Pure autonomic failure (PAF) is an uncommon sporadic alpha-synucleinopathy disorder affecting the periperhal innervation characterized by failure of blood pressure control and dysregulated cardiovascular  reflexes, without other neurological symptoms and signs. 25% of patients however phenoconvert over time,  and can present later with a central neurological disorder such as Multiple System Atrophy, Parkinson’s Disease or Dementia with Lewy Bodies[1]. 

Cardiovascular autonomic failure , characterized by postural hypotension and supine hypertension, is the clinical  hallmark finding in Pure autonomic failure (PAF), though other autonomic functions are often affected. A recent natural history study suggested that lower urinary tract symptoms (LUTS) and erectile dysfunction are common[2]. Nevertheless, systematic evaluation of LUTS, bowel and sexual symptoms has never been investigated and the prevalence of these symptoms and their associations with features of PAF remain unclear. This study aims to characterise LUTS, bowel and sexual dysfunction in PAF patients and explore their relationship with cardiovascular autonomic dysfunction.

All patients fulfilled the diagnostic criteria of PAF and had been followed up for at least 5 years without other emerging neurological features.

PAF patients who underwent cardiovascular autonomic testing were prospectively recruited consecutively between November 2019- October 2021. Self-administered questionnaires evaluating lower urinary tract, gastrointestinal and sexual symptoms including Urinary Symptom Profile (USP), Constipation Scoring System (CSS), The Wexner incontinence score, The Arizona Sexual Experiences Scale (ASEX) and Quality of life questionnaire (SF-Qualiveen) were completed.  A 3-day bladder diary measuring fluid intake and urine output were also evaluated.  Demographic, clinical features, disease duration and related medical comorbidities were assessed.  A subset of patients who underwent cardiovascular autonomic testing (head-up tilt test and 24-hour ambulatory blood pressure monitoring;24hr-ABPM) and urodynamic studies were examined.

25 PAF patients (10 males) were included (mean age 71+8 years; disease duration 13+8 years). All patients developed LUTS after orthostatic intolerance symptoms (median 4 years, IQR 2-9 years). Lower urinary tract symptoms were reported by 96% (24/25) using the Urinary Symptom Profile. Among these, overactive bladder symptoms (n=23; 92%; median overactive subscore 8 (IQR 3-11)) were more frequently reported than voiding symptoms (n=19; 76%; median low stream subscore 2 (IQR 1-3)).  Four (16%) patients required catheterisation. 

The CSS and the Wexner incontinence median score were 7 (IQR 4-13) and 7 (IQR 3-9), respectively.  Sexual dysfunction was present in 91% (21/23) using ASEX with the median score of 17 (IQR 14-19). The median SF-Qualiveen score was 1.56 (IQR 0.69-2.31). 

13 patients underwent uroflowmetry and 77% (10/13) had abnormal flow patterns including intermittent/irregular and prolonged flow. 31% (4/13) had a significant post-void residual urine (PVR>100 ml) and required intermittent self-catheterisation. 6 patients underwent urodynamics, which showed detrusor overactivity and large bladder capacity (n=2 for both), detrusor underactivity (n=1) and early sensation during fill phase with no detrusor overactivity (n=1).  

22 patients completed a bladder diary and 19 (86%) had nocturnal polyuria (NP), defined as NP index > 0.3 (nocturnal urine volume/24-hour urine volume), mean NP index 0.45 (range, 0.20-0.73). 

21 patients underwent autonomic function tests including a 10-minute tilt table test and 24hr-ABPM. All patients had confirmed cardiovascular autonomic failure and orthostatic hypotension on head-up tilt. With 24hr-ABPM, supine hypertension and reversed circadian blood pressure rhythm (average BP higher during night-time than daytime) was present in 81% (17/21) and 57% (12/21), respectively. There were no significant correlations between age, disease duration and cardiovascular parameters (orthostatic BP drop, supine hypertension and abnormal blood pressure circadian rhythm) with urogenital parameters including need for catheterisation and degree of NP (p>0.05).

Our study demonstrated that LUTS, bowel and sexual symptoms are common in patients with PAF. Nocturnal polyuria is highly prevalent in patients with PAF. Possible mechanisms include improved renal perfusion due to supine hypertension when adopting a recumbent position at night and pressure natriuresis, and renal ischemia as a result of long-standing changes from postural hypotension [3].  However the lack of  direct correlation between nocturnal polyuria and demographics or any of the measures of cardiovascular autonomic failure suggests that the pathophysiology of NP in Pure Autonomic Failure is likely to be multifactorial, and raises the possibility whether NP can occur independent of cardiovascular failure in this cohort.    Longitudinal follow up is required to assess whether there is a relationship between NP and phenoconversion to other central neurological disorders later in the course of the disease.

Urogenital and bowel dysfunction is common in patients with Pure Autonomic Failure  and majority of  patients have nocturnal polyuria.   Self-reported questionnaires and bladder diary are useful as part of uro-neurological assessment of patients with PAF. Screening for, and treating, pelvic autonomic symptoms in patents with PAF are strongly recommended given their impact on quality of life.

Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Neurology, 1996. 46(5): p. 1470.
Kaufmann, H., et al., Natural history of pure autonomic failure: A United States prospective cohort. Ann Neurol, 2017. 81(2): p. 287-297.
Sakakibara R, Hattori T, Uchiyama T, Asahina M, Yamanishi T. Micturitional disturbance in pure autonomic failure. Neurology. 2000 Jan 25;54(2):499-501. doi: 10.1212/wnl.54.2.499

Continence 2S2 (2022) 100335
DOI: 10.1016/j.cont.2022.100335