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The phenotype Hp 2-1 of haptoglobin has been previously associated with increased risk of Parkinson disease (PD) and with serum iron abnormalities in PD patients. Tobacco smoking has been consistently observed in epidemiology studies to be inversely related to PD risk, with mechanisms that remain uncertain. We recently observed that the protective effect of smoking on PD risk is stronger among subjects of haptoglobin Hp 2-2 and Hp 1-1 phenotypes, and weaker among subjects of haptoglobin Hp 2-1 phenotype. In this PD case-control study, we investigated whether tobacco smoking was associated with changes in serum haptoglobin and ferritin concentration that depended on haptoglobin phenotype among 106 PD patients and 238 controls without PD or other neurodegenerative disorders. Serum ferritin concentration, serum haptoglobin concentration, haptoglobin phenotype, and smoking data information of cases and controls were obtained. Differences in haptoglobin and ferritin concentration by smoking status and pack-years of smoking were calculated as well as regression between pack-years and haptoglobin and ferritin concentration, and the effect of haptoglobin phenotype on these parameters. Tobacco smoking was associated with an elevation in serum haptoglobin concentration, especially among healthy controls of haptoglobin Hp 2-2 phenotype, and with an elevation in ferritin concentration especially among PD patients of haptoglobin Hp 2-1 phenotype. These findings suggest that an elevation in haptoglobin concentration, preferentially among subjects of haptoglobin Hp 2-2 phenotype, could be a contributing factor to the protective effect of smoking on PD risk. [ABSTRACT FROM AUTHOR]

Extracellular α-synuclein is important in the pathogenesis of Parkinson's disease (PD) and also as a potential biomarker when tested in the cerebrospinal fluid (CSF). The performance of blood plasma or serum α-synuclein as a biomarker has been found to be inconsistent and generally ineffective, largely due to the contribution of peripherally derived α-synuclein. In this study, we discovered, via an intracerebroventricular injection of radiolabeled α-synuclein into mouse brain, that CSF α-synuclein was readily transported to blood, with a small portion being contained in exosomes that are relatively specific to the central nervous system (CNS). Consequently, we developed a technique to evaluate the levels of α-synuclein in these exosomes in individual plasma samples. When applied to a large cohort of clinical samples (267 PD, 215 controls), we found that in contrast to CSF α-synuclein concentrations, which are consistently reported to be lower in PD patients compared to controls, the levels of plasma exosomal α-synuclein were substantially higher in PD patients, suggesting an increased efflux of the protein to the peripheral blood of these patients. Furthermore, although no association was observed between plasma exosomal and CSF α-synuclein, a significant correlation between plasma exosomal α-synuclein and disease severity ( r = 0.176, p = 0.004) was observed, and the diagnostic sensitivity and specificity achieved by plasma exosomal α-synuclein were comparable to those determined by CSF α-synuclein. Further studies are clearly needed to elucidate the mechanism involved in the transport of CNS α-synuclein to the periphery, which may lead to a more convenient and robust assessment of PD clinically. [ABSTRACT FROM AUTHOR]

Movement disorder emergencies occur in both hypokinetic and hyperkinetic patients. Prompt recognition of these emergencies is crucial, and diagnosis is based on history and phenomenology. Supportive and temporizing measures must be implemented immediately before disease-specific therapy is begun. For neuroleptic malignant syndrome and related conditions, we recommend a three-tier approach depending on severity, starting with benzodiazepines, dopamine agonists or levodopa, and dantrolene or electroconvulsive therapy. Methylprednisolone pulse therapy also is beneficial for neuroleptic malignant syndrome due to abrupt medication withdrawal in patients with Parkinson’s disease. In treatment of other acute antidopaminergic-induced emergencies, anticholinergics usually suffice. To manage airway obstruction related to movement disorders, we rely on laryngoscopic evaluation to determine whether noninvasive or invasive interventions are needed. Hyperkinetic emergencies are treated individually based on the type of abnormal movements. If an antidopaminergic is needed, we prefer a dopamine depletor to a dopamine receptor blocker because of the risk of tardive syndromes with the latter. When focal hyperkinetic movements dominate the picture, botulinum toxin injection is a useful adjunct to medications. [ABSTRACT FROM AUTHOR]