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.

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.

Patients with definite polyneuropathy (confirmed by nerve conductions study) diagnosed in Jutland, Denmark and orthostatic hypotension or non-nocturnal blood pressure reduction.