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BACKGROUND: Wolfram syndrome (WFS) is a rare autosomal recessive disease characterized by insulin-dependent diabetes mellitus (IDDM), optic nerve atrophy, diabetes insipidus, deafness and neurological dysfunction. Bladder dysfunction is known to be widespread, however, the presence and duration of other syndrome manifestations do not correlate with the type of bladder dysfunction seen. This suggests that bladder dysfunction may be a primary rather than secondary component of the syndrome. It has been shown that compared to healthy and IDDM control groups, WFS patients have smaller intracranial volumes with specific abnormalities in the brainstem. We sought to determine whether pons volumes in WFS patients were associated with objective measures of voiding dysfunction and lower urinary tract symptoms (LUTS).
METHODS: Participants with WFS were evaluated clinically by a multi-disciplinary team of investigators including a pediatric neurologist, audiologist, endocrinologist, ophthalmologist and urologist. Patients underwent investigations and completed self-reported questionnaires in the form of non-invasive urodynamic testing, pelvic US, one week voiding diary, 48-hour voiding log, bowel diary, Incontinence Scoring System Questionnaire and MRI scans of the brain and brainstem.
RESULTS: A total of 18 patients were prospectively recruited and underwent urological investigations as outlined above. Overall, 89% (16/18 patients) had evidence of voiding dysfunction and/or LUTS. Twelve patients (6 males) between the age of 7 and 26 years (mean = 15 years) underwent MRI of the brain and brainstem (6 patients had contraindications to MRI scanning). An inverse relationship trend was noted for WFS patients such that those with smaller volume pons measurements had a higher incidence of voiding dysfunction: mean pons volume of 7941 versus 9801. Those children with smaller pons measurements had an increased incidence of less than expected functional bladder capacity (40% vs. 0%), disordered uroflow pattern (80% vs. 57%), and self-reported LUTS (100% vs. 0%). Those children with more normal pons volumes had lower post-void residual urine measurements (30 vs. 48 mL) and a lower incidence of urinary incontinence (60% vs. 0%).
CONCLUSIONS: A significant number of WFS patients have both objective and subjective evidence of voiding dysfunction and LUTS. There seems to be an inverse association between pons volumes and voiding dysfunction in WFS patients. This finding implies an interrelationship between bladder and brainstem dysfunction in these individuals. Further study with functional MRI evaluation may be warranted to further elucidate the brain mechanisms that are involved in voiding dysfunction in this complex group of patients.