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Objective: Cerebral small vessel disease (SVD) is associated with motor impairments and parkinsonian signs cross-sectionally, however, there are little longitudinal data on whether SVD increases risk of incident parkinsonism itself. We investigated the relation between baseline SVD severity as well as SVD progression, and incident parkinsonism over a follow-up of 14 years., Methods: This study included 503 participants with SVD, and without parkinsonism at baseline, from the RUN DMC prospective cohort study. Baseline inclusion was performed in 2006 and follow-up took place in 2011, 2015, and 2020, including magnetic resonance imaging (MRI) and motor assessments. Parkinsonism was diagnosed according to the UK Brain Bank criteria, and stratified into vascular parkinsonism (VaP) and idiopathic Parkinson's disease (IPD). Linear mixed-effect models were constructed to estimate individual rate changes of MRI-characteristics., Results: Follow-up for incident parkinsonism was near-complete (99%). In total, 51 (10.2%) participants developed parkinsonism (33 VaP, 17 IPD, and 1 progressive supranuclear palsy). Patients with incident VaP had higher SVD burden compared with patients with IPD. Higher baseline white matter hyperintensities (hazard ratio [HR] = 1.46 per 1-SD increase, 95% confidence interval [CI] = 1.21-1.78), peak width of skeletonized mean diffusivity (HR = 1.66 per 1-SD increase, 95% CI = 1.34-2.05), and presence of lacunes (HR = 1.84, 95% CI = 0.99-3.42) were associated with increased risk of all-cause parkinsonism. Incident lacunes were associated with incident VaP (HR = 4.64, 95% CI = 1.32-16.32)., Interpretation: Both baseline SVD severity and SVD progression are independently associated with long-term parkinsonism. Our findings indicate a causal role of SVD in parkinsonism. Future studies are needed to examine the underlying pathophysiology of this relation. ANN NEUROL 2023;93:1130-1141., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

A reliable biomarker is needed for accurate and early differentiation between Parkinson disease and the various forms of atypical parkinsonism. We used a novel real-time quaking-induced conversion (RT-QuIC) assay to detect α-synuclein (α-syn) aggregates in cerebrospinal fluid (CSF) of 118 patients with parkinsonism of uncertain clinical etiology and 52 controls. Diagnostic accuracy to distinguish α-synucleinopathies from non-α-synucleinopathies and controls was 84% (sensitivity = 75%, specificity = 94%, area under the curve = 0.84, 95% confidence interval = 0.78-0.91, p < 0.0001, positive predictive value = 93%). CSF α-syn RT-QuIC could be a useful diagnostic tool to help clinicians differentiate α-synucleinopathies from other forms of parkinsonism when the clinical picture is uncertain. Ann Neurol 2019;85:777-781., (© 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Deep brain stimulation of the subthalamic nuclei (STN) is a good therapeutic option to reduce dyskinesias and improve appendicular motor signs in well-selected patients with advanced Parkinson's disease (PD). Concerns about long-term adverse effects play an increasingly role in the decision whether or not to refer patients for this treatment. Worsening of gait as a consequence of STN stimulation for PD has been described, but may be under-recognized in clinical practice. The aim of this study was to evaluate the effects of STN stimulation on gait relative to global outcome in a group of consecutively operated patients. For this purpose, we used a standardized patient questionnaire that asked about global outcome and specific effects on gait, as experienced both 6 months postoperatively and currently (at the time of completing the questionnaire; mean: 2.7 +/- 1.1 years). A delayed worsening of gait after bilateral STN stimulation was experienced by a considerable proportion of patients (42% of subjects, for gait in the OFF phase), and this was apparently relatively "selective" because their global outcome scores continued to be improved. These findings highlight the presence of a hitherto poorly recognized long-term complication of bilateral STN stimulation. Further systematic studies are required to pinpoint the clinical and surgical determinants of this late gait deterioration., ((c) 2008 Movement Disorder Society.)

Postural instability and gait disability (PIGD) are disabling signs of Parkinson's disease. Stereotactic surgery aimed at the internal globus pallidus (GPi) or subthalamic nucleus (STN) might improve PIGD, but the precise effects remain unclear. We performed a systematic review of studies that examined the effects of GPi or STN surgery on PIGD. Most studies examined the effects of bilateral GPi stimulation, bilateral STN stimulation, and unilateral pallidotomy; we, therefore, only performed a meta-analysis on these studies. Bilateral GPi stimulation, bilateral STN stimulation, and to a lesser extent, unilateral pallidotomy significantly improved PIGD, and more so during the ON phase than during the OFF phase.

We evaluated the effects of bilateral pallidotomy in patients with advanced Parkinson's disease. Thirteen patients with Parkinson's disease had a staged bilateral pallidotomy if they had severe response fluctuations, dyskinesias, painful dystonia, or bradykinesia despite optimum pharmacological treatment. Assessment scales were the Unified Parkinson's Disease Rating scale (UPDRS), the Schwab and England scale, and a questionnaire on the effects of disability in activities of daily living and adverse effects. Postoperative magnetic resonance imaging was evaluated for lesion location and extension. The median off-phase UPDRS motor score was reduced from 43.5 to 29 after the first pallidotomy, and it was further reduced to 23.5 after the second pallidotomy (n = 8). The UPDRS activities of daily living off-phase score improved from 28.5 to 20.5 after the first pallidotomy and to 19 after the second pallidotomy (n = 6). The Schwab and England scale off-phase score showed an improvement after both procedures, first from 40 to 60, and thereafter to 90 (n = 8). On-phase dyskinesias were reduced substantially. Eight patients had adverse effects, of whom five had problems with speech. One patient became hemiplegic due to a delayed infarction. Ten patients experienced further benefit from the second procedure. Bilateral pallidotomy reduces dyskinesias. A second contralateral pallidotomy may reduce parkinsonism, although to a lesser degree compared with the first pallidotomy and with an increased risk for adverse effects., (Copyright 2002 Movement Disorder Society)

The role of the motor thalamus as surgical target in stereotactic neurosurgery for different kinds of tremor is discussed. For tremor in Parkinson's disease, the subthalamic nucleus becomes more and more often the surgical target, because this target also gives relief of other and more incapacitating symptoms (hypokinesia, rigidity). Stimulation is as effective in tremor suppression as coagulation but has less adverse events and permits bilateral surgery. In selected cases, thalamotomy can still be indicated., (Copyright 2002 Movement Disorder Society)