Lower Urinary Tract Dysfunction and Associated Pons Volume in Patients with Wolfram Syndrome

Abstract

Purpose: Wolfram syndrome is a neurodegenerative disorder characterized by childhood onset diabetes mellitus, optic nerve atrophy, diabetes insipidus, hearing impairment, and commonly bladder and bowel dysfunction. We hypothesized that there is an association between a smaller pons, which contains the pontine micturition center, and abnormal lower urinary tract function.

Materials and methods: Patients with genetically confirmed Wolfram syndrome attended an annual multidisciplinary research clinic. Subjects underwent noninvasive urodynamic testing and brain magnetic resonance imaging, and completed validated patient reported outcome measures. Bowel and bladder diaries were completed before visits. Age and gender corrected linear and logistic mixed effects models were used to correlate pons volume, corrected for whole brain size, to urodynamic and patient reported outcomes.

Results: A total of 36 patients attended 142 visits between 2010 and 2016. Mean age was 16.9 years (range 7 to 30) and 64% of patients were female. Functional bladder capacity was decreased in 31% of the patients, normal in 54% and increased in 14%. Of the patients 44% and 54% had abnormal uroflowmetry and post-void residual, respectively, on at least 1 occasion. There was no increase through time in incidence of lower urinary tract dysfunction. Decreased pons volume was associated with increased post-void residual (p = 0.048) and higher PinQ (Pediatric Incontinence Questionnaire) score (p = 0.011), indicating lower quality of life and higher levels of dysfunction.

Conclusions: A significant number of children, adolescents and young adults with Wolfram syndrome have objective evidence of lower urinary tract dysfunction. Decreased pons volume is associated with more abnormal urinary function and lower quality of life in patients with Wolfram syndrome.

Keywords: Wolfram syndrome; urination; urination disorders; urodynamics.

Figure 1.

Scatterplots of various important measures. Individual patients have multiple values shown over time, connected with a solid line. A) Plot of WFS patients age versus pre-void bladder volumes. Expected capacity (as a function of age) is shown in gray for comparison. Mean across the whole population is shown as solid line and increases slightly over time as expected. B) Post-void residual bladder volumes. C) Functional bladder capacity for all patients, categorized as either decreased (< 66% estimated bladder capacity), normal, or increased (> 133% estimated bladder capacity).

Figure 2.

Scatterplots of pons volumes corrected for whole brain volume on annual MRI correlated to three validated patient-reported outcome measures, including A) Pediatric Incontinence Quality of Life (PinQ), B) Toronto Bowel and Bladder score, and C) Compass-31 questionnaire, which assesses autonomic function. Trendlines correspond to individual patients in each linear mixed-model, adjusted for age and sex (projected using mean values of non-visualized variables). P value for each model is shown.