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Background: Sarcopenia is characterized by a progressive loss of muscle mass, strength, and function resulting in adverse health outcomes. Current assessment strategies are bothersome and means to simplify the diagnosis are an unmet medical need in Parkinson’s disease (PD). Objective: To evaluate temporal muscle thickness (TMT) obtained on routine cranial MRI as a surrogate marker of sarcopenia in PD patients. Methods: We correlated TMT from axial non-contrast-enhanced T1-weighted sequences of MRI close (±12 months) to an outpatient visit including sarcopenia (EWGSOP1, EWGSOP2, SARC-F), frailty (Fried’s criteria, clinical frailty scale), and disease characteristics of Parkinson’s patients (Hoehn and Yahr-scale, Movement Disorder Society-Unified Parkinson’s Disease Rating Scale, quality of life with the Parkinson’s Disease Questionnaire-8) assessments. Results: Cranial MRI was available in 32 patients with a mean age of 73.56±5.14 years, mean disease duration of 11.46±5.66 years, and median Hoehn and Yahr stage of 2.5. The mean TMT was 7.49±2.76 (7.15) mm. Mean TMT was significantly associated with sarcopenia (EWGSOP2, p = 0.018; EWGSOP1, p = 0.023) and frailty status (physical phenotype; p = 0.045). Moreover, there were significant moderate to strong correlations between TMT measurement and appendicular skeletal muscle mass index (r: 0.437, p = 0.012), as well as handgrip strength (r: 0.561, p

BackgroundParkinson’s Disease (PD) has been associated with a distinct odour, strongest in sebum-rich areas. Thermal Desorption – Gas Chromatography – Mass Spectrometry (TD-GC-MS) has revealed volatile signatures that distinguish individuals with Parkinson’s Disease (PD) from healthy controls. Here, we applied the same method, including subjects with isolated REM sleep behaviour disorder (iRBD) to examine the volatiles in sebum and compare this with that found in PD subjects and control participants. Participants with iRBD have a high likelihood for conversion to overt clinical synucleinopathies like PD, Dementia with Lewy Bodies (DLB) or (less commonly) Multiple System Atrophy (MSA).MethodsSubjects with clinically established PD (n=16) or iRBD (n=9) as well as healthy controls (n=9) were included. Following methods established in our laboratory, sebum was sampled from each participant using cotton gauze and the headspace from these swabs, analysed directly with TD-GC-MS1,2. Univariate and multivariate analysis was employed to probe the differences between volatile metabolites found for each phenotype. Putative identifications were assigned using spectral matching against the Golm metabolome and NIST spectral databases.FindingsWe can completely classify each phenotype using the sampled volatilome from which we built models with logistic regression analysis. The classification between PD and control improved on previously published work, from 85% to 100%. Putatively annotated molecules include alkanes, aldehydes, fatty acid methyl esters (FAMEs), and three metabolites namely purine, tropinone and oleamide. Investigation of highly ranked features revealed 18 features that showed intermediate expression in samples from iRBD participants.InterpretationTD-GC-MS can differentiate volatile metabolite signatures from sebum between PD, RDB and control samples. More than 70% of the identifiable metabolites that permit this discrimination were putatively annotated as hydrocarbons and fatty acid methyl esters (FAMEs). Our prior work indicates that these components arise from larger lipid molecules that decompose during the experiment2. Features putatively annotated as tropinone, oleamide and purine, have previously been linked with neuroprotection, sleep induction and antioxidation, respectively, are significantly different between the three groups of participants, along with FAMEs and hydrocarbons.FundingWe thank Michael J Fox Foundation (grant ref:12921) and Parkinson’s UK (grant ref: K-1504) for funding this study and Community of Analytical and Measurement Sciences (CAMS) for supporting DT’s research position. This work was supported by the BBSRC (award BB/L015048/1) for instrumentation used in this work and by a DTA to CW-D (project ref. 2113640). We also thank our recruitment centres for their enthusiasm and rigor during the recruitment process. We are very grateful to all the participants who took part in this study as well as PIs and nurses at the recruiting centres.

Background: Essential tremor (ET) and the tremor of Parkinson’s disease (PD) are the most common tremors encountered in clinical practice. Especially in early disease stages, discrimination between the tremors of ET and PD can be challenging. Objective: The aim of this study was to evaluate the diagnostic accuracy of transcranial sonography (TCS) of the substantia nigra echogenicity for differential diagnosis of PD versus ET. Methods: A systematic PubMed search identified 512 studies. Sensitivity and specificity of substantia nigra hyperechogenicity was estimated. Data synthesis was carried applying a random effects bivariate binomial model. To assess study quality and risk of bias, the QUADAS-2 tool was used. Results: Eighteen studies were suitable for analysis including 1,264 PD and 824 ET patients. The meta analysis showed a pooled sensitivity and specificity for TCS in the differential diagnosis of PD versus ET of 84.6% (95% CI, 79.4–88.6%) and 83.9% (95% CI, 78.4–88.2%), respectively. Furthermore, we found nearly similar results in sensitivity and specificity comparing TCS and DaTSCAN in a subgroup-analysis of three studies using both diagnostic tools including 107 patients with PD and 62 patients with ET. The QUADAS-2 toolbox revealed a high risk of bias regarding the methodological quality of patient selection. Conclusion: Substantia nigra hyperechogenicity yield high diagnostic accuracy for the discrimination of PD from ET. TCS is a low cost, widely available, non-invasive marker without radiation Therefore, a diagnostic algorithm based on presence or absence of substantia nigra hyperechogenicity is highly warranted.

Without any disease-modifying treatment strategy for multiple system atrophy (MSA), the therapeutic management of MSA patients focuses on a multidisciplinary strategy of symptom control. In the present review, we will focus on state of the art treatment in MSA and additionally give a short overview about ongoing randomized controlled trials in this field.

Neurological sequelae from coronavirus disease 2019 (COVID-19) may persist after recovery from acute infection. Here, the aim was to describe the natural history of neurological manifestations over 1 year after COVID-19.A prospective, multicentre, longitudinal cohort study in COVID-19 survivors was performed. At a 3-month and 1-year follow-up, patients were assessed for neurological impairments by a neurological examination and a standardized test battery including the assessment of hyposmia (16-item Sniffin' Sticks test), cognitive deficits (Montreal Cognitive Assessment26) and mental health (Hospital Anxiety and Depression Scale and Post-traumatic Stress Disorder Checklist 5).Eighty-one patients were evaluated 1 year after COVID-19, out of which 76 (94%) patients completed a 3-month and 1-year follow-up. Patients were 54 (47-64) years old and 59% were male. New and persistent neurological disorders were found in 15% (3 months) and 12% (10/81; 1 year). Symptoms at 1-year follow-up were reported by 48/81 (59%) patients, including fatigue (38%), concentration difficulties (25%), forgetfulness (25%), sleep disturbances (22%), myalgia (17%), limb weakness (17%), headache (16%), impaired sensation (16%) and hyposmia (15%). Neurological examination revealed findings in 52/81 (64%) patients without improvement over time (3 months, 61%, p = 0.230) including objective hyposmia (Sniffin' Sticks test13; 51%). Cognitive deficits were apparent in 18%, whereas signs of depression, anxiety and post-traumatic stress disorders were found in 6%, 29% and 10% respectively 1 year after infection. These mental and cognitive disorders had not improved after the 3-month follow-up (all p 0.05).Our data indicate that a significant patient number still suffer from neurological sequelae including neuropsychiatric symptoms 1 year after COVID-19 calling for interdisciplinary management of these patients.

Background: Early identification of Parkinson’s disease (PD) patients at risk for becoming functionally dependent is important for patient counseling. Several models describing the relationship between predictors and outcome have been reported, however, most of these require computer software for practical use. Objective: Here we report the development of a risk nomogram allowing an approximate graphical computation of the risk of becoming functionally dependent in early PD. Methods: We analyzed data form the Parkinson’s Progression Markers Initiative cohort of newly diagnosed PD patients from baseline through the first 5 years of follow-up. Functional dependence was defined as a score

Purpose To assess patient characteristics associated with health-related quality of life (HR-QoL) and its mental and physical subcategories 3 months after diagnosis with COVID-19. Methods In this prospective multicentre cohort study, HR-QoL was assessed in 90 patients using the SF-36 questionnaire (36-item Short Form Health Survey), which consists of 8 health domains that can be divided into a mental and physical health component. Mental health symptoms including anxiety, depression, and post-traumatic stress disorders were evaluated using the Hospital Anxiety and Depression Scale (HADS) and Post-traumatic Stress Disorder Checklist-5 (PCL-5) 3 months after COVID-19. Using descriptive statistics and multivariable regression analysis, we identified factors associated with impaired HR-QoL 3 months after COVID-19 diagnosis. Results Patients were 55 years of age (IQR, 49–63; 39% women) and were classified as severe (23%), moderate (57%), or mild (20%) according to acute disease severity. HR-QoL was impaired in 28/90 patients (31%). Younger age [per year, adjOR (95%CI) 0.94 (0.88–1.00), p = 0.049], longer hospitalization [per day, adjOR (95%CI) 1.07 (1.01–1.13), p = 0.015], impaired sleep [adjOR (95%CI) 5.54 (1.2–25.61), p = 0.028], and anxiety [adjOR (95%CI) 15.67 (3.03–80.99), p = 0.001) were independently associated with impaired HR-QoL. Twenty-nine percent (n = 26) scored below the normal range on the mental health component of the SF-36 and independent associations emerged for anxiety, depression, and self-reported numbness. Impairments in the physical health component of the SF-36 were reported by 12 (13%) patients and linked to hypogeusia and fatigue. Conclusion Every third patient reported a reduction in HR-QoL 3 months after COVID-19 diagnosis and impairments were more prominent in mental than physical well-being.

BackgroundOlfactory dysfunction (OD) often accompanies acute coronavirus disease 2019 (COVID-19) and its sequelae. Herein, we investigated OD during COVID-19 recovery in the context of other symptoms, quality of life, physical and mental health.MethodsSymptom recovery patterns were analyzed in a bi-national, ambulatory COVID-19 survey (n = 906, ≥ 90 days follow-up) and a multi-center observational cross-sectional cohort of ambulatory and hospitalized individuals (n = 108, 360 days follow-up) with multi-dimensional scaling, association rule mining and partitioning around medoids clustering.ResultsBoth in the ambulatory collective (72%, n = 655/906) and the cross-sectional ambulatory and hospitalized cohort (41%, n = 44/108) self-reported OD was frequent during acute COVID-19, displayed a slow recovery pace (ambulatory: 28 days, cross-sectional: 90 days median recovery time) and commonly co-occurred with taste disorders. In the ambulatory collective, a predominantly young, female, comorbidity-free group of convalescents with persistent OD and taste disorder (>90 days) was identified. This post-acute smell and taste disorder phenotype was characterized by a low frequency of other leading post-acute symptoms including fatigue, respiratory and neurocognitive complaints. Despite a protracted smell and taste dysfunction, this subset had high ratings of physical performance, mental health, and quality of life.ConclusionOur results underline the clinical heterogeneity of post-acute COVID-19 sequelae calling for tailored management strategies. The persistent smell and taste disorder phenotype may represent a distinct COVID-19 recovery pathway characterized by a good recovery of other COVID-19 related symptoms.Study registrationClinicalTrials.gov: NCT04661462 (ambulatory collective), NCT04416100 (cross-sectional cohort).

Introduction Quantitative MR planimetric measurements were reported to discriminate between progressive supranuclear palsy (PSP) and non-PSP parkinsonism, yet few data exist on the usefulness of these markers in early disease stages. Methods The pons-to-midbrain area ratio (P/M) and the Magnetic Resonance Parkinsonism Index (MRPI) as well as new indices, termed P/M2.0 and MRPI2.0, multiplying the former by a ratio of the third ventricle (3rdV) width/frontal horns (FH) width, were calculated on T1-weighted images in 84 patients with clinically unclassifiable neurodegenerative parkinsonism (CUP) at the time of imaging. Areas under the curve (AUCs) of these markers for predicting future PSP was determined. The final clinical diagnosis was made after at least 24 months of follow-up. Results Final diagnosis was Parkinson's disease in 55 patients, multiple system atrophy in 12 cases, and PSP in 17. At baseline imaging, patients with a final PSP diagnosis had significantly higher MRPI, P/M, MRPI2.0 and P/M2.0 values compared to the other groups. AUCs in discriminating between future PSP and non-PSP parkinsonism were 0.91 for both the P/M and the MRPI and 0.98 for the P/M2.0 and the MRPI2.0. Conclusions Brainstem-derived MR planimetric measures yield high diagnostic accuracy for separating PSP from non-PSP parkinsonism in early disease stages when clinical criteria are not yet fully met. Consistent with the underlying pathology in PSP, our study suggests that inclusion of 3rdV width makes P/M2.0 and MRPI2.0 more accurate in diagnosing early stage PSP patients than the P/M and MRPI.

Objective The objective of this study was to assess the efficacy and safety of nabilone, a synthetic tetrahydrocannabinol analogue, as a treatment for non-motor symptoms (NMS) in Parkinson's disease (PD). Methods This was a phase II placebo-controlled, double-blind, parallel-group, enriched enrollment randomized withdrawal trial conducted at the Medical University Innsbruck. A random sample of 47 patients with PD with stable motor disease and disturbing NMS defined by a score of ≥4 points on the Movement Disorder Society - Unified PD Rating Scale-I (MDS-UPDRS-I) underwent open-label nabilone titration (0.25 mg once daily to 1 mg twice daily, phase I). Responders were randomized 1:1 to continue with nabilone or switch to placebo for 4 weeks (phase II). The primary efficacy criterion was the change of the MDS-UPDRS-I between randomization and week 4. Safety was analyzed in all patients who received at least one nabilone dose. Results Between October 2017 and July 2019, 19 patients received either nabilone (median dose = 0.75 mg) or placebo. At week 4, mean change of the MDS-UPDRS-I was 2.63 (95% confidence interval [CI] 1.53 to 3.74, p = 0.002, effect size = 1.15) in the placebo versus 1.00 (95% CI -0.16 to 2.16, p = 0.280, effect size = 0.42) in the nabilone-group (difference: 1.63, 95% CI 0.09 to 3.18, p = 0.030, effect size = 0.66). Seventy-seven percent of patients had adverse events (AEs) during open-label titration, most of them were transient. In the double-blind phase, similar proportions of patients in each group had AEs (42% in the placebo group and 32% in the nabilone group). There were no serious AEs. Interpretation Our results highlight the potential efficacy of nabilone for patients with PD with disturbing NMS, which appears to be driven by positive effects on anxious mood and night-time sleep problems. Trial registry ClinicalTrials.gov (NCT03769896) and EudraCT (2017-000192-86). ANN NEUROL 2020;88:712-722.

Objective Cognitive impairment in multiple system atrophy (MSA) is common, but remain poorly characterized. We evaluated cognitive and behavioral features in MSA patients and assessed between‐group differences for MSA subtypes and the effect of orthostatic hypotension (OH) on cognition. Methods This retrospective study included 54 patients with clinical diagnosis of possible and probable MSA referred to the Department of Neurology at Medical University of Innsbruck between 2000 and 2018. Neurological work‐up included comprehensive neuropsychological testing including Consortium to Establish a Registry for Alzheimer's Disease (CERAD‐plus) test battery, Frontal Assessment Battery (FAB), digit span test (DST), clock drawing task (CLOX1), and Hospital Anxiety and Depression Scale (HADS‐D). Results The mean MMSE score was 27.6 points. Overall, slight to moderate cognitive impairment was noted in up to 40% of patients, with predominant impairment of executive function and verbal memory. Patients with the cerebellar variant performed significantly worse than patients with the parkinsonian type (P

The synthetic tetrahydrocannabinol analogue nabilone improved overall non-motor symptom (NMS) burden in Parkinson's disease (PD) patients in comparison to placebo.To characterize the effects of nabilone on different sleep outcomes in PD patients.We performed a post-hoc analysis of the controlled, double-blind, enriched enrollment randomized withdrawal NMS-Nab study to assess the effects of nabilone on sleep outcomes in study participants who reported clinically-relevant sleep problems (MDS-UPDRS-1.7 ≥ 2 points).After open-label nabilone administration, 77.4% reported no relevant sleep problem. In the withdrawal phase of the trial, the MDS-UPDRS-1.7. and the NMS-Scale Domain 2 (i.e., Sleep/Fatigue) significantly worsened only in PD patients in the placebo group, which was mostly driven by a significant worsening of insomnia (question 5 of the NMS-Scale Domain 2).This post-hoc analysis of the NMS-Nab trial suggests that nabilone has beneficial effects on sleep outcomes in PD patients experiencing sleep problems at baseline.The original trial was registered with ClinicalTrials.gov (NCT03769896, https://clinicaltrials.gov/ct2/show/NCT03769896) and EudraCT (2017-000192-86).

Huntington's Disease (HD) is a relentlessly progressive genetic neurodegenerative disorder with characteristic motor, psychiatric, and behavioral abnormalities that inevitably results in severe disability and death. Many patients have multiple hospital admissions during the disease course, but there is limited information which problems lead to hospitalization.To assess acute reasons for hospital admissions, discharge routes, and clinical characteristics of HD patients in a retrospective analysis.We reviewed all medical records of patients with an established diagnosis of Huntington's Disease and hospital admissions between 2011 and 2016 in our local hospital-based database.There were 135 hospital admissions in 53 HD patients during the review period, representing a median of two admissions per patient. Median duration of hospitalization was seven days. The most frequent reason for admission was a worsening of HD motor symptoms (n = 77, 57.0%) such as chorea, parkinsonism, gait problems, falls, and dysphagia. Psychiatric symptoms related to HD were the second most common reason for admission (n = 58, 43.0%). Infections (including aspiration pneumonia) and traumas/surgical procedures were only responsible for 6.7% and 5.9% of admissions, respectively. Emergency admissions were not common (42.2%), and the majority of patients were able to return to their previous residency upon discharge (85.2%, home or nursing home). Recurrent admissions were associated with worse motor function and functional capacity.Worsening of motor and psychiatric symptoms associated with Huntington's Disease were the most common reasons for hospital admissions. Therefore, our data highlight the importance of optimal symptom control in HD patients.

Objective We assessed frontal executive functions in patients with RLS/WED with and without augmentation and compared the results to healthy controls. Methods We recruited 38 patients with RLS/WED. A total of 23 patients were treated with dopaminergic therapy and showed no signs of augmentation and 15 patients had a history of augmentation (AUG). Results were compared to 21 healthy controls. All individuals were assessed by the Frontal Assessment Battery (FAB) and the MMSE. Furthermore, impulsivity was assessed during a semi-structured interview. Results Patients with AUG performed worse in the FAB than healthy controls and RLS/WED patients without AUG (p = 0.001, η2 = 0.201). When we assessed the subtests of the FAB separately, we found a significant difference in the subtest assessing inhibitory control (p = 0.008, η2 = 0.138). Conclusions Our findings suggest an impaired executive function in RLS/WED patients with augmentation compared to RLS/WED patients without augmentation and healthy controls. Long term neuroplastic changes within the prefrontal cortex may be the underlying cause for these results. However, further studies in a larger sample size and with a more extensive neuropsychological test battery are needed to confirm our preliminary results.

Differential diagnosis of parkinsonian syndromes is considered one of the most challenging in neurology. Quantitative MR planimetric measurements were reported to discriminate between progressive supranuclear palsy (PSP) and non-PSP-parkinsonism. Several studies have used midbrain to pons ratio (M/P) and the Magnetic Resonance Parkinsonism Index (MRPI) in distinguishing PSP patients from those with Parkinson's disease. The current meta-analysis aimed to compare the performance of these measures in discriminating PSP from multiple system atrophy (MSA). A systematic MEDLINE review identified 59 out of 2984 studies allowing a calculation of sensitivity and specificity using the MRPI or M/P. Meta-analyses of results were carried out using random effects modelling. To assess study quality and risk of bias, the QUADAS-2 tool was used. Eight studies were suitable for analysis. The meta‐analysis showed a pooled sensitivity and specificity for the MRPI of PSP versus MSA of 79.2% (95% CI 72.7–84.4%) and 91.2% (95% CI 79.5–96.5%), and 84.1% (95% CI 77.2–89.2%) and 89.2% (95% CI 81.8–93.8%), respectively, for the M/P. The QUADAS-2 toolbox revealed a high risk of bias regarding the methodological quality of patient selection and index test, as all patients were seen in a specialized outpatient department without avoiding case control design and no predefined threshold was given regarding MRPI or M/P cut-offs. Planimetric brainstem measurements, in special the MRPI and M/P, yield high diagnostic accuracy for the discrimination of PSP from MSA. However, there is an urgent need for well-designed, prospective validation studies to ameliorate the concerns regarding the risk of bias.

Background and purpose To assess neurological manifestations and health‐related quality of life (QoL) 3 months after COVID‐19. Methods In this prospective, multicenter, observational cohort study we systematically evaluated neurological signs and diseases by detailed neurological examination and a predefined test battery assessing smelling disorders (16‐item Sniffin Sticks test), cognitive deficits (Montreal Cognitive Assessment), QoL (36‐item Short Form), and mental health (Hospital Anxiety and Depression Scale, Posttraumatic Stress Disorder Checklist–5) 3 months after disease onset. Results Of 135 consecutive COVID‐19 patients, 31 (23%) required intensive care unit (ICU) care (severe), 72 (53%) were admitted to the regular ward (moderate), and 32 (24%) underwent outpatient care (mild) during acute disease. At the 3‐month follow‐up, 20 patients (15%) presented with one or more neurological syndromes that were not evident before COVID‐19. These included polyneuro/myopathy (n = 17, 13%) with one patient presenting with Guillain‐Barré syndrome, mild encephalopathy (n = 2, 2%), parkinsonism (n = 1, 1%), orthostatic hypotension (n = 1, 1%), and ischemic stroke (n = 1, 1%). Objective testing revealed hyposmia/anosmia in 57/127 (45%) patients at the 3‐month follow‐up. Self‐reported hyposmia/anosmia was lower (17%) at 3 months, however, improved when compared to the acute disease phase (44%; p, Three months after COVID‐19, 20/135 patients (15%) presented with one or more neurological syndromes that were not evident before disease onset. Objective testing revealed hyposmia/anosmia in 45% of patients at the 3‐month follow‐up in comparison to 17% who reported hyposmia/anosmia. Cognitive deficits were apparent in 23%, quality of life was impaired in 31%, depression was found in 11%, anxiety in 25% and posttraumatic stress disorders in 11%.

Isolated REM sleep behaviour disorder (RBD) is an early-stage α-synucleinopathy in most, if not all, affected subjects. Detection of pathological α-synuclein in peripheral tissues of patients with isolated RBD may identify those progressing to Parkinson’s disease, dementia with Lewy bodies or multiple system atrophy, with the ultimate goal of testing preventive therapies. Real-time quaking-induced conversion (RT-QuIC) provided evidence of α-synuclein seeding activity in CSF and olfactory mucosa of patients with α-synucleinopathies. The aim of this study was to explore RT-QuIC detection of α-synuclein aggregates in olfactory mucosa of a large cohort of subjects with isolated RBD compared to patients with Parkinson’s disease and control subjects. This cross-sectional case-control study was performed at the Medical University of Innsbruck, Austria, the Hospital Clinic de Barcelona, Spain, and the University of Verona, Italy. Olfactory mucosa samples obtained by nasal swab in 63 patients with isolated RBD, 41 matched Parkinson’s disease patients and 59 matched control subjects were analysed by α-synuclein RT-QuIC in a blinded fashion at the University of Verona, Italy. Median age of patients with isolated RBD was 70 years, 85.7% were male. All participants were tested for smell, autonomic, cognitive and motor functions. Olfactory mucosa was α-synuclein RT-QuIC positive in 44.4% isolated RBD patients, 46.3% Parkinson’s disease patients and 10.2% control subjects. While the sensitivity for isolated RBD plus Parkinson’s disease versus controls was 45.2%, specificity was high (89.8%). Among isolated RBD patients with positive α-synuclein RT-QuIC, 78.6% had olfactory dysfunction compared to 21.4% with negative α-synuclein RT-QuIC (P

Objective To investigate cognitive flexibility in premanifest and manifest Huntington's disease (HD). Background HD is an autosomal dominant neurodegenerative disease characterized by motor, cognitive, and behavioral abnormalities with typical motor symptoms. In this study, we wanted to assess decision making in premanifest (pre‐HD) and manifest HD patients. Methods A total of 77 non‐demented subjects including 29 pre‐HD, 22 manifest HD patients, and 26 healthy controls (HC) were included. We stratified the pre‐HD group based on their estimated years to disease onset into a far (FAR, n = 13) and a near (NEAR, n = 16) group. Furthermore, participants performed the Montreal cognitive assessment battery (MoCA), the trail making task part A and B (TMT A, TMT B), the Symbol digit modalities test (SDMT), and the beads task. Results In the beads task, HD patients gathered less information than all other groups (all p‐values, In this study, we assessed decision making in manifest Huntington's disease (HD) and premanifest HD patients. We could show that jumping to conclusions is an early marker of cognitive dysfunction in premanifest HD patients prior to reaching criteria for the motor diagnosis of HD.

Isolated REM sleep behaviour disorder is an early-stage α-synucleinopathy in most, if not all, affected subjects. Detection of pathological alpha-synuclein in peripheral tissues of isolated REM sleep behaviour disorder patients may identify those progressing to Parkinson’s disease, dementia with Lewy bodies or multiple system atrophy, with the ultimate goal of testing preventive therapies. Real-Time Quaking-Induced Conversion provided evidence of α-synuclein seeding activity in cerebrospinal fluid and olfactory mucosa of patients with α-synucleinopathies. Aim of this study was to explore Real-Time Quaking-Induced Conversion detection of α-synuclein aggregates in olfactory mucosa of large cohort of subjects with isolated REM sleep behavior disorder compared to Parkinson’s disease and controls.This prospective bicentric case-control study was performed between October 2017 and December 2018 at the Medical University of Innsbruck, Austria, and the Hospital Clinic de Barcelona, Spain. Olfactory mucosa samples obtained by nasal swab in 63 patients with isolated REM sleep behavior disorder, 31 matched Parkinson’s disease patients and 59 matched controls were analysed by α-synuclein Real-Time Quaking-Induced Conversion in a blinded fashion at the University of Verona, Italy. Median age of isolated REM sleep behavior disorder patients was 70 years, 85.7% were male. All participants were tested for smell, autonomic, cognitive and motor functions.Olfactory mucosa was α-synuclein Real-Time Quaking-Induced Conversion positive in 44.4% isolated REM sleep behavior disorder patients, 41.9% Parkinson’s disease and 10.2% controls. While the sensitivity for isolated REM sleep behavior disorder plus Parkinson’s disease versus controls was 40.9%, specificity was high (89.8%). Among isolated REM sleep behavior disorder patients with positive α-synuclein Real-Time Quaking-Induced Conversion, 78.6% had olfactory dysfunction as compared to 21.4% with negative α-synuclein Real-Time Quaking-Induced Conversion, pReal-Time Quaking-Induced Conversion olfactory mucosa isolated REM sleep behavior disorder patients (pWe provide evidence that α-synuclein Real-Time Quaking-Induced Conversion assay enables the molecular detection of neuronal α-synuclein aggregates in olfactory mucosa of patients with isolated REM sleep behavior disorder and Parkinson’s disease. Although the overall sensitivity was moderate in this study, nasal swabbing is attractive as simple, non-invasive test, with a potential of use as screening test to identify subjects in the prodromal stages of α-synucleinopathies. Further studies are needed to enhance sensitivity, and better understand the temporal dynamics of α-synuclein seeding in the olfactory mucosa and spreading to other brain areas during the progression from isolated REM sleep behavior disorder to overt α-synucleinopathy.

BACKGROUND: Increasing evidence suggests the involvement of the central and peripheral nervous system in patients with coronavirus disease 2019 (COVID-19). Little is known about neurological outcomes and quality of life (QoL) after recovery from acute infection. METHODS: In this prospective, multicentre, observational cohort study we systematically evaluated neurological signs and diseases by detailed neurological examination and a predefined test battery assessing smelling disorders (16-item Sniffin-Sticks-test), cognitive deficits (Montreal Cognitive Assessment), QoL (36-item Short Form), and mental health (Hospital Anxiety and Depression Scale, Post-traumatic Stress Disorder Checklist-5) three months after disease onset. FINDINGS: Of 135 COVID-19 patients included, 31 (23%) required ICU-care (severe), 72 (53%) were admitted to the regular ward (moderate), and 32 (24%) underwent outpatient-care (mild) during acute disease. At three-month follow-up, 20 patients (15%) presented with one or more neurological syndromes that were not evident before COVID-19. These included poly-neuro/myopathy (n=16, 12%), mild encephalopathy (n=2, 2%), parkinsonism (n=1, 1%), orthostatic hypotension (n=1, 1%), Guillain-Barre-Syndrome (n=1, 1%) and ischemic stroke (n=1, 1%). Self-reported hyposmia/anosmia was noted in 23/135 patients (17%), which was significantly lower compared to those documented during acute COVID-19 (44%; p

BACKGROUND In 2015, the International Parkinson and Movement Disorder Society published clinical diagnostic criteria for Parkinson's disease. These criteria aimed to codify/reproduce the expert clinical diagnostic process and to help standardize diagnosis in research and clinical settings. Their accuracy compared with expert clinical diagnosis has not been tested. The objectives of this study were to validate the International Parkinson and Movement Disorder Society diagnostic criteria against a gold standard of expert clinical diagnosis, and to compare concordance/accuracy of the International Parkinson and Movement Disorder Society criteria to 1988 United Kingdom Brain Bank criteria. METHODS From 8 centers, we recruited 626 parkinsonism patients (434 PD, 192 non-PD). An expert neurologist diagnosed each patient as having PD or non-PD, regardless of International Parkinson and Movement Disorder Society criteria (gold standard, clinical diagnosis). Then a second neurologist evaluated the presence/absence of each individual item from the International Parkinson and Movement Disorder Society criteria. The overall accuracy/concordance rate, sensitivity, and specificity of the International Parkinson and Movement Disorder Society criteria compared with the expert gold standard were calculated. RESULTS Of 434 patients diagnosed with PD, 94.5% met the International Parkinson and Movement Disorder Society criteria for probable PD (5.5% false-negative rate). Of 192 non-PD patients, 88.5% were identified as non-PD by the criteria (11.5% false-positive rate). The overall accuracy for probable PD was 92.6%. In addition, 59.3% of PD patients and only 1.6% of non-PD patients met the International Parkinson and Movement Disorder Society criteria for clinically established PD. In comparison, United Kingdom Brain Bank criteria had lower sensitivity (89.2%, P = 0.008), specificity (79.2%, P = 0.018), and overall accuracy (86.4%, P

Objectives The objective of this study was to investigate perceptual decision‐making and reflection impulsivity in drug naïve patients with restless legs syndrome (RLS) and patients with dopaminergic therapy. Methods A total of 35 RLS patients (20 who were drug naïve regarding dopaminergic medication and 15 patients treated with dopaminergic therapy without augmentation or impulse control disorders) were included in this study. We used the Beads task and the Pixel task which assess reflection impulsivity and perceptual decision‐making, respectively. Results were compared to 20 healthy controls. Results Both RLS patient groups gathered less evidence than healthy controls in the Beads task before making a decision (P < 0.001), but patients with dopaminergic treatment gathered less information than drug naïve patients (P = 0.026). Moreover, both patient groups made more choices against the evidence than healthy controls (both P < 0.01), but there was no difference between the two patient groups. In the Pixel task, we found an effect of task difficulty on reaction times with patients and controls responding faster with reduced task difficulty. There was neither an effect of group on reaction times nor an effect of group on error rates. Conclusions Reflection impulsivity is common in RLS patients, regardless whether they are drug naïve or treated with dopaminergic therapy. Thus, RLS patients tend to gather less information compared to healthy controls which could have a negative effect on decision‐making in daily life and should be investigated further.

The differential diagnosis of parkinsonian syndromes is considered one of the most challenging in neurology and error rates in the clinical diagnosis can be high even at specialized centres. Despite several limitations, magnetic resonance imaging (MRI) has undoubtedly enhanced the diagnostic accuracy in the differential diagnosis of neurodegenerative parkinsonism over the last three decades. This review aims to summarize research findings regarding the value of the different MRI techniques, including advanced sequences at high- and ultra-high-field MRI and modern image analysis algorithms, in the diagnostic work-up of Parkinson’s disease. This includes not only the exclusion of alternative diagnoses for Parkinson’s disease such as symptomatic parkinsonism and atypical parkinsonism, but also the diagnosis of early, new onset, and even prodromal Parkinson’s disease.

Background: Augmentation (AUG) in patients with restless legs syndrome (RLS) can be associated with impulse control disorder (ICD) symptoms, such as compulsive sexual behavior, gambling disorder or compulsive shopping. In this study, we wanted to assess whether RLS patients with AUG differ in decision making from those patients who have augmentation and in addition ICD symptoms (AUG + ICD) in a post hoc analysis of a patient cohort assessed in a previous study. Methods: In total, 40 RLS patients with augmentation (19 AUG + ICD, 21 AUG without ICDs) were included. RLS diagnosis, severity, and diagnosis of augmentation were made by sleep disorder specialists. ICD symptoms were assessed using semi-structured interviews. All patients performed the beads task, which is an information sampling task where participants must decide from which of the two cups colored beads were drawn. Results were compared to 21 healthy controls (HC). Results: There was no difference in information sampling or irrational decision making between AUG and AUG + ICD patients (p = 0.67 and p = 1.00, respectively). Both patient groups drew less beads and made more irrational decisions than HC (all p-values < 0.03, respectively). Conclusions: Our results suggest that augmentation itself is associated with poorer decision making even in the absence of ICD symptoms. Further studies are necessary to explore whether rapid and hasty decision making are a harbinger of augmentation in RLS.

Background Cerebral hemiatrophy syndromes can present with variable neurological symptoms. In childhood epilepsy, mental retardation and neuropsychiatric disorders are common while in adults movement disorders, such as highly asymmetric parkinsonism or hemidystonia as well as neuropsychiatric problems have been reported. Methods Here, we present three adult patients with features that expand the clinical spectrum and give an overview of the most common clinical signs associated with this rare condition. Results All three patients had prominent neuropsychiatric symptoms such as mood swings and increased irritability. Furthermore, one patient developed hemichorea which can be a rare presentation of cerebral hemiatrophy. Conclusions Cerebral hemiatrophy syndromes are a heterogeneous group of disorders that may also present with neuropsychiatric symptoms or hemichorea.

Qualitative and quantitative structural magnetic resonance imaging offer objective measures of the underlying neurodegeneration in atypical parkinsonism. Regional changes in tissue volume, signal changes and increased deposition of iron as assessed with different structural MRI techniques are surrogate markers of underlying neurodegeneration and may reflect cell loss, microglial proliferation and astroglial activation. Structural MRI has been explored as a tool to enhance diagnostic accuracy in differentiating atypical parkinsonian disorders (APDs). Moreover, the longitudinal assessment of serial structural MRI-derived parameters offers the opportunity for robust inferences regarding the progression of APDs. This review summarizes recent research findings as (1) a diagnostic tool for APDs as well as (2) as a tool to assess longitudinal changes of serial MRI-derived parameters in the different APDs.

The hummingbird sign and the morning glory flower sign, reflecting midbrain pathology on MRI, have previously been shown to separate patients with progressive supranuclear palsy (PSP) from those with Parkinson's disease (PD) and multiple system atrophy (MSA). The aim of the present study was to determine the diagnostic accuracy and reproducibility of visual assessment of midbrain atrophy patterns in a large cohort of patients with neurodegenerative parkinsonism.Retrospective analysis of midbrain atrophy patterns on T1-weighted MRI in a large cohort of patients with neurodegenerative parkinsonism and healthy controls who underwent MR imaging during their diagnostic work-up.481 patients with neurodegenerative parkinsonism and 79 healthy controls were included in the present study. The presence of the hummingbird sign had a specificity of 99.5% and a positive predictive value of 96.1% for a diagnosis of PSP while sensitivity was suboptimal with 51.6%. Similarly, the presence of the morning glory flower sign yielded a specificity of 97.7% for a diagnosis of PSP, but sensitivity was only 36.8%. Sensitivity of both signs was 35.3% in early, clinically unclassifiable parkinsonism. Visual assessment of these midbrain alterations showed excellent inter-rater agreement.Midbrain atrophy patterns are useful in the differential diagnosis of neurodegenerative parkinsonism but both the hummingbird sign and more so the morning glory flower sign suffer from low sensitivity, especially in early disease stages.

Qualitative and quantitative structural magnetic resonance imaging offer objective measures of the underlying neurodegeneration in atypical parkinsonism. Regional changes in tissue volume, signal changes and increased deposition of iron as assessed with different structural MRI techniques are surrogate markers of underlying neurodegeneration and may reflect cell loss, microglial proliferation and astroglial activation. Structural MRI has been explored as a tool to enhance diagnostic accuracy in differentiating atypical parkinsonian disorders (APDs). Moreover, the longitudinal assessment of serial structural MRI-derived parameters offers the opportunity for robust inferences regarding the progression of APDs. This review summarizes recent research findings as (1) a diagnostic tool for APDs as well as (2) as a tool to assess longitudinal changes of serial MRI-derived parameters in the different APDs.

In 2015, the International Parkinson and Movement Disorder Society published clinical diagnostic criteria for Parkinson's disease. These criteria aimed to codify/reproduce the expert clinical diagnostic process and to help standardize diagnosis in research and clinical settings. Their accuracy compared with expert clinical diagnosis has not been tested. The objectives of this study were to validate the International Parkinson and Movement Disorder Society diagnostic criteria against a gold standard of expert clinical diagnosis, and to compare concordance/accuracy of the International Parkinson and Movement Disorder Society criteria to 1988 United Kingdom Brain Bank criteria.From 8 centers, we recruited 626 parkinsonism patients (434 PD, 192 non-PD). An expert neurologist diagnosed each patient as having PD or non-PD, regardless of International Parkinson and Movement Disorder Society criteria (gold standard, clinical diagnosis). Then a second neurologist evaluated the presence/absence of each individual item from the International Parkinson and Movement Disorder Society criteria. The overall accuracy/concordance rate, sensitivity, and specificity of the International Parkinson and Movement Disorder Society criteria compared with the expert gold standard were calculated.Of 434 patients diagnosed with PD, 94.5% met the International Parkinson and Movement Disorder Society criteria for probable PD (5.5% false-negative rate). Of 192 non-PD patients, 88.5% were identified as non-PD by the criteria (11.5% false-positive rate). The overall accuracy for probable PD was 92.6%. In addition, 59.3% of PD patients and only 1.6% of non-PD patients met the International Parkinson and Movement Disorder Society criteria for clinically established PD. In comparison, United Kingdom Brain Bank criteria had lower sensitivity (89.2%, P = 0.008), specificity (79.2%, P = 0.018), and overall accuracy (86.4%, P 0.001). Diagnostic accuracy did not differ according to age or sex. Specificity improved as disease duration increased.The International Parkinson and Movement Disorder Society criteria demonstrated high sensitivity and specificity compared with the gold standard, expert diagnosis, with sensitivity and specificity both higher than United Kingdom Brain Bank criteria. © 2018 International Parkinson and Movement Disorder Society.

Different neuroimaging modalities hold potential as surrogate markers of underlying neurodegeneration in multiple system atrophy (MSA) and may reflect cell loss, altered glucose metabolism, microglial proliferation, astroglial activation, and nigrostriatal denervation. Multiple studies have demonstrated that serial structural and functional imaging studies are capable of demonstrating neurodegeneration in MSA patients quantitatively, which allows sample size estimates based on rates of progression of these neuroimaging markers. This review summarizes recent research findings as a tool to assess longitudinal changes of serial neuroimaging-derived parameters in MSA.

Editors' Note: In WriteClick this week, Dr. Nirenberg responds to “Augmentation and impulsive behaviors in restless legs syndrome: Coexistence or association?” with the hypothesis that augmentation in restless legs syndrome may be a forme fruste of dopamine agonist withdrawal syndrome. Authors Djamshidian et al. report no association between augmentation and medication nonadherence, but agree with monitoring these patients closely for addictive behaviors. In reference to “Spatial-temporal functional mapping of language at the bedside with electrocorticography,” Drs. Babajani-Feremi et al. and authors Wang et al. discuss the use of high-gamma …

Background and objective There is limited evidence about the efficacy and safety of cannabinoids in the treatment of patients with Huntington’s disease (HD). Five patients with HD were treated with nabilone, a synthetic cannabinoid, in order to alleviate therapy-resistant symptoms. Methods All patients and caregivers were informed about the off-label use of nabilone and gave written informed consent. A Clinical Global Impression Scale (CGI) and the Unified Huntington9s Disease Rating Scale (UHDRS) were applied prior, after one and four weeks to decide on the continuation of nabilone treatment. Case reports Patient 1 is a 20-year-old male who presented with disabling tics, generalised chorea and increased irritability. He developed severe parkinsonism during therapy with amisulpiride and olanzapine. Amisulpiride was stopped and he was treated with nabilone 1 mg/d. Patient 2 is a 48-year-old female with 10 years history of HD and chronic pain. Multiple treatment trials were ineffective. Nabilone 2 mg/d was introduced. Patient 3 is a 62-year-old female with disabling chorea and increased irritability. She developed severe akathisia as a side effect of several antidopaminergic therapies. Treatment with nabilone 1.5 mg/d was commenced. Patient 4 is a 46-year-old female who had parkinsonism and depression under therapy with tetrabenazine. Treatment with nabilone 3 mg/d was introduced as monotherapy. Patient 5 is a 67-year-old female with disabling chorea and increased irritability. She developed parkinsonism during therapy with tetrabenazine. Medication was changed to 2 mg/d nabilone. Results Transient mild sedation during titration occurred in patients 3, 4 and 5, mild non-disturbing xerostomia in patient 3. All patients reported improved symptoms as assessed by the CGI. UHDRS and Chorea-scores improved in all patients. A reduction of tics without worsening of parkinsonism with nabilone was seen in patient 1. Patient 2 reported that her pain completely subsided. Irritability substantially improved with nabilone in patients 1, 3 and 5. Moreover, tetrabenazine could be stopped in patients 3, 4 and 5. This resulted in a remission of akathisia in patient 3, in improved parkinsonism in patients 4 and 5 as well as in ameliorated mood in patient 4. Conclusions These case series suggest that nabilone may be an effective and well tolerated adjunct to the drug treatment of HD. However, larger controlled trials are needed to confirm these preliminary open-label observations.