Objective: This study aims to evaluate the role of post-void urinary residual volume (PVR) in Pure Autonomic Failure (PAF) and its prognostic value as a marker of phenoconversion to Multiple System Atrophy (MSA) or Lewy Body disease (LBD).

Background: PVR exceeding 100 mL is a recognized non-motor feature of MSA and represents an entry criteria for possible prodromal MSA[1]. Moreover, PVR serves as a valuable tool for differentiating MSA and Parkinson Disease (PD)[2]. However, its clinical significance in PAF remains unclear.

Method: We analysed clinical data and laboratory findings related to urinary dysfunction in PAF patients from our “IAF-BO cohort”[3]. PVR was measured using a bladder ultrasound scanner. Patients were classified as PVR+ (>100 mL) or PVR- (≤100 mL) based on PVR values. Comparisons between the two group were performed using non-parametric tests (Mann-Whitney U, Chi-square). Kaplan-Meier survival curves were used to assess phenoconversion risk over time.

Results: Our PAF cohort included 65 patients. Of these, 50 exhibited urinary symptoms, specifically urinary urgency (32%), urinary incontinence (34%) and urinary retention (34%). PVR was measured in 41 patients, with 22 (53.7%) classified as PVR+ and 19 (46.3%) as PVR-. No significant differences were observed between the two groups in terms of disease duration (p=0.063), survival (p=0.839), risk of phenoconversion (p=0.233) and latency to phenoconversion (p=0.153)[Figure1]. Specifically, phenoconversion occurred in 7 PVR+ patients (1 PD, 3 DLB, 3 MSA) and 3 PVR- patients (1 MSA, 2 DLB). Further analysis showed no significant correlation between PVR+ and other supportive biomarkers of MSA. In PVR+ patients 123I-MIBG scintigraphy was normal in 18.2% individuals while showed cardiac denervation in 72.7% cases including all 4 patients who later phenoconverted to PD/LBD as well as one who phenoconverted to MSA. Supine plasma norepinephrine levels above 100 pg/ml were observed in 4 PVR+ patients, of whom 2 phenoconverted to LBD and 2 to MSA. Video-polysomnography proven REM Sleep Behavior Disorder (RBD) was diagnosed in 54.5% of PVR+ patients, including all who phenoconverted to PD/DLB and 1 patient who phenoconverted in MSA.

Conclusion: Urinary dysfunction with PVR exceeding 100 mL is commonly observed in PAF. However, although PVR is valuable for the differential diagnosis between MSA and PD, it does not appear to reliably predict phenoconversion to MSA in patients with PAF.

Figure1

References: 1. Wenning GK, Stankovic I, Vignatelli L, Fanciulli A, Calandra-Buonaura G, Seppi K, Palma JA, Meissner WG, Krismer F, Berg D, Cortelli P, Freeman R, Halliday G, Höglinger G, Lang A, Ling H, Litvan I, Low P, Miki Y, Panicker J, Pellecchia MT, Quinn N, Sakakibara R, Stamelou M, Tolosa E, Tsuji S, Warner T, Poewe W, Kaufmann H. The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy. Mov Disord. 2022 Jun;37(6):1131-1148. doi: 10.1002/mds.29005. Epub 2022 Apr 21. PMID: 35445419; PMCID: PMC9321158.
2. Fanciulli A, Goebel G, Lazzeri G, Granata R, Kiss G, Strano S, Colosimo C, Pontieri FE, Kaufmann H, Seppi K, Poewe W, Wenning GK. Urinary retention discriminates multiple system atrophy from Parkinson’s disease. Mov Disord. 2019 Dec;34(12):1926-1928. doi: 10.1002/mds.27917. Epub 2019 Nov 11. PMID: 31710392.
3. Giannini G, Calandra-Buonaura G, Asioli GM, Cecere A, Barletta G, Mignani F, Ratti S, Guaraldi P, Provini F, Cortelli P. The natural history of idiopathic autonomic failure: The IAF-BO cohort study. Neurology. 2018 Sep 25;91(13):e1245-e1254. doi: 10.1212/WNL.0000000000006243. Epub 2018 Aug 22. PMID: 30135257.

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