Prodromal Model of Parkinson's Disease Confined to The Peripheral Nervous System

Brief Summary

Detailed Description

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.

Primary Outcomes

Secondary Outcomes

• Number of participants with Parkinson's Disease (PD) or related alpha-synucleinopathies (Dementia with Lewy bodies (DLB), Multiple System atrophy (MSA)), REM-Sleep without atonia (RSWA)(Assessed at baseline (at the time of enrollment) and at 5-year follow-up)