Clinical autonomic nervous system laboratories in Europe: a joint survey of the European Academy of Neurology and the European Federation of Autonomic Societies

© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.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.info:eu-repo/semantics/publishedVersio

EFAS/EAN survey on the influence of the COVID-19 pandemic on European clinical autonomic education and research

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.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.info:eu-repo/semantics/publishedVersio

Estudio del sistema nervioso autónomo en la enfermedad de Parkinson y otras alfasinucleinopatías

[spa] INTRODUCCIÓN: Las sinucleinopatías son enfermedades neurodegenerativas que se definen por la presencia de agregados anómalos de alfa sinucleína (AS) intraneuronales (principalmente cuerpos de Lewy-LB) o gliales. Clínicamente se caracterizan por la presencia de los llamados síntomas motores (parkinsonismo) junto con los no motores, entre los que se encuentran los síntomas de disautonomía. El sustrato de los síntomas de disfunción autonómica de la sinucleinopatía más frecuente, la enfermedad de Parkinson (PD), no está claro. Se piensa que la disautonomía cardiovascular es una de las primeras alteraciones que ocurren en la PD y que también el tracto gastrointestinal se encuentra alterado desde el inicio más temprano. Esta hipótesis está basada en hallazgos histopatológicos, estudios epidemiológicos y funcionales. La detección post-mortem de depósitos anómalos de AS en pacientes sin sintomatología motora ha permitido acuñar el término de “enfermedad de cuerpos de Lewy incidentales” (iLBD). El hallazgo post-mortem de cuerpos de Lewy no se considera un simple marcador de envejecimiento celular. En los últimos años se está trabajando en detectar en vida a sujetos con cuerpos de Lewy incidentales sin clínica sugestiva de enfermedad neurológica para poder confirmar o descartar su progresión a una sinucleinopatía clínica. OBJETIVOS: Describir las características del sistema nervioso autónomo en la enfermedad de Parkinson y otras sinucleinopatías, partiendo de la hipótesis de que en las enfermedades neurodegenerativas asociadas a cuerpos de Lewy a nivel del SNC existe una afectación generalizada del SNAP. Apoyar que la alteración en el SNAP permite la distinción entre enfermedad de Parkinson y otros parkinsonismos no asociados a cuerpos de Lewy. RESULTADOS: Realizamos un estudio post-mortem en el que todos los sujetos con confirmación patológica de tener una enfermedad ligada a LB incluyendo 1 caso con iLBD tenían agregados de AS en el sistema nervioso autónomo periférico (pANS) con un gradiente descendente cráneo-caudal de patología en la cadena simpática y en el tracto gastrointestinal. En un segundo estudio exponemos que los agregados de AS pueden ocurrir in vivo en el pANS epicárdico de sujetos sin parkinsonismo, sugiriendo el diagnóstico de iLBD. La presencia en algunos de estos sujetos de síntomas no-motores como sueños vivos y estreñimiento que aparecen también en la PD premotora apoya esta interpretación. Por último, un tercer estudio sugiere que el uso del 123I-MIBG SPECT cardiaco podría ayudar en el diagnóstico diferencial entre los pacientes PD y otros parkinsonismos en los que el diagnóstico quede incierto a pesar de otros estudios. CONCLUSIONES: En las enfermedades asociadas a agregados patológicos de alfa sinucleína en forma de cuerpos y neuritas de Lewy a nivel del sistema nervioso central existe depósito de estos agregados en el sistema nervioso autónomo periférico que no aparece en otras enfermedades neurodegenerativas. El plexo cardíaco, ganglio estrellado y cadena simpática ganglionar se encuentran afectados por depósitos de alfa sinucleína en todos los sujetos con confirmación neuropatológica de enfermedad de Parkinson, demencia con cuerpos de Lewy y cuerpos de Lewy incidentales. La distribución de agregados de alfa sinucleína en cadena simpática y tracto gastrointestinal presenta un gradiente descendente cráneo-caudal. Hasta un 8% de sujetos asintomáticos presentan en vida agregados de alfa sinucleína a nivel del plexo cardiaco. Ello sugeriría que estos sujetos podrían encontrarse en una etapa pre-motora de una sinucleinopatía. Dada la frecuente afectación del pANS cardiaco, el estudio funcional de la inervación autonómica cardiaca mediante SPECT miocárdico con 123I-MIBG podría ser de utilidad en el estudio del parkinsonismo vascular cuando se sospeche una enfermedad de Parkinson coexistente.[eng]INTRODUCTION: Alphasinucleinopathies are neurodegenerative disorders defined by the presence of abnormal alpha-synuclein (AS) aggregates. These aggregates can be localized intraneuronally ( mainly Lewy bodies, LB) or in the neuroglia. These disorders are clinically characterized by motor symptoms (parkinsonism) and other so called “non-motor symptoms”, including here dysautonomic features. The final cause of dysautonomic dysfunction in the most common synucleinopathy (Parkinson´s disease, PD) is still unclear. However, cardiovascular dysautonomia could be one of the first features of PD. Also, gastrointestinal tract is thought to be involved even in early PD. This idea is supported by histopathological studies, epidemiologic research and functional studies. AS aggregates can be also detected post-mortem in subjects without clinical parkinsonism, who are now known as subjects affected from “incidental Lewy body disease” (iLBD). Several study groups are trying to detect living iLBD subjects in order to study their progression, if any, to clinical synucleinopahies. OBJECTIVES: To describe the characteristic of the autonomic nervous system (ANS) in PD and other synucleinopathies based on the hypothesis of a widespread ANS involvement in diseases with presence of LB at central nervous system (CNS) level. To describe the utility of applying functional ANS studies as a tool in the differential diagnosis of synucleinopathies. RESULTS: We described in a post-mortem study that every subject with confirmed diagnosis of a LB-related disease (including one iLBD) presented abnormal AS aggregates at peripheral ANS level. On our second paper, we described in vivo AS epicardic fat involvement in subjects without parkinsonism, that is, living iLBD subjects. Some of these subjects also presented with non-motor symptoms suggestive of PD such as constipation and vivid dreams. Our third study supports the role of cardiac 123I-MIBG SPECT as an useful tool in the differential diagnosis between PD and vascular parkinsonism. CONCLUSIONS: If a disorder is related to abnormal CNS LB or Lewy neurites, the peripheral ANS is going to be also involved by abnormal AS aggregates. Cardiac plexus, stellate ganglia and sympathetic chain are involved by AS aggregates in every subject with the diagnosis of PD, dementia with Lewy bodies and iLBD. Up to 8% of asymptomatic subjects could present in vivo AS aggregates in cardiac plexus. Due to the high prevalence of cardiac ANS in synucleinopathies, its functional study using 123I-MIBG SPECT could be useful in the differential diagnosis of vascular parkinsonism if a co-existent PD is suspected

Diagnosing Premotor Multiple System Atrophy: Natural History and Autonomic Testing in an Autopsy Confirmed Cohort

BACKGROUND AND OBJECTIVES: Non-motor features precede motor symptoms in many patients with multiple system atrophy (MSA). However, little is known about differences between the natural history, progression and prognostic factors for survival in MSA subjects with non-motor versus motor presentations. We aimed to compare initial symptoms, disease progression and clinical features at final evaluation and investigate differences in survival and natural history between MSA patients with motor and non-motor presentations. METHODS: Medical records of autopsy-confirmed MSA cases at Queen Square Brain Bank who underwent both clinical examination and cardiovascular autonomic testing were identified. Clinical features, age at onset, gender, time from onset to diagnosis, disease duration, autonomic function tests and plasma noradrenaline levels were evaluated. RESULTS: 47 autopsy-confirmed MSA patients (60+8 years; 28 males) were identified. Time from symptom onset to first autonomic evaluation was 4+2 years and disease duration was 7.7+2.2 years. Fifteen (32%) patients presented with non-motor features including genitourinary dysfunction, orthostatic hypotension or REM sleep behaviour disorder prior to developing motor involvement (median delay 1-6 years). A third (5/15) were initially diagnosed with pure autonomic failure (PAF) before evolving into MSA. All these patients had normal supine plasma noradrenaline levels (332.0+120.3 pg/ml) with no rise on head-up tilt (0.1+0.3 pg/ml).MSA patients with early cardiovascular autonomic dysfunction (within 3 years of symptom onset) had shorter survival compared to those with later onset of cardiovascular autonomic impairment (6.8 years [5.6-7.9] vs 8.5 years [7.9-9.2]; p=0.026).Patients with early urinary catheterisation had shorter survival than those requiring catheterisation later (6.2 years [4.6-7.8] vs 8.5 years [7.6-9.4]; p=0.02). The survival of MSA patients presenting with motor and non-motor symptoms did not differ (p>0.05). DISCUSSION: Almost one-third of MSA patients presented with non-motor features, which could predate motor symptoms by up to 6 years. Cardiovascular autonomic failure and early urinary catheterisation were predictors of poorer outcomes. A normal supine plasma noradrenaline level in patients presenting with PAF phenotype is a possible autonomic biomarker indicating later conversion to MSA

Clinical autonomic nervous system laboratories in Europe: A joint survey of the European Academy of Neurology and the European Federation of Autonomic Societies

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