Virus-related neurological lower urinary tract dysfunction: Lessons learned during 4-year follow-up of patients with Congenital Zika Syndrome

Abstract

Introduction: We have previously reported on neurogenic bladder dysfunction among Congenital Zika Vírus Syndrome (CZS) patients, but it is unknown how they will respond to treatment.

Objective: To assess whether children with neurological lower urinary tract dysfunction and CZS will respond to Standard therapies.

Methodology: A prospective observational cohort study of children with CZS referred for urological assessment between 2016 and 2020 to our quaternary center in Brazil. Urological protocol included clinical history, urinalysis and culture, renal and bladder ultrasonography and urodynamic study. Patients were treated based on findings from the first evaluation, with oxybutynin chloride for overactive bladder and low bladder compliance, clean intermittent catheterization for ineffective bladder emptying, or dual therapy when both were observed. Urological outcomes were evaluated between the first and second visits considering patient's adherence. Outcomes measured included clinical, imaging, and urodynamic variables. Data was analyzed using the IBM SPSS 22 software.

Results: From the cohort of 90 patients, 56 completed the second urodynamic assessment and were included. One presented underactive bladder and 55 overactive bladder. Among these 55, 39 were adherent and 16 non-adherents to the prescribed treatment. Among the 39 adherents, 8 adhered regularly to oxybutynin and clean intermittent catheterization (CIC), 29 to oxybutynin alone, and two to catheterization alone. During follow-up, the number of patients with urinary tract infection and postvoid residual increased, but all other parameters had improved. Renal and bladder ultrasonography improved in 10, maximum bladder pressure decreased in 22 and maximum cystometric capacity and compliance increased in 14 patients. Sixteen patients did not adhere regularly to the prescribed treatment and although the number of patients with urinary tract infection reduced with antibiotic therapy, their bladder capacity and compliance did not improve during follow-up.

Discussion: Ultrasonographic and urodynamic improvements were observed after 10.8 ± 7.5 months of treatment, including one patient with ureterohydronephrosis that resolved. Adherence to CIC remains a challenge and reflected in the number of patients presenting urinary tract infection and postvoid residual. The immediate clinical relevance is the major study strength, given the previously uncharacterized therapy options for this patient population. The number of patients remains one of the study limitations, reducing our ability to perform more advanced statistical analyses.

Conclusion: Patients with Zika-related neurological lower urinary tract dysfunction may benefit from conventional therapies. Results confirmed ultrasonographic and urodynamic improvements after treatment, although not statically significant. Adherence to treatment, specifically to CIC, remains a challenge.

Keywords: Congenital Zika syndrome; Congenital Zika virus syndrome; Microcephaly; Neurological lower urinary tract dysfunction; Urinary tract infection; Zika virus.

Fig 1

A: CMG showing bladder contractions (20–50 cm H₂O) starting at the first 1/3 of the filling phase. Incomplete voiding triggered at half the expected bladder capacity (31 mL, 40 cm H₂O), leaving a high PVR of 50%. EMG showing an intense and uncoordinated sphincter activity throughout the exam. B. Urodynamic improvement after 8 months of treatment with oxybutynin chloride 1.5 mg twice a day, and CIC. CMG showing a more stable bladder, that stayed relaxed during the entire filling phase. At 135 mL (twice the expected capacity for the age group) voiding was triggered by a non-sustained contraction of 50 cm H₂O, leaving a high PVR of 50%. EMG also showing a more coordinated sphincter activity throughout the exam, except by a short increase at the end, in response to the voiding contraction.