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Background Several studies have reported an increased risk for patients with essential tremor to develop Parkinson's disease. In addition, hyperechogenicity in the area of the substantia nigra has been associated with a markedly increased risk for Parkinson's disease. The objective of this study was to evaluate the validity of substantia nigra hyperechogenicity in patients with essential tremor as a risk marker for Parkinson's disease. Methods Transcranial sonography was performed in 70 patients suffering from essential tremor. Fifty-four of these patients were available for follow-up after a mean of 6.16 ± 2.05 years and were assessed for the incidence of new-onset Parkinson's disease. Results The relative risk for developing Parkinson's disease in patients with essential tremor who had hyperechogenicity at baseline versus those without this hyperechogenicity was 7.00 (95% confidence interval, 1.62–30.34; sensitivity, 77.8%; specificity, 75.6%). Conclusions Substantia nigra hyperechogenicity is also associated with an increased risk for Parkinson's disease in patients with essential tremor. These findings further support the potential role of this echofeature as a risk marker for Parkinson's disease. © 2016 Movement Disorder Society

Background and Methods To investigate the possible efficacy of an elastic abdominal binder to control orthostatic hypotension (OH) associated with Parkinson's disease (PD), 15 patients with PD and OH were enrolled in a single-blind crossover study with elastic abdominal versus placebo binder on two different days, separated by a 1-day interval, followed by a 4-week open-label follow-up. Results Intervention significantly reduced blood pressure fall upon tilting. The mean difference (standard deviation; 95% confidence intervals) between abdominal binder versus placebo was +10 mm Hg (10.2; +3.5, +16.5; P = 0.006). No significant effect on supine mean blood pressure values was observed compared to placebo (P = 0.3). Symptoms of OH decreased significantly during follow-up (P = 0.003), as assessed by means of the Orthostatic Hypotension Questionnaire. Conclusions Our findings suggest that elastic abdominal binders may be a simple complementary tool to alleviate OH in PD.

Menstrual-cycle–related aggravations of parkinsonism resulting from a transient loss of dopaminergic responsiveness in premenopausal women have occasionally been reported in Parkinson’s disease (PD). Thus far, underlying mechanisms remain unclear and treatment options are not well established. We present 2 cases of premenopausal sisters with early-onset PD and severe menstrual-cycle–related reduced responsiveness to medication. A 45-year-old woman diagnosed with early-onset PD at the age of 34 presented with akinetic-rigid right-sided parkinsonism. Initially, she was treated with pramipexole 0.35 mg three times daily (TID), which was increased in the first 4 years to 0.7 mg once-daily (QID) and later switched to ropinirole 5 mg QID. During the switch, the patient felt optimally controlled when she was on pramipexole 0.7 mg twice-daily (BID) and ropinirole 5 mg BID and subsequently refused to complete the switch to ropinirole monotherapy. Over the following 2 years on double-agonist therapy, the patient began to notice mild wearing-off fluctuations approximately 3 hours after each dose. Total daily OFF-time was

Importance We observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and α-synuclein, but not β-amyloid 1-42 (Aβ1-42), and lower concentration of CSF biomarkers, as compared with healthy controls, in a cohort of entirely untreated patients with Parkinson disease (PD) at the earliest stage of the disease studied so far. Objective To evaluate the baseline characteristics and relationship to clinical features of CSF biomarkers (Aβ1-42, total tau [T-tau], tau phosphorylated at threonine 181 [P-tau 181 ], and α-synuclein) in drug-naive patients with early PD and demographically matched healthy controls enrolled in the Parkinson’s Progression Markers Initiative (PPMI) study. Design, Setting, and Participants Cross-sectional study of the initial 102 research volunteers (63 patients with PD and 39 healthy controls) of the PPMI cohort. Main Outcomes and Measures The CSF biomarkers were measured by INNO-BIA AlzBio3 immunoassay (Aβ1-42, T-tau, and P-tau 181 ; Innogenetics Inc) or by enzyme-linked immunosorbent assay (α-synuclein). Clinical features including diagnosis, demographic characteristics, motor, neuropsychiatric, and cognitive assessments, and DaTscan were systematically assessed according to the PPMI study protocol. Results Slightly, but significantly, lower levels of Aβ1-42, T-tau, P-tau 181 , α-synuclein, and T-tau/Aβ1-42 were seen in subjects with PD compared with healthy controls but with a marked overlap between groups. Using multivariate regression analysis, we found that lower Aβ1-42 and P-tau 181 levels were associated with PD diagnosis and that decreased CSF T-tau and α-synuclein were associated with increased motor severity. Notably, when we classified patients with PD by their motor phenotypes, lower CSF Aβ1-42 and P-tau 181 concentrations were associated with the postural instability–gait disturbance–dominant phenotype but not with the tremor-dominant or intermediate phenotype. Finally, we found a significant correlation of the levels of α-synuclein with the levels of T-tau and P-tau 181 . Conclusions and Relevance In this first report of CSF biomarkers in PPMI study subjects, we found that measures of CSF Aβ1-42, T-tau, P-tau 181 , and α-synuclein have prognostic and diagnostic potential in early-stage PD. Further investigations using the entire PPMI cohort will test the predictive performance of CSF biomarkers for PD progression.

Parkinson's disease (PD) is the second most common neurodegenerative disorder that affects approximately 1 % of people over the age of 60 years. Accurate diagnosis and individualized assessment of the risks and benefits of available antiparkinsonian medications as well as specific clinical features and the phase of disease should guide treatment for patients with PD. Levodopa still remains the gold standard for the treatment of motor symptoms of PD but dopamine agonists (DAs), catechol-O-methyltransferase (COMT) inhibitors and monoamine oxidase B (MAO-B) inhibitors have also been developed to provide more continuous oral delivery of dopaminergic stimulation in order to improve motor outcomes and decrease the risk of levodopa-induced motor complications. Deep-brain stimulation as well as other invasive therapies can be used for the treatment of drug-refractory levodopa-induced motor complications. Despite all of the therapeutic advances achieved within the last 20 years, PD continues to be a progressive disorder leading to severe disability caused by motor and non-motor symptoms. To date, neuroprotective interventions able to modify PD progression are not available. This review focuses on medical and invasive treatment strategies for early and advanced stages of PD as well as on the treatment of PD non-motor symptoms such as mood and behavioural disorders, cognitive and autonomic dysfunction, and sleep disorders, which can antedate PD motor symptoms for years.

Background Microarray technology may offer a new opportunity to gain insight into disease-specific global protein expression profiles. The present study was performed to apply a serum antibody microarray to screen for differentially regulated cytokines in Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Results Serum samples were obtained from patients with clinical diagnoses of PD (n = 117), MSA (n = 31) and PSP/CBS (n = 38) and 99 controls. Cytokine profiles of sera from patients and controls were analyzed with a semiquantitative human antibody array for 174 cytokines and the expression of 12 cytokines was found to be significantly altered. In a next step, results from the microarray experiment were individually validated by different immunoassays. Immunoassay validation confirmed a significant increase of median PDGF-BB levels in patients with PSP/CBS, MSA and PD and a decrease of median prolactin levels in PD. However, neither PDGF-BB nor prolactin were specific biomarkers to discriminate PSP/CBS, MSA, PD and controls. Conclusions In our unbiased cytokine array based screening approach and validation by a different immunoassay only two of 174 cytokines were significantly altered between patients and controls.

The Parkinson Progression Marker Initiative (PPMI) is a comprehensive observational, international, multi-center study designed to identify PD progression biomarkers both to improve understanding of disease etiology and course and to provide crucial tools to enhance the likelihood of success of PD modifying therapeutic trials. The PPMI cohort will comprise 400 recently diagnosed PD and 200 healthy subjects followed longitudinally for clinical, imaging and biospecimen biomarker assessment using standardized data acquisition protocols at twenty-one clinical sites. All study data will be integrated in the PPMI study database and will be rapidly and publically available through the PPMI web site- www.ppmi-info.org. Biological samples including longitudinal collection of blood, cerebrospinal fluid (CSF) and urine will be available to scientists by application to an independent PPMI biospecimen review committee also through the PPMI web site. PPMI will rely on a partnership of government, PD foundations, industry and academics working cooperatively. This approach is crucial to enhance the potential for success of this ambitious strategy to develop PD progression biomarkers that will accelerate research in disease modifying therapeutics.

The efficacy of deep brain stimulation (DBS) to treat medically intractable motor complications in advanced Parkinson’s disease (PD) has been established in multiple randomized controlled long-term trials of 6 months duration or longer. These have revealed consistent findings of markedly reduced motor complications and improved quality of life (QoL) as compared with best medical management in advanced PD patients with a mean duration of levodopa treatment usually above 10 years, such that current medical practice is to reserve DBS for those PD subjects with a prolonged history of intractable response oscillations and dyskinesias. 1,2 Recently, Schuepbach et al. 3 investigated the effect of DBS on QoL in PD patients with significantly shorter disease duration and a history of motor complications from Ldopa of 3 years. Their EARLYSTIM trial randomized 251 patients to either DBS plus medical therapy or medical therapy alone demonstrating significant improved QoL, motor disability, activities of daily living, and L-dopa‐induced motor complications in the DBS-treated patients versus those on best medical therapy alone after 2 years of follow-up. The authors suggested to consider earlier use of DBS than is currently reflected by clinical practice and to potentially opt for surgical treatment in patients within the first 3 years after the onset of motor complications. An accompanying editorial to this publication, however, cautioned that the investigated population in the EARLYSTIM trial might only represent a small fraction of PD patients, 4 possibly less than 10%. The authors themselves point out that their study population might not be 100% representative for the general PD population to explain the usually high rate of suicide and suicide attempts during the trial. We sought to better define the percentage of PD patients seen in a tertiary movement disorders center of the type recruited and participating in EARLYSTIM for whom the current trial results might prompt a change in the timing of DBS. For this purpose we retrospectively applied the main inclusion and exclusion criteria of EARLYSTIM to all PD patients seen at the movement disorders center at the Department of Neurology of the Medical University Inns