Abstract
Activation of the cellular immune system is discussed to be partly responsible in the neurodegenerative process of Parkinson's disease. We determined concentrations of neopterin, of cytokine ...interleukin-6, and of soluble cytokine receptors sIL-2Rα, sTNF-R75α in plasma and cerebrospinal fluid in controls and patients with vascular parkinsonism and idiopathic Parkinson's disease diagnosed according to published clinical diagnostic criteria, to examine if the cellular immune system is activated locally or peripherally or both. Our results show no activation in idiopathic Parkinson's disease and controls, but a significant increased activation in vascular parkinsonism, where concomitant signs of cerebrovascular disease are present.
Abstract Introduction Virchow-Robin spaces (VRS), or perivascular spaces, are compartments of interstitial fluid enclosing cerebral blood vessels and are potential imaging markers of various ...underlying brain pathologies. Despite a growing interest in the study of enlarged VRS, the heterogeneity in rating and quantification methods combined with small sample sizes have so far hampered advancement in the field. Methods The Uniform Neuro-Imaging of Virchow-Robin Spaces Enlargement (UNIVRSE) consortium was established with primary aims to harmonize rating and analysis ( www.uconsortium.org ). The UNIVRSE consortium brings together 13sub cohorts from five countries, totaling 16,000 subjects and over 25,000 scans. Eight different magnetic resonance imaging protocols were used in the consortium. Results VRS rating was harmonized using a validated protocol that was developed by the two founding members, with high reliability independent of scanner type, rater experience, or concomitant brain pathology. Initial analyses revealed risk factors for enlarged VRS including increased age, sex, high blood pressure, brain infarcts, and white matter lesions, but this varied by brain region. Discussion Early collaborative efforts between cohort studies with respect to data harmonization and joint analyses can advance the field of population (neuro)imaging. The UNIVRSE consortium will focus efforts on other potential correlates of enlarged VRS, including genetics, cognition, stroke, and dementia.
Abstract Background and purpose Magnetization transfer imaging detects cerebral microstructural tissue alterations. We examined the association between the Framingham Stroke Risk Profile (FSRP) score ...and magnetization transfer imaging (MTI) measures in pathological and normal appearing brain tissue in clinically normal elderly subjects to determine if stroke risk leads to brain tissue destruction beyond what is visible in conventional MRI scans. Methods The study cohort is from the Austrian Stroke Prevention Study (ASPS). A total of 316 subjects underwent MTI and had a complete risk factor assessment sufficient to calculate the FSRP score. There were 205 women and 111 men with a mean age of 70.2 years ranging from 54 to 82 years. Subjects were grouped into four categories of stroke risk probability ranging from 3% to 88% for men and 1% to 84% for women. Results A higher FSRP score was significantly and independently associated with a MTR peak position shift indicating global microstructural alterations in brain tissue (BT) and in normal appearing brain tissue (NABT). The mean MTR in white matter hyperintensities (WMH) correlated inversely with increasing stroke risk. Age explained most of the variance in MTR peak position, all other risk factors of the FSRP score contributed significantly but explained an additional 2% of the variance of this MRI measure, only. Conclusion Increasing risk for stroke leads to microstructural brain changes invisible by standard MRI. The validity, the underlying pathogenic mechanisms and the clinical importance of these abnormalities needs to be further determined.
Abstract Motor sequence learning and motor adaptation rely on overlapping circuits predominantly involving the basal ganglia and cerebellum. Given the importance of these brain regions to the ...pathophysiology of primary dystonia, and the previous finding of abnormal motor sequence learning in DYT1 gene carriers, we explored motor sequence learning and motor adaptation in patients with primary cervical dystonia. We recruited 12 patients with cervical dystonia and 11 healthy controls matched for age. Subjects used a joystick to move a cursor from a central starting point to radial targets as fast and accurately as possible. Using this device, we recorded baseline motor performance, motor sequence learning and a visuomotor adaptation task. Patients with cervical dystonia had a significantly higher peak velocity than controls. Baseline performance with random target presentation was otherwise normal. Patients and controls had similar levels of motor sequence learning and motor adaptation. Our patients had significantly higher peak velocity compared to controls, with similar movement times, implying a different performance strategy. The preservation of motor sequence learning in cervical dystonia patients contrasts with the previously observed deficit seen in patients with DYT1 gene mutations, supporting the hypothesis of differing pathophysiology in different forms of primary dystonia. Normal motor adaptation is an interesting finding. With our paradigm we did not find evidence that the previously documented cerebellar abnormalities in cervical dystonia have a behavioral correlate, and thus could be compensatory or reflect “contamination” rather than being directly pathological.
Bradykinesia—the cardinal symptom in Parkinson’s disease (PD)—affects both upper and lower limbs. While several functional imaging studies investigated the impact of levodopa on movement-related ...neural activity in Parkinson’s disease during upper limb movements, analogue studies on lower limb movements are rare. We studied 20 patients with PD (mean age 66.8 ± 7.2 years) after at least 12 h drug withdrawal (OFF-state) and a second time approximately 40 min after oral administration of 200 mg levodopa (ON-state) behaviourally and by functional magnetic resonance imaging (fMRI) at 3 T during externally cued active ankle movements of the more affected foot at fixed rate. Results were compared with that obtained in ten healthy controls (HC) to separate pure pharmacological from disease-related levodopa-induced effects and to allow for interaction analyses. Behaviourally, all patients improved by at least 20 % regarding the motor score of the Unified Parkinson’s disease rating scale after levodopa-challenge (mean scores OFF-state: 38.4 ± 10.1; ON-state: 25.5 ± 8.1). On fMRI, levodopa application elicited increased activity in subcortical structures (contralateral putamen and thalamus) in the patients. In contrast, no significant levodopa-induced activation changes were found in HC. The interaction between “PD/HC group factor” and “levodopa OFF/ON” did not show significant results. Given the levodopa-induced activation increases in the putamen and thalamus with unilateral ankle movements in patients with PD but not in HC, we speculate that these regions show the most prominent response to levodopa within the cortico-subcortical motor-circuit in the context of nigrostriatal dysfunction.
Dopamine transporter imaging is typically abnormal in Parkinson’s disease and shows reduced striatal uptake, which is typically greater contralateral to the clinically more affected side. However, ...tremor-dominant Parkinson’s disease patients may have significantly lower uptake in the striatum ipsilateral to the rest-tremor compared to akinetic-rigid PD patients, implying a possible role of an ipsilateral deficit in the generation of rest-tremor.We report here three patients with rest-tremor and the unexpected finding of an ipsilateral presynaptic dopaminergic deficit with normal uptake contralateral to the rest-tremor in dopamine transporter imaging. We divided them in two groups, with and without a corresponding structural lesion in brain imaging. These data may suggest a role of ipsilateral dopaminergic deficit in the generation of rest-tremor. An explanation of these findings could be damage of crossed dopaminergic fibres from the substantia nigra to thalamus, which can cause motor impairment ipsilateral to dopamine depletion experimentally. This is speculative but there is no doubt that these cases exist and we encourage others to report similar cases, as this may assist in the better understanding of the yet unknown pathophysiology of rest-tremor.
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