Idiopathic polyneuropathy with neurogenic autonomic failure – an early manifestation of Lewy body disease? a case report

With the present case we suggest that idiopathic large-fiber polyneuropathy with autonomic failure, pathological cardiac [123I]Metaiodobenzylguanidine (MIBG) scintigraphy and α-synuclein positivity in cutaneous autonomic nerves is a prodromal manifestation of body-first Lewy body disease (LBD).Case Presentation: A previously healthy 74-year-old man presented with painful polyneuropathy and orthostatic intolerance. Phenotypic characterization demonstrated small- and large-fiber sensory-motor-autonomic polyneuropathy, cardiac sympathetic denervation and cardiovagal and cardiovascular adrenergic dysfunction. Despite thorough examination and exclusion of diabetes, primary- and hereditary transthyretin amyloidosis, no underlying cause was found. Interestingly, LBD was suspected due to abnormal cardiac MIBG scintigraphy, constipation, hyposmia, REM sleep behavior disorder (RBD), and mild cognitive impairment. Seed amplification assay (SAA) for pathological α-synuclein was positive in a skin biopsy (neck) with deposits localized in the autonomic nerves based on immunohistochemistry. He was clinically diagnosed with mild dementia with Alzheimer's Disease (AD) pathology. However, given the presence of severe autonomic dysfunction, RBD, pathological α-synuclein in addition to AD pathology, dual pathology with Lewy bodies (representing a body-first LBD) should be considered. Conclusion: This case highlights the importance of evaluating patients with idiopathic large-fiber polyneuropathy with autonomic failure for underlying LBD. We propose that both neuropathy and cardiac denervation may stem from the widespread peripheral neurodegeneration associated with pre-motor body-first LBD, although there is no direct evidence of causality. In this case, with idiopathic small- and large-fiber sensory-motor-autonomic neuropathy and abnormal MIBG scintigraphy, detection of α-synuclein in cutaneous autonomic nerves, supports our proposal. Thus, we suggest idiopathic polyneuropathy with autonomic failure to represent a non-motor prodromal manifestations in LBD.