Prevalence and clinical impact of alpha-synuclein pathology in idiopathic normal pressure hydrocephalus: Insights from RT-QuIC assay

Abstract

Background: The relationship between idiopathic normal pressure hydrocephalus (iNPH) and synucleinopathy remains unclear. This study aimed to explore the prevalence of α-synuclein pathology in iNPH patients and its impact on clinical outcomes.

Methods: We enrolled 33 iNPH patients without evidence of nigrostriatal degeneration. Cerebrospinal fluid (CSF) was analyzed using the real-time quaking-induced conversion (RT-QuIC) assay to detect α-synuclein aggregates. Clinical assessments included the Timed Up and Go (TUG) test and Mini-Mental State Examination (MMSE), performed before and after a CSF tap test.

Results: Among the 33 patients, 11 (33.3 %) tested positive for α-synuclein pathology. Baseline demographic and clinical characteristics were similar between α-synuclein positive and negative groups (p > 0.05). The MMSE and TUG tests showed no significant differences between the groups before or after the tap test. However, the RT-QuIC negative group showed significant improvement in TUG times and steps post-tap test (p < 0.05), while the positive group showed a non-significant trend towards improvement (p = 0.06). Clinical global impression improved in 26 patients after CSF drainage, with similar rates in both groups (p = 0.88). Eleven patients (5 α-synuclein RT-QuIC positive and 6 negative) underwent shunt surgery, all of whom reported improvement over a median follow-up of 1.29 years.

Conclusion: α-synuclein pathology is present in a significant proportion of iNPH patients. Although gait improvement during the tap test was evident in α-synuclein negative group, both groups showed improvement. These findings underscore the need for further longitudinal studies to elucidate the long-term clinical impact of α-synuclein pathology in iNPH.

Keywords: Idiopathic normal pressure hydrocephalus; Neurodegenerative disorders; RT-QuIC; α-synucleinopathy.