Ryuji Sakakibara

Questionnaire-based assessment of pelvic organ dysfunction in Parkinson's disease

Although patients with Parkinsons disease (PD) experience pelvic organ dysfunction of the urinary bladder, bowel and genital organs, an accurate incidence of the dysfunction and its characteristics have yet to be ascertained. We devised a detailed questionnaire on these three pelvic organ functions in PD patients and control subjects, in our search for a hallmark that would distinguish between the two groups. The PD group comprised 115 patients; 52 men and 63 women, age range 35-69 (average 59) years old, average duration of illness 6 years, median Hoehn and Yahr stage 3. All were taking levodopa with/without dopamine agonists. The control group comprised 391 local individuals who were undergoing an annual health survey; 271 men and 120 women, age range 30-69 (average 48) years old. The questionnaire had three parts: bladder (nine questions), bowel (four questions), and sexual (three questions for women, five for men) function. Each question was scored from 0 (none) to 3 (severe) with an additional quality of life (QOL) index scored from 0 (satisfied) to 3 (extremely dissatisfied). The completion rate was 100% for bladder and bowel functions, whereas for sexual function, it was 95% (control) and 88% (PD) for men and 82% (control) and 60% (PD) for women. As compared with the control group, the frequency of dysfunction in the PD group was significantly higher for urinary urgency (women 42%, men 54%), daytime frequency (28%, 16%), nighttime frequency (53%, 63%), urgency incontinence (25%, 28%), retardation (44% of men), prolongation/poor stream (men 70%), straining (women 28%); constipation (63%, 69%), difficulty in expulsion (men 57%), diarrhea (men 21%); decrease in libido (84%, 83%), decrease in sexual intercourse (55%, 88%), decrease in orgasm (men 87%), and in men, decreases in erection (79%) and ejaculation (79%). The QOL index for the PD patients was significantly higher for bladder (27%, 28%) and bowel (46%, 59%) but not for sexual dysfunction, despite the groups high prevalence of sexual dysfunction. In the PD patients, fecal incontinence was associated with urinary incontinence. Stress urinary incontinence and a decrease in libido were more common in women than in men. Bladder and bowel dysfunction, but not sexual dysfunction increased with the Hoehn and Yahr stage. Sexual dysfunction, but neither bladder nor bowel dysfunction, increased with age. Patients taking levodopa and bromocriptine more frequently had bladder (voiding phase) dysfunction than those taking levodopa only. The findings show that bladder, bowel and sexual dysfunction are all prominent in patients with PD. Amelioration of pelvic organ dysfunction, particularly bowel dysfunction which most affects the quality of life, therefore should be a primary target in the treatment of patients with PD.

Micturitional disturbance after acute hemispheric stroke: analysis of the lesion site by CT and MRI

Micturitional histories and urodynamic studies were performed in 72 acute hemispheric stroke patients. Within 3 months from the onset, 53% of the patients had urinary symptoms including irritative as well as obstructive, and the most common symptom was nocturnal urinary frequency in 36%, which was followed by urge urinary incontinence in 29% and difficulty of voiding in 25% of the patients. We found a correlation between micturitional disturbance with hemiparesis (p <0.05) and not with hemianopsia (p <0.05). Micturitional disturbance was more common in lesions of the frontal lobe (p <0.05) than in those of the occipital lobe. Brain CT or MRI in symptomatic patients showed lesions of anterior and medial surface of the frontal lobe, anterior edge of the paraventricular white matter, genu of the internal capsule and large lesions of putamen or thalamus. Urodynamic studies of 22 symptomatic patients revealed various findings in 91% of them, including detrusor hyperreflexia in 68%, detrusor-sphincter dyssynergia (DSD) in 14% and uninhibited sphincter relaxation in 36%. Patients with urinary retention had atonic cystometrogram and DSD. Detrusor hyperreflexia was noted in lesions of the frontal lobe as well as the basal ganglia, uninhibited sphincter relaxation in the frontal lobe, and detrusor-sphincter dyssynergia common in the basal ganglia. Above findings seem to indicate that anteromedial frontal lobe and its descending pathway, and the basal ganglia seem to be mainly responsible for supranuclear types of pelvic and pudendal nerve dysfunction in our patients with stroke.

Videourodynamic and sphincter motor unit potential analyses in Parkinson's disease and multiple system atrophy

OBJECTIVES Urinary dysfunction is a prominent autonomic feature in Parkinsons disease (PD) and multiple system atrophy (MSA), which is not only troublesome but also a cause of morbidity in these disorders. Recent advances in investigative uroneurology offer a better insight into the underlying pathophysiology and appropriate management for urinary dysfunction. METHODS twenty one patients with PD (15 men, six women, mean age 64 (49–76), mean disease duration 4 years (1–8 years), median Hoehn and Yahr grade 3 (1–4), all taking 300 mg/day of levodopa (100–500 mg)) and 15 with MSA (eight men, seven women, mean age 59 (48–72), mean disease duration 3 years (0.5–6 years)) were recruited. Videourodynamic and sphincter motor unit potential analyses in the patients with PD and MSA were carried out, looking for distinguishing hallmarks that might be useful in the differential diagnosis of these two diseases. RESULTS Urinary symptoms were found in 72% of patients with PD and in 100% with MSA. Filling phase abnormalities in the videourodynamic study included detrusor hyperreflexia in 81% of patients with PD and 56% with MSA, and uninhibited external sphincter relaxation in 33% of patients with PD and 33% of those with MSA. However, open bladder neck at the start of filling was not seen in patients with PD but was present in 53% of those with MSA, suggestive of internal sphincter denervation. Sphincter motor unit potential analysis showed neurogenic motor unit potentials in 5% of patients with PD and in 93% of those with MSA, suggestive of external sphincter denervation. On voiding, detrusor-external sphincter dyssynergia was not seen in patients with PD but was present in 47% of those with MSA. Pressure-flow analysis showed that the Abrams-Griffiths number, a grading of urethral obstruction (outflow obstruction >40), in PD (40 in women and 43 in men) was larger than that in MSA (12 in women and 28 in men). Weak detrusor in PD (66% of women and 40% of men) was less common than that in MSA (71% of women and 63% of men). Postmicturition residuals >100 ml were absent in patients with PD but were present in 47% of patients with MSA. CONCLUSION Patients with PD had less severe urinary dysfunction with little evidence of internal or external sphincter denervation, by contrast with the common findings in MSA. The findings of postmicturition residuals >100 ml, detrusor-external sphincter dyssynergia, open bladder neck at the start of bladder filling, and neurogenic sphincter motor unit potentials are highly suggestive of MSA.

Mosapride citrate, a novel 5-HT4 agonist and partial 5-HT3 antagonist, ameliorates constipation in Parkinsonian patients

Mosapride citrate is a novel selective 5‐HT4 receptor agonist. It facilitates acetylcholine release from the enteric cholinergic neurons. In contrast to cisapride, mosapride does not block K+ channels or D2 dopaminergic receptors. The objective of this study is to perform an open study of mosapride citrates effects on constipation, a prominent lower gastrointestinal tract disorder in parkinsonian patients. A total of 14 parkinsonian patients (7 with Parkinsons disease, 7 with multiple system atrophy; 10 men, 4 women; mean age, 67 years) with constipation (10 with bowel movement < 3 times/week; 14 with difficulty in defecation) were treated with 15 mg/day of mosapride citrate for 3 months. Pre‐ and posttreatment objective parameters in colonic transit time (CTT) and rectoanal videomanometry were obtained. Statistical analysis was made by Students t test. Mosapride was well tolerated by all patients except for 1, who discontinued use of the drug because of epigastric discomfort. None had a worsening of parkinsonism or other adverse events. Thirteen patients reported subjective improvements in bowel frequency (>3 times/week, 13) and difficult defecation (13). Mosapride shortened CTT of the left colon (P < 0.01) and the total colon (P < 0.05). During rectal filling, mosapride lessened the first sensation (P < 0.05) and augmented the amplitude in phasic rectal contraction. During defecation, mosapride augmented the amplitude in rectal contraction (P < 0.05) and lessened the volume of postdefecation residuals. The present study showed for the first time that mosapride citrate augmented lower gastrointestinal tract motility, as shown in CTT and videomanometry, and thereby ameliorated constipation in parkinsonian patients without serious adverse effects.

Urinary function in elderly people with and without leukoaraiosis: relation to cognitive and gait function

OBJECTIVES To investigate urinary function in the elderly with and without white matter lesion (leukoaraiosis) in relation to cognitive and gait function. METHODS Sixty three subjects were examined, with mean age 73 (range 62 to 86 years). Subjects with brainstem stroke or with large hemispheric lesions were excluded. Spin echo 1.5 T MRI images were graded from 0 to 4 for severity of white matter lesions. Urinary function was assessed by detailed questionnaire and urodynamic studies were performed in 33 of the subjects, including measurement of postmicturition residuals, water cystometry, and sphincter EMG. A mini mental state examination (MMSE) and examination of gait was also performed and compared with urinary function. RESULTS Urodynamic studies showed subjects with grade 1–4 white matter lesions to have detrusor hyperreflexia more commonly (82%) than those with grade 0 white matter lesions (9%) (p<0.05), indicating that leukoaraiosis was a factor associated with geriatric urinary dysfunction. Postmicturition residuals, low compliance, detrusor-sphincter dyssynergia, and uninhibited sphincter relaxation were also more common in grade 1–4 than in grade 0 white matter lesions, though the difference was not significant. In grade 1 white matter lesions urinary dysfunction (urge urinary incontinence) was more common than cognitive (MMSE<19) (p<0.05) and gait disorders (slowness, short step/festination, and loss of postural reflex) (p<0.05), which increased together with the grade of white matter lesions (p<0.05). CONCLUSIONS Urinary dysfunction is common and probably the early sign in elderly people with leukoaraiosis on MRI.

Colonic transit time and rectoanal videomanometry in Parkinson’s disease

Background: Constipation is a prominent lower gastrointestinal tract dysfunction that occurs frequently in Parkinson’s disease (PD). Objective: To investigate colonic transport and dynamic rectoanal behaviour during filling and defecation in patients with PD. Methods: Colonic transit time (CTT) and rectoanal videomanometry analyses were performed in 12 patients with PD (10 men and 2 women; mean age, 68 years, mean duration of disease, five years; mean Hoehn and Yahr grade, 3; decreased stool frequency (<3 times a week) in six, difficulty in stool expulsion in eight) and 10 age matched normal control subjects (7 men and 3 women; mean age, 62 years; decreased stool frequency in two, difficulty in stool expulsion in two). Results: In the PD patients, CTT was significantly prolonged in the rectosigmoid segment (p<0.05) and total colon (p<0.01) compared with the control subjects. At the resting state, anal closure and squeeze pressures of PD patients were lower than those in control subjects, though not statistically significant. However, the PD patients showed a smaller increase in abdominal pressure on coughing (p<0.01) and straining (p<0.01). The sphincter motor unit potentials of the patients were normal. During filling, PD patients showed normal rectal volumes at first sensation and maximum desire to defecate, and normal rectal compliance. However, they showed smaller amplitude in phasic rectal contraction (p<0.05), which was accompanied by an increase in anal pressure that normally decreased, together with leaking in two patients. During defecation, most PD patients could not defecate completely with larger post-defecation residuals (p<0.01). PD patients had weak abdominal strain and smaller rectal contraction on defecation than those in control subjects, though these differences were not statistically significant. However, the PD patients had larger anal contraction on defecation (p<0.05), evidence of paradoxical sphincter contraction on defecation (PSD). Conclusions: Slow colonic transit, decreased phasic rectal contraction, weak abdominal strain, and PSD were all features in our PD patients with frequent constipation.

Randomized, double-blind study of electrical stimulation for urinary incontinence due to detrusor overactivity.

OBJECTIVES To evaluate the usefulness of electrical stimulation for urinary incontinence due to detrusor overactivity in a randomized, double-blind manner. METHODS Sixty-eight patients (29 men, 39 women, 70.0 +/- 11.2 years) were studied. Detrusor overactivity was urodynamically defined as involuntary detrusor contractions of more than 15 cm H(2)O during the filling phase. Ten-hertz square waves of 1-ms pulse duration were used. A vaginal electrode was used in the women and an anal or surface electrode in the men. The stimulation was given for 15 minutes twice daily for 4 weeks. The efficacy was evaluated on the basis of a frequency/volume chart and urodynamic study before and after treatment. RESULTS Thirty-two patients in the active group and 28 in the sham group completed the study. The patient impressions were very good or good in 59% and 39% of the active and the sham group, respectively (P = 0.0354). On the cystometrogram, the bladder capacity at the first desire to void and the maximum desire to void increased significantly (P = 0.0104 and P = 0.0046, respectively) in the active group, but not in the sham group. Seven patients in the active group and 1 patient in the sham group were cured (P = 0.0324); 26 patients (81.3%) in the active group and 9 (32.1%) in the sham group improved (P = 0.0001). Of 17 patients in the active group, 13 remained cured or improved for an average of 8.4 months after completion of the 4-week treatment; in the sham group, 3 of 6 patients were cured or improved for an average of 4.7 months after completion of the 4-week treatment. CONCLUSIONS Electrical stimulation was useful in treating urinary incontinence due to detrusor overactivity.

Bladder and bowel dysfunction in Parkinson’s disease

Summary.Bladder dysfunction (urinary urgency/frequency) and bowel dysfunction (constipation) are common non-motor disorders in Parkinson’s disease (PD). In contrast to motor disorder, the pelvic autonomic dysfunction is often non-responsive to levodopa treatment. Brain pathology mostly accounts for the bladder dysfunction (appearance of overactivity) via altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. In contrast, peripheral enteric pathology mostly accounts for the bowel dysfunction (slow transit and decreased phasic contraction) via altered dopamine-enteric nervous system circuit, which normally promotes the peristaltic reflex. In addition, weak strain and paradoxical anal contraction might be the results of brain pathology. Pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore it might aid the differential diagnosis. Drugs to treat bladder dysfunction in PD include anticholinergic agents. Drugs to treat bowel dysfunction in PD include dietary fibers, peripheral dopaminergic antagonists, and selective serotonergic agonists. These treatments might be beneficial not only in maximizing patients’ quality of life, but also in promoting intestinal absorption of levodopa and avoiding gastrointestinal emergency.

Urinary dysfunction and orthostatic hypotension in multiple system atrophy: which is the more common and earlier manifestation?

OBJECTIVES Urinary dysfunction and orthostatic hypotension are the prominent autonomic features in multiple system atrophy (MSA). A detailed questionnaire was given and autonomic function tests were performed in 121 patients with MSA concerning both urinary and cardiovascular systems. METHODS Replies to the questionnaire on autonomic symptoms were obtained from 121 patients including three clinical variants; olivopontocerebellar atrophy (OPCA) type in 48, striatonigral degeneration (SND) type in 17, and Shy-Drager type in 56. Urodynamic studies comprised measurement of postmicturition residuals, EMG cystometry, and bethanechol injection. Cardiovascular tests included head up tilt test, measurement of supine plasma noradrenaline (norepinephrine,NA), measurement of R-R variability (CV R-R), and intravenous infusions of NA and isoproterenol. RESULTS Urinary symptoms (96%) were found to be more common than orthostatic symptoms (43%) (p<0.01) in patients with MSA, particularly with OPCA (p<0.01) and SND (p<0.01) types. In 53 patients with both urinary and orthostatic symptoms, patients who had urinary symptoms first (48%) were more common than those who had orthostatic symptoms first (29%), and there were patients who developed both symptoms simultaneously (23%). Post-micturition residuals were noted in 74% of the patients. EMG cystometry showed detrusor hyperreflexia in 56%, low compliance in 31%, atonic curve in 5%, detrusor-sphincter dyssynergia in 45%, and neurogenic sphincter EMG in 74%. The cystometric curve tended to change from hyperreflexia to low compliance, then atonic curve in repeated tests. Bethanechol injection showed denervation supersensitivity of the bladder in 19%. Cardiovascular tests showed orthostatic hypotension below –30 mm Hg in 41%, low CV R-R below 1.5 in 57%, supine plasma NA below 100 pg/ml in 28%, and denervation supersensitivity of the vessels (α in 73%; β2 in 60%) and of the heart (β1 in 62%). CONCLUSION It is likely that urinary dysfunction is more common and often an earlier manifestation than orthostatic hypotension in patients with MSA, although subclinical cardiovascular abnormalities appear in the early stage of the disease. The responsible sites seem to be central and peripheral for both dysfunctions.

Short-term effect of a single levodopa dose on micturition disturbance in Parkinson's disease patients with the wearing-off phenomenon

We investigated the short‐term effects of a single dose of levodopa (L‐dopa) on micturition function in PD patients with wearing‐off phenomenon. Eighteen PD patients who had median Hoehn and Yahr scores of 5 during the off phase and 3 during the on phase were recruited. We carried out urodynamic studies before and about 1 hour after the patients had taken 100 mg of L‐dopa with dopa‐decarboxylase inhibitor (DCI). After taking the L‐dopa/DCI, urinary urgency and urge incontinence aggravated, whereas voiding difficulty was alleviated in all 12 patients. When compared to the baseline assessment, urodynamic study results after taking 100 mg of L‐dopa/DCI showed aggravated detrusor hyperreflexia; decreased maximum bladder capacity (P = 0.006); an increased maximum Watts Factor value (P = 0.001), reflecting the detrusor power on voiding; an increased Abrams‐Griffiths number (P = 0.042), reflecting urethral obstruction on voiding; decreased residual urine volume (P = 0.025); and increased static urethral closure pressure (P = 0.012). One hundred milligrams of L‐dopa/DCI worsened detrusor hyperreflexia, producing worsened urinary urgency and urge incontinence during the storage (bladder‐filling) phase. It also increased detrusor contractility much more than it did urethral obstruction in the voiding phase, producing overall lessening of voiding difficulty and improving voiding efficiency in our PD patients with the wearing‐off phenomenon.