BACKGROUND:Pain affects up to 87% of people with multiple system atrophy (MSA), but it remains unclear which types of pain contribute most to the overall burden. OBJECTIVE:To estimate the frequency of different types of pain in MSA individuals. METHODS:In 2023, individuals with MSA completed a web-based survey that included the King's Parkinson's Disease Pain Questionnaire (KPPQ) and additional questions addressing pain related to MSA core features (eg, coat-hanger pain, pain due to bladder-issues, cold extremities, bruises, and pressure sores). Respondents were matched by age, gender, and disease duration with historical cohorts of individuals with Parkinson's disease (PD) and healthy controls (n = 96 each) who had previously completed the KPPQ. RESULTS:One hundred and fifty-seven MSA individuals with pain completed the survey. The most frequently reported KPPQ types of pain were nocturnal pain (73%), musculoskeletal pain (63%), and fluctuation-related pain (62%). Common additional pain sources included coat-hanger pain (59%), cold extremities (48%), and bruises (44%). All KPPQ pain types were significantly more frequent in MSA than in healthy controls, except for musculoskeletal pain (63% vs. 66%, P = 0.722). Compared with PD, MSA individuals reported less musculoskeletal (63% vs. 78%, P = 0.023), but more orofacial pain (32% vs. 12%, P < 0.001) on the KPPQ. CONCLUSIONS:MSA is associated with both non-specific and disease-related pain types, which may be neuropathic, nociceptive, nociplastic, or mixed in nature. These findings inform the development of tailored tools for identifying distinct pain sources in MSA, as each may require a specific therapeutic approach, including targeted treatment of motor and non-motor symptoms. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Autonomic dysfunction is well recognized in hereditary transthyretin amyloidosis (ATTRv), but it has not been systematically studied in wild-type transthyretin amyloidosis (ATTRwt). Because ATTRwt primarily presents with cardiomyopathy, autonomic symptoms may mimic heart failure and lead to inappropriate treatment. Here we aimed to investigate the presence and extent of autonomic dysfunction in ATTRwt. In ATTRwt patients and controls, we performed an extensive autonomic examination, including standardized questionnaires, passive and active orthostatic challenges, Valsalva maneuver, deep breathing and sudomotor assessment. 20 ATTRwt patients and 20 controls were included. Composite Autonomic Symptom Score 31-scores were similar between the groups. Orthostatic challenges revealed impaired blood pressure (BP) and heart rate regulation in ATTRwt compared to controls (for passive orthostatic challenge: HR p = 0.001, systolic BP p = 0.010) and diastolic BP p = 0.006; for active orthostatic challenge: HR p = 0.001, systolic BP p = 0.002, diastolic BP p = 0.002). A lack of late phase 2 BP overshoot during Valsalva maneuver was observed in ATTRwt and Valsalva Ratio was pathological in 83

OBJECTIVE:Delayed orthostatic hypotension (dOH) is defined by a sustained blood pressure (BP) fall ≥20/10 mmHg occurring beyond 3 minutes in the upright position, whose clinical relevance is yet undetermined. We investigated frequency, associated features and treatment strategies of dOH in Parkinson's Disease (PD) and ageing individuals with history of syncope or orthostatic intolerance. METHODS:We retrospectively studied 213 individuals with PD and 213 age-matched individuals without parkinsonism referred for tilt-table testing to the Innsbruck and Florence Dysautonomia centres. In both cohorts, we reviewed the medical records of the 6 months before testing for history of syncope and falls, and of the 6 months afterwards for the recommended dOH treatment and clinical outcome. RESULTS:dOH was twice as frequent in PD than in ageing individuals [18% versus 9%; OR = 2.9 (95 CI.: 1.3-6.5), P = .007]. Upon prolonged head-up tilt, PD individuals showed a more severe systolic BP fall (P < .001). PD individuals with history of syncope also exhibited a sustained systolic BP fall from the 3rd minute of head-up tilt onward compared to those without (P = .014). Both non-pharmacological and pharmacological OH treatment strategies were associated with symptomatic improvement at follow-up. CONCLUSIONS:In PD individuals referred to tertiary settings, tilt-table testing more frequently disclosed dOH compared to age-matched individuals without parkinsonism. In PD, dOH is mainly driven by a progressive orthostatic systolic BP fall, increasing the risk of syncope. Given its prevalence and the potential for effective treatment, dOH should be actively screened for in clinical practice.

Multiple system atrophy (MSA) is a fatal neurodegenerative disorder characterized by abnormal accumulation of α-synuclein, progressive neuronal loss, motor impairment and widespread pathological changes, which include significant involvement of the cerebellum. To understand the early molecular mechanisms that might underlie α-synuclein-triggered MSA cerebellar pathology, we performed RNA sequencing (RNA-Seq) of cerebellar samples from a well-established model of MSA. RNA-Seq and differential gene expression analysis was conducted in the PLP-αSyn model of MSA. Cerebellum from two and 12-month-old MSA and wildtype mice were used. Gene ontology (GO) and KEGG enrichment analyses of the differentially expressed genes (DEGs) were performed to explore processes involved in MSA-like disease progression. The overlap between transcriptional changes in MSA and those associated with aging was also evaluated. RNA-Seq analysis demonstrated significant transcriptional dysregulation in cerebellum from MSA mice, even at early stages. GO and KEGG analyses of DEGs point to a potential role of synaptic dysfunction, cellular signaling dysregulation and inflammation in the cerebellar pathology of MSA mice. In addition, those changes exacerbate with disease progression. Additionally, our analysis of aging in both control and PLP-αSyn mice showed that age-related transcriptional changes in mid-aged controls seem to be present in young MSA mice. Thus, MSA-like pathology might lead to an acceleration of aging-related mechanisms. Our findings demonstrate significant cerebellar transcriptional dysregulation triggered by oligodendroglial α-synucleinopathy in PLP-αSyn mice, revealing pathways that might be critical for the early cerebellar pathology of MSA, and that may serve as potential molecular targets for therapeutic interventions in this devastating disorder.

Objective:A wide range of non-motor symptoms such as pain, mood disorders, insomnia, and executive dysfunction may occur in focal dystonia. Little is known, however, about emotional processing. We aim to assess emotion recognition and alexithymia in patients with cervical dystonia (CD) compared to healthy age-, sex- and education-matched controls (HC). Methods:Emotion processing was assessed with an eye-tracking paradigm using a validated dataset of facial expressions and the Toronto Alexithymia Scale (TAS-20). Dystonia severity and disability, cognition, and comorbid depression and anxiety were also assessed. Results:We recruited 35 CD patients and 17 matched HC. In the eye-tracking task, CD patients recognized emotions less accurately than HCs (77.0% vs. 84.4%; p = 0.001), primarily based on difficulties in identification of fear (p = 0.003) and surprise (p = 0.037). Moreover, patients had longer fixations within the mouth region (p = 0.027) and left eye (p = 0.037) than HC. CD patients also had significantly higher total TAS-20 scores (p = 0.002) and subscores (difficulty identifying and describing feelings; all p ≤ 0.026). Five patients (14.3%) reached the threshold for alexithymia and 6 (17.1%) for possible alexithymia. No HC scored positive for alexithymia and only 2 (11.8%) did for possible alexithymia. TAS-20 score correlated inversely with emotion recognition task performance (r = -0.411; p = 0.014). Interpretation:We found poorer performance in emotion recognition in CD patients compared to HC. Together with a different gaze pattern and higher scores for alexithymia our results highlight deficits in emotion processing in CD.

BACKGROUND:Pain is a frequent yet poorly characterized symptom of multiple system atrophy (MSA). Understanding the factors influencing pain and its burden is crucial for improving the symptomatic treatment and quality of life of MSA individuals. OBJECTIVE:This study aimed at assessing the prevalence, characteristics, and current treatment strategies for pain in MSA. METHODS:A community-based, online survey was conducted from February to May 2023. Invitations were extended to MSA individuals and informal MSA caregivers through patient advocacies and social media. RESULTS:We included 190 persons with MSA and 114 caregivers. Eighty-seven percent of MSA individuals reported pain, which was more prevalent among women (odds ratio [OR]: 6.38 [95% confidence interval, CI: 1.27-32.08], P = 0.025) and low-income groups (OR: 5.02 [95% CI: 1.32-19.08], P = 0.018). Neck and shoulders (58%), back (45%), and legs (45%) were mostly affected. In the neck and shoulders, pain was associated with MSA core features, like orthostatic intolerance (OR: 4.80 [95% CI: 1.92-12.02], P = 0.001) and antecollis (OR: 3.24 [95% CI: 1.54-6.82], P = 0.002). Seventy-six percent of individuals experiencing pain received treatment, mostly nonsteroidal anti-inflammatory drugs (47%), acetaminophen (39%), and opioids (28%). Only 53% of respondents reported at least partial satisfaction with their current pain management. Pain mostly impacted work, household activities, and hobbies of MSA individuals, and caregivers' social activities. CONCLUSIONS:Pain is more prevalent than previously reported in MSA and particularly affects women and low-income groups. Despite its frequency, pain management remains suboptimal, highlighting an urgent therapeutic need, likely entailing an optimized management of MSA core motor and non-motor features. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

To investigate sex-related differences in the clinical presentation of multiple system atrophy (MSA) through a literature review and an analysis of a retrospective cohort. The PubMed database was searched for articles including sex-related information in MSA. In a retrospective Innsbruck cohort, we investigated the baseline to last available follow-up clinical-demographic differences between men and women with MSA in a univariate fashion, followed by multivariable binary regression analysis. The literature search yielded 46 publications with sex-related information in MSA. Most studies found comparable survival rates between the sexes, while some recent reports suggested a potential survival benefit for women, possibly due to initial motor onset and overall less severe autonomic failure compared to men. The retrospective Innsbruck MSA cohort comprised 56 female and 60 male individuals with a comparable median follow-up of 27 months. At baseline, female sex was independently associated with depression (odds ratio [OR] 4.7; p = 0.007) and male sex with severe orthostatic hypotension (OR 5.5; p = 0.016). In addition, at last follow-up, female sex was associated with the intake of central nervous system-active drugs (OR 4.1; p = 0.029), whereas male sex was associated with the presence of supine hypertension (OR 3.0; p = 0.020) and the intake of antihypertensive medications (OR 8.7; p = 0.001). Male sex was also associated with initiation of antihypertensive medications over the observation period (OR 12.4; p = 0.004). The available literature and findings of the present study indicate sex-related differences in the clinical presentation of MSA and its evolution over time, highlighting the importance of considering sex in symptom exploration, therapeutic decision-making, and future clinical trial design.

Background:Individuals with multiple system atrophy (MSA) often complain about pain, nonetheless this remains a poorly investigated non-motor feature of MSA. Objectives:Here, we aimed at assessing the prevalence, characteristics, and risk factors for pain in individuals with MSA. Methods:Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines, we systematically screened the PubMED, Cochrane, and Web of Science databases for papers published in English until September 30, 2022, combining the following keywords: "pain," "multiple system atrophy," "MSA," "olivopontocerebellar atrophy," "OPCA," "striatonigral degeneration," "SND," "Shy Drager," and "atypical parkinsonism." Results:The search identified 700 records. Sixteen studies provided information on pain prevalence in cohorts of MSA individuals and were included in a qualitative assessment based on the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Thirteen studies (11 cross-sectional, two longitudinal) scored ≥14 points on QUADAS assessment and were included in a quantitative analysis, pooling data from 1236 MSA individuals. The resulting pooled prevalence of pain in MSA was 67% (95% confidence intervals [CI] = 57%-75%), and significantly higher in individuals with MSA of parkinsonian rather than cerebellar type (76% [95% CI = 63%-87%] vs. 45% [95% CI = 33%-57%], P = 0.001). Pain assessment tools and collected information were highly heterogeneous across studies. Two studies reported pain treatment strategies and found that only every second person with MSA complaining about pain had received targeted treatment. Conclusions:We found that pain is a frequent, but still under-recognized and undertreated feature of MSA. Further research is needed to improve pain detection and treatment in MSA.

Purpose To understand the influence of the coronavirus disease 2019 (COVID-19) pandemic on clinical autonomic education and research in Europe. Methods We invited 84 European autonomic centers to complete an online survey, recorded the pre-pandemic-to-pandemic percentage of junior participants in the annual congresses of the European Federation of Autonomic Societies (EFAS) and European Academy of Neurology (EAN) and the pre-pandemic-to-pandemic number of PubMed publications on neurological disorders. Results Forty-six centers answered the survey (55%). Twenty-nine centers were involved in clinical autonomic education and experienced pandemic-related didactic interruptions for 9 (5; 9) months. Ninety percent ( n = 26/29) of autonomic educational centers reported a negative impact of the COVID-19 pandemic on education quality, and 93% ( n = 27/29) established e-learning models. Both the 2020 joint EAN–EFAS virtual congress and the 2021 (virtual) and 2022 (hybrid) EFAS and EAN congresses marked higher percentages of junior participants than in 2019. Forty-one respondents (89%) were autonomic researchers, and 29 of them reported pandemic-related trial interruptions for 5 (2; 9) months. Since the pandemic begin, almost half of the respondents had less time for scientific writing. Likewise, the number of PubMed publications on autonomic topics showed the smallest increase compared with other neurological fields in 2020–2021 and the highest drop in 2022. Autonomic research centers that amended their trial protocols for telemedicine (38%, n = 16/41) maintained higher clinical caseloads during the first pandemic year. Conclusions The COVID-19 pandemic had a substantial negative impact on European clinical autonomic education and research. At the same time, it promoted digitalization, favoring more equitable access to autonomic education and improved trial design.

OBJECTIVE:To investigate the impact of the coronavirus-disease-2019 (COVID-19) pandemic on European clinical autonomic practice.METHODS:Eighty-four neurology-driven or interdisciplinary autonomic centers in 22 European countries were invited to fill in a web-based survey between September and November 2021.RESULTS:Forty-six centers completed the survey (55%). During the first pandemic year, the number of performed tilt-table tests, autonomic outpatient and inpatient visits decreased respectively by 50%, 45% and 53%, and every-third center reported major adverse events due to postponed examinations or visits. The most frequent newly-diagnosed or worsened cardiovascular autonomic disorders after COVID-19 infection included postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension, and recurrent vasovagal syncope, deemed likely related to the infection by ≥50% of the responders. Forty-seven percent of the responders also reported about people with new-onset of orthostatic intolerance, but negative tilt-table findings, and 16% about people with psychogenic pseudosyncope after COVID-19. Most patients were treated non-pharmacologically and symptomatic recovery at follow-up was observed in ≥45% of cases. By contrast, low frequencies of newly-diagnosed cardiovascular autonomic disorders following COVID-19 vaccination were reported, most frequently POTS and recurrent vasovagal syncope, and most of the responders judged a causal association unlikely. Non-pharmacological measures were the preferred treatment choice, with 50-100% recovery rates at follow-up.CONCLUSIONS:Cardiovascular autonomic disorders may develop or worsen following a COVID-19 infection, while the association with COVID-19 vaccines remains controversial. Despite the severe pandemic impact on European clinical autonomic practice, a specialized diagnostic work-up was pivotal to identify non-autonomic disorders in people with post-COVID-19 orthostatic complaints.

BACKGROUND AND PURPOSE:Disorders of the autonomic nervous system (ANS) are common conditions, but it is unclear whether access to ANS healthcare provision is homogeneous across European countries. The aim of this study was to identify neurology-driven or interdisciplinary clinical ANS laboratories in Europe, describe their characteristics and explore regional differences. METHODS:We contacted the European national ANS and neurological societies, as well as members of our professional network, to identify clinical ANS laboratories in each country and invite them to answer a web-based survey. RESULTS:We identified 84 laboratories in 22 countries and 46 (55%) answered the survey. All laboratories perform cardiovascular autonomic function tests, and 83% also perform sweat tests. Testing for catecholamines and autoantibodies are performed in 63% and 56% of laboratories, and epidermal nerve fiber density analysis in 63%. Each laboratory is staffed by a median of two consultants, one resident, one technician and one nurse. The median (interquartile range [IQR]) number of head-up tilt tests/laboratory/year is 105 (49-251). Reflex syncope and neurogenic orthostatic hypotension are the most frequently diagnosed cardiovascular ANS disorders. Thirty-five centers (76%) have an ANS outpatient clinic, with a median (IQR) of 200 (100-360) outpatient visits/year; 42 centers (91%) also offer inpatient care (median 20 [IQR 4-110] inpatient stays/year). Forty-one laboratories (89%) are involved in research activities. We observed a significant difference in the geographical distribution of ANS services among European regions: 11 out of 12 countries from North/West Europe have at least one ANS laboratory versus 11 out of 21 from South/East/Greater Europe (p = 0.021). CONCLUSIONS:This survey highlights disparities in the availability of healthcare services for people with ANS disorders across European countries, stressing the need for improved access to specialized care in South, East and Greater Europe.

AbstractBackground and purposeDisorders of the autonomic nervous system (ANS) are common conditions, but it is unclear whether access to ANS healthcare provision is homogeneous across European countries. The aim of this study was to identify neurology‐driven or interdisciplinary clinical ANS laboratories in Europe, describe their characteristics and explore regional differences.MethodsWe contacted the European national ANS and neurological societies, as well as members of our professional network, to identify clinical ANS laboratories in each country and invite them to answer a web‐based survey.ResultsWe identified 84 laboratories in 22 countries and 46 (55%) answered the survey. All laboratories perform cardiovascular autonomic function tests, and 83% also perform sweat tests. Testing for catecholamines and autoantibodies are performed in 63% and 56% of laboratories, and epidermal nerve fiber density analysis in 63%. Each laboratory is staffed by a median of two consultants, one resident, one technician and one nurse. The median (interquartile range [IQR]) number of head‐up tilt tests/laboratory/year is 105 (49–251). Reflex syncope and neurogenic orthostatic hypotension are the most frequently diagnosed cardiovascular ANS disorders. Thirty‐five centers (76%) have an ANS outpatient clinic, with a median (IQR) of 200 (100–360) outpatient visits/year; 42 centers (91%) also offer inpatient care (median 20 [IQR 4–110] inpatient stays/year). Forty‐one laboratories (89%) are involved in research activities. We observed a significant difference in the geographical distribution of ANS services among European regions: 11 out of 12 countries from North/West Europe have at least one ANS laboratory versus 11 out of 21 from South/East/Greater Europe (p = 0.021).ConclusionsThis survey highlights disparities in the availability of healthcare services for people with ANS disorders across European countries, stressing the need for improved access to specialized care in South, East and Greater Europe.

Multiple system atrophy (MSA) is a rare, rapidly-progressive neurodegenerative disorder, neuropathologically characterized by oligodendroglial α-synuclein aggregates.1 While in Parkinson's disease (PD), a neuronal α-synucleinopathy, both monogenic forms and a polygenic risk profile are known,2 MSA is generally considered a sporadic disorder.1 A family history (FH) for parkinsonism or other neurodegenerative disorders may in fact occur in people with MSA, but the contribution of genetic factors to MSA pathogenesis is not fully understood to date.3, 4 Here we retrospectively assessed the frequency rates of FH for parkinsonism, dementia, tremor, ataxia, or motor neuron disease within first-to-third-degree relatives of people included in the Innsbruck MSA Registry (n = 144), and compared them with historical MSA cohorts (cumulative n = 1173), Innsbruck-based PD cases (n = 226), and published population-based controls (cumulative n = 20,784). A detailed methodological description is provided in Supplementary Document 1. Forty-five MSA cases (40%) had a positive FH for neurodegenerative disorders, with parkinsonism being most prevalent (n = 26, 18%). FH rates mostly matched or exceeded those of historical MSA cohorts (Fig. 1A). The cumulative first-to-third-degree FH rates for neurodegenerative disorders and familial clustering (ie, ≥2 affected relatives) remained comparable between the MSA and PD cohort (Fig. 1B). Compared to pooled population-based controls, first-degree FH rates for dementia were significantly lower in both the MSA and PD cohorts, whereas the rate of first-degree FH for parkinsonism in MSA cases (10%, 95% CI 6–17) was between that of PD (17%, 95% CI 13–23; P = 0.079) and population-based controls (6%, 95% CI 5–6; P = 0.012; Fig. 1C and Supplementary Document 2). The ultimate mechanisms underlying MSA pathogenesis remain largely unknown.1, 5 The high frequency of FH for parkinsonism in people with MSA, close to that of PD and exceeding the one observed in population-based elderly controls, supports the contention that multiple, yet unidentified genetic variants might contribute to MSA pathogenesis. It also suggests a shared genetic susceptibility to the development of MSA and PD. Our study has limitations. FH history was collected retrospectively, carrying the risk for a documentation bias, and with the FH method, which obtains information on FH exclusively from patients and may both under- and overestimate FH rates.6 In the age of genomic medicine, however, FH still represents a valuable tool to assess the heritability of a given disorder, especially if genetic methods fail to disclose a causal relation. Non-neurodegenerative causes of tremor, dementia, or parkinsonism were also not systematically excluded in the relatives of our patients; genetic testing was available in a small percentage of patients only; and neuropathological confirmation in none. We also did not include an age- and sex-matched control group, but compared our data with the cumulative results of historical MSA cohorts and large population-based studies in aging individuals. Similar to PD, genetic susceptibility variants — if discovered for MSA — may be exploited for identifying persons at risk of developing the disease or in very early stages thereof, when putative neuroprotective strategies should ideally be most effective.7 Understanding the genetic underpinnings of the MSA pathological cascade might ultimately point out new therapeutic targets for this currently untreatable condition. Academic study without external funding. Dr Leys was supported by the Stichting ParkinsonFonds, US MSA Coalition and Dr Johannes & Hertha Tuba Foundation. Due to its retrospective nature and initiation before July 2020, neither written informed consent nor ethic approval was required for the present study. This study was conducted in accordance with the Declaration of Helsinki and the current European Data Protection Regulation. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. The first and last named authors take full responsibility for the integrity of the data and the accuracy of the data analysis. The data supporting the findings of this study are available upon reasonable request from any qualified investigator. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the First Draft, B. Review and Critique. F.L.: 1B, 1C, 2B, 3A S.E.: 1C, 2C, 3B N.C.: 1C, 2C, 3B P.M.: 1A, 1C, 2C, 3B M.P.: 1C, 2C, 3B G.G.: 1A, 2A, 2C, 3B V.S.: 1A, 2C, 3B R.G.: 1A, 2C, 3B V.B.: 1A, 2C, 3B J.Z.: 1A, 2C, 3B S.K.: 1A, 2C, 3B W.P.: 1A, 2C, 3B K.S.: 1A, 2C, 3B G.K.W.: 1A, 2C, 3B A.F.: 1A, 1B, 1C, 2A, 2C, 3B F.L., S.E., N.C., P.M., M.P., G.G., V.S., R.G.: none. V.B.: receives research grants from the Stichting ParkinsonFonds and from Alzheimer Nederland (The Netherlands); honoraria from the International Parkinson and Movement Disorder Society, as Chair of the Congress Scientific Program Committee 2019–2021; and from Elsevier Ltd, as Co-Editor-in-Chief of Parkinsonism & Related Disorders, outside of the submitted work. J.Z.: none. S.K.: reports support from the Austrian Research Promotion Agency FFG, outside of the submitted work. W.P.: reports receiving personal fees from AbbVie, AFFiRiS, AstraZeneca, BIAL, Boston Scientific, Britannia, Intec, Ipsen, Lundbeck, NeuroDerm, Neurocrine, Denali Pharmaceuticals, Novartis, Orion Pharma, Prexton, Teva, UCB, and Zambon. He receives royalties from Thieme, Wiley Blackwell, Oxford University Press, and Cambridge University Press and grant support from The Michael J. Fox Foundation, EU FP7, and Horizon 2020, outside of the submitted work. K.S.: reports personal fees from Teva, UCB, Lundbeck, AOP Orphan Pharmaceuticals AG, Roche, Grünenthal, Stada, Licher Pharma, Biogen, BIAL, and Abbvie; honoraria from the International Parkinson and Movement Disorders Society; research grants from FWF Austrian Science Fund, The Michael J. Fox Foundation, and AOP Orphan Pharmaceuticals AG, outside the submitted work. G.K.W.: reports consultancy and lecture fees from AbbVie, AFFiRiS AG, AstraZeneca, Biogen, Biohaven, Inhibicase, Lundbeck, Merz, Ono, Teva, and Theravance, and research grants from the Austrian Science Fund (FWF), the Austrian National Bank, the US MSA Coalition, Parkinson Fonds Austria, the Dr Johannes und Hertha Tuba Foundation, and the International Parkinson and Movement Disorder Society, outside of the submitted work. A.F.: reports royalties from Springer Verlag, speaker fees and honoraria from Impact Medicom, Theravance Biopharma, AbbVie, the International Parkinson Disease and Movement Disorders Society, the Austrian Neurology Society, the Austrian Autonomic Society, and research grants from the Parkinson Fond, the US MSA Coalition, the Dr Johannes and Hertha Tuba Foundation, and the Austrian Exchange Program, outside of the submitted work. The data supporting the findings of this study are available upon reasonable request from any qualified investigator. Appendix S1. Supporting Information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

BACKGROUND:The pathophysiology of cervical dystonia is still unclear. Recent evidence points toward a network disorder affecting several brain areas. The objective of this study was to assess the saccadic inhibition as a marker of corticostriatal function in cervical dystonia. METHODS:We recruited 31 cervical dystonia patients and 17 matched healthy controls. Subjects performed an overlap prosaccade, an antisaccade, and a countermanding task on an eye tracker to assess automatic visual response and response inhibition. RESULTS:Cervical dystonia patients made more premature saccades (P = 0.041) in the overlap prosaccade task and more directional errors in the antisaccade task (P = 0.011) and had a higher rate of failed inhibition in the countermanding task (P = 0.001). CONCLUSIONS:The results suggest altered saccadic inhibition in cervical dystonia, possibly as a consequence of dysfunctional corticostriatal networks. Further studies are warranted to confirm whether these abnormalities are affected by the available therapies and whether this type of impairment is found in other focal dystonias. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: The pathophysiology of cervical dystonia is still unclear. Recent evidence points toward a network disorder affecting several brain areas. The objective of this study was to assess the saccadic inhibition as a marker of corticostriatal function in cervical dystonia. Methods: We recruited 31 cervical dystonia patients and 17 matched healthy controls. Subjects performed an overlap prosaccade, an antisaccade, and a countermanding task on an eye tracker to assess automatic visual response and response inhibition. Results: Cervical dystonia patients made more premature saccades (P = 0.041) in the overlap prosaccade task and more directional errors in the antisaccade task (P = 0.011) and had a higher rate of failed inhibition in the countermanding task (P = 0.001). Conclusions: The results suggest altered saccadic inhibition in cervical dystonia, possibly as a consequence of dysfunctional corticostriatal networks. Further studies are warranted to confirm whether these abnormalities are affected by the available therapies This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. *Correspondence to: Dr. Atbin Djamshidian, Department of Neurology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria; E-mail: atbin.djamshidian-tehrani@i-med.ac.at Relevant conflicts of interest/financial disclosures: Nothing to report. Funding agencies: The authors received no specific funding for this work. Received: 24 September 2020; Revised: 24 November 2020; Accepted: 16 December 2020 Published online 8 January 2021 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.28486 1246 Movement Disorders, Vol. 36, No. 5, 2021 C A R B O N E E T A L

Every third person with Parkinson’s disease (PD) may suffer from orthostatic hypotension (OH). Besides classic OH (cOH), transient orthostatic blood pressure (BP) drops may occur within the first minute upon standing, qualifying for transient OH (tOH). It is unclear whether morphometric factors, such as height and body mass index (BMI), promote OH in people with PD. For this reason, we analyzed a previously published cohort of 173 European patients with PD for differences in height and BMI across individuals with laboratory-confirmed cOH, tOH, or no OH. After comparing the morphometric and other clinicodemographic characteristics across patients with and without OH, we tested the association between BMI, height, and cOH or tOH, by calculating the area under the receiver operating characteristic (ROC) curve in males and females separately. The Youden index applied to the coordinates of the ROC curves determined the most accurate BMI and height cut-offs distinguishing patients with either cOH or tOH from those without. Whenever significant cut-offs were found, we compared the derived subgroups for differences in clinicodemographic features and autonomic function indices by means of univariate, binary logistic regression analysis and age-adjusted ANOVA for repeated measurements. The clinicodemographic features of the study population are reported elsewhere. In our cohort, cOH occurred in 19% (n = 32) of patients and tOH in 24% (n = 41). BMI did not differ between patients with either cOH (P = 0.270) or tOH (P = 0.798) compared with those without OH (Fig. 1). The ROC curve analysis excluded any differences in height among female patients with or without OH, but pinpointed a positive association between cOH and taller stature in male patients (Fig. 1). Male patients with cOH did not otherwise differ for any other clinicodemographic characteristic from those with tOH or no OH. The Youden index identified a height cutoff of ≥172.5 cm for predicting cOH in male patients with PD (Fig. 1). Both univariate and age-adjusted logistic regression analysis confirmed a negative association between cOH and shorter stature in males (odds ratio = 0.14 [95% confidence interval, 0.03–0.66]; P = 0.013), despite higher, yet not significant after Benjamini–Hochberg correction, frequencies of cardiovascular comorbidities and use of antihypertensive medications (Supporting Information Table S1). At hemodynamic monitoring, shorter patients showed an average systolic BP increase after 3 minutes on standing, while patients ≥172.5 cm tall had a decrease (P = 0.030; Supporting Information Fig. S1). The remaining cardiovascular autonomic function indices did not differ across the height groups (Supporting Information Fig. S1). Pilot studies in Asian PD populations suggested an association between lower BMI and cOH. Here we did not observe any difference in BMI across male or female patients with PD with either cOH, tOH or no OH. This inconsistency possibly reflects ethnic and morphometric differences between European and Asian natives. Elderly, otherwise healthy, shorter subjects show higher BP values compared with taller subjects, potentially reflecting underlying hydrostatic mechanisms. The fact that cardiovascular autonomic function indices other than cOH were equally impaired in shorter and taller patients suggests that analogous, non-neurogenic mechanisms may prevent shorter individuals with PD from developing clinically relevant BP declines on standing. Identifying individual OH risk factors may optimize screening measures for this frequently overlooked condition.

BackgroundThe treatment of patients with recurrent and/or metastatic (R/M) salivary gland adenoid cystic carcinoma (ACC) remains an unmet need.MethodsPatients with R/M disease with a history of clinical or symptomatic disease progression within 6 months and a maximum of 1 previous line of chemotherapy or a multiple kinase inhibitor received oral lenvatinib at a dose of 24 mg/day. The primary endpoint was the objective response rate; secondary endpoints included quality of life (QOL) (according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 Items [EORTC QLQ‐C30] and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core Module Head and Neck Module [EORTC QLQ‐H&N35]), progression‐free survival and overall survival, duration of response, and toxicities.ResultsTwenty‐eight patients with R/M ACC were enrolled. Among 26 evaluable patients, 3 partial responses (11.5%) were reported. Target lesion reductions between 23% to 28% were observed in 4 of 20 patients with stable disease. Treatment‐related adverse events were frequent (all grades, 96%; grade≥3 in 50% of cases according to version 4.03 of the National Cancer Institute Common Terminology Criteria for Adverse Events). The dose of lenvatinib was reduced in 24 patients, whereas in 21 patients the dose was reduced within the first 12 weeks and 4 patients maintained the full dose throughout treatment. The QOL deteriorated between baseline and 6 months with regard to Fatigue and Dry Mouth. There was no evidence of changes in Swallowing and Physical Functioning. At a median follow‐up of 29 months, 2 patients remained on treatment, 10 patients were off protocol for disease progression and were alive with disease, and 14 patients had died of disease progression. The median overall survival, progression‐free survival, and duration of response were 27 months, 9.1 months, and 3.1 months, respectively.ConclusionsLenvatinib appears to have modest activity in ACC. Toxicities are common but manageable and QOL was found to deteriorate in some domains.

Background Gait impairment is a pivotal feature of parkinsonian syndromes and increased gait variability is associated with postural instability and a higher risk of falls. Objectives We compared gait variability at different walking velocities between and within groups of patients with Parkinson-variant multiple system atrophy, idiopathic Parkinson's disease, and a control group of older adults. Methods Gait metrics were recorded in 11 multiple system atrophy, 12 Parkinson's disease patients, and 18 controls using sensor-based gait analysis. Gait variability was analyzed for stride, swing and stance time, stride length and gait velocity. Values were compared between and within the groups at self-paced comfortable, fast and slow walking speed. Results Multiple system atrophy patients displayed higher gait variability except for stride time at all velocities compared with controls, while Parkinson's patients did not. Compared with Parkinson's disease, multiple system atrophy patients displayed higher variability of swing time, stride length and gait velocity at comfortable speed and at slow speed for swing and stance time, stride length and gait velocity (all P < 0.05). Stride time variability was significantly higher in slow compared to comfortable walking in patients with multiple system atrophy (P = 0.014). Variability parameters significantly correlated with the postural instability/gait difficulty subscore in both disease groups. Conversely, significant correlations between variability parameters and MDS-UPDRS III score was observed only for multiple system atrophy patients. Conclusion This analysis suggests that gait variability parameters reflect the major axial impairment and postural instability displayed by multiple system atrophy patients compared with Parkinson's disease patients and controls.