Glucose metabolism has been associated with magnitude of blood oxygen level-dependent (BOLD) signal and connectivity across subjects within the default mode and dorsal attention networks. Similar correlations within subjects across the entire brain remain unexplored. [18 F]-fluorodeoxyglucose positron emission tomography ([ 18 F]-FDG PET), [ 11 C]-flumazenil PET, and resting-state functional magnetic resonance imaging (fMRI) scans were acquired in eight healthy individuals and nine with temporal lobe epilepsy (TLE). Regional metabolic rate of glucose (rMRGlu) was correlated with amplitude of low frequency fluctuations (ALFFs) in the fMRI signal, global fMRI connectivity (GC), regional homogeneity (ReHo), and gamma-aminobutyric acid A-binding potential (GABA A BP ND ) across the brain. Partial correlations for ALFFs, GC, and ReHo with GABA A BP ND were calculated, controlling for rMRGlu. In healthy subjects, significant positive correlations were observed across the brain between rMRGlu and ALFF, ReHo and GABA A BP ND , and between ALFFs and GABA A BP ND , controlling for rMRGlu. Brain-wide correlations between rMRGlu and ALFFs were significantly lower in TLE patients, and correlations between rMRGlu and GC were significantly greater in TLE than healthy subjects. These results indicate that the glutamatergic and GABAergic systems are coupled across the healthy human brain, and that ALFF is related to glutamate use throughout the healthy human brain. TLE may be a disorder of altered long-range connectivity in association with glutamate function.

Objective: To study 5-HT transport and 5-HT 1A receptors in temporal lobe epilepsy (TLE) and depression. Conclusions: Our study showed increased [ Methods11 C]DASB asymmetry in insula and fusiform gyrus, and relatively reduced transporter activity, in subjects with both TLE and depression, as compared to subjects with TLE alone, implying reduced reuptake and thus increased synaptic 5-HT availability. This finding may represent a compensatory mechanism for 5-HT 1A receptor loss. Altered serotonergic mechanisms have an important role in TLE and concomitant depression. Serotonin (5-HT) exerts antiseizure effects in experimental models mediated by 5-HT 1A receptors, by hyperpolarizing hippocampal CA3 membranes.1 Some antiepileptic drugs (AEDs) may exert antiseizure effects by blocking 5-HT reuptake. 2PET studies showed reduced 5-HT 1A receptor binding ipsilateral to temporal lobe epilepsy (TLE) foci.3-5 Not due to hippocampal atrophy, reductions are more pronounced in seizure onset than secondary spread regions. 5,6 Epidemiologic and clinical data support relationships between epilepsy and depression, one of the most common epilepsy comorbidities.7 A history of depression increases risk for later epilepsy development.8 Otherwise healthy patients with major depressive disorders (MDD) may have limbic 5-HT 1A receptor binding reductions.9-11 5-HT 1A receptor PET studies in patients with both TLE and depression showed additional binding alterations compared to TLE alone.

Purpose Memory deficits and depression are common in patients with temporal lobe epilepsy (TLE). Previous PET studies have shown reduced mesial temporal 5HT1A receptor binding in these patients. We examined the relationships among verbal memory performance, depression, and 5HT1A receptor binding binding measured with 18FCWAY positron emission tomography (PET) in a cross sectional study. Methods We studied 40 patients (24 male; mean age 34.5 ±10.7) with TLE. Seizure diagnosis and focus localization were based on ictal Video-Electoencephalographic recording. Patients had neuropsychological testing with Weschler Adult Intelligence Score III (WAIS III) and Weschler Memory Score III (WMS III) on stable AED regimens at least 24 hours since the last seizure. Beck Depression Inventory (BDI) scores were obtained. We performed interictal PET with [18F]FCWAY, a fluorinated derivative of WAY100635, a highly specific 5HT1A ligand, and structural magnetic resonance imaging (MRI) scans to estimate partial volume and plasma free fraction corrected [18F]FCWAY volume of distribution (V/f1). Key Findings Hippocampal V/f1 was significantly lower ipsilateral than contralateral to the epileptic focus (73.7 ± 27.3 versus 95.4 ± 28.4; p<.001). We found a significant relation between both left hippocampal FCWAY V/f1 (r= 0.41; p < 0.02) and left hippocampal volume (r=0.36; p < 0.03) and delayed auditory memory score. On multiple regression there was a significant effect of the interaction of left hippocampal FCWAY V/f1 and left hippocampal volume on delayed auditory memory, but not of either alone. High collinearity was present. In an analysis of variance including the side of the seizure focus, the effect of left hippocampal FCWAY V/f1 but not focus laterality retained significance. Mean BDI was 8.3 ±7.0. There was a significant inverse relation between BDI and FCWAY V/f1 ipsilateral to the patient’s epileptic focus (r= 0.38 p<0.02) There was no difference between patients with a right or left temporal focus. There was no relation between BDI and immediate or delayed auditory memory. Significance Our study suggests that reduced left hippocampal 5-HT1A receptor binding may play a role in memory impairment in patients with TLE.

Background: Atypical language dominance is common in patients with temporal lobe epilepsy. We

The objective of this study was to compare 5-hydroxytryptamine receptor 1A (5-HT1A) PET with cerebral metabolic rate of glucose (CMRglc) PET for temporal lobectomy planning. Methods We estimated 5-HT1A receptor binding preoperatively with 18F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl) piperazin-1-yl]ethyl-N-(2-pyridyl) cyclohexane carboxamide (18F-FCWAY) PET and CMRglc measurement with 18F-FDG in regions drawn on coregistered MRI after partial-volume correction in 41 patients who had anterior temporal lobectomy with at least a 1-y follow-up. Surgery was tailored to individual preresection evaluations and intraoperative electrocorticography. Mean regional asymmetry values and the number of regions with asymmetry exceeding 2 SDs in 16 healthy volunteers were compared between seizure-free and non–seizure-free patients. 18F-FCWAY but not 18F-FDG and MRI data were masked for surgical decisions and outcome assessment. Results Twenty-six of 41 (63%) patients seizure-free since surgery had significantly different mesial temporal asymmetries, compared with 15 non-seizure-free patients for both 18F-FCWAY (F1,39 = 5.87; P = 0.02) and 18F-FDG PET (F1,38 = 5.79; P = 0.021). The probability of being seizure-free was explained by both 18F-FDG and 18F-FCWAY PET, but not MRI, with a significant additional 18F-FCWAY effect (χ22=9.8796; P = 0.0072) after the probability of being seizure-free was explained by 18F-FDG. Although MRI alone was not predictive, any combination of 2 lateralizing imaging studies was highly predictive of seizure freedom. Conclusion Our study provides class III evidence that both 5-HT1A receptor PET and CMRglc PET can contribute to temporal lobectomy planning. Additional studies should explore the potential for temporal lobectomy based on interictal elec-troencephalography and minimally invasive imaging studies.

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Purpose BOLD fMRI, an important research and clinical tool, depends on relatively greater transient increases in (cerebral blood flow) rCBF than CMRO2 during neural activity. We investigated whether reduced resting rCBF in patients with TLE affects BOLD signal during fMRI language mapping. Methods We used [15O] water PET to measure rCBF, and 3T EPI BOLD fMRI with an auditory description decision task in 33 patients with temporal lobe epilepsy (16 men; age 33.6±10.6 years; epilepsy onset 14.8±10.6 years; mean duration 18.8±13.2 years; 23 left focus, 10 right focus). Anatomical regions drawn on structural MRI, based on the Wake Forest PickAtlas, included Wernicke’s area (WA), inferior frontal gyrus (IFG), middle frontal gyrus (MFG), and hippocampus (HC)]. Laterality indices (LI), and Asymmetry Indices (AI), were calculated on co-registered fMRI and PET. Key findings Twelve patients had mesial temporal sclerosis (7 left), two a tumor or malformation of cortical development (both left), one a right temporal cyst and 18 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 AI. 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.

A 13-year-old male patient with a history of pre-B cell acute lymphoblastic leukaemia (ALL) with isolated central nervous system relapse on maintenance chemotherapy presented with severe thrombocytopenia refractory to platelet transfusions. The patient showed only modest responses to two courses of intravenous immunoglobulin and steroids. He was found to be positive for cytomegalovirus (CMV) with modest viral load. His thrombocytopenia normalised with rituximab therapy and CMV treatment supporting the diagnosis of CMV-associated immune thrombocytopenic purpura (ITP). Following treatment, the patient continued to have a stable platelet count well above the threshold for transfusions. He continued to be intermittently treated for CMV when viral loads became detectable. This report discusses the unique management considerations of ITP in a patient undergoing therapy for ALL with a review of previously reported cases and discusses the possibility of CMV viraemia as a modulating factor.