Cortical,Spinal, Sacral,and Peripheral Neuromodulations as Therapeutic Approaches for the Treatment of Lower Urinary Tract Symptoms in Multiple Sclerosis Patients: A Review

IntroductionMultiple sclerosis (MS) is often associated with urological disorders, mainly urinary incontinence and retention, the management of which being necessary to improve patient's quality of life (QOL) and to reduce potential urological complications. Besides the classical treatments based mainly on anticholinergics and/or self-catheterization, several neuromodulation techniques have been tried in recent years to improve these urinary disorders. By this review, we aim at providing an overview of neuromodulation and electrostimulation approaches to manage urinary symptoms in MS patients.Materials and MethodsA literature search using MEDLINE was performed. Only papers in English, and describing the effects of neuromodulation in MS patients, were considered.ResultsA total of 18 studies met inclusion criteria and were reviewed. Of them, four related to sacral neuromodulation (SNM), seven to percutaneous tibial nerve stimulation (PTNS), six to spinal cord stimulation (SCS), and one to transcranial magnetic stimulation (TMS).DiscussionPTNS and SNM seem to be effective and safe therapeutic options for treating lower urinary tract symptoms in MS patients principally in case of overactive bladder (OAB) symptoms. Similarly, also SCS and TMS have been shown to be effective, despite the very limited number of patients and the small number of studies found in the literature. Interestingly, these techniques are effective even in patients who do not respond well to conservative therapies, such as anticholinergics. Furthermore, given their safety and efficacy, stimulations such as PTNS could be considered as a first-line treatment for OAB in MS patients, also considering that they are often preferred by patients to other commonly used treatments.     

Efficacy and Effectiveness of Percutaneous Tibial Nerve Stimulation in the Treatment of Pelvic Organ Disorders: A Systematic Review

Objective: This systematic review aimed to determine the efficacy and effectiveness of percutaneous tibial nerve stimulation (PTNS) on symptoms of overactive bladder (OAB) and pelvic organ disorders, pain, adverse events (AEs), and quality of life (QoL). Methods: A literature search was performed in September 2011 in the databases MEDLINE, CINAHL, and EMBASE. Hand searching of references was conducted. Only randomized controlled trials (RCTs) and controlled clinical trials (CCTs) with adult patients were included. Results: Seven studies met the eligibility criteria. Five RCTs indicated improvement (range 36.7–80%) on OAB symptoms, frequency, urgency, nocturia, and incontinence. One CCT reported improvement (mean 15.7) in 53% of the subjects on fecal incontinence (FI) symptoms on an FI Questionnaire (range 0–20). One RCT showed more than 50% improvement on pain (40%) and symptom scores (66.6%) in chronic pelvic pain (CPP). Limitations are the small amount, overall low quality, and variety in outcome measures of included studies. Only minor AEs were reported. No meta‐analysis was performed as a consequence of heterogeneous data. Conclusions: This systematic review provides evidence for the efficacy of PTNS on symptoms, pain, and QoL measures of OAB, FI and category IIIB CP/CPP. Evidence of effectiveness was found on symptoms and QoL for OAB. The total amount of seven included studies, from which even the most favorable study has some potential bias, is too small to draw firm conclusions. Independent high quality RCTs are necessary to confirm and delineate the range of therapeutic effects of PTNS in this region. PTNS is a safe intervention.     

Implant‐Driven Tibial Nerve Stimulation in the Treatment of Refractory Overactive Bladder Syndrome: 12‐Month Follow‐up

Objectives. To investigate feasibility and safety of implant‐driven tibial nerve stimulation. Materials and Methods. Eight patients with refractory overactive bladder were successfully treated with implanted percutaneous tibial nerve stimulation (PTNS). Patients were evaluated with bladder diaries, quality of life questionnaires, and physical examination before implantation, and at 3, 6, and 12 months of follow‐up. The primary objective was ≥ 50% reduction of the number of incontinence episodes and/or voids on bladder diary. The Wilcoxon signed ranks test was used. Results. At 3, 6 and 12 months, respectively five, six, and four patients met the primary objective. At 3‐ and 6‐month follow‐up, voiding and quality of life parameters had significantly (p < 0.05) improved. Urinary tract infection, temporarily walking difficulties, and spontaneous radiating sensations were reported as adverse events and no local infection, erosion, or dislocation. Conclusions. Implant‐driven tibial nerve stimulation seems to be feasible and safe.     

Temporary sacral and tibial neuromodulation in treating patients with overactive urinary bladder

The effects of temporary sacral (S3) stimulation and posterior tibial nerve stimulation were studied in patients with the overactive urinary bladder. Unilateral temporal (10 days) electrical stimulation of the S3 sacral spinal nerve (32 patients) and posterior tibial nerve stimulation (18 patients) were used to treat this abnormality. There was a decrease in the average frequency of voiding, in the number of leakage episodes and used pads per day after both stimulations. An over 50% symptomatic improvement was achieved in 19 of the 32 patients and after temporary sacral (S3) stimulation and in 14 of the patients following posterior tibial nerve stimulation. Neuromodulation is an effective treatment in patients with the overactive bladder.     

Imidafenacin on bladder and cognitive function in neurologic OAB patients

Objective

To explore imidafenacin’s effects on bladder and cognitive function in neurologic overactive bladder (OAB) patients.

Methods

Sixty-two subjects (25 men, 37 women; mean age 70 years (25–86) with OAB due to neurologic diseases) were enrolled in the study. We conducted a urinary symptom survey and cognitive tests (MMSE, FAB, ADAS-cog) in all patients. We performed urodynamics in 35 patients and measured real-time near-infrared spectroscopy (NIRS)-urodynamics in eight patients before and after the administration of imidafenacin, an anticholinergic agent, for 3 months at 0.2 mg/day.

Results

Imidafenacin significantly ameliorated urinary urgency, nighttime urinary frequency, and quality of life index (p < 0.05). Three cognitive measures did not change significantly. Urodynamics showed increased bladder capacity (p < 0.05) but detrusor overactivity did not change significantly. NIRS showed that the subtraction of oxyhemoglobin between the start of filling and the first sensation increased in the bilateral prefrontal area but without statistical significance.

Conclusions

Imidafenacin ameliorated bladder sensation without cognitive worsening, with a trend of prefrontal activation. Regarding cognitive function, imidafenacin is safely used in OAB patients due to neurologic diseases.

Synopsis

In order to explore imidafenacin (anticholinergic agent)’s effects on bladder and brain function, we performed urinary questionnaire, cognitive tests, urodynamics and near-infrared spectroscopy (selected cases) in 62 overactive bladder (OAB) patients due to various neurologic diseases. As a result, imidafenacin ameliorated bladder sensation without cognitive worsening, with a trend of prefrontal activation. Imidafenacin seems safe in treating OAB patients due to neurologic diseases.     

Management of urinary incontinence in children with myelomeningocele

Several forms of treatment of lower urinary tract functional disorders have been attempted in children with myelomeningocele (MMC). Intravesical electrical stimulation was attempted in 10 patients. Urinary control was achieved in one and in the remaining 9 either the bladder was resistant to stimulation or the children discontinued the treatment due to loss of interest. A combined anticholinergic and calcium blocking agent, terodiline, was tested in 8: symptoms improved in 4, but bladder compliance was unchanged. Clean intermittent catheterization, either alone or in combination with medication, seems to be the most beneficial treatment.     

Anticholinergics for overactive bladder therapy: central nervous system effects

The mainstay of pharmacological treatment of overactive bladder (OAB) is anticholinergic therapy using muscarinic receptor antagonists (tertiary or quaternary amines). Muscarinic receptors in the brain play an important role in cognitive function, and there is growing awareness that antimuscarinic OAB drugs may have adverse central nervous system (CNS) effects, ranging from headache to cognitive impairment and episodes of psychosis. This review discusses the physicochemical and pharmacokinetic properties of OAB antimuscarinics that affect their propensity to cause adverse CNS effects, as observed in phase III clinical trials and in specific investigations on cognitive function and sleep architecture. PubMed/MEDLINE was searched for "OAB" plus "muscarinic antagonists" or "anticholinergic drug." Additional relevant literature was identified by examining the reference lists of papers identified through the search. Preclinical and clinical trials in adults were assessed, focusing on the OAB antimuscarinics approved in the United States. The blood-brain barrier (BBB) plays a key role in protecting the CNS, but it is penetrable. The lipophilic tertiary amines, particularly oxybutynin, are more likely to cross the BBB than the hydrophilic quaternary amine trospium chloride, for which there are very few reports of adverse CNS effects. In fact, in 2008 the US product labels for oral oxybutynin were modified to include the potential for anticholinergic CNS events and a warning to monitor patients for adverse CNS effects. Even modest cognitive impairment in the elderly may negatively affect independence; therefore, selection of an antimuscarinic OAB drug with reduced potential for CNS effects is advisable.     

Prolonged Inhibitory Effects of Repeated Tibial Nerve Stimulation on the Micturition Reflex in Decorticated Rats

ObjectiveThis study aimed to determine whether a short-term repeated stimulation of tibial nerve afferents induces a prolonged modulation effect on the micturition reflex in a decorticated rat model.Material and MethodsFifteen female Sprague-Dawley rats (250–350 g) were fully decorticated and paralyzed in the study. Tibial nerve stimulation (TNS) was delivered by inserting two pairs of needle electrodes close to the nerves at the level of the medial malleolus. Constant flow cystometries (0.07 mL/min) at approximately ten-minute intervals were performed, and the micturition threshold volume (MTV) was recorded and used as a dependent variable. After four to five stable recordings, the tibial nerves of both sides were stimulated continuously for five minutes at 10 Hz and at an intensity of three times the threshold for α-motor axons. Six same stimulations were applied repeatedly, with an interval of five minutes between each stimulation. Mean MTV was calculated on the basis of several cystometries in each half-hour period before, during, and after the six repeated TNS.ResultsDuring the experiment, all the animals survived in good condition with relatively stable micturition reflexes, and a significant increase in MTV was detected after TNS. The strongest effect (mean = 178%) was observed during the first 30 minutes after six repeated stimulations. This obvious threshold increase remained for at least five hours.ConclusionsA prolonged poststimulation modulatory effect on the micturition reflex was induced by short-term repeated TNS in decorticated rats. This study provides a theoretical explanation for the clinical benefit of TNS in patients with overactive bladder and suggests decorticated rats as a promising model for further investigation of the neurophysiological mechanisms underlying the bladder inhibitory response induced by TNS.     

Sympathetic skin response in myelopathies

Autonomic dysfunctions cause significant morbidity and mortality among patients with spinal cord disorders. Sympathetic skin response (SSR), a simple, noninvasive electrophysiological technique, may be useful for assessing sympathetic functions in patients with myelopathies. Our aim was to study SSR in patients with myelopathy and correlate it with clinical features, severity of the impairment, somatosensory evoked potentials. and outcome. Thirty patients (15 men, 15 women) 12 to 60 years old with myelopathies of different etiology were studied. Subjects with clinical, electrophysiologic, or radiologic evidence of lesions outside the spinal cord were excluded. Somatosensory evoked potentials (SSEP) were recorded from scalp with median nerve stimulation at the wrist and posterior tibial nerve below the medial malleolus. The SSR was recorded from palm and sole after stimulating the supraorbital nerve at forehead, median nerve at wrist, and posterior tibial nerve below medial malleolus. The SSR was considered abnormal when absent. The sites of the lesions in these patients were cervical (13), thoracic (16), and lumbar (1). The lesion was clinically complete in six patients. Good motor recovery was noted in 16 subjects. SSR was absent from sole in 25 and palm in 10 patients from all three sites of stimulation. In addition, three patients also had absent SSR from palm on posterior tibial nerve (PTN) stimulation. SSEP was absent from median (N₁₉) in three and posterior tibial (N₃₉) in 20 patients. Among 10 patients with absent SSR from palm, only three had a good outcome. Presence of SSR from palm to PTN stimulation correlated with sparing of bladder sensations and good outcome. However, absent SSR from sole did not correlate with clinical features, bladder dysfunction, or outcome.Sympathetic skin response is frequently abnormal in patients with myelopathies. Spinal afferent and efferent tracts for SSR are different and may be affected individually. The afferent pathways are closely related to tracts conveying bladder sensation. Preserved palmar SSR on PTN stimulation may suggest good motor outcome. SSR may be a valuable adjunct in evaluating patients with myelopathies.     

Neuromodulation for Storage Lower Urinary Tract Symptoms in Parkinson Disease: A Systematic Review

BackgroundBladder symptoms are common in Parkinson disease (PD), affecting quality of life. Medications commonly used such as antimuscarinics can cause frequently intolerable side effects, and therefore, new, better tolerated approaches are needed. Neuromodulation techniques have an established role in urologic disorders; these techniques include tibial nerve stimulation (TNS) and sacral neuromodulation (SNM), which are localized therapies lacking the side effects associated with medication.ObjectivesThis study aimed to undertake a systematic review of the literature reporting the use of neuromodulation techniques for the treatment of bladder symptoms in PD and related conditions.Materials and MethodsA systematic search of data bases was conducted including MEDLINE, CENTRAL, and Web of Science. Studies were required to present specific outcomes for individuals with PD for neuromodulation interventions.ResultsTen primary studies were identified concerning detailed outcomes of neuromodulation on bladder symptoms in PD, including seven for TNS, one for SNM, and one using transcranial magnetic stimulation (TMS). Two further mixed cohort studies documented minimal data on individuals with PD. All studies demonstrated benefit in a range of outcome measures following neuromodulation. Two randomized sham-controlled studies were carried out using TNS, with one clearly demonstrating superiority over sham, although difficulties with achieving believable yet ineffective sham treatment are highlighted. Further studies reported limited, uncontrolled outcomes of SNM in patients with PD, demonstrating benefit.ConclusionsEvidence from case series suggests benefit from TNS in PD, with limited literature on SNM or TMS. Placebo effect from neuromodulation is a concern, and only limited controlled data exist. Future well-designed and sham-controlled studies need to be completed to provide definitive data on the benefit of neuromodulation in PD. Definitively proving the utility of a neuromodulation modality will allow better treatment of bladder symptoms without the need for pharmacologic measures that cause side effects.     

H-reflex to S1-root stimulation improves utility for diagnosing S1 radiculopathy

ObjectiveThe H-reflex on stimulation of the tibial nerve in the popliteal fossa is routinely used in the diagnosis of first sacral (S1) nerve-root radiculopathy. The H-reflex latency, however, is considered to lack sensitivity since a small change from the focal root pathology can be diluted in a relatively long reflex latency. We have studied the soleus H-reflex elicited by stimulation of the S1 nerve root at the S1 foramen. The normal values for the S1-foramen H-reflex have been reported in a previous study, but there are no definitive reports in patients with S1 radiculopathy. This study was undertaken to determine whether stimulating at the S1 nerve root can improve the utility of the H-reflex for detecting an S1-root lesion.MethodsA randomised paired-study design was utilised to evaluate two H-reflexes: one elicited with tibial nerve stimulation and one elicited with S1-root stimulation. Fifty-five patients with unilateral S1 radiculopathy, confirmed by clinical, electrodiagnostic and magnetic resonance imaging (MRI) evidences were studied. A high-voltage electrical stimulator was used to elicit H-reflexes bilaterally at the S1 foramen and L4/L5 spine level. Latencies were compared with previously generated normal values and similar responses from the asymptomatic leg, focussing on the interval between the peak of M- and H-waves (HMI).ResultsOn the symptomatic side, 39 of the 55 patients had abnormal tibial H-reflex latencies and 54 patients had abnormal responses on S1-foramen stimulation (absent in 18; HMI prolonged >0.4 ms in 36). On the asymptomatic side, all 55 patients had normal tibial H-reflexes, and 52 had normal responses on S1-foramen stimulation. In three patients, the HMI was abnormal on S1-foramen stimulation. In 46 patients tested with L4/L5-level stimulation, H-reflex was present in 39 and absent in seven. The latency of the M-wave to S1 stimulation was normal.ConclusionsAbnormal S1-root H-reflexes reveal lesions at the S1 root in patients with normal tibial H-reflexes; therefore, enhancing diagnostic sensitivity. The appearance of the H-reflex to L4/L5-level stimulation in patient with absent H-reflex to S1-foramen stimulation further localises the site of S1 nerve-root lesion to the L5/S1 spine level. Thus, H-reflex to S1-root stimulation significantly increases the diagnostic sensitivity for S1 radiculopathy.SignificanceIn our study, the S1-root H-reflex with high-voltage electrical stimulation has shown greater sensitivity than the tibial H-reflex in evaluating S1 compressive radiculopathies. An abnormal S1-root H-reflex helps to localise the lesion to the S1 root in patients with concurrent abnormal tibial nerve H-reflex, which may increase diagnostic specificity.     

Effects of spinal cord stimulation on the cortical somatosensory evoked potentials in failed back surgery syndrome patients

ObjectiveTo evaluate the functional activation of the somatosensory cortical regions in neuropathic pain patients during therapeutic spinal cord stimulation (SCS).MethodsIn nine failed back surgery syndrome patients, the left tibial and the left sural nerves were stimulated in two sessions with intensities at motor and pain thresholds, respectively. The cortical somatosensory evoked potentials were analyzed using source dipole analysis based on 111 EEG signals.ResultsThe short-latency components of the source located in the right primary somatosensory cortex (SI: 43, 54 and 65 ms) after tibial nerve stimulation, the mid-latency SI component (87 ms) after sural nerve stimulation, and the mid-latency components in the right (≈161 ms) and left (≈168 ms) secondary somatosensory cortices (SII) were smaller in the presence of SCS than in absence of SCS. The long-latency source component arising from the mid-cingulate cortex (≈313 ms) was smaller for tibial and larger for sural nerve stimuli during SCS periods compared to periods without SCS.ConclusionsSCS attenuates the somatosensory processing in the SI and SII. In the mid-cingulate cortex, the effect of SCS depends on the type of stimulation and nerve fibers involved.SignificanceResults suggest that the effects of SCS on cortical somatosensory processing may contribute to a reduction of allodynia during SCS.     

Transcranial magnetic stimulation and bladder function: A systematic review

ObjectiveWe aimed at assessing the usefulness of motor evoked potentials (MEPs) for exploring the integrity of striated sphincters and pelvic floor motor innervation in normal subjects and of repetitive transcranial magnetic stimulation TMS (rTMS) in patients with neurogenic bladder dysfunction.MethodsA systematic literature search was conducted using PubMed and Embase.ResultsWe identified, reviewed and discussed 11 articles matching the inclusion criteria.ConclusionsThe assessment of MEPs could represent a useful tool in the investigation of patients with urologic disorders. High frequency rTMS can improve detrusor contraction and/or urethral sphincter relaxation in patients with multiple sclerosis and bladder dysfunction. Low frequency (LF) rTMS seems to be an effective treatment of neurogenic lower urinary tract dysfunctions in subjects with Parkinson’s disease and possibly other neurodegenerative disorders. Furthermore, rTMS might have the potential to restore bladder and bowel sphincter function after incomplete spinal cord injury. LF rTMS could also relieve some symptoms of bladder pain syndrome and chronic pelvic pain.SignificanceThe clinical applicability of MEPs appears to be questionable, since a poor reproducibility was detected for all pelvic floor muscles. The use of rTMS in this field is emerging and the results of a few preliminary studies should be replicated in controlled, randomized studies with larger sample sizes.     

High frequency of overlap between functional dyspepsia and overactive bladder

Background Overactive bladder syndrome (OAB) is defined as a symptom complex comprising urgency, with or without urge incontinence, and usually frequency and nocturia. The association between irritable bowel syndrome (IBS) and bladder symptoms has been reported. This study is designed to investigate whether functional dyspepsia (FD), like IBS, is associated with OAB. Methods A web surveys containing questions about OAB, FD, IBS, and demographics were completed by 5494 public individuals (2302 men and 3192 women) who have no history of severe illness. The prevalence and overlap of OAB, FD, and IBS were examined. Key Results Among participants with FD, 20.5% could also be diagnosed with OAB (odds ratio [OR]: 2.85; 95% confidence interval [CI]: 2.21-3.67). Although concomitant FD and IBS were more strongly associated with OAB (OR: 4.34; 95% CI: 2.81-6.73), OAB was also highly prevalent among participants with FD but without IBS (OR: 3.09; 95% CI: 2.29-4.18). Among participants with FD, an overlapping OAB condition was more prevalent in those with both postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) (OR: 3.75; 95% CI: 2.48-5.67) than in those with PDS or EPS alone. Among participants with OAB, the severity of bladder symptoms was greater in participants with dyspeptic symptoms than without them. Conclusions & Inferences Overactive bladder syndrome is common among FD patients, even if they do not have IBS. To improve FD patients' quality of life, it will be important to provide management for OAB.     

Differential induction of c-Fos and phosphorylated ERK by a noxious stimulus after peripheral nerve injury

Purpose: In this study, we compared induction of c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) in the spinal dorsal horn after peripheral nerve injury.

Materials and methods: We examined the spinal dorsal horn for noxious heat-induced c-Fos and p-ERK protein-like immunoreactive (c-Fos- and p-ERK-IR) neuron profiles after tibial nerve injury. The effect of administration of a MEK 1/2 inhibitor (PD98059) on noxious heat-induced c-Fos expression was also examined after tibial nerve injury.

Results: A large number of c-Fos- and p-ERK-IR neuron profiles were induced by noxious heat stimulation to the hindpaw in sham-operated animals. A marked reduction in the number of c-Fos- and p-ERK-IR neuron profiles was observed in the medial 1/3 (tibial territory) of the dorsal horn at 3 and 7 days after nerve injury. Although c-Fos-IR neuron profiles had reappeared by 14 days after injury, the number of p-ERK-IR neuron profiles remained decreased in the tibial territory of the superficial dorsal horn. Double immunofluorescence labeling for c-Fos and p-ERK induced by noxious heat stimulation to the hindpaw at different time points revealed that a large number of c-Fos-IR, but not p-ERK-IR, neuron profiles were distributed in the tibial territory after injury. Although administration of a MEK 1/2 inhibitor to the spinal cord suppressed noxious heat-induced c-Fos expression in the peroneal territory, this treatment did not alter c-Fos induction in the tibial territory after nerve injury.

Conclusions: ERK phosphorylation may be involved in c-Fos induction in normal nociceptive responses, but not in exaggerated c-Fos induction after nerve injury.     

Influence of antimuscarinic therapy on cognitive functions and quality of life in geriatric patients treated for overactive bladder

Objectives: Incidences of overactive bladder (OAB) and cognitive dysfunction increase with aging. Treatment of OAB with antimuscarinic agents may result in cognitive decline, especially in patients with Alzheimer's disease (AD). The aim of this study is to evaluate the effect of antimuscarinic treatment on cognitive functions, depression, and quality of life (QOL) of patients with OAB.

Methods: This non-interventional prospective observational study was conducted in a geriatric medicine outpatient clinic. Overall, 168 OAB patients were enrolled. Patients were followed up in five groups: oxybutynin, darifenacin, tolterodine, trospium, and control groups. Follow-up visits were done at second, third, and sixth months. Comprehensive geriatric assessment, cognitive and mood assessment, QOL scales (IIQ-7, UDI-6) were performed.

Results: Mean age of the patients was 73.5 ± 6.1. Of the 168 patients, 92.3% were female, 83.3% benefited from the treatment, and 37.1% discontinued the medication. Discontinuation rate and frequency of side effects were more frequent in the oxybutynin group. Mini Mental State Examination scores did not decline after treatment, even in AD patients. Geriatric Depression Scale scores, Activities of Daily Living scores, and QOL scores significantly improved after treatment.

Conclusion: Antimuscarinic agents are effective in OAB treatment. They have a positive impact on daily life activities, depression, and QOL indices. Furthermore, they do not have a negative effect on cognitive function in older adults with or without AD.     

Bladder symptoms assessed with overactive bladder questionnaire in Parkinson's disease

In Parkinson's disease (PD) the urinary dysfunction manifests primarily with symptoms of overactive bladder (OAB). The OAB questionnaire (OAB‐q) is a measure designed to assess the impact of OAB symptoms on health‐related quality of life. In this study, we quantified the urinary symptoms in a large cohort of PD patients by using the OAB‐q short form. Possible correlations between the OAB‐q and clinical features were tested. Three hundred and two PD patients were enrolled in the study. Correlations between the OAB‐q and sex, age, Unified Parkinson's Disease Rating Scale part III (UPDRS‐III), Hoehn‐Yahr (H‐Y) staging, disease duration, and treatment were analyzed. Data were compared with a large cohort of 303 age‐matched healthy subjects. The OAB‐q yielded significantly higher scores in PD patients than in healthy subjects. In the group of PD patients, all the variables tested were similar between men and women. Pearson's coefficient showed a significant correlation between mean age, disease duration, mean OAB‐q scores, UPDRS‐III scores, and H‐Y staging. A multiple linear regression analysis showed that OAB‐q values were significantly influenced by age and UPDRS‐III. No statistical correlations were found between OAB‐q scores and drug therapy or the equivalent levodopa dose, whilst the items relating to the nocturia symptoms were significantly associated with the equivalent levodopa dose. Our findings suggest that bladder dysfunction assessed by OAB‐q mainly correlates with UPDRS‐III scores for severity of motor impairment, possibly reflecting the known role of the decline in nigrostriatal dopaminergic function in bladder dysfunction associated with PD and patients' age. Our study also suggests that the OAB‐q is a simple, easily administered test that can objectively evaluate bladder function in patients with PD. © 2010 Movement Disorder Society     

Pudendal-to-bladder reflex in chronic spinal-cord-injured cats

The effects of pudendal nerve stimulation on reflex bladder activity were investigated in cats with chronic spinal cord injury (6-12 months) under alpha-chloralose anesthesia. Electrical stimulation of the pudendal nerve on one side at different frequencies and intensities induced either inhibitory or excitatory effects on bladder activity. The inhibitory effect peaked at a stimulation frequency of 3 Hz and gradually decreased at lower or higher frequencies. The inhibitory effect could occur at stimulation intensities between 0.3 and 1 V (pulse width 0.1 ms) and increased at intensities up to 10 V. Stimulation of the central end of transected pudendal nerve also inhibited bladder activity, indicating that afferent axons in pudendal nerve are involved. Nerve transections also showed that both hypogastric and pelvic nerves might be involved in the inhibitory pudendal-to-bladder spinal reflex. Pudendal nerve stimulation at 20 Hz and at the same intensities (1-10 V) elicited a bladder excitatory response. Although this excitatory effect could not sustain a long lasting bladder contraction at small bladder volumes, it did induce continuous rhythmic bladder contractions at large bladder volumes. This study indicated the possibility of developing a neuroprosthetic device based on pudendal nerve electrical stimulation to restore micturition function after spinal cord injury.