Since the 1980s patients with spinal dysraphism have had aggressive bladder management with clean intermittent catheterisation and anticholinergic therapy from early on in life. This strategy aims at improving lower and therefore upper urinary tract function thus decreasing the risk of renal failure. Currently only oxybutynin is licensed for paediatric use in the Netherlands (as in the UK). This works mainly by blocking efferent M3 receptors in the detrusor muscle and hence decreasing bladder contraction. However, oxybutynin is not uro-selective and also blocks other muscarinic receptor subtypes such as M1 and M2. This leads to those common side-effects of dry mouth and constipation. Due to its small molecular structure and high lipophilicity, oxybutynin also crosses the blood-brain barrier. All muscarinic receptor subtypes are present in the brain. M1 receptors are thought to be important for cognitive function. Impairment of cognition is a known complication of treatment with oxybutynin. This retrospective case-control study set out to investigate whether long-term use of such agents could alter behaviour in patients with spinal dysraphism. Patients were matched for age, gender, presence of hydrocephalus +/– shunt, and number of shunt revisions. Neurological level and presence of an open or closed lesion at diagnosis were also matched characteristics. A four-page validated questionnaire (CBCL) evaluating behavioural and emotional issues was completed by parents in both groups – those treated with long-term anticholinergics and those without (n=16 in both groups). Median age was just over 10 years in each group. Those in the oxybutynin group had used it regularly for just over eight years. According to the parental ratings, there were no significant differences in behaviour between the two groups. This is encouraging for those who regularly prescribe oxybutynin long-term for patients with spinal dysraphism. However, there is at least one major multicentre trial ongoing looking at a more uro-selective drug for this group of paediatric patients. Furthermore, the authors concede that the questionnaire used is not a comprehensive cognitive assessment tool and that although they made significant attempts to match cases with controls, there will inevitably be a degree of bias. Indeed, cases came almost exclusively from one centre (Utrecht) with controls from another (Amsterdam) where management strategies differ significantly.

Behavioural effects of long-term antimuscarinic use in patients with spinal dysraphism: a case control study.
Veenboer PW, Huisman J, Chrzan RJ, et al.
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