The Northeastern Society of Plastic Surgeons

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Lower Urinary Tract Dysfunction and Associated Pons Volume in Wolfram Syndrome
Kyle O. Rove, MD1, Gino J. Vricella, MD1, Tamara Hershey, PhD2, Maung H. Thu, MD1, Heather Lugar, MA3, Joel Vetter, MS1, Bess Marshall, MD4, Paul F. Austin, MD1.
1Division of Urology, St. Louis Children's Hospital, Washington University, St. Louis, MO, USA, 2Departments of Psychiatry, Neurology, and Radiology, Washington University, St. Louis, MO, USA, 3Department of Psychiatry, Washington University, St. Louis, MO, USA, 4Division of Endocrinology, St. Louis Children's Hospital, Washington University, St. Louis, MO, USA.

BACKGROUND: Wolfram syndrome (WFS) is a rare, autosomal recessive neurodegenerative disorder characterized by childhood-onset diabetes mellitus, optic nerve atrophy, diabetes insipidus, and sometimes hearing impairment. In addition, WFS patients can develop a wide array of complex sensory, motor, and neurological issues, including bladder and bowel dysfunction. We sought to prospectively assess lower urinary tract function in WFS patients and correlate these to brain imaging, specifically volume of the pons, which contains the pontine micturition center. We hypothesized there would be an association between smaller pons and abnormal lower urinary tract function.
METHODS: Patients attended the Washington University WFS Research Clinic annually to undergo multidisciplinary testing. Patients had to be age 30 or younger and have genetically confirmed WFS (mutations of the WFS1 gene). All participants gave written informed consent prior to testing. Patients underwent non-invasive urodynamic testing including pre- and post-void pelvic ultrasound, uroflowmetry testing, and MRI scans of the brain, in addition to other exams. Patients were contacted several weeks prior to clinic and provided instructions on completing 7-day bowel and bladder diaries. Participants were invited to fill out the Pediatric Incontinence Quality of Life (PinQ), Toronto Bowel and Bladder Dysfunction, and Compass-31 questionnaires. Study data were managed using REDCap tools and analyzed with R, version 3.3.2. Descriptive statistics were calculated. Age and sex-corrected linear or logistic mixed-effects models were used to correlate pons volume, corrected for whole brain size, to non-invasive urodynamic measures. P values < 0.05 were considered significant.
RESULTS: 36 unique patients were seen at 142 separate visits that included urologic testing between 2010 and 2016. In the most recent year, mean age was 16.9 years (range 7-30) and 64% were female. Functional bladder capacity was decreased in 31%, normal in 54% and increased in 14%. 82% and 77% of patients had abnormal uroflowmetry testing and post-void residual, respectively, on at least one occasion. Objective evidence of polyuria was noted in 29% of patients. About 1/2 of patients had normal daytime voiding patterns, while 1/4 of patients each had increased or decreased voiding frequency. Bowel function was highly variable in both frequency and consistency across patients who completed a bowel diary. 50% noted issues with bowel dysfunction (Bristol 1-2) and/or encopresis. Lower pons volume was associated with abnormal urinary function testing across all modalities. Lower pons volume was associated with lower pre-void bladder volume (p = 0.043), lower voided volume on uroflowmetry (p = 0.008), and greater post-void residual (p = 0.048). Lower pons volume also correlated with higher PinQ score (p = 0.011), Toronto BBD and Compass-31 scores, with higher scores indicating lower quality of life and higher levels of dysfunction.
CONCLUSIONS: A significant number of children, adolescents and young adults with WFS patients have objective and subjective evidence of lower urinary tract dysfunction. Lower whole pons volume was associated with more abnormal urinary function and lower quality of life in WFS patients.


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