[Bladder Dysfunction and Neurology: How to Assess Neurogenic Bladder Dysfunction?]

Here we reviewed bladder dysfunction in neurological diseases. Diseases of the brain cause overactive bladder (OAB); peripheral neuropathy including lumbar spondylosis results in postvoid residual; and spinal cord diseases cause a combination of OAB and postvoid residual. Multiple system atrophy mimics bladder dysfunction related to spinal cord disease. Conversely, in cases of bladder dysfunction of unknown etiologies, the underlying disease can be identified by the bladder dysfunction pattern. Aging also causes nocturnal polyuria. The collaboration between neurologists and urologists is highly recommended to maximize the quality of life of neurological patients.

Variants associated with Gaucher disease in multiple system atrophy.

OBJECTIVE: Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case-control series. METHODS: We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants. RESULTS: In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel-Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14-5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15-5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 × 10(-3)). INTERPRETATION: The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA.

A 3-year cohort study of the natural history of spinocerebellar ataxia type 6 in Japan.

BACKGROUND: Only a few prospective studies have determined which clinical symptoms and factors are associated with the disease severity of spinocerebellar ataxia type 6 (SCA6). A multicenter longitudinal cohort study was conducted to clarify both the natural history of SCA6 in Japan and the factors influencing disease progression. METHODS: Patients were consecutively recruited between 2007 and 2008. Scores from the Scale for the Assessment and Rating of Ataxia (SARA) and Barthel Index (BI) were collected prospectively each year. Additionally, data from the Japan intractable diseases research (IDR) registry were collected both retrospectively, from 2003 to 2006, and prospectively, from 2007 to 2010. As a result, we were able to collect 3 years of retrospective data and 4 years of prospective data during the course of 3 yearly visits. RESULTS: Forty-six patients were registered. The follow-up rate of the third year was 93%. The SARA scores worsened significantly each year. Over 3 years, the decline of the SARA scores was 1.33 ± 1.40 points/year. The results of multivariate analysis of the decline of the SARA score were not significant. The IDR scores correlated well with the SARA and BI scores. Kaplan-Meier curves of 7 years of data from the IDR registry illustrated the correlation between the ability to walk and the time course of the disease. CONCLUSIONS: Information regarding the progression of ataxia and the decline in the activities of daily living (ADL) in patients with SCA6 was obtained by a 3-year cohort study and a 7-year IDR study. The decline of the SARA score of patients with SCA6 was 1.33 ± 1.40 points/year. The results elucidate the natural history of SCA6, factors influencing disease severity, and utility of data from the IDR registry of Japan.

Time-dependent changes and gender differences in urinary dysfunction in patients with multiple system atrophy.

AIMS: Because time-dependent changes and gender differences in urinary dysfunction in patients with multiple system atrophy (MSA) are yet unknown, we aimed to determine these parameters through a combination of urodynamic examination and the results of a questionnaire on urinary symptoms. METHODS: We retrospectively reviewed 66 patients with MSA who responded to a urinary symptoms questionnaire and underwent urodynamic examination more than twice. The participants' mean age was 62 years and mean disease duration at the first urodynamic examination was 3.2 years. Mean duration between the first and second urodynamic examination was 441 days. RESULTS: With regard to overall (both genders) time-dependent change, none of the urinary symptoms showed significant differences. In the urodynamic examination there were significant differences in reduced urine flow, increased post-void residuals, and decreased detrusor contractility at the second examination. With regard to gender differences, at the first examination, night-time urinary frequency, and voiding symptoms were significantly more severe in male than in female patients; however, at the second examination, except for urinary urgency, gender differences were not observed for any other symptoms. In urodynamic examination, the degree of detrusor contraction was significantly less in male patients at the first examination. However, no significant differences were found in urodynamic examination at the second examination. CONCLUSIONS: The present study indicates that voiding dysfunction progressed without significant worsening of voiding symptoms. In addition, gender differences are important in evaluating urinary dysfunction being basically less severe in female than in male patients, at least during the early stage. Neurourol. Urodynam. 33:516-523, 2014. © 2013 Wiley Periodicals, Inc.

Receiver operating characteristic analysis of sphincter electromyography for parkinsonian syndrome.

AIMS: We performed receiver operating characteristic (ROC) analysis to determine the ability of sphincter electromyography (EMG) to distinguish multiple system atrophy (MSA) from other parkinsonisms. The following was determined: (1) the appropriate motor unit potential (MUP) parameter among duration, phase, and amplitude; (2) the desirable parameter of our duration criteria; that is, more than 20% MUPs having >10 ms duration (criteria a) or mean duration >10 ms (criteria b). METHODS: We retrospectively reviewed 441 case records where sphincter EMG were performed in patients with parkinsonian syndromes: MSA, n = 263; Parkinson's disease, n = 129; dementia with Lewy bodies, n = 25; and progressive supranuclear palsy, n = 24. We performed ROC analysis of the data sets. RESULTS: The area under the curve used to differentiate MSA from other parkinsonian syndromes was 0.68 in duration, 0.57 in phase, and 0.51 in amplitude, respectively; these values were statistically significant. With regard to our duration criteria, area under the curve was 0.69 for the average duration of MUPs (criteria b) and 0.67 for percentage of MUPs of duration >10 ms (criteria a); these values were also statistically significant. CONCLUSIONS: This study suggests that duration is appropriate parameter for the differentiation of MSA. However, the area under the curve of the mean duration was insufficient to confirm the diagnosis; sphincter EMG should be used as a supportive diagnostic tool for the diagnosis of MSA.

Urinary dysfunction in early and untreated Parkinson's disease.

BACKGROUND: Urinary dysfunction is common in Parkinson's disease (PD); however, little is known about urinary dysfunction in early and untreated PD patients. METHODS: Fifty consecutive untreated PD patients (mean age, 66.7; mean disease duration, 23.6 months; and mean Hoehn & Yahr scale, 1.9) were recruited; those with other conditions that might have influenced urinary function were excluded. Patients were evaluated using a urinary questionnaire and urodynamic studies. RESULTS: Sixty-four per cent complained of urinary symptoms (storage, 64.0%; voiding, 28.0%). Urodynamic studies showed abnormal findings in the storage phase in 84%, with detrusor overactivity (DO) and increased bladder sensation without DO in 58.0% and 12.0% of patients, respectively. In the voiding phase, detrusor underactivity, impaired urethral relaxation such as detrusor sphincter dyssynergia, and bladder outlet obstruction were present in 50.0%, 8.0% and 16% of patients, respectively. In patients with both storage and voiding phase abnormalities, DO+detrusor underactivity was the most common finding. Few patients experienced urge incontinence and/or quality-of-life impairment owing to urinary dysfunction; none had low-compliance bladder or abnormal anal-sphincter motor unit potential. These urinary symptoms and urodynamic findings were not correlated with gender, disease severity or motor symptom type. CONCLUSION: Urinary dysfunction, manifested primarily as storage disorders with subclinical voiding disorders and normal anal-sphincter electromyography, occurs in early and untreated PD patients. In cases with severe voiding disorder and/or abnormal anal-sphincter electromyography, other diagnoses should be considered.

Neuronal activities of forebrain structures with respect to bladder contraction in cats.

The forebrain is one of the important suprapontine micturition centres. Previous studies have shown that electrical stimulation of the frontal lobe and the anterior cingulate gyrus elicited either inhibition or facilitation of bladder contraction. Patients with frontal lobe tumours and aneurysms showed micturition disorders. Functional brain imaging studies showed that several parts of the forebrain are activated during bladder filling. We aimed to examine neuronal activities of forebrain structures with respect to bladder contraction in cats. In 14 adult male cats under ketamine anaesthesia in which a spontaneous isovolumetric bladder-contraction/relaxation cycle had been generated, we carried out extracellular single-unit recording in forebrain with respect to the contraction/relaxation cycles in the bladder. We recorded 112 neurons that were related to the bladder-contraction/relaxation cycles. Ninety-four neurons were found to be tonically activated during the bladder-relaxation phase, whereas the remaining 18 neurons were tonically activated during the bladder-contraction phase. Both types of neuron were widely distributed around the cruciate sulcus. Most were located medially (medial and superior frontal gyrus) and the rest were located laterally (middle and inferior frontal gyrus). Neurons recorded in forebrain structures were activated with respect to the contraction/relaxation cycles in the bladder. Forebrain structures may have a significant role in regulating bladder contraction in cats.

Comparing bromocriptine effects with levodopa effects on bladder function in Parkinson's disease.

To evaluate the effects of bromocriptine on bladder function in Parkinson's disease (PD) patients and compare these effects with those of (L-dopa). We recruited 8 patients with PD. Urodynamic study (UDS) was performed before and 1 hour after administering 100 mg L-dopa/decarboxylase inhibitor (DCI) and 2.5 hours after administering 7.5 mg bromocriptine. After the bromocriptine administration, urinary urgency aggravated. UDS revealed a decreased bladder volume at which detrusor overactivity (DO) was initiated, a decreased bladder volume at first sensation of bladder filling (FSV) (P < 0.05), an increased maximum Watts Factor value (WFmax) (detrusor contractility), a decreased Abrams-Griffiths (AG) number (urethral obstruction), and a decreased postvoid residual (PVR) (P < 0.01). Similarly, after the L-dopa administration, urinary urgency aggravated. UDS revealed an aggravated DO (P < 0.05), a decreased FSV and bladder capacity (P < 0.01, 0.05), an increased WFmax (P < 0.05), an increased AG number, and a decreased PVR (P < 0.01). A single dose of bromocriptine proved to exacerbate urinary urgency and DO in the storage phase, and improve bladder emptying through increased detrusor contractility and decreased bladder outlet obstruction, within hours. With the exception of bladder outlet obstruction, these effects of bromocriptine are similar to the effects of L-dopa, albeit slightly less pronounced.

Gastric myoelectrical differences between Parkinson's disease and multiple system atrophy.

The electrogastrogram (EGG) was recorded for 24 hours in 17 Parkinson's disease (PD) patients, 17 multiple system atrophy (MSA) patients, and 8 healthy control subjects to elucidate the differences in the EGG findings between the two diseases. Eight EGG segments (3 preprandial, 3 postprandial, and 2 sleep segments) were selected from the total recording for spectral analysis, from which we obtained the dominant frequency (DF), instability coefficient of DF (ICDF), and low (LFR%), normal (NFR%), and high (HFR%) range power percentages of the total power. PD patients showed irregular slow waves, high HFR%, and high ICDF, whereas MSA patients showed regular slow waves and low ICDF. Although DF and NFR% increased after meal in controls, postprandial increases in DF and NFR% were less significant in both patient groups compared to the controls. The PD patients presented gastric dysrhythmias indicating gastric pacemaker disturbances. The MSA patients showed regular slow waves with low variability of the slow wave rhythm (low ICDF), which might have resulted from the involvement of gastric autonomic nerve function.

Effects of electrical stimulation of the striatum on bladder activity in cats.

AIMS: Parkinson's disease (PD) affects the nigrostriatal projections leading to micturition disturbance in most cases. Overactive bladder (OAB) symptoms such as urinary urgency or urgent urinary incontinence are common amongst PD patients. Several urodynamic studies have revealed that detrusor overactivity causes OAB symptoms in PD patients. We assert that striatal dysfunction might contribute to the pathogenesis of detrusor overactivity in PD patients. However, the role of the striatum in bladder contraction remains unclear. METHODS: We generated spontaneous isovolumetric bladder contractions in 12 ketamine-anesthetized adult male cats and subsequently performed electrical stimulation and extracellular single-unit recording in the striatum. RESULTS: Electrical stimulation applied to the posterior ventral caudate nucleus and the adjacent putamen reduced inhibition of the spontaneous bladder contraction. None of the responses were facilitatory. Electrical stimulation was most effective at an amplitude of 70-400 microA. Forty-six neurons that exhibited correlation to spontaneous bladder contraction were recorded in the striatum. Thirty-five neurons were found to be tonically active throughout the bladder relaxation phase, and the remaining 11 neurons were active during the bladder contraction phase. These particular neurons were located within the area in which spontaneous bladder contraction was inhibited by electrical stimulation. CONCLUSIONS: Electrical stimulation was found to inhibit bladder contraction, and a correlation was observed between spontaneous bladder relaxation/contraction and neuronal firing in the posterior ventral striatum.

Questionnaire-based assessment of pelvic organ dysfunction in multiple system atrophy.

Multiple system atrophy (MSA) is a neurodegenerative disease characterized clinically by any combination of autonomic, cerebellar, and extrapyramidal symptoms. Autonomic symptoms are usually severe, and urinary symptoms are one of the cardinal features of MSA. Bowel dysfunction and sexual dysfunction are also common in MSA. Quality of life (QOL) in patients with MSA is severely impaired by the presence of pelvic organ dysfunction. Therefore, we aimed to examine the prevalence of pelvic organ dysfunction in patients with MSA. We recruited 256 patients with MSA seen at our neurology clinic. The mean age was 62 years. The control group comprised 158 individuals, and the mean age was 52 years. We administered a questionnaire on pelvic organ dysfunction to the MSA and control groups. The questionnaire had sections focusing on the bladder, bowel, and sexual function. Dysfunction, as described in the responses, was evaluated as normal, mild (>once a month), moderate (>once a week), or severe (>once a day). The Mann-Whitney's U-test was used for statistical analysis. When compared with the control group, the prevalence of pelvic organ dysfunction in the MSA group was significantly higher for urinary storage and voiding dysfunction, bowel dysfunction, and sexual dysfunction. QOL in the MSA group was therefore significantly impaired because of urinary dysfunction (70%, 76%), bowel dysfunction (40% of the men), and sexual dysfunction (26%, 45%). Pelvic organ dysfunction is common in MSA, and QOL is severely impaired in patients with MSA.

Differences in skin sympathetic involvements between two chronic autonomic disorders: multiple system atrophy and pure autonomic failure.

OBJECTIVE: Certain stimuli evoke increased sweat secretion (sympathetic sweat response; SSwR) and reduced skin blood flow (skin vasomotor reflex; SkVR) in the palm/sole. We evaluated SSwR and SkVR in patients with multiple system atrophy (MSA) and pure autonomic failure (PAF). METHODS: SSwR and SkVR on the palm in response to deep inspiration and mental arithmetic were recorded in 11 MSA patients, 11 PAF patients, and 11 healthy controls. In addition, the head-up tilt test was performed, and the coefficient of variation of R-R intervals (CV(R-R)) was obtained. RESULTS: SSwR amplitudes were significantly lower in the MSA and PAF patients than the controls. SkVR amplitudes in the PAF patients were significantly lower than the controls, but preserved in the MSA patients. In head-up tilt tests, all MSA and PAF patients showed orthostatic hypotension, with similar severity. CV(R-R) was low in the MSA and PAF patients, but a significant difference was found only between the PAF and control groups. CONCLUSION: In the MSA patients, SkVR was preserved, but SSwR was diminished. In the PAF patients, both SkVR and SSwR were attenuated. The combination of SkVR and SSwR tests may differentiate MSA and PAF.

Altered heart rate control in response to postural change in patients with Machado-Joseph disease (SCA3).

To assess heart rate (HR) regulation in Machado-Joseph disease (MJD), we evaluated HR variability at rest and the initial HR response to standing suddenly in 13 MJD patients and 26 normal control subjects. A head-up tilt (HUT) test involving the monitoring of blood pressure, HR, and cerebral oxy/deoxyhemoglobin concentration was also performed in each participant. There was no significant difference in HR variability at rest between the two groups, but the transient HR rise just after standing suddenly in the MJD group was significantly less than that in the control group (p < 0.01). The HUT test, where each participant was gradually tilted upward, induced a significantly greater HR increase in the MJD group compared with the controls (p < 0.01), while there were no significant differences in the blood pressure and cerebral oxygenation changes between the two groups. In our MJD study, the transient HR rise just after standing suddenly was diminished, and HR markedly increased during sustained orthostatic stress.

Cerebral oxygenation monitoring for detecting critical cerebral hypoperfusion in patients with multiple system atrophy during the head-up tilt test.

OBJECTIVE: Near infrared spectroscopy (NIRS) is a non-invasive optical technique to monitor cerebral tissue oxygen saturation (ScO(2)). The purpose of this study was to reveal the usefulness of ScO(2) monitoring in evaluating cerebral circulation in patients with autonomic failure. METHODS: Nineteen patients with multiple system atrophy (MSA), who had autonomic failure, and 10 age-matched normal control subjects participated. In addition to blood pressure monitoring, ScO(2) was recorded by a near-infrared spectroscopy instrument during head-up tilt (HUT) test. RESULTS: HUT tests induced postural symptoms in 9 MSA patients (presyncopal group), but not in 10 MSA patients (non-presyncopal group) or in any of the controls. ScO(2), which decreased slightly in the controls and MSA patients, did not differ significantly between the MSA and control groups. With regard to MSA subgroups, the ScO(2) reduction in the presyncopal group (-3.1+/-1.7%) was significantly larger than in the non-presyncopal group (-0.9+/-0.5%, P<0.005) and controls (-1.1+/-1.0%, P<0.05). The systolic blood pressure decreases during HUT in the non-presyncopal (-35.2+/-16.1 mmHg, P<0.01) and presyncopal (-54.3+/-27.5 mmHg, P<0.0005) groups were significantly greater than that in the control group (4.0+/-10.7 mmHg), but the difference between presyncopal and non-presyncopal groups was not significant. CONCLUSION: In our study, ScO(2) reduction seemed to be associated with presyncopal symptoms. ScO(2) monitoring may be useful to detect cerebral hypoperfusion in MSA patients with autonomic failure.

A case report of plasmapheresis in the treatment of acute disseminated encephalomyelitis.

Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease of the central nervous system associated with significant morbidity and mortality. High-dose corticosteroid administration has been considered the mainstay of treatment for ADEM; however, some patients with ADEM are refractory to steroid therapy. We report a case of a 17-year-old man suffering from ADEM who did not respond to corticosteroid therapy, but who exhibited a dramatic recovery with plasmapheresis. He became comatose, requiring ventilatory support, and exhibited abnormalities of some brainstem reflexes prior to treatment. He underwent sequential courses of plasma exchange therapy for three days. Plasma exchanges were carried out with concomitant continuous hemodiafiltration (CHDF) to control intracranial pressure by stabilizing pH, plasma Na+ concentration, and colloid osmotic pressure. After plasma exchanges, his reflexes and level of consciousness gradually improved. Eleven months after this treatment, he had only minimal neurological deficit that did not interfere with any of his activities of daily living. The efficacy of plasmapheresis for ADEM has not yet been established. Plasmapheresis may be indicated for ADEM, not only for patients with severe disease in whom high-dose corticosteroid treatment has failed, but also as first-line treatment for ADEM. Early initiation of plasmapheresis appears to be associated with moderate to marked improvement. Early recognition and early treatment of ADEM are thus of paramount importance.

Effects of milnacipran and paroxetine on overactive bladder due to neurologic diseases: a urodynamic assessment.

AIMS: To determine the effects of milnacipran hydrochloride, a serotonin-norepinephrine reuptake inhibitor (SNRI), or paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on overactive bladder (OAB) in neurologic diseases, given by objective measures of urodynamic studies. METHODS: This is a prospective open trial, and we enrolled 24 patients (16 men, 8 women; mean age, 63.9 years) with OAB in a neurology clinic. They were randomly allocated into two groups: the milnacipran group (11 patients), and paroxetine group (13 patients). We started with 100 mg/day of milnacipran or 40 mg/day of paroxetine. Before and 3 months after the treatment, we performed a urinary questionnaire and urodynamic studies. RESULTS: Milnacipran reduced daytime urinary frequency (average, from 9.4 to 7.1 times, p < 0.001), improved the quality of life index (p = 0.023), and increased bladder capacity (average, from 289 to 377 ml, p = 0.009) as shown in urodynamic studies. No such changes were noted in the other categories of the lower urinary tract symptoms questionnaire or urodynamic studies, or in the paroxetine group. One male patient complained of mild voiding difficulty. Other adverse effects were not seen during the observation period. CONCLUSION: Milnacipran, an SNRI, increased bladder capacity as shown in urodynamic studies, and thereby ameliorated OAB in patients with neurologic diseases without serious adverse effects.