Anosmia and Upper Limb Rigidity—A Potential Phenotype of Idiopathic Normal Pressure Hydrocephalus with Cerebrospinal Fluid α‐Synuclein Seeds

• DOI: 10.1002/mds.30184
• Publication Date: 2025-04-09T08:24:06Z
• Authors: Sandrina Weber; Carly M. Farris; Yihua Ma; Mohammed Dakna; Maritta Starke; Sebastian Schade; Michael Bartl; Claudia Trenkwalder; Luis Concha‐Marambio; Brit Mollenhauer

AbstractBackgroundThe pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) and its association with neurodegenerative disorders is poorly understood.ObjectivesThe aim was to determine the prevalence of α‐synuclein pathology in iNPH and its associations with clinical characteristics.MethodsWe used α‐synuclein seed amplification assay (synSAA) to retrospectively analyze cerebrospinal fluid (CSF) from a large single‐center iNPH cohort (n = 144). Clinical assessments comprised Unified Parkinson's Disease Rating Scale part III, Mini‐Mental State Examination, levodopa‐challenge test, and olfactory identification test. Degenerative biomarkers (total‐tau, phospho‐tau, β‐amyloid 1–42, and β‐amyloid 1–40) were measured in CSF.ResultsA total of 30.1% of iNPH patients were synSAA+, and presented significantly more upper limb (UL) rigidity, hallucinations, and worse olfactory performance than synSAA− cases. Anosmia was higher in synSAA+ patients (64.0%) than synSAA− patients (15.3%). Clinical assessments and other biomarkers did not significantly vary with synSAA status.ConclusionsUnderlying α‐synuclein pathology is common in iNPH and presents with UL rigidity and olfactory dysfunction, suggesting a distinct synSAA+ phenotype in iNPH. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.