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Parkinson&rsquo, s disease Multimodal Complex Treatment (PD-MCT) is a multidisciplinary inpatient treatment approach that has been demonstrated to improve motor function and quality of life in patients with Parkinson&rsquo, s disease (PD). In this study, we assessed the efficacy of PD-MCT and calculated predictors for improvement. We performed a prospective analysis in a non-randomized, open-label observational patient cohort. Study examinations were done at baseline (BL), at discharge after two-weeks of inpatient treatment (DC) and at a six-week follow-up examination (FU). Besides Movement Disorders Society Unified Parkinson&rsquo, s Disease Rating Scale (MDS-UPDRS) III as a primary outcome, motor performance was measured by the Timed Up-and-Go (TUG), the Berg Balance Scale (BBS) and the Perdue Pegboard Test (PPT). Until DC, motor performance improved significantly in several parameters and was largely maintained until FU (MDS-UPDRS III BL-to-DC: &minus, 4.7 &plusmn, 1.2 (SE) p = 0.0012, BL-to-FU: &minus, 6.1 &plusmn, 1.3 p = 0.0001, TUG BL-to-DC: &minus, 2.5 &plusmn, 0.9 p = 0.015, BL-to-FU: 2.4 &plusmn, 0.9 p = 0.027, BBS BL-to-DC: 2.4 &plusmn, 0.7 p = 0.003, BL-to-FU: 1.3 &plusmn, 0.7 p = 0.176, PPT BL-to-DC: 3.0 &plusmn, 0.5 p = 0.000004, BL-to-FU: 1.7 &plusmn, 0.7 p = 0.059). Overall, nontremor items were more therapy responsive than tremor items. Motor complications evaluated with MDS-UPDRS IV occurred significantly less frequent at DC (&minus, 1.8 &plusmn, 0.5 p = 0.002). Predictor analyses revealed an influence of initial motor impairment and disease severity on the treatment response in different motor aspects. In summary, we demonstrate a significant positive treatment effect of PD-MCT on motor function of PD patients which can be maintained in several parameters for an extended time period of six weeks and identify predictors for an improvement of motor function.

Objective Magnetic resonance spectroscopy (MRS) is a non-invasive method to quantify neurometabolite concentrations in the brain. Within the framework of the WELDOX II study, we investigated the association of exposure to manganese (Mn) and iron (Fe) with γ-aminobutyric acid (GABA) and other neurometabolites in the striatum and thalamus of 154 men. Material and methods GABA-edited and short echo-time MRS at 3T was used to assess brain levels of GABA, glutamate, total creatine (tCr) and other neurometabolites. Volumes of interest (VOIs) were placed into the striatum and thalamus of both hemispheres of 47 active welders, 20 former welders, 36 men with Parkinson’s disease (PD), 12 men with hemochromatosis (HC), and 39 male controls. Linear mixed models were used to estimate the influence of Mn and Fe exposure on neurometabolites while simultaneously adjusting for cerebrospinal fluid (CSF) content, age and other factors. Exposure to Mn and Fe was assessed by study group, blood concentrations, relaxation rates R1 and R2* in the globus pallidus (GP), and airborne exposure (active welders only). Results The median shift exposure to respirable Mn and Fe in active welders was 23 μg/m3 and 110 μg/m3, respectively. Airborne exposure was not associated with any other neurometabolite concentration. Mn in blood and serum ferritin were highest in active and former welders. GABA concentrations were not associated with any measure of exposure to Mn or Fe. In comparison to controls, tCr in these VOIs was lower in welders and patients with PD or HC. Serum concentrations of ferritin and Fe were associated with N-acetylaspartate, but in opposed directions. Higher R1 values in the GP correlated with lower neurometabolite concentrations, in particular tCr (exp(β) = 0.87, p Conclusions Our results do not provide evidence that striatal and thalamic GABA differ between Mn-exposed workers, PD or HC patients, and controls. This may be due to the low exposure levels of the Mn-exposed workers and the challenges to detect small changes in GABA. Whereas Mn in blood was not associated with any neurometabolite content in these VOIs, a higher metal accumulation in the GP assessed with R1 correlated with generally lower neurometabolite concentrations.

The etiology of Parkinson’s disease (PD) is significantly influenced by disease-causing changes in the protein alpha-Synuclein (aSyn). It can trigger and promote intracellular stress and thereby impair the function of dopaminergic neurons. However, these damage mechanisms do not only extend to neuronal cells, but also affect most glial cell populations, such as astroglia and microglia, but also T lymphocytes, which can no longer maintain the homeostatic CNS milieu because they produce neuroinflammatory responses to aSyn pathology. Through precise neuropathological examination, molecular characterization of biomaterials, and the use of PET technology, it has been clearly demonstrated that neuroinflammation is involved in human PD. In this review, we provide an in-depth overview of the pathomechanisms that aSyn elicits in models of disease and focus on the affected glial cell and lymphocyte populations and their interaction with pathogenic aSyn species. The interplay between aSyn and glial cells is analyzed both in the basic research setting and in the context of human neuropathology. Ultimately, a strong rationale builds up to therapeutically reduce the burden of pathological aSyn in the CNS. The current antibody-based approaches to lower the amount of aSyn and thereby alleviate neuroinflammatory responses is finally discussed as novel therapeutic strategies for PD.

Objective Magnetic resonance imaging is a non-invasive method that allows the indirect quantification of manganese (Mn) and iron (Fe) accumulation in the brain due to their paramagnetic features. The WELDOX II study aimed to explore the influence of airborne and systemic exposure to Mn and Fe on the brain deposition using the relaxation rates R1 and R2* as biomarkers of metal accumulation in regions of interest in 161 men, including active and former welders. Material and methods We obtained data on the relaxation rates R1 and R2* in regions that included structures within the globus pallidus (GP), substantia nigra (SN), and white matter of the frontal lobe (FL) of both hemispheres, as well as Mn in whole blood (MnB), and serum ferritin (SF). The study subjects, all male, included 48 active and 20 former welders, 41 patients with Parkinson's disease (PD), 13 patients with hemochromatosis (HC), and 39 controls. Respirable Mn and Fe were measured during a working shift for welders. Mixed regression models were applied to estimate the effects of MnB and SF on R1 and R2*. Furthermore, we estimated the influence of airborne Mn and Fe on the relaxation rates in active welders. Results MnB and SF were significant predictors of R1 but not of R2* in the GP, and were marginally associated with R1 in the SN (SF) and FL (MnB). Being a welder or suffering from PD or HC elicited no additional group effect on R1 or R2* beyond the effects of MnB and SF. In active welders, shift concentrations of respirable Mn > 100 μg/m3 were associated with stronger R1 signals in the GP. In addition to the effects of MnB and SF, the welding technique had no further influence on R1. Conclusions MnB and SF were significant predictors of R1 but not of R2*, indicative of metal accumulation, especially in the GP. Also, high airborne Mn concentration was associated with higher R1 signals in this brain region. The negative results obtained for being a welder or for the techniques with higher exposure to ultrafine particles when the blood-borne concentration was included into the models indicate that airborne exposure to Mn may act mainly through MnB.

Application of oral fast release amantadine and levodopa may induce an improvement of motor symptoms in patients with Parkinson’s disease (PD). The objective of this trial was to investigate the clinical efficacy of a fast release amantadine sulfate formulation on simple and complex movement performance and putative relations to the pharmacokinetic behavior in PD patients. We challenged two cohorts of 12 PD patients, who were taken off their regular antiparkinsonian treatment for at least 12 hours, with oral 300 mg amantadine sulfate. We scored motor symptoms and performed instrumental tasks, which ask for performance of simple or complex motion series under cued conditions. Motor symptoms and performance of complex movements significantly improved in contrast to the carrying-out of simple motions. N-methyl-D-aspartic acid antagonistic and dopaminomimetic amantadine also influences altered higher predominant prefrontal cognitive functions. Therefore, performance of complex motion series improved, whereas carrying-out of simple repetitive movements is more associated to the striatal dopamine dependent basal ganglia function.

Background Following cued levodopa (LD) intake, endurance exercise showed a beneficial effect on scored motor performance in patients with Parkinson9s disease (PD) in comparison with rest. This may result from an exercise induced increase in endogenous dopamine synthesis. As a result, beneficial effects on movement and reactivity may occur. Objectives To measure reactivity and motor performance in a repeated fashion with instrumental tasks after cued administration of soluble 200 mg of LD/50 mg of benserazide. Design PD patients consecutively performed paradigms, which assess reactivity and movement performance, after a standardised period of rest or of age-related, heart rate adapted endurance exercise on two consecutive days in a random order. Results Reactivity and execution of simple and complex motion series were significantly better following exercise than after rest. Discussion Endurance exercise has a beneficial effect on reactivity and movement behaviour in PD patients following cued application of LD probably due to an augmented synthesis and release of dopamine and other catecholamines and release in the prefrontal cortex, the nucleus accumbens and the basal ganglia. Small changes in catecholamine modulation of prefrontal cortex cells can have profound effects on the ability of the prefrontal cortex to guide behaviour. Previous exercise may also improve pedunculopontine nucleus function, which is involved in motor-related attention processes.