Cerebral blood flow and fMRI BOLD auditory language activation in temporal lobe epilepsy.

PURPOSE: Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), an important research and clinical tool, depends on relatively greater transient increases in (regional cerebral blood flow) rCBF than cerebral metabolic rate for oxygen during neural activity. We investigated whether reduced resting rCBF in patients with temporal lobe epilepsy affects BOLD signal during fMRI language mapping. METHODS: We used [(15)O] water positron emission tomography (PET) to measure rCBF, and 3 Tesla echo planar imaging (EPI) BOLD fMRI with an auditory description decision task in 33 patients with temporal lobe epilepsy (16 men; mean age 33.6 ± standard deviation [SD] 10.6 years; epilepsy onset 14.8 ± 10.6 years; mean duration 18.8 ± 13.2 years; 23 left focus, 10 right focus). Anatomic regions drawn on structural MRI, based on the Wake Forest Pick Atlas, included Wernicke's area (WA), inferior frontal gyrus (IFG), middle frontal gyrus (MFG), and hippocampus (HC). Laterality indices (LIs), and asymmetry indices (AIs), were calculated on coregistered fMRI and PET. KEY FINDINGS: Twelve patients had mesial temporal sclerosis (seven on the left), two patients had a tumor or malformation of cortical development (both left), one patient a right temporal cyst, and 18 patients had normal MRI (14 left). Decreasing relative left WA CBF correlated with decreased left IFG voxel activation and decreasing left IFG LI. However, CBF WA AI was not related to left WA voxel activation itself or WA LI. There was a weak positive correlation between absolute CBF and fMRI activation in left IFG, right IFG, and left WA. Patients with normal and abnormal MRI did not differ in fMRI activation or rCBF AIs. SIGNIFICANCE: Reduced WA rCBF is associated with reduced fMRI activation in IFG but not WA itself, suggesting distributed network effects, but not impairment of underlying BOLD response. Hypoperfusion in TLE does not affect fMRI clinical value.

18F-FCWAY and 18F-FDG PET in MRI-negative temporal lobe epilepsy.

BACKGROUND: Positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) shows widespread hypometabolism even in temporal lobe epilepsy (TLE) patients with mesial temporal foci. (18)F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl) piperazin-1-yl]ethyl-N-(2-pyridyl)cyclohexane carboxamide ((18)F-FCWAY) PET may show more specific 5-HT(1A)-receptor binding reduction in seizure initiation than in propagation regions. (18)FCWAY PET might be valuable for detecting epileptic foci, and distinguishing mesial from lateral temporal foci in MRI-negative patients with TLE. METHODS: We performed (18)F-FCWAY-PET and (18)F-FDG-PET in 12 MRI-negative TLE patients who had had either surgery or subdural electrode recording, and 15 healthy volunteers. After partial volume correction for brain atrophy, free fraction-corrected volume of distribution (V/f1) measurement and asymmetry indices (AIs) were computed. We compared (18)F-FCWAY-PET and (18)F-FDG-PET results with scalp video electroencephalography (EEG), invasive EEG, and surgical outcome. RESULTS: Mean (18)F-FCWAY V/f1, compared with normal controls, was decreased significantly in fusiform gyrus, hippocampus, and parahippocampus ipsilateral to epileptic foci, and AIs were significantly greater in hippocampus, parahippocampus, fusiform gyrus, amygdala, and inferior temporal regions. Eleven patients had clearly lateralized epileptogenic zones. Nine had congruent, and two nonlateralized, (18)F-FCWAY PET. One patient with bitemporal seizure onset had nonlateralized (18)F-FCWAY-PET. (18)F-FDG-PET showed congruent hypometabolism in 7 of 11 EEG-lateralized patients, bilateral hypometabolic regions in one, contralateral hypometabolism in one, as well as lateralized hypometabolism in the patient with bitemporal subdural seizure onset. Patients with mesial temporal foci tended to have lower superior and midtemporal (18)F-FCWAY V/f1 binding AI than those with lateral or diffuse foci. CONCLUSION: (18)F-FCWAY-PET can detect reduced binding in patients with normal MRI, and may be more accurate than (18)F-FDG-PET.

Polysomnographic abnormalities in succinic semialdehyde dehydrogenase (SSADH) deficiency.

OBJECTIVES: Patients with SSADH deficiency, a disorder of chronically elevated endogenous GABA and GHB, were studied for sleep symptoms and polysomnography. We hypothesized that patients would have excessive daytime somnolence and decreased REM sleep. DESIGN: Polysomnography and MSLT were performed on patients enrolled for comprehensive clinical studies of SSADH deficiency. SETTING: Sleep studies were obtained in the sleep laboratories at CNMC and NIH. PATIENTS: Sleep recordings were obtained in 10 patients with confirmed SSADH deficiency. INTERVENTIONS: Thirteen overnight polysomnograms were obtained in 10 patients (7 male, 3 female, ages 11-27 y). Eleven MSLT studies were completed in 8 patients. MEASUREMENTS AND RESULTS: Polysomnograms showed prolongation of REM stage latency (mean 272 +/- 89 min) and decreased percent stage REM (mean 8.9%, range 0.3% to 13.8%). Decreased mean sleep latency was present in 6 of 11 MSLTs. CONCLUSIONS: SSADH deficiency is associated with prolonged latency to stage REM and decreased percent stage REM. This disorder represents a model of chronic GABA and GHB accumulation associated with suppression of REM sleep.

The effect of antiepileptic drugs on 5-HT-receptor binding measured by positron emission tomography.

PURPOSE: To study the effect of antiepileptic drugs (AEDs) on 5-HT(1A)-receptor binding in patients with temporal lobe epilepsy. 5-HT(1A)-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-HT(1A)-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 >or=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 co-registered 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/f1 reduction in epileptic foci was not affected by AEDs. CONCLUSIONS: 5-HT(1A)-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.