Autonomic Small Fiber Neuropathy and Ehlers Danlos Syndromes - Prospective Study and Registry

Study Overview
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Brief Summary
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We examine patients with different autonomic neuropathies and Ehlers Danlos syndromes compared to healthy controls at three different points over time (baseline, after 3 months and after 1.5 years) to gain knowledge about the course of this disease and understand its pathophysiology, with a focus on Small Fiber neuropathy. Moreover we will validate the german version of the Malmö POTS Score and establish an easy diagnostic scheme for patients in outpatient care.

Detailed Description
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Inclusion of patients with autoimmune autonomic neuropathies/ pure autonomic failure, postural orthostatic tachycardia syndrome, small fiber neuropathies, Ehlers-Danlos syndromes, Mast cell activation syndrom, Chronic fatigue syndrome and PostCOVID syndrome in our Registry study with follow up visits. Comparison to healthy controls concerning selected examinations. Planned examinations are laboratory tests, questionnaires on mental and physical health status and circulatory disorders, attention tests, tilt table testing, standing test, sweat function, investigation of small fiber function via quantitative sensory testing as well as the density of nerve fibers in the skin. Measurements are performed at baseline mostly in clinical routine and follow up visits are offered.

Official Title
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Autonomic Neuropathy and Its Pathophysiology in Autoimmune Autonomic Neuropathies, Postural Orthostatic Tachycardia Syndrome and Ehlers Danlos Syndromes: Peripheral Autonomic Small Fiber Neuropathy or Central Autonomic Failure? Validation of the Malmö POTS Score and a Better Diagnosis of POTS in Patientes With Autnomic Failure (VaGeMAPS-3-step-Diag)

Conditions
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Autonomic Neuropathy, Ehlers-Danlos Syndrome Hypermobility Type, Small Fiber Neuropathy, Postural Tachycardia Syndrome

Intervention / Treatment
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* Other: No intervention planned, but all patients get our standart treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: autonomic neuropathy Postural orthostatic tachycardia syndrome hypermobile or classical Ehlers Danlos syndromes Chronic fatigue syndrome, mast cell activation syndrome and/or PostCOVID healty controls between 18-80 years in patients: diagnosis and clinical testing in our outpatient clinic German speaking Exclusion Criteria: pregnancy Pacemaker or Deep brain Stimulation sensory or motor Polyneuropathy neurodegenerative disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Postural Orthostatic Tachycardia Syndrome<br>Patients with orthostatic intolerance because of Postural orthostatic tachycardia syndrome diagnosed in our outpatient clinic by tilt table examination. | Other: No intervention planned, but all patients get our standart treatment<br>* Patients are selected from clinical Routine and get our standart Treatment based on their disease<br>|
| Ehlers Danlos Syndrome<br>Patients with hypermobile or classical EDS who are already diagnosed including genetical testing for classical or vascular EDS and Marfan Syndromes | Other: No intervention planned, but all patients get our standart treatment<br>* Patients are selected from clinical Routine and get our standart Treatment based on their disease<br>|
| Autoimmune autonomic neuropathy/Pure autonomic failure<br>Patients who have an autoimmune autonomic neuropathy based on clinical diagnosis and antibody testing in our outpatient clinic. Cardial MIBG Scintigraphy should have been performed. | Other: No intervention planned, but all patients get our standart treatment<br>* Patients are selected from clinical Routine and get our standart Treatment based on their disease<br>|
| Healthy controls<br>Healthy controls with no documented cardiovascular or neurological disorders and no symtoms of autonomic failure/dizziness/fainting | |
| others<br>Patients who have comorbidities as mast cell activation syndrome, chronic fatigue and/or Post COVID syndrome, based on clinical diagnosis in our outpatient clinic. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure | Change in systolic and diastolic blood pressure over time | baseline, 3 months and 18 months | 
| Heart frequency | Change in heart frequency over time | baseline, 3 months and 18 months | 
| Skin biopsy | intraepithelial nerve fiber density between groups | baseline | 
| Composite autonomic severity Score | Change of the Score over time, the results are interpreted as normal (score=0), mild (score=1-3), moderate (score=4-6) or severe (score=7-10) | baseline, 3 months and 18 months |