) shows widespread hypometabolism even in temporal lobe epilepsy (TLE) patients with mesial temporal foci. 18F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl) piperazin-1-yl]ethyl-N-(2-pyridyl)cyclohexanecarboxamide (18F-FCWAY) PET may show more specific 5-HT1A receptor binding reduction in seizure initiation than propagation regions. 18FCWAY PET might be valuable for detecting epileptic foci, and distinguishing mesial from lateral temporal foci in MRI negative TLE patients.

Summary: Purpose: To study the effect of antiepileptic drugs (AEDs) on 5-HT1A‐receptor binding in patients with temporal lobe epilepsy. 5-HT1A‐receptor binding, measured by positron emission tomography, is reduced in patients with temporal lobe epilepsy. Antiepileptic drugs may act on the serotonergic system, as shown in animal models, and thus affect receptor-binding measurements. Methods: We analyzed the effect of AEDs on 5-HT1A‐receptor binding in 31 patients and 10 normal controls. Patients with structural lesions, progressive neurologic disorders, or taking other medications were excluded. None had a seizure for ≥2 days before positron emission tomography (PET). [ 18 F]FCWAY PET was performed on a GE Advance scanner with continuous EEG monitoring. Functional images of the distribution volume (V) were generated. Anatomic regions of interest were applied to coregistered PET images, after correction for partial-volume effect. Results: Patients had significantly higher [ 18 F]FCWAY free fraction (f 1) than did controls. No AED effects were observed on interictal [ 18 F]FCWAY binding after correction for plasma free fraction. [ 18 F]FCWAY V/f 1 reduction in epileptic foci was not affected by AEDs. Conclusions: 5-HT1A-receptor binding is reduced in temporal lobe epileptic foci after partial-volume correction. AED plasma free fractions should be measured when PET receptor studies are performed in patients with epilepsy. Key Words: Serotonin receptors—Positron emission tomography—Antiepileptic drug.

We studied the efficacy of felbamate (FBM) in combination with valproic acid (VPA) in 13 patients with the Lennox-Gastaut syndrome and evaluated the contribution of each drug. Following stabilization on VPA monotherapy, FBM or placebo titration was performed for two observation periods lasting 7 weeks with a washout period between them. 6-h video-electroencephalography was recorded following each observation period. In addition to examining the effects of the drugs with parental reports and video-EEG, we compared video-EEG data with families' seizure reports. Based on parental counts for the 7-week observation periods, patients had 40% fewer drop attacks (p < 0.03, Wilcoxon rank sum test) and 60% fewer total seizures (p < 0.02) on VPA and FBM. VPA level rose by 12.7% when FBM was added (p < 0.01). When the effect of FBM was factored out, VPA had a significant effect on drop attack frequency, although not total number of seizures. FBM's therapeutic effect on drop attacks is due in part to increased VPA levels, although the combination may be synergistic for the effect on total seizure number.

Objective: To perform a controlled trial of transcranial magnetic stimulation (TMS). Methods: Twenty-four patients with localization-related epilepsy were randomized to blinded active or placebo stimulation. Weekly seizure frequency was compared for 8 weeks before and after 1 week of 1-Hz TMS for 15 minutes twice daily. Results: When the 8-week baseline and post-stimulation periods were compared, active patients had a mean seizure frequency reduction of 0.045 ± 0.13 and sham-stimulated control subjects −0.004 ± 0.20. Over 2 weeks, actively treated patients had a mean reduction in weekly seizure frequency of 0.16 ± 0.18 and sham-stimulated control subjects 0.01 ± 0.24. Neither difference was significant. Conclusion: The effect of TMS on seizure frequency was mild and short lived.

SUCCINIC SEMIALDEHYDE DEHYDROGENASE (SSADH) DEFICIENCY (OMIM # 271980) IS ONE OF THE FEW GENETIC DISORDERS AFFECTING GABA METABOLISM and homeostasis. The clinical phenotype is generally nonspecific, featuring seizures, developmental delay, intellectual disability, delayed or absent speech, hypotonia, behavioral problems, and ataxia, with a typically static clinical course.1 Neuroimaging has most consistently demonstrated abnormalities in the globus pallidus, subthalamic nucleus, and cerebellar dentate nucleus.2 The biochemical hallmark is accumulation of γ-hydroxybutyric acid (GHB) (Figure 1). In addition, there is significant elevation in GABA in physiologic fluids as well as brain parenchyma, as measured by MR spectroscopy with special editing.3,4 GHB may act directly as a partial weak GABAB receptor agonist or as a direct neuromodulator on GHB receptors at pharmacologic concentrations, in addition to its interconversion to GABA.5 Exogenous GHB administration is associated with disinhibition, drowsiness, and ultimately coma at high doses.6 Chronic GHB administration in patients with narcolepsy-cataplexy increases delta sleep and suppresses REM intrusions with decreased awakenings and percentage of time awake during stage REM.7 We hypothesized that patients with SSADH deficiency have increased symptoms of sleep disorders and abnormal sleep architecture characterized by increased delta sleep and decreased stage REM sleep. Figure 1 Biochemical Pathway of GABA Metabolism.

Background: Autosomal dominant partial epilepsy with auditory features (ADPEAF) is an idiopathic focal epilepsy syndrome with auditory symptoms or receptive aphasia as major ictal manifestations, frequently associated with mutations in the leucine-rich, glioma inactivated 1 ( LGI1 ) gene. Although affected subjects do not have structural abnormalities detected on routine MRI, a lateral temporal malformation was identified through high resolution MRI in one family. We attempted to replicate this finding and to assess auditory and language processing in ADPEAF using fMRI and magnetoencephalography (MEG). Methods: We studied 17 subjects (10 affected mutation carriers, 3 unaffected carriers, 4 noncarriers) in 7 ADPEAF families, each of which had a different LGI1 mutation. Subjects underwent high-resolution structural MRI, fMRI with an auditory description decision task (ADDT) and a tone discrimination task, and MEG. A control group comprising 26 volunteers was also included. Results: We found no evidence of structural abnormalities in any of the 17 subjects. On fMRI with ADDT, subjects with epilepsy had significantly less activation than controls. On MEG with auditory stimuli, peak 2 auditory evoked field latency was significantly delayed in affected individuals compared to controls. Conclusions: These findings do not support the previous report of a lateral temporal malformation in autosomal dominant partial epilepsy with auditory features (ADPEAF). However, our fMRI and magnetoencephalography data suggest that individuals with ADPEAF have functional impairment in language processing.