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Background:To investigate the relative contributions of cerebral cortex and basal ganglia to movement stopping, we tested the optimum combination Stop Signal Reaction Time (ocSSRT) and median visual reaction time (RT) in patients with Alzheimer’s disease (AD) and Parkinson’s disease (PD) and compared values with data from healthy controls.Methods:Thirty-five PD patients, 22 AD patients, and 29 healthy controls were recruited to this study. RT and ocSSRT were measured using a hand-held battery-operated electronic box through a stop signal paradigm.Result:The mean ocSSRT was found to be 309 ms, 368 ms, and 265 ms in AD, PD, and healthy controls, respectively, and significantly prolonged in PD compared to healthy controls (p = 0.001). The ocSSRT but not RT could separate AD from PD patients (p = 0.022).Conclusion:Our data suggest that subcortical networks encompassing dopaminergic pathways in the basal ganglia play a more important role than cortical networks in movement-stopping. Combining ocSSRT with other putative indices or biomarkers of AD (and other dementias) could increase the accuracy of early diagnosis.

The extent of gait abnormality is non-uniform across motor phenotypes of Parkinson's disease (PD). The biological basis of this heterogeneity remains intriguing. Moreover, the relationship of gait impairment with various neurodegenerative protein markers in PD is not well established.Here, we aimed to explore the interplay between gait parameters and specific serum protein markers in PD.A total of 62 PD patients were consecutively recruited. Blood samples and gait data were acquired from 37 and 34 patients respectively. Two-dimensional spatio-temporal gait parameters were estimated using an electronic walkway (GAITRite®, CIR Systems Inc., USA). Serum phosphorylated alpha synuclein (p-Ser129-a-syn) and total a-syn levels were measured using commercially available ELISA kit. Data was analyzed using SPSS Version 20 (IBM).We found that phosphorylated a-syn levels were significantly higher in PD patients with postural instability and gait difficulty compared to tremor dominant variant. Significant reduction in gait velocity was also observed with increasing levels of this pathological form of a-syn. Regression modelling showed that phosphorylated a-syn is an independent predictor of gait velocity.Our findings indicate that concentrations of peripheral p-Ser129-a-syn but not total a-syn could be a potential contributor of gait impairment in PD. Further investigation on the systemic role of phosphorylated a-syn on gait would bridge the gap between central and peripheral mechanisms underlying phenotypic variability in PD.

Background Literature shows that home confinement during coronavirus disease 2019 (COVID-19) pandemic has significantly affected sleep. However, such information regarding subjects having Parkinson’s disease (PD) is unavailable. Methods This cross-sectional study was conducted using a questionnaire, developed and validated by experts. PD subjects from nine centers across India were included. Questionnaire assessed presence as well as change in sleep-related parameters and PD symptoms during home confinement. Restless legs syndrome (RLS) and REM sleep behavior disorder (REMBD) was diagnosed using validated questionnaire. Additionally, changes in physical activity, adoption of new hobbies during home confinement and perceived quality of life were assessed. Results Of 832 subjects, 35.4% reported sleep disturbances. New-onset/worsening of sleep disturbances (NOWS) was reported by 23.9% subjects. Among those with sleep disturbances (n=295), insomnia symptoms worsened in half (51.5%) and nearly one-fourth reported worsening of RLS (24.7%) and REMBD (22.7%) each. NOWS was common in subjects lacking adequate family support during home confinement (P=0.03); home confinement > 60 days (P=0.05) and duration of PD > 7 years (P=0.008). Contrarily, physical activity > 1 hour/day and engagement in new hobbies during home confinement were associated with better sleep. NOWS was associated with worsening of motor as well as non-motor symptoms of PD (P 1 hour/day and adoption of new hobbies during home confinement were associated with better sleep., Highlights • New onset/worsening of sleep (NOWS) was reported by one-fourth subjects with Parkinson’s disease (PD) during home confinement. • While insomnia symptoms worsened in half, RLS and REMBD worsened in one-fourth of those with sleep disturbances. • Duration of PD >7 years, home confinement >60 days and absence of emotional support contributed to NOWS. • Adequate physical activity and adoption of hobbies during home confinement were protective factors.

Applause sign (AS) is a clinical phenomenon observed in several neurological disorders including progressive supranuclear palsy (PSP). We investigated the factors associated with AS in patients with PSP. PSP patients with AS showed greater motor impairment compared to those with negative AS. Global cognition including attention and memory were affected more in patients with positive AS. We also observed that gait variability, a known marker for unstable gait is pronounced in those who presented with positive AS. Hence, the clinician might expect a more severe disease and an unstable gait in a PSP patient presenting with AS.

Background Complex parkinsonism is the commonest phenotype in late-onset PLA2G6-associated neurodegeneration. Objectives The aim of this study was to deeply characterize phenogenotypically PLA2G6-related parkinsonism in the largest cohort ever reported. Methods We report 14 new cases of PLA2G6-related parkinsonism and perform a systematic literature review. Results PLA2G6-related parkinsonism shows a fairly distinct phenotype based on 86 cases from 68 pedigrees. Young onset (median age, 23.0 years) with parkinsonism/dystonia, gait/balance, and/or psychiatric/cognitive symptoms were common presenting features. Dystonia occurred in 69.4%, pyramidal signs in 77.2%, myoclonus in 65.2%, and cerebellar signs in 44.6% of cases. Early bladder overactivity was present in 71.9% of cases. Cognitive impairment affected 76.1% of cases and psychiatric features 87.1%, the latter being an isolated presenting feature in 20.1%. Parkinsonism was levodopa responsive but complicated by early, often severe dyskinesias. Five patients benefited from deep brain stimulation. Brain magnetic resonance imaging findings included cerebral (49.3%) and/or cerebellar (43.2%) atrophy, but mineralization was evident in only 28.1%. Presynaptic dopaminergic terminal imaging was abnormal in all where performed. Fifty-four PLA2G6 mutations have hitherto been associated with parkinsonism, including four new variants reported in this article. These are mainly nontruncating, which may explain the phenotypic heterogeneity of childhood- and late-onset PLA2G6-associated neurodegeneration. In five deceased patients, median disease duration was 13.0 years. Brain pathology in three cases showed mixed Lewy and tau pathology. Conclusions Biallelic PLA2G6 mutations cause early-onset parkinsonism associated with dystonia, pyramidal and cerebellar signs, myoclonus, and cognitive impairment. Early psychiatric manifestations and bladder overactivity are common. Cerebro/cerebellar atrophy are frequent magnetic resonance imaging features, whereas brain iron deposition is not. Early, severe dyskinesias are a tell-tale sign. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Introduction There is some evidence regarding the role of LAG-3, TLR mediated neuroinflammation in PD. Methods sLAG-3, TOLLIP, NLRP3 levels were measured in PD and healthy controls. Results These markers were significantly higher in PD and were associated with progression. Conclusion sLAG3 and TOLLIP are involved in the NLRP3 mediated inflammatory activation in PD.

Introduction Spinocerebellar ataxia type 12 (SCA 12) is characterized by late onset tremor, ataxia and pyramidal signs. Parkinsonism and cognitive decline may appear with time. It is considered as slowly progressive but temporal evolution of symptoms has not been reported. Method We report the evolution of symptoms in three SCA12 patients followed over a range of 5–6 years. We focused on the evolution of gait abnormality as it becomes the most disabling symptom as disease advances. Two-dimensional gait parameters were studied using an electronic walkway at various time points to measure objective changes in gait. Result All patients presented with tremor in the upper extremity at baseline which progressed non-uniformly over the years. Progression of gait variability measures of step length, stance time and step time were also observed. Conclusion Gait characteristics such as variability may precede clinical gait abnormality and could serve as a sensitive marker for disease progression for better therapeutic intervention in disease management. Future studies with larger sample size should be undertaken to conclusively validate this observation.

Highlights • Parkinson's disease symptoms worsened during home confinement. • Difficulty in availing formal neurology consultations and/or medicines. • Quality of life in Parkinson's disease patients declined during home confinement. • Use of telemedicine may benefit patients.

Background Alpha-synuclein and inflammatory pathology are evident in Parkinson's disease (PD) but, their link to disease pathogenesis needs further elucidation. Objectives To explore α-synuclein-mediated inflammation in the serum of PD patients and its link with disease severity. Methods Serum levels of IL-1β, NLRP3, total and phosphorylated α-synuclein were compared. Results IL-1β, NLRP3 levels were significantly increased in PD. We also observed a linear correlation of NLRP3 with α-synuclein. Phosphorylated α-synuclein levels were significantly elevated in later stages of PD. Conclusions The α-synuclein-NLRP3 mediated inflammation may underline the pathophysiology of PD and might serve as a novel therapeutic target in PD.

Context: Progressive supranuclear palsy (PSP) is a large-scale network disease resulting in variable signs and symptoms including gait impairment and higher order cognitive dysfunction. Despite few studies showing the association of falls and cognitive dysfunction, the existing literature is yet to establish the exact relationship of discrete characteristics of gait with cognitive function in PSP. Aims: In this cross-sectional study, we aimed to characterize and explore the relationship of these two apparently distinct physiological phenomena in patients with PSP and across its different variants. Methods and Material: Quantitative assessment of two-dimensional gait parameters was measured using an electronic walkway (GAITRite®). Dementia Rating Scale-2 was used to assess global as well as higher order cognitive functions. Statistical Analysis Used: A regression model was used to interpret results. Results: We observed that the variability domain of gait was significantly impaired in PSP patients with severe cognitive impairment compared to that of intact cognition. Moreover, initiation/perseveration (I/P), a higher order cognitive process, and one of its specific components, i.e., complex verbal task (β = 2.39, P < 0.001), significantly predict gait velocity in PSP [F (1, 40) = 16.102, P < 0.001]. Conclusions: Our findings indicate that the severity of cognitive functions affects gait variability, which might lead to frequent falls as observed in PSP. Furthermore, semantic fluency task of I/P function may act as a predictor of gait velocity. We suspect that higher order cognitive dysfunction through the damage of frontal lobe structure including dorsolateral prefrontal cortex or related network may influence gait in PSP.