Study design, materials and methods
A systematic review of the literature was performed in PubMed, EMBASE and COCHRANE. The search in PubMed brought together the Mesh terms for Parkinson's disease, overactive bladder (OA) and the Mesh category for implantable devices used for neurostimulation "electrical equipment and supplies" in the following way: (("Parkinson Disease"[Mesh]) AND "Urinary Bladder, Overactive"[Mesh]) AND "Electrical Equipment and Supplies"[Mesh]. The EMBASE + MEDLINE database was searched for the terms Parkinson disease and overactive bladder, present in the title, abstract or keywords of the articles, as follows 'parkinson disease':ti,ab,kw AND 'overactive bladder':ti,ab,kw AND ('nerve stimulation':ti,ab,kw OR neuromodulation:ti,ab,kw). Regarding the inclusion criteria, english-language literature was selected in an adult population with a diagnosis of Parkinson disease and symptoms of OAB, undergoing neuromodulation or deep brain stimulation without time constrains. Animal studies, ongoing studies with results not yet available, multiple simultaneous interventions and unclear outcomes or interventions were excluded.
Results
The PubMed search yielded a total of 3 articles, 1 of them, a clinical trial on sacral nerve neurostimulation in patients with PD and OABa(1), 1 on tibial neurostimulation (TTNS) using a self-sustainable device (2) in patients with PD and OAB symptoms, and 1 clinical trial on deep brain stimulation in the subthalamic nucleus. One article was excluded because it is still ongoing, with no results yet available. EMBASE + MEDLINE yielded a total of 4 articles, of which 2 were finally included (1 article on tibial neurostimulation and 1 article on sacral neurostimulation). One article was excluded because it was originally written in French, and another article was excluded because it worked on a diverse population among which 2% were patients with Parkinson's disease, and the specific performance of this group was not specified in the results. Finally, 4 articles were reviewed.
Deep brain stimulation: Winge et al (1). Investigated the effects of deep brain stimulation in the subthalamic nucleus on lower urinary tract symptoms and bladder control in patients with advanced PD in a group of 16 patients. The study found that deep brain stimulation significantly improved storage bladder symptoms (frequency, urgency and nocturia) but did not significantly improve other lower urinary tract symptoms (LUTS). Despite evidencing a downward trend in Danish Prostate Symptom Score (DanPSS) and International Prostate Symptom Score (IPSS) when comparing total, preoperative, 3-month and 6-month scores, the only significant difference evident was found in the IPSS storage symptoms. The study also found that functional bladder control, understood as the interval between first sensation and cystometric capacity (a measure of the brain's ability to integrate complex sensory stimuli) was reduced at the postoperative evaluation with the stimulator turned on. No changes were found in urodynamic parameters. The article concluded that deep brain stimulation in the subthalamic nucleus can improve symptoms of OAB in patients with advanced Parkinson's disease, especially storage symptoms. On the other hand, Bapir et al. Showed that Deep brain stimulation as treatment reduces LUTS in advanced Parkinson disease.
Sacral nerve stimulation: Greenberg et al (2). Developed a study evaluating the effectiveness and safety of sacral nerve stimulation (SNS) for PD patients with OAB. The study included 15 PD patients who underwent Stage I SNS. The results showed that 60% of patients experienced a significant improvement in urinary symptoms and proceeded to Stage II. Female patients had a higher success rate than male patients. Patients with >12-month follow-up experienced an average reduction of 6 voids/day. No patients required revision or explantation of their device at the latest clinic follow-up. Urodynamic parameters associated with obstruction may be predictive of SNS failure in PD patients. The success rate of SNS in PD patients is similar to that of the general population. The study also suggests that urodynamic parameters associated with obstruction may help predict which PD patients with OAB will respond to SNS. However, larger, prospective studies are needed to validate these findings. The article concluded that sacral nerve stimulation (SNS) is an effective and safe therapy for Parkinson's disease (PD) patients with OAB.
Transcutaneous tibial nerve stimulation (TTNS): Double-Blind Clinical Trial where 8 patients were exposed twice a week during 5 weeks with TTNS vs 5 patients with SHAM. Following 5 weeks of treatment, patients allocated to TTNS demonstrated statistically significant reductions in the number of urgency episodes (P = .004) and reductions in nocturia episodes (P < .01). Participants allocated to active treatment also showed better results after treatment in the OAB-V8 and ICIQ-SF scores (P < .01, respectively). Urodynamic testing revealed that patients in the active treatment group showed improvements in intravesical volume at strong desire to void (P < .05) compared to subjects in the SHAM treatment group. Furthermore, Bapir et al. Quantitative analysis among 53 patients found a statistically significant decrease in episodes of nocturia in patients exposed to TTNS, although no significant variations were found of OAB scores between interventions (4).
Interpretation of results
The limitations of the literature found include a small sample size which may limit the generalizability of the findings. Additionally, deep brain stimulation study only evaluated patients 6 months postoperatively, and longer-term follow-up may be necessary to fully understand the effects of deep brain stimulation on lower urinary tract symptoms and bladder control in patients with PD. Also, researchers did not find significant changes in urodynamic parameters after the implantation of electrodes and after stimulation in the subthalamic nucleus, which may suggest that other factors beyond the subthalamic nucleus may be involved in the regulation of bladder function in patients with PD. Regarding sacral neurostimulation, the limitations of the article include the retrospective nature of the study, which may result in patients being lost to follow-up or having other comorbidities not documented in their medical chart. Lastly, Unified Parkinson’s Disease Rating Scale (UPDRS) scores and Hoehn and Yahr (H-Y) staging scale of PD were available for less than 50% of patients and were therefore not included in the analysis. Concerning the Tibial stimulation study, the limitations are due to a high rate of dropout because of the difficulty attending twice weekly sessions.
Concluding message
The literature on neurostimulation is promising and still requires further research to evaluate its efficacy. Although a significant percentage of patients have an adequate response to neurostimulation in the management of their urinary symptomatology, it is important to remember that response is variable. To select the ideal therapy, correct phenotyping of the patient should be performed, and the baseline state of the symptomatology should be known for an adequate comparison between before and after treatment. Regarding deep brain stimulation, it is important to recognize that although patients do respond to this therapy, if the patient is a candidate for this therapy, it should be performed, and the response should be evaluated regularly before considering other therapeutic alternatives. These studies present several important missings that can be related to the physical limitations presented by a patient with Parkinson's disease. Therefore, it is worthwhile to investigate new management strategies that consider this limitation.