Florian Wilke

Anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis show distinct patterns of brain glucose metabolism in 18F-fluoro-2-deoxy-d-glucose positron emission tomography.

BackgroundPathogenic autoantibodies targeting the recently identified leucine rich glioma inactivated 1 protein and the subunit 1 of the N-methyl-D-aspartate receptor induce autoimmune encephalitis. A comparison of brain metabolic patterns in 18F-fluoro-2-deoxy-d-glucose positron emission tomography of anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis patients has not been performed yet and shall be helpful in differentiating these two most common forms of autoimmune encephalitis.MethodsThe brain 18F-fluoro-2-deoxy-d-glucose uptake from whole-body positron emission tomography of six anti-N-methyl-D-aspartate receptor encephalitis patients and four patients with anti-leucine rich glioma inactivated 1 protein encephalitis admitted to Hannover Medical School between 2008 and 2012 was retrospectively analyzed and compared to matched controls.ResultsGroup analysis of anti-N-methyl-D-aspartate encephalitis patients demonstrated regionally limited hypermetabolism in frontotemporal areas contrasting an extensive hypometabolism in parietal lobes, whereas the anti-leucine rich glioma inactivated 1 protein syndrome was characterized by hypermetabolism in cerebellar, basal ganglia, occipital and precentral areas and minor frontomesial hypometabolism.ConclusionsThis retrospective 18F-fluoro-2-deoxy-d-glucose positron emission tomography study provides novel evidence for distinct brain metabolic patterns in patients with anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis.

Blood–brain barrier permeability for ammonia in patients with different grades of liver fibrosis is not different from healthy controls

Increased blood-brain barrier (BBB) permeability for ammonia is considered to be an integral part of the pathophysiology of hepatic encephalopathy (HE) in patients with liver cirrhosis. Increased glutamate-/glutamine-signal intensity in magnetic resonance spectroscopic studies of the brain in cirrhotic patients was explained as a consequence of increased cerebral ammonia uptake. As similar spectroscopic alterations are present in patients with liver fibrosis, we hypothesized that BBB permeability for ammonia is already increased in liver fibrosis, and thereby contributing to the development of HE. To test this hypothesis, cerebral perfusion and ammonia metabolism were examined through positron emission tomography with 15O-water, respectively, 13N-ammonia in patients with Ishak grades 2 and 4 fibrosis, cirrhosis, and healthy controls. There were neither global nor regional differences of cerebral blood flow, the rate constant of unidirectional transport of ammonia from blood into brain tissue, the permeability surface area product of the BBB for ammonia, the net metabolic clearance rate constant of ammonia from blood into glutamine in brain, or the metabolic rate of ammonia. The hypothesis that increased permeability of the BBB for ammonia in patients with liver fibrosis contributes to the later development of HE could not be supported by this study.

Cerebral microglia activation in hepatitis C virus infection correlates to cognitive dysfunction.

Hepatitis C virus (HCV) infection may induce chronic fatigue and cognitive dysfunction. Virus replication was proven within the brain and HCV‐positive cells were identified as microglia and astrocytes. We hypothesized that cerebral dysfunction in HCV‐afflicted patients is associated with microglia activation. Microglia activation was assessed in vivo in 22 patients with chronic HCV infection compared to six healthy controls using [11C]‐PK11195 Positron Emission Tomography (PET) combined with magnetic resonance tomography for anatomical localization. Patients were subdivided with regard to their PCR status, Fatigue Impact Scale score (FIS) and attention test sum score (ATS). A total of 12 patients (54.5%) were HCV PCR positive [of which 7 (58.3%) had an abnormal FIS and 7 (58.3%) an abnormal ATS], 10 patients (45.5%) were HCV PCR negative (5 (50%) each with an abnormal FIS or ATS). Patients without attention deficits showed a significantly higher accumulation of [11C]‐PK11195 in the putamen (P = 0.05), caudate nucleus (P = 0.03) and thalamus (P = 0.04) compared to controls. Patients with and without fatigue did not differ significantly with regard to their specific tracer binding in positron emission tomography. Preserved cognitive function was associated with significantly increased microglia activation with predominance in the basal ganglia. This indicates a probably neuroprotective effect of microglia activation in HCV‐infected patients.

Reduced thalamic 18F-flurodeoxyglucose retention in adults with neurofibromatosis type 1.

ObjectiveNeurofibromatosis type1 (NF1) is associated with cognitive and motor deficits whose pathogenesis is not well understood. 18F-Flurodeoxyglucose positron emission tomography (FDG PET) might be used to investigate putative functional correlates in the brain. MethodsWhole-body FDG PET including the brain had been performed in 29 NF1 patients suspected for malignant peripheral nerve sheath tumours (20 females, nine males, age 31.2±11.8 years). Twenty-nine age-matched and sex-matched subjects without evidence of neurological/psychiatric disease in whom FDG PET had been performed for NF1-unrelated oncological indication served as controls. Individual brain FDG retention images were stereotactically normalized and scaled to a common median retention value within the brain. Scaled FDG retention was compared between the NF1 group and the control group on a voxel-by-voxel base using ANCOVA in SPM2 with the FDG uptake period as covariate. The corrected significance level &agr;=0.05 was used. Voxel-based analysis was complemented by volume of interest (VOI)-based analysis using predefined standard VOIs. ResultsThe voxel-based group comparison revealed a significant reduction of scaled FDG retention in the thalamus of the NF1 subjects within a cluster of 11.6 ml. There were no further significant effects, neither hypo-retention nor hyper-retention. Reduction of relative FDG retention in the thalamus in the NF1 subjects was confirmed by VOI analysis. The magnitude of the reduction was about 8%. ConclusionsThe thalamus appears to be affected in adults with NF1. The observed magnitude of the reduction of scaled thalamic FDG retention in adults is smaller than previously reported in children. This may be consistent with a stabilization of the disease process with age.

Effect of Deep Brain Stimulation on Regional Cerebral Blood Flow in Patients with Medically Refractory Tourette Syndrome

In this study, alterations in brain perfusion have been investigated in patients with Tourette syndrome (TS) compared with control subjects. In addition, we investigated the effects of deep brain stimulation (DBS) in both globus pallidus internus (GPi) and centromedian-parafascicular/ventralis oralis internus nuclei of the thalamus (CM/Voi) and sham (SHAM) stimulation on cerebral blood flow. In a prospective controlled, randomized, double-blind setting, five severely affected adult patients with TS with predominant motor or vocal tics (mean total tic score on the Yale Global Tic Severity Scale: 39) underwent serial brain perfusion single photon emission computed tomography with 99mTc-ECD. Results were compared with data from six age-matched control subjects. All patients were investigated at four different time points: once before DBS implantation (preOP) and three times postoperatively. Postoperative scans were performed in a randomized order, each after 3 months of either GPi, CM/Voi, or SHAM stimulation. At each investigation, patients were injected at rest while awake, but scanned during anesthesia. This procedure ensured that neither anesthesia nor movement artifacts influenced our results. Control subjects were investigated only once at baseline (without DBS or anesthesia). At baseline, cerebral blood flow was significantly reduced in patients with TS (preOP) compared with controls in the central region, frontal, and parietal lobe, specifically in Brodmann areas 1, 4–9, 30, 31, and 40. Significantly increased perfusion was found in the cerebellum. When comparing SHAM stimulation to preOP condition, we found significantly decreased perfusion in basal ganglia and thalamus, but increased perfusion in different parts of the frontal cortex. Compared with SHAM condition both GPi and thalamic stimulation resulted in a significant decrease in cerebral blood flow in basal ganglia and cerebellum, while perfusion in the frontal cortex was significantly increased. Our results provide substantial evidence that, in TS, brain perfusion is altered in the frontal cortex and the cerebellum and that these changes can be reversed by both GPi and CM/Voi DBS.

Visualization of the auditory pathway in rats with 18F-FDG PET activation studies based on different auditory stimuli and reference conditions including cochlea ablation

Activation studies with positron emission tomography (PET) in auditory implant users explained some of the mechanisms underlying the variability of achieved speech comprehension. Since future developments of auditory implants will include studies in rodents, we aimed to inversely translate functional PET imaging to rats. In normal hearing rats, activity in auditory and non-auditory regions was studied using 18F-fluorodeoxyglucose (18F-FDG) PET with 3 different acoustic conditions: sound attenuated laboratory background, continuous white noise and rippled noise. Additionally, bilateral cochlea ablated animals were scanned. 3D image data were transferred into a stereotaxic standard space and evaluated using volume of interest (VOI) analyses and statistical parametric mapping (SPM). In normal hearing rats alongside the auditory pathway consistent activations of the nucleus cochlearis (NC), olivary complex (OC) and inferior colliculus (IC) were seen comparing stimuli with background. In this respect, no increased activation could be detected in the auditory cortex (AC), which even showed deactivation with white noise stimulation. Nevertheless, higher activity in the AC in normal hearing rats was observed for all 3 auditory conditions against the cochlea ablated status. Vice versa, in ablated status activity in the olfactory nucleus (ON) was higher compared to all auditory conditions in normal hearing rats. Our results indicate that activations can be demonstrated in normal hearing animals based on 18F-FDG PET in nuclei along the central auditory pathway with different types of noise stimuli. However, in the AC missing activation with respect to the background advises the need for more rigorous background noise attenuation for non-invasive reference conditions. Finally, our data suggest cross-modal activation of the olfactory system following cochlea ablation–underlining, that 18F-FDG PET appears to be well suited to study plasticity in rat models for cochlear implantation.