Gregor K Wenning

..Here we present the final analysis of a prospective multicentre study by the European MSA Study Group to investigate the natural history of MSA...

..Differences in brainstem pathology are likely to account for the tight association of MSA-C and OH. A simple standing test should be obligatory in the work-up of patients with sporadic late-onset ataxias...

..An outline of the rationale for managing symptomatic deterioration in MSA is provided together with a summary of novel experimental therapeutic approaches to decrease disease progression...

..Early-investigation-assisted clinical diagnosis has become more crucial than ever because disease-modifying therapies will hopefully become available within this decade...

..Although these syndromes vary in their respective cause of oligodendrogliopathy, they have in common myelin disruption that is often followed by axonal dysfunction...

..Based on literature published in 2010, we here review recent advances in the APD field...

..We suggest that the quantification of midbrain DAT signal should be included in the routine clinical analysis of [123I]beta-CIT SPECT in patients with uncertain parkinsonism...

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..We observed a volume loss shared by both disorders comprising the cerebellum, vermis, pons, mesencephalon, orbitofrontal, mid-frontal, and temporomesial cortex of both hemispheres as well as the left insular cortex...

..Therefore, striatal transplantation should be further defined preclinically as a possible therapeutic option for patients with MSA-P and a failing L-Dopa response...

..Diffusion-weighted imaging appears to be a promising surrogate marker for disease severity in HD. Sensitivity to change remains to be established longitudinally...

..9 (+/-7.0) months earlier than with the Consensus criteria alone. We propose a combination of two out of six red flag categories as additional diagnostic criteria for probable MSA-P...

..5 mg/kg rasagiline. The results of the study indicate that rasagiline confers neuroprotection in a transgenic mouse model of MSA and may therefore be considered a promising disease-modifying candidate for human MSA...

..To this end, nine patients were studied with [(123)I]beta-CIT SPECT...

..7 years). The majority (n = 17, 61%) who scored positive for RLS reported that the urge to move the legs and unpleasant sensations were associated with wearing off, raising the possibility of RLS mimics in fluctuating patients with PD...

..SPECT-MRI-based estimation of regional [123I]IBZM uptake provides a cost effective and widely available in vivo imaging technique for assessing striatal integrity in animal studies...

..593; P = 0.01) in the stepping test. These findings contribute further to the behavioral characterization of the double lesion rat model of MSA, improving its value in the evaluation of future neurorestorative strategies...

..This effect is associated with improved motor function. Further studies are warranted to develop erythropoietin as a potential interventional therapy in multiple system atrophy...

..In summary, we have established the behavioral deficit profile of a partial double-lesion rat model mimicking the early stage of MSA-P...

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..6% vs. 100%, specificity 88.8% vs. 100%, and area under the curve 0.802 vs. 1.000. Our data suggest that DWI is superior to both tilt table testing and MIBG scintigraphy in the differential diagnosis of PD versus MSA-P...

..In the present study, the intrarater agreement of the motor examination part of the UMSARS was determined...

..Our data contribute to the ongoing validation process of UMSARS, and they facilitate the planning and implementation of future neuroprotective intervention trials...

..Our results indicate that combined mitochondrial inhibition and overexpression of oligodendroglial alpha-SYN generates a novel model of MSA that may be useful for evaluating both pathogenesis and treatment strategies...

..Whether DWI can be used as a marker to identify individuals at risk to develop this disease remains to be shown...

..Most previous SPECT studies have adopted region-of-interest methods for analysis, which are subjective and operator dependent...

..Our study demonstrates prominent involvement of the posterior putamen in early disease stages of MSA-P in vivo by assessing putaminal diffusivity with the help of DWI...

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..We review the present state of the best practice in the clinical diagnosis of DLB. Future modifications of diagnostic criteria would ideally include the full range of clinical presentations that can be associated with LB disease...

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..To assess and compare biochemical and volumetric features of the cerebellum in patients with spinocerebellar ataxia type 2 (SCA2) and patients with the cerebellar variant of multiple system atrophy (MSA-C)...

..Our data suggest that the presence of MSA-like alpha-synuclein oligodendrogliopathy and related to it pro-inflammatory microenvironment may compromise the connectivity and neurorestorative outcome of striatal grafts...

..e. early stage disease with limited striatal dysfunction...

..This is the first study using VBM in patients with different types of primary dystonia, showing a common pattern of gray matter changes...

..None of the patients had REM sleep behaviour disorder. Only one patient had mild REM sleep without atonia. CONCLUSIONS: Our pilot study suggests only minor sleep abnormalities in SCA6...

..The UPDRS-III score was not significantly correlated with any brain region. Our data suggest that cortical atrophy is prominent in MSA-P and early degeneration of the basal ganglia drives late onset cortical atrophy...

..With this simplified system, we have demonstrated that alpha-synuclein significantly affects the survival of glia and its vulnerability to environmental stress, which might represent a major step in the pathogenesis of MSA...

..The observed differences in diagnostic and therapeutic management including lack of therapy for dysautonomia emphasize the need for future guidelines in these areas...

..These findings suggest greater potential of levodopa to induce sleepiness in MSA compared with PD, which may be related to differences in basal ganglia and brainstem pathology between the two disorders...

..We suggest that these abnormalities reflect the motor cortex pathology found in MSA-P...

..Furthermore, motor progression appeared to be accelerated during the early disease stages.Our data allow sample size calculations that may be helpful for the planning of future therapeutic trials...

..In summary, we provide new evidence supporting a primary role of proteolytic failure and suggesting a neurodegenerative pathomechanism related to disturbed oligodendroglial/myelin trophic support in the pathogenesis of MSA...

..Whether FoG and urinary incontinence share similar neuropathological substrates remains to be determined by future studies...

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..These findings might correspond to an increased risk of ET patients to develop PD. Long-term follow-up will show if those with hyperechogenic SN develop PD, while these without will not...

..Further studies are required to determine clinical and/or subclinical correlates of cortical atrophy in MSA-P...

..A fifth of all movement disorders were diagnosed to be probably drug-induced. INTERPRETATION: There is a high prevalence of and substantial under-recognition and under-treatment of movement disorders in the general community...

..Based on our findings, the UMSARS appears to be a multidimensional, reliable, and valid scale for semiquantitative clinical assessments of MSA patients...

..The study supports TLR4 signaling as innate neuroprotective mechanism acting through clearance of α-synuclein...

..Striatal rADCs had a significant higher overall predictive accuracy than D2R binding with IBZM. In summary, our data suggest that DWI may be more accurate compared to IBZM-SPECT in the differential diagnosis of MSA-P versus PD...

..Abnormal motor control during sleep with periodic leg movements and REM sleep without atonia occurs frequently in SCA2. This finding may reflect a dysfunction of dopaminergic and/or brainstem and cerebellar outflow pathways...

..We conclude that despite its astrocytic and microglial suppression, minocycline failed to attenuate lesion-induced neuronal damage in the SND rat model...

..Because no drug treatment consistently benefits patients with this disease in the long-term, palliative therapies are all the more important. Novel symptomatic and neuroprotective therapies are urgently required...

..Our data provide novel insights into the mechanisms of α-synuclein-induced microglial and astroglial activation which may have an impact on understanding the pathogenesis of ASP...

..Reduced ASR probability and magnitude as well as prolonged EMG activity after the proper startle response corroborate and extend previous findings on brainstem dysfunction in CD...

..This study suggests that MPO inhibition may represent a novel candidate treatment strategy against MSA-like neurodegeneration acting through its anti-inflammatory and anti-oxidative properties...

..Both slowness of limb movements as well as dystonia in the ataxic SCA2 phenotype may reflect dysfunction not only at cerebellar but also at basal ganglia level...

..In this study we investigated the efficacy of intravenously applied MSCs in terms of behavioural improvement, neuroprotection and modulation of neuroinflammation in the (PLP)-αsynuclein (αSYN) MSA model...

..Here, the currently available MSA animal models will be reviewed and leads for future research will be identified...

..Follow-up studies are needed to determine whether iRBD patients with dysfunction on several autonomic domains are at particular risk for developing one of these diseases...

..Several research groups have been formed in Europe (EMSA-SG, NNIPPS) and United States (NAMSA-SG), providing a framework for coordinated trial activity in MSA...

..The article reviews the current state of the art focusing on three atypical parkinsonian disorders: multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and dementia with Lewy bodies (DLB)...

..Finally, major therapeutic strategies targeting glial pathology in α-synucleinopathies as well as current pitfalls for disease-modification in clinical trials are discussed...

..Transgenic MSA mouse models are now available to determine these aspects of cellular disturbance experimentally...

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..In this review, we discuss the emerging evidence in favor of genetic players in MSA...

..CCD patients are subject to serious prejudice and enacted stigmatization. There is a need for informing the public about the nature and symptoms of this disorder and a need to support patients to cope with stigmatization...

..Atrophy of insular cortex was found in both patient groups...

..At 4-week follow-up, none of the patients showed improvement of dystonia, mild side-effects were observed in 3 patients...

..These results highlight the need for further prospective studies of the prevalence and underlying mechanisms of cardiac valvulopathy in PD patients treated with different dopamine agonists...

..These findings lend further support to nigral iron deficiency as a pathogenetic factor in RLS...

..We conclude that alpha-synuclein overexpression significantly increases the vulnerability of U373 cells to apoptosis through TNF-alpha-mediated pathways...

..HCY is a neuronal excitotoxic amino acid and hyperhomocysteinemia is considered an independent vascular risk factor. Further studies are required to define the background of hyperhomocysteinemia in primary dystonia...

..This suggests that complex integrative mechanisms are likely to regulate the vulnerability of the striatum and SNc to cell death in SND/MSA-P...

..Finally, some cellular mechanisms are discussed in this paper because they are essential for future neuroprotective modalities, such as minocycline, unsaturated fatty acids or riluzole...

..Reports on the open-label use of amantadine in MSA suggest variable antiparkinsonian efficacy. The authors therefore conducted a double-blind, placebo-controlled crossover trial of amantadine in MSA patients...

..Symptomatic therapeutic strategies are still limited; however, several candidate neuroprotective agents have entered phase II and phase III clinical trials...

..Two mechanisms could contribute to the observed cortical atrophy. It could be either the result of primary supratentorial degeneration as part of the disease process and/or secondary atrophy due to cerebellar deafferentation...

..Because rADCs in one direction are dependent on the slice orientation relative to the directions of fiber tracts, Trace(D) imaging appears to be more accurate in the separation of MSA-P from PD...

..There remains no conclusive evidence to support the notion of hereditary MSA...

..In this group, the allelic variation on locus S18Y is responsible for 1.1% of the variance in the HD age-at-onset, and the rare Y allele is associated with younger-aged cases...

..The ICARS appears a useful tool to extract and rate the severity of cerebellar signs in MSA; however, it is clearly contaminated by parkinsonian features...

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..In each of these areas, diagnosis continues to rest on clinical findings and the judicious use of ancillary studies...

..Although some of the factors have been defined as genetic modifier factors in previous studies, none of the genes encoding GRIK2, TBP, BDNF and ZDHHC17 could be identified as a genetic modifier for HD...

..49, 95% CI 0.97-2.31, P = 0.07). Except for rediagnosis as PD, no predictive factors for better survival could be identified. These data confirm the relatively poor prognosis of MSA of less than 9 years on average...

..Our review suggests that the label "OPCA" is useful to designate a clinicopathological syndrome that has a variety of etiologies carrying a poor prognosis, particularly if associated with autonomic failure as occurs in MSA...

..It also indicates that the UPDRS-III provides a useful severity measure of parkinsonism in MSA, albeit contaminated by additional cerebellar dysfunction...