Amino Acid Uptake, Glucose Metabolism, and Neuroinflammation in John Cunningham Virus Associated Progressive Multifocal Leukoencephalopathy.

ABSTRACT: A 69-year-old woman presented with progressive dysarthria and cognitive deficits. On MRI, a T2-hyperintense, non-contrast-enhancing lesion was found in the left precentral area. 18F-FET and 18F-FDG PET scans revealed faint amino acid uptake and glucose hypometabolism of the lesion. To assess a neuroinflammatory component, TSPO PET with 18F-GE-180 was performed, where tracer uptake markedly exceeded the T2-hyperintense areas. Histology derived from a stereotactic biopsy findings confirmed John Cunningham virus-associated progressive multifocal leukoencephalopathy. This case underlines that TSPO PET comprises distinct imaging advantages over other established radioligands such as 18F-FET and 18F-FDG in progressive multifocal leukoencephalopathy.

Cathodal tDCS Over Motor Cortex Does Not Improve Tourette Syndrome: Lessons Learned From a Case Series.

Introduction: Current pathophysiological hypotheses of Gilles de la Tourette Syndrome (GTS) refer to temporally abnormal neuronal activation in cortico-striato-thalamo-cortical (CSTC) networks. Modifying cortical activity by non-invasive brain-stimulation appears to be a new treatment option in GTS. Background: Previous studies suggested therapeutic effects of cathodal transcranial direct current stimulation (tDCS) to pre-supplementary motor areas (SMA), however, treatment modalities concerning electrode placement, current intensity and stimulation-rate have not been systematically explored. Aim of this study was to assess efficacy of an alternative stimulation regime on GTS symptoms in a pilot study. To test a treatment protocol with tDCS twice a day, we administered 10 sessions over 5 days of bilateral cathodal tDCS (30 min, 2 mA) over the pre-SMA in three patients with severe GTS. Tic severity as well as obsessive-compulsive (OC) symptoms and affective scales were rated before and after tDCS treatment. Discussion: Only one out of three patients showed a 34.5% reduction in tic severity. The two other patients showed an increase in tic severity. All patients showed a mild increase in positive affect and a reduction in negative affect, OC symptom changes were heterogeneous. Our results do not support earlier findings of extensive therapeutic effects of cathodal tDCS on tics in patients with GTS and show that prediction of stimulation effects on a targeted brain area remains inaccurate. Concluding Remarks: Future research will have to focus on the determination of most effective stimulation modes regarding site, polarity and frequency of tDCS in GTS patients.

Vertigo and dizziness in adolescents: Risk factors and their population attributable risk.

OBJECTIVES: To assess potential risk factors for vertigo and dizziness in adolescents and to evaluate their variability by different vertigo types. The role of possible risk factors for vertigo and dizziness in adolescents and their population relevance needs to be addressed in order to design preventive strategies. STUDY DESIGN: The study population consisted of 1482 school-children between the age of 12 and 19 years, who were instructed to fill out a questionnaire on different vertigo types and related potential risk factors. The questionnaire specifically asked for any vertigo, spinning vertigo, swaying vertigo, orthostatic dizziness, and unspecified dizziness. Further a wide range of potential risk factors were addressed including gender, stress, muscular pain in the neck and shoulder region, sleep duration, migraine, coffee and alcohol consumption, physical activity and smoking. RESULTS: Gender, stress, muscular pain in the neck and shoulder region, sleep duration and migraine were identified as independent risk factors following mutual adjustment: The relative risk was 1.17 [1.10-1.25] for female sex, 1.07 [1.02-1.13] for stress, 1.24 [1.17-1.32] for muscular pain, and 1.09 [1.03-1.14] for migraine. The population attributable risk explained by these risk factors was 26%, with muscular pain, stress, and migraine accounting for 11%, 4%, and 3% respectively. CONCLUSION: Several established risk factors in adults were also identified in adolescents. Risk factors amenable to prevention accounted for 17% of the total population risk. Therefore, interventions targeting these risk factors may be warranted.

Altered experimental pain perception after cerebellar infarction.

Animal studies have suggested that the cerebellum, in addition to its motor functions, also has a role in pain processing and modulation, possibly because of its extensive connections with the prefrontal cortex and with brainstem regions involved in descending pain control. Consistently, human imaging studies have shown cerebellar activation in response to painful stimulation. However, it is presently not clear whether cerebellar lesions affect pain perception in humans. In the present study, we used experimental pain testing to compare acute pain perception and endogenous pain inhibition in 30 patients 1 to 11 years after cerebellar infarction and in 30 sex- and age-matched healthy control subjects. Compared to controls, patients exhibited a significantly increased pain perception in response to acute heat stimuli (44 °C-48 °C, average pain intensity rating for patients 3.4±2.8 and for controls 1.5±1.7 [on a numeric rating scale of 0-10], P<.01) and to repeated 256 mN pinprick stimuli (1.3±1.9 vs. 0.6±1.0 [0-10], P<.05). Heat hyperalgesia in patients was more pronounced on the body side ipsilateral to the infarction. In addition, patients showed reduced offset analgesia (change in pain intensity rating: 0.0%±15.8% vs. -16.9%±36.3%, P<.05) and reduced placebo analgesia (change in pain intensity rating: -1.0±1.1 vs. -1.8±1.3 [0-10], P<.05) compared to controls. In contrast, heat and pressure pain thresholds were not significantly different between groups. These results show that, after cerebellar infarction, patients perceive heat and repeated mechanical stimuli as more painful than do healthy control subjects and have deficient activation of endogenous pain inhibitory mechanisms (offset and placebo analgesia). This suggests that the cerebellum has a previously underestimated role in human pain perception and modulation.

Correlation of headache frequency and psychosocial impairment in migraine: a cross-sectional study.

OBJECTIVE: To investigate if a headache frequency of 15 days per month constitutes a turning point in the psychosocial impairment associated with migraine. BACKGROUND: Migraine is differentiated into episodic and chronic forms based on a headache frequency criterion (< vs ≥15 headache days per month). It is presently not clear if this criterion represents a clinically and pathophysiologically meaningful turning point of the disease. METHODS: Six hundred and one migraine patients completed measures of pain-specific disability (Migraine Disability Assessment Scale, von Korff scale), health-related quality of life (Short Form-12 Health Survey), habitual well-being (Marburg questionnaire), and anxiety and depression (Hospital Anxiety and Depression Score). RESULTS: A significant increase of psychosocial impairment with the number of headache days per month was found at lower headache frequencies, but leveled off at higher headache frequencies. Visual inspection and spline interpolation suggested that the turning point was not exactly at 15 headache days per month but rather around 13.3 (confidence interval: 8.9-17.7) days. Accordingly, significant correlations between headache days and psychosocial impairment were found in the group with ≤13 headache days per month (Spearman's rho = 0.25, P < .001) but not in the group with >13 headache days (rho = -0.02, n.s.). CONCLUSION: These results suggest that a meaningful turning point in psychosocial impairment associated with migraine is located around 13.3 headache days per month, somewhat below the 15-headache days criterion that by definition separates chronic from episodic migraine. However, confidence intervals surrounding the turning point were large. Further studies will be needed to more exactly localize the turning point.