Treatment of immune thrombocytopenic purpura associated with cytomegalovirus infection in a child with pre-B cell acute lymphoblastic leukaemia after central nervous system relapse.

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.

PET of serotonin 1A receptors and cerebral glucose metabolism for temporal lobectomy.

UNLABELLED: The objective of this study was to compare 5-hydroxytryptamine receptor 1A (5-HT(1A)) PET with cerebral metabolic rate of glucose (CMRglc) PET for temporal lobectomy planning. METHODS: We estimated 5-HT(1A) receptor binding preoperatively with (18)F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl) piperazin-1-yl]ethyl-N-(2-pyridyl) cyclohexane carboxamide ((18)F-FCWAY) PET and CMRglc measurement with (18)F-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. (18)F-FCWAY but not (18)F-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 (18)F-FCWAY (F(1,39) = 5.87; P = 0.02) and (18)F-FDG PET (F(1,38) = 5.79; P = 0.021). The probability of being seizure-free was explained by both (18)F-FDG and (18)F-FCWAY PET, but not MRI, with a significant additional (18)F-FCWAY effect (chi(2)(2) = 9.8796; P = 0.0072) after the probability of being seizure-free was explained by (18)F-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-HT(1A) receptor PET and CMRglc PET can contribute to temporal lobectomy planning. Additional studies should explore the potential for temporal lobectomy based on interictal electroencephalography and minimally invasive imaging studies.

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.

Serotonin 1A receptors, depression, and memory in temporal lobe epilepsy.

PURPOSE: Memory deficits and depression are common in patients with temporal lobe epilepsy (TLE). Previous positron emission tomography (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 measured with 18F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl-N-(2-pyridyl) cyclohexane carboxamide (18FCWAY) PET in a cross-sectional study. METHODS: We studied 40 patients (24 male; mean age 34.5 ± 10.7 years) with TLE. Seizure diagnosis and focus localization were based on ictal video-electroencephalography (EEG) recording. Patients had neuropsychological testing with Wechsler Adult Intelligence Score III (WAIS III) and Wechsler Memory Score III (WMS III) on stable antiepileptic drug (AED) regimens at least 24 h since the last seizure. Beck Depression Inventory (BDI) scores were obtained. We performed interictal PET with 18FCWAY, a fluorinated derivative of WAY 100635, a highly specific 5HT1A ligand, and structural magnetic resonance imaging (MRI) scans to estimate partial volume and plasma free fraction corrected 18FCWAY volume of distribution (V/f1). KEY FINDINGS: Hippocampal V/f1 was significantly lower in area ipsilateral than contralateral to the epileptic focus (73.7 ± 27.3 vs. 95.4 ± 28.4; p < 0.001). We found a significant relation between both left hippocampal 18FCWAY 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 18FCWAY 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 18FCWAY V/f1 but not focus laterality retained significance. Mean BDI was 8.3 ± 7.0. There was a significant inverse relation between BDI and 18FCWAY 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 5HT1A-receptor binding may play a role in memory impairment in patients with TLE.

Effects of gestational allopregnanolone administration in rats bred for high affective behavior.

The anxiolytic neurosteroid allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one or 3alpha,5alpha-THP) has been proposed to play a developmental role in emergent neural regulation of affective behavior. This experiment examined whether allopregnanolone administered during the last week of gestation in rats would alter neonatal and adult offspring behaviors in the selectively-bred High vocalizing line, who have low levels of allopregnanolone and high levels of anxious/depressive behaviors. Dams were injected twice a day with the neurosteroid or vehicle, or handled as controls, and were tested on the elevated plus maze just before parturition. Maternal behavior was assessed throughout the first week of life, and affective behavior in the offspring was tested at one week of age (ultrasonic vocalizations test) and as adults (plus maze and forced swim tests). Offspring prenatally exposed to allopregnanolone were less anxious as neonates and less depressed as adults compared to both control groups. Only male adult offspring, however, revealed less anxious behavior on the plus maze. Neither the dams' anxiety behavior measured in late gestation nor their postnatal maternal behavior was altered compared to controls, suggesting a direct, long-lasting effect of gestational allopregnanolone on the developing fetal brain independent of mediating maternal factors. These results are discussed in light of new evidence about the developmental role of the GABA-A receptor prenatally.