Association of exposure to manganese and fine motor skills in welders - Results from the WELDOX II study.

The aim of this study was to evaluate the effect of exposure to manganese (Mn) on fine motor functions. A total of 48 welders and 30 unexposed workers as controls completed questionnaires, underwent blood examinations, and a motor test battery. The shift exposure of welders to respirable Mn was measured with personal samplers. For all subjects accumulations of Mn in the brain were assessed with T1-weighted magnetic resonance imaging. Welders showed normal motor functions on the Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale part III. Furthermore welders performed excellent on a steadiness test, showing better results than controls. However, welders were slightly slower than controls in motor tests. There was no association between fine motor test results and the relaxation rates R1 in globus pallidus and substantia nigra as MRI-based biomarkers to quantify Mn deposition in the brain.

Hospitalization Rates and Comorbidities in Patients with Progressive Supranuclear Palsy in Germany from 2010 to 2017.

Progressive supranuclear palsy (PSP) belongs to the disease spectrum of Parkinsonian syndromes. Due to the chronic and progressive neurodegenerative course of the disease, PSP patients often have to be hospitalized to undergo diagnostic and therapeutic measures. The dynamics and characteristics of PSP inpatient treatment in Germany have not been investigated thus far. The current study analyzed trends of inpatient treatment in Germany for the years 2010-2017 based on the German DRG statistics ("diagnostic-related groups") in the category G23.- (other degenerative diseases of the basal ganglia) and with special focus on PSP (G23.1). Inpatient case numbers of the G23.- category comprised a total of 21,196 patients from 2010-2017, whereas the PSP subcategory (G23.1) amounted to 10,663 cases. In the analyzed time period, PSP patient numbers constantly increased from 963 in 2010 to 1780 in 2017 with yearly growth rates of up to 20%. Similar trends were observed for other Parkinsonian syndromes such as multiple system atrophy (MSA). Differentiating PSP inpatients by gender demonstrated a higher proportion of males (55-60%) in comparison to female patients for the entire observation period. The average age of hospitalized PSP patients over these years was between 72.3 and 73.4 years without relevant differences for gender. The most common comorbidities consisted of cardiovascular, neurological, muscular and urological disorders. In summary, the analysis demonstrates that PSP patients are increasingly hospitalized in Germany and the current concepts of stationary care have to differentiate standard practices for Parkinson's disease (PD) to also address the needs of patients with PSP and other Parkinsonian syndromes.

Novel Immunotherapeutic Approaches to Target Alpha-Synuclein and Related Neuroinflammation in Parkinson's Disease.

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.

Impairment of Motor Function Correlates with Neurometabolite and Brain Iron Alterations in Parkinson's Disease.

We took advantage of magnetic resonance imaging (MRI) and spectroscopy (MRS) as non-invasive methods to quantify brain iron and neurometabolites, which were analyzed along with other predictors of motor dysfunction in Parkinson's disease (PD). Tapping hits, tremor amplitude, and the scores derived from part III of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS3 scores) were determined in 35 male PD patients and 35 controls. The iron-sensitive MRI relaxation rate R2* was measured in the globus pallidus and substantia nigra. γ-aminobutyric acid (GABA)-edited and short echo-time MRS was used for the quantification of neurometabolites in the striatum and thalamus. Associations of R2*, neurometabolites, and other factors with motor function were estimated with Spearman correlations and mixed regression models to account for repeated measurements (hands, hemispheres). In PD patients, R2* and striatal GABA correlated with MDS-UPDRS3 scores if not adjusted for age. Patients with akinetic-rigid PD subtype (N = 19) presented with lower creatine and striatal glutamate and glutamine (Glx) but elevated thalamic GABA compared to controls or mixed PD subtype. In PD patients, Glx correlated with an impaired dexterity when adjusted for covariates. Elevated myo-inositol was associated with more tapping hits and lower MDS-UPDRS3 scores. Our neuroimaging study provides evidence that motor dysfunction in PD correlates with alterations in brain iron and neurometabolites.

Landscape of pain in Parkinson's disease: impact of gender differences.

Background/Aims: Pain is a non-motor symptom of Parkinson's disease (PD). Few systematic studies have been carried out and there are still no guidelines on pain therapy in PD. Additionally, within the studies that do exist, gender-specific differences in pain perception are often the focus, though no consistent results have to date been obtained. The first main aim of our study was therefore to map pain in the largest PD study group to date, with the second being the analysis of the impact of different pain therapies in PD. The third and main aim was to correlate the obtained results with gender. Methods: A structured questionnaire with questions focusing on pain was sent to PD patients, with a subsequent statistical analysis correlating the data on pain features and pain therapy with gender. Results: The study included 1204 female and 1610 male PD patients. Spinal-paravertebral pain emerged as the dominant form of pain. A significant correlation was further demonstrated between gender and pain localization, pain intensity (p-value < 0.05), and pain as impairment to quality of life (p-value < 0.05). Nonsteroidal anti-inflammatory drugs were the painkillers most frequently used by the patients. Aside from non-opioid analgesics (p-value < 0.05), there was no demonstrated significant correlation between pain treatments and gender. Conclusion: This study found that gender influenced pain perception in the PD patients tested but did not impact the approach to pain therapy.

Supplementary Tests in Idiopathic Normal Pressure Hydrocephalus: A Single-Center Experience with a Combined Lumbar Infusion Test and Tap Test.

BACKGROUND: The lumbar infusion test (LIT) and tap test (TT) have previously been described for the diagnosis and selection of appropriate surgical candidates in idiopathic normal pressure hydrocephalus (iNPH). METHODS: We retrospectively reviewed 81 consecutive patients with a clinical diagnosis of iNPH selected for supplementary testing. Clinical evaluation was scored with the Japanese Grading Scale for Normal Pressure Hydrocephalus, the Global Deterioration Score, and the modified Rankin Scale (mRS). The test protocol included a cerebrospinal fluid pressure monitoring (PMi), an LIT, and a TT. Patients were selected for surgery if outflow resistance was ≥14 mm Hg/mL/minute or if a clinical improvement was recorded after TT. RESULTS: Sixty-eight patients were selected for ventriculoperitoneal shunting; 72.8% had a positive PMi or LIT, 74.1% had a positive TT, and 63.0% were positive to both tests. Complications were all transient. Clinical evaluation at 12 months after shunting showed a global improvement in 60 patients (88.2%). Overall, 75.0% of patients had no significant disability (mRS score, 1 and 2), 20.6% had an mRS score of 3 or 4, and 4.4% had severe disability after surgery. The positive predictive value of PMi/LIT, TT, or both combined was similar (89.8, 90.0, and 88.2%); however, 21.7% of patients who improved after surgery were selected with either a positive LIT or TT alone. CONCLUSIONS: LIT and TT are complementary and they can easily be combined in sequence with a low complication rate and high probability of selecting patients with iNPH who may benefit from ventriculoperitoneal shunt surgery.