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

Multiple system atrophy (MSA) is a rare and rapidly progressive neurodegenerative disorder characterized by a variable combination of autonomic failure, parkinsonism, and cerebellar ataxia, with a median survival of 8–10 years from symptom onset. Its aetiology remains poorly understood, as most cases are sporadic and environmental contributors remain unclear. Neuropathologically, MSA is defined by the accumulation of α-synuclein within oligodendroglial cells, forming glial cytoplasmic inclusions that drive widespread neurodegeneration in striatonigral and olivopontocerebellar systems. Recent advances in diagnostic criteria and biomarker development have improved disease recognition; however, early diagnosis remains challenging, particularly during the prodromal phase, when clinical features overlap with other α-synucleinopathies. Advances in fluid biomarkers and multimodal imaging are expected to facilitate earlier detection, improve diagnostic accuracy, and provide more robust tools for monitoring disease progression. Therapeutic development has largely focused on targeting α-synuclein pathology, but these approaches have not yet demonstrated consistent clinical benefit, highlighting the biological complexity of MSA. In the absence of curative treatments, management remains largely supportive, aimed at symptom control, particularly addressing autonomic dysfunction and motor impairment. Emerging care models, including telemedicine and multidisciplinary management, are reshaping clinical practice and may improve access to specialized care. Bridging advances in pathophysiology with patient-centred care will be essential for improving outcomes in MSA.

Cardiovascular autonomic failure is a frequent non-motor feature of Parkinson’s disease (PD) that affects up to one third of individuals from the premotor to the advanced stages of the disease, with major diagnostic, therapeutic and prognostic implications. It may manifest with orthostatic, post-prandial or exercise-induced hypotension, as well as hypertensive episodes in the supine position during wakefulness or nocturnal sleep. Hypotensive episodes may remain asymptomatic or manifest with symptoms of end-organ hypoperfusion in the upright position, after meals or during exertion that may include lightheadedness, blurred vision, cognitive slowness, shuffling gait, back pain, fatigue or, in severe cases, syncope. Supine and nocturnal hypertension are likewise often asymptomatic, yet may cause nocturnal polyuria, and disrupt sleep through frequent nocturnal toilet visits. Bedside screening for cardiovascular autonomic failure relies on targeted history taking, eventually supported by validated questionnaires, and supine to standing heart rate and blood pressure measurements. A more detailed assessment is obtained with cardiovascular autonomic function tests under continuous, non-invasive, hemodynamic monitoring, complemented by 24-hours ambulatory blood pressure monitoring and home blood pressure diaries. Hypotensive episodes are managed by addressing potential triggers, such as infections, anemia, dehydration and polypharmacy, followed by a stepwise implementation of behavioral, non-pharmacological and pharmacological strategies. Individuals with orthostatic hypotension should be constantly monitored for concomitant supine and nocturnal hypertension, especially if treatment with pressor agents has been recently started. Hypertensive episodes are likewise treated in a stepwise fashion with preventive, non-pharmacological and pharmacological measures, prioritizing hypotension control during daytime and mitigating hypertension overnight.

Multiple system atrophy (MSA) represents a management challenge due to its variable clinical presentation, and lack of established multidisciplinary care protocols. In advanced stages, physical barriers often prevent access to specialized care, leaving patients and caregivers to face complications and fear alone. This 18-month, monocentric, open-label study evaluates the impact of a personalized, multidisciplinary treatment, integrating mobile palliative care, on the quality of life (QoL, measured by EQ-5D-5L indices) of MSA individuals compared to a matched historical European MSA cohort. Forty-six participants will undergo baseline clinical, psychological, and neuro-rehabilitation assessments, along with an online interview to identify individual healthcare preferences. These assessments will guide personalized therapeutic plans, including palliative care, self-directed physio-, speech, and occupational exercises, based on operational protocols informed by evidence and good clinical practice. Six-, 12-, and 18-month follow-ups will reassess needs and adapt plans to address disease progression and changing preferences, ensuring continuous personalization. Repeated interviews at month-12, phone-calls and satisfaction surveys at month-1, 7, 13, and 18 will monitor compliance, identify barriers, and gather feedback. A subgroup of 23 participants will be block-wise randomized to additionally receive monthly and on-demand telemedicine visits for tailored support. Informal caregivers will join an 18-month observational study assessing their QoL and burden through repeated evaluations, offering insights into evolving challenges. We expect that multidisciplinary, patient-centered care with integrated mobile palliative and telemedicine support helps to warrant continuity of care and improve the QoL of MSA individuals throughout the disease course. Its acceptance, safety, and cost-effectiveness will be also assessed.

Cardiovascular autonomic disorders (CAD) were described following COVID-19 infection and vaccination, but previous reports were limited in size and follow-up. Here, we aimed to investigate the type and frequency of newly diagnosed and exacerbated CAD following COVID-19 infection or vaccination, and assessed their associated autonomic and non-autonomic complaints, applied treatment, and clinical outcome at last follow-up. Medical records of individuals referred to the Innsbruck Dysautonomia Center between March 2020 and March 2023 were reviewed for new onset of orthostatic intolerance, recurrent syncope, OR exacerbation of previously diagnosed CAD within 6 weeks from a passed COVID-19 infection or vaccination. Following COVID-19 infection (n = 75), 22 (29

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.

BackgroundUrinary and sexual symptoms are common following neurological disease, and we aimed to develop multidisciplinary inter-society evidence-based management guidelines.MethodsThe ADAPTE framework was used, and a systematic search of guidelines published in different languages was performed. Guidelines, consensus statements, and systematic reviews were included, and guideline quality was appraised using AGREE II. Patient representatives reviewed the relevance and suitability of recommendations. A modified Delphi process integrating the Evidence to Decision framework adapted from GRADE and the Oxford Centre for Evidence Based Medicine system was used to reach consensus on recommendation wording and strength.ResultsRecommendations were drafted, using guidelines/consensus statements (59 urinary, 50 sexual), systematic reviews (8 urinary, 2 sexual) and others (7 urinary,13 sexual), and wordings/strengths achieved at least 80% consensus through 2 Delphi rounds. Eleven evidence-based recommendations, 19 good practice statements, and 8 consensus-based recommendations were made. Individuals with neurological diseases should be asked about urogenital symptoms and undergo targeted physical examination when appropriate. Urinary symptom assessments include urinalysis, bladder diary completion, and post-void residual volume measurement. Treatments include fluid intake optimization, pelvic physiotherapy, tibial nerve stimulation, and oral medications. Urinary retention is managed by intermittent catheterization. Antibiotics should not be recommended to treat asymptomatic bacteriuria. Suprapubic catheterization is preferred for long-term catheterization. A comprehensive sexual history should be taken, focusing on multidimensional factors affecting sexual health. Treatments include lubricants, vibrators, and phosphodiesterase-5 inhibitors. Red flag symptoms warrant a shared-care approach with specialist colleagues.ConclusionsThe 38 NEUROGED recommendations will guide neurologists to comprehensively manage urogenital symptoms reported by individuals with neurological diseases.

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.

Multiple system atrophy (MSA) is an adult-onset, sporadic synucleinopathy characterized by parkinsonism, cerebellar ataxia, and dysautonomia. The genetic architecture of MSA is poorly understood, and treatments are limited to supportive measures. Here, we performed a comprehensive analysis of whole genome sequence data from 888 European-ancestry MSA cases and 7,128 controls to systematically investigate the genetic underpinnings of this understudied neurodegenerative disease. We identified four significantly associated risk loci using a genome-wide association study approach. Transcriptome-wide association analyses prioritized USP38-DT, KCTD7, and lnc-KCTD7-2 as novel susceptibility genes for MSA within these loci, and single-nucleus RNA sequence analysis found that the associated variants acted as cis-expression quantitative trait loci for multiple genes across neuronal and glial cell types. In conclusion, this study highlights the role of genetic determinants in the pathogenesis of MSA, and the publicly available data from this study represent a valuable resource for investigating synucleinopathies.

BackgroundA 4-item score based on >= 2 features out of orthostatic hypotension, overactive bladder, urinary retention and postural instability was previously shown to early distinguish the Parkinson-variant of multiple system atrophy (MSA-P) from Parkinson's disease (PD) with 78% sensitivity and 86% specificity. ObjectivesTo replicate and improve the 4-item MSA-P score. MethodsWe retrospectively studied 161 patients with early parkinsonism [ie, <= 2 years disease duration or no postural instability, aged 64 (57; 68) years, 44% females] and a diagnosis of clinically established MSA-P (n = 38) or PD (n = 123) after >= 24 months follow-up. ResultsThe 4-item MSA-P score had a 92% sensitivity and 78% specificity for a final MSA-P diagnosis. By including dopaminergic responsiveness and postural deformities into a 6-item score (range: 0-6), reaching >= 3 points at early disease identified MSA-P patients with 89% sensitivity and 98% specificity. ConclusionsThe 6-item MSA-P score is a cost-effective tool to pinpoint individuals with early-stage MSA-P.

Sleep disorders, daytime sleepiness, and autonomic dysfunction are commonly reported among patients with multiple system atrophy and Parkinson disease (PD). We aimed to assess sleep and autonomic function in these patients to evaluate the relationships between sleep disorders, excessive daytime sleepiness, and autonomic function. Twenty patients with multiple system atrophy (n = 7) and PD (n = 13) underwent clinical assessment including questionnaires for autonomic function and sleep. Cardiovascular autonomic function tests and 2-night video-polysomnography were followed by administration of the Multiple Sleep Latency Test. Rapid eye movement sleep without atonia was quantified in the chin, flexor digitorum superficialis, tibial anterior, and sternocleidomastoid muscles. Rapid eye movement sleep behavior disorder was associated with orthostatic hypotension (P = .017) and constipation (P = .019) in PD. Patients with orthostatic hypotension had higher rapid eye movement sleep without atonia indices than those without orthostatic hypotension (P < .001). The Sleep Innsbruck Barcelona rapid eye movement sleep without atonia index (“any” chin and/or flexor digitorum superficialis) correlated with systolic/diastolic blood pressure fall upon tilt-table examination in patients with multiple system atrophy (P < .05) and with gastrointestinal (P = .010), urinary (P = .022), and total Scales for Outcomes in Parkinson’s Disease-Autonomic Dysfunction scores (P = .006) in all patients. Patients with a pathological deep breathing ratio showed higher Sleep Innsbruck Barcelona indices (P = .031). Objective daytime sleepiness was exclusively present in PD (P = .034) and correlated with levodopa-equivalent dosage (P = .031). The relationship of autonomic dysfunction with rapid eye movement sleep without atonia in PD and multiple system atrophy is accounted for by shared brainstem neuropathology and likely identifies patients in a more advanced stage of disease. Excessive daytime sleepiness is found exclusively in PD and may be secondary to levodopa treatment and not related to α-synuclein disease. Eckhardt C, Fanciulli A, Högl B, et al. Analysis of sleep, daytime sleepiness, and autonomic function and multiple system atrophy and Parkinson disease: A prospective study. J Clin Sleep Med. 2023;19(1):63–71.

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.

Dementia with Lewy bodies (DLB) is a fatal α-synucleinopathy characterized by progressive cognitive decline with fluctuations in attention and alertness, visual hallucinations, rapid-eye-movement sleep behavior disorder, and parkinsonism. The features are often variable, reflecting the diffuse distribution of Lewy bodies in the central nervous system. Many individuals with DLB also suffer from severe progressive autonomic failure, with a significant impact on quality of life and prognosis. The associated disturbances are a consequence of predominantly postganglionic impairment of the autonomic nervous system. Although consensus criteria were revised several times, the diagnostic accuracy of premortem DLB remains suboptimal. At pathological examination, one-fifth of clinical DLB diagnoses turn out to be Parkinson's or Alzheimer’s disease. Vice versa, in clinical practice, DLB may be misdiagnosed with other α-synucleinopathies, such as multiple system atrophy, due to prominent autonomic failure. Treatment targets both motor and non-motor features; however, beneficial effects are usually short-lived and treating one symptom may exacerbate another. The DLB-specific evidence-base remains insufficient; therefore, therapeutic approaches are often based on clinical experience, expert opinion, or follow recommendations for related disorders. We here present an overview of the clinical aspects, differential diagnosis, and practical management in DLB.

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.