prodromal model of parkinson's disease confined to the peripheral nervous system

Conditions: Polyneuropathy; Alpha-Synucleinopathy; Lewy Body Disease; Parkinson Disease (PD); Lewy Body Dementia (LBD); Multiple System Atrophy; Autonomic Failure; Cardiac Imaging; Rapid Eye Movement Sleep Behavior Disorder; REM Sleep Behavior Disorder (iRBD); REM Behavior Disorder

Summary: description of a method to detect parkinson's disease or parkinson's-like disease at an early stage (prodromal parkinson's disease) where damage is still confined to the peripheral nervous system damage. simultaneous collection of biological material to establish a biobank for use as prognostic biomarkers for the development of parkinson's disease and other neurodegenerative diseases in which pathological alpha-synuclein deposits accumulate.

primary aim (baseline): to assess the prevalence of isolated rem sleep behavior disorder (irbd) or rem sleep without atonia (rswa) in patients with idiopathic polyneuropathy with as to without abnormal cardiac 123i-metaiodobenzylguanidine (mibg) scintigraphy (assessment of cardiac sympathetic innervation) secondary aim (baseline): to assess the prevalence of parkinson's disease (pd), dementia with lewy bodies (dlb) and multiple system atrophy (msa) in patients with idiopathic polyneuropathy. hypothesis (baseline): irbd is more prevalent in patients known with idiopathic polyneuropathy and abnormal sympathetic innervation of the heart (assessed by cardiac 123i-mibg scintigraphy) as compared to normal cardiac sympathetic innervation. primary aim (5-follow-up): to assess whether patients with idiopathic polyneuropathy develop rswa, irbd, pd, dlb or msa over a periode of five years. hypothesis (5-follow-up): patients known with idiopathic polyneuropathy and abnormal sympathetic innervation of the heart (assessed by cardiac 123i-mibg scintigraphy) will convert to rswa, irbd, pd, dlb or msa more often than those with normal cardiac sympathetic innervation. methods: clinical evaluation in combination with questionnaires, multi-modal imaging methods and polysomnography. (assessment of neuropathy: neuropathy impairment score - lower leg (nis-ll), utah early neurological scale (uens), kumamoto neurological scale and autonomic function test including tilt table test, valsalva maneuver, deep breathing test, the quantitative sensory axon reflex test (qsart). cognition: the montreal cognitive assessment (moca), trail making test b (tmt-b). motor function: mds-unified parkinson's disease rating scale part iii (mds-updrs-iii). multi-modal imaging: cardiac 123i-mibg scintigraphy, pe2i-pet-ct, mr-neuromelanin. sleep: rem sleep behavior disorder screening questionnaire (rbdsq), one-night video polysomnography (psg).) statistics: the researchers expect to enroll 100 participants with idiopathic polyneuropathy and orthostatic hypotension or abnormal 24-hour blood pressure measurement (non-nocturnal blood pressure dip) who have undergone cardiac 123i-mibg scintigraphy. based on preliminary results, the investigators expect that 1/3 (30 participants) will have abnormal cardiac mibg scintigraphy (cases; suggested to have prodromal pd or dlb) and 2/3 (70 participants) with normal mibg scintigraphy (controls). the prevalence of irbd detected by video-psg is assumed to be 5% in participants with normal cardiac mibg scintigraphy and 35% in participants with abnormal mibg scintigraphy. to achieve a power of 88%, 81 participants have to be included (54 with normal and 27 with abnormal cardiac mibg scintigraphy). power calculation was based on fisher's exact-test. fisher's exact test was used because of an expected small number of participants with video psg-detected irbd. biobank: simultaneously collection of body tissue/fluids: skin, blood, cerebrospinal fluid and faeces. analysis of the levels of phosphorylated tau, total-tau and amyloid beta in cerebrospinal fluid is performed at baseline.

Eligibility criteria:
inclusion criteria: * definite polyneuropathy without known etiology (idiopathic) and orthostatic hypotension (active stand test) or non-nocturnal blood pressure reduction (24 hour blood pressure measurement) exclusion criteria: * known etiology of polyneuropathy * a diagnosis of either dementia, parkinson's disease, dementia with lewy bodies or multiple system atrophy.

Keywords: isolated rapid eye movement sleep behavior disorder rem sleep behavior disorder polyneuropathy idiopathic polyneuropathy cardiac mibg scintigraphy prodromal lewy body disease lewy body disease alpha-synucleinopathy