Tomoyuki Uchiyama

Neuromodulation for the Treatment of Lower Urinary Tract Symptoms

Neuromodulation therapy incorporates electrical stimulation to target specific nerves that control lower urinary tract symptoms (LUTS). The objectives of this article are to review the mechanism of action, the type of neuromodulation, and the efficacy of neuromodulation mainly according to the results of randomized controlled trials. Neuromodulation includes pelvic floor electrical stimulation (ES) using vaginal, anal and surface electrodes, interferential therapy (IF), magnetic stimulation (MS), percutaneous tibial nerve stimulation, and sacral nerve stimulation (SNS). The former four stimulations are used for external periodic (short‐term) stimulation, and SNS are used for internal, chronic (long‐term) stimulation. All of these therapies have been reported to be effective for overactive bladder or urgency urinary incontinence. Pelvic floor ES, IF, and MS have also been reported to be effective for stress urinary incontinence. The mechanism of neuromodulation for overactive bladder has been reported to be the reflex inhibition of detrusor contraction by the activation of afferent fibers by three actions, i.e., the activation of hypogastric nerve, the direct inhibition of the pelvic nerve within the sacral cord and the supraspinal inhibition of the detrusor reflex. The mechanism of neuromodulation for stress incontinence is contraction of the pelvic floor muscles through an effect on the muscle fibers as well as through the stimulation of pudendal nerves. Overall, cure and improvement rates of these therapies for urinary incontinence are 30–50, and 60–90% respectively. MS has been considered to be a technique for stimulating nervous system noninvasively. SNS is indicated for patients with refractory overactive bladder and urinary retention.

Usefulness of Cardiac MIBG Scintigraphy, Olfactory Testing and Substantia Nigra Hyperechogenicity as Additional Diagnostic Markers for Distinguishing between Parkinson’s Disease and Atypical Parkinsonian Syndromes

Background We aimed to evaluate the utility of the combined use of cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy, olfactory testing, and substantia nigra (SN) hyperechogenicity on transcranial sonography (TCS) in differentiating Parkinson’s disease (PD) from atypical parkinsonian syndromes (APSs), such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Methods Cardiac MIBG scintigraphy, card-type odor identification testing (Open Essence (OE), Wako, Japan), and TCS were performed with 101 patients with PD and 38 patients with APSs (MSA and PSP). Receiver operating characteristic (ROC) curve analysis was used to assess the sensitivity and specificity of these batteries for diagnosing PD from APSs. The diagnostic accuracy of the three tests was also assessed among patients at the early disease stage (drug-naïve patients with a disease duration of 3 years or less). Results In differentiating PD from APSs, the area under the ROC curve was 0.74 (95% CI, 0.65–0.83), 0.8 (95% CI, 0.73–0.87), and 0.75 (95% CI, 0.67–0.82) for TCS, cardiac MIBG scintigraphy, and olfactory testing, respectively. The diagnostic sensitivity and specificity were 53.1% and 91.7%, respectively, for TCS, 70.3% and 86.8%, respectively, for cardiac MIBG scintigraphy, 58.4% and 76.3%, respectively, for OE. Among early-stage patients, sensitivity and specificity were 50.0% and 93.8%, respectively, for TCS, 57.1% and 87.5%, respectively, for cardiac MIBG scintigraphy, and 54.8% and 79.2%, respectively, for OE. At least one positive result from 3 tests improved sensitivity (86.1%) but decreased specificity (63.2%). In contrast, at least 2 positive results from 3 tests had good discrimination for both early-stage patients (50.0% sensitivity and 93.8% specificity) and patients overall (57.8% sensitivity and 95.8% specificity). Positive results for all 3 tests yielded 100% specificity but low sensitivity (25%). Conclusions At least 2 positive results from among TCS, cardiac MIBG scintigraphy, and olfactory testing can support clinical diagnosis in distinguishing PD from APSs.

Istradefylline improves daytime sleepiness in patients with Parkinson's disease: An open-label, 3-month study

BACKGROUNDnIstradefylline, a selective adenosine A2A receptor antagonist, has been reported to improve daily off time and motor symptoms in patients with Parkinsons disease (PD). However, the effect of istradefylline on sleep problems has not been thoroughly investigated.nnnMETHODSnWe evaluated the effect of istradefylline on daytime sleepiness, sleep disturbances, and motor symptoms in 22 PD patients who were affected by the wearing off phenomenon in an open-label, 3-month study. Participants received 20-40mg/day istradefylline once daily (morning) over a 3-month period. The Epworth Sleepiness Scale (ESS), PD sleep scale (PDSS)-2 and PD Questionnaire (PDQ-8) were administered at baseline, 2weeks, 1month, 2months and 3months. At baseline and 3months, patients were evaluated on the Movement Disorder Society Revision of the Unified PD Rating Scale (MDS-UPDRS) parts III and IV.nnnRESULTSnTwenty-one patients (95.5%) completed the study. At 3months, MDS-UPDRS part III (-5.3, p=0.0002) and part IV (-2.5, p=0.001) scores improved and off time decreased significantly (-50.1min, p=0.0004). PDQ-8 scores were unchanged at 3months. ESS scores decreased significantly at 2months and 3months (-2.4 and -3.3, respectively, p<0.0001), but the total PDSS-2 scores did not change.nnnCONCLUSIONnIstradefylline improved daytime sleepiness in PD patients, possibly through its effect on enhancing alertness. In addition, the lack of significant changes in the total PDSS-2 scores over the study period suggests istradefylline had no negative impact on sleep.

The role of muscarinic receptor subtypes on carbachol-induced contraction of normal human detrusor and overactive detrusor associated with benign prostatic hyperplasia

The aim of this study was to compare the effect of antimuscarinic antagonists on carbachol-induced contraction of normal human bladder and detrusor overactivity associated with benign prostatic hyperplasia (DO/BPH). Samples of human bladder muscle were obtained from patients undergoing total cystectomy for bladder cancer (normal bladder), and those undergoing retropubic prostatectomy for BPH. All of the patients with DO/BPH had detrusor overactivity according to urodynamic studies. Detrusor muscle strips were mounted in 10-ml organ baths containing Krebs solution, and concentration-response curves for carbachol were obtained in the presence of antimuscarinic antagonists (4-DAMP, methoctramine, pirenzepine, tolterodine, solifenacin, trospium, propiverine, oxybutynin, and imidafenacin) or vehicle. All antagonists competitively antagonized concentration-response curves to carbachol with high affinities in normal bladder. The rank order of mean pA2 values was as follows: trospium (10.1) > 4-DAMP (9.87), imidafenacin (9.3) > solifenacin (8.8) > tolterodine (8.6) > oxybutynin (8.3) > propiverine (7.7) > pirenzepine (7.4) > methoctramine (6.6). The effects of these antimuscarinic antagonists did not change when tested with DO/BPH bladder, suggesting that each antimuscarinic antagonist has a similar effect in this condition. Schild plots showed a slope corresponding to unity, except for propiverine with DO/BPH detrusor. In conclusion, M3-receptors mainly mediate contractions in human bladder strips with normal state and DO/BPH.

Six-year follow up of silodosin monotherapy for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia: What are the factors for continuation or withdrawal?

To investigate the factors for continuation or withdrawal as an extension of a prospective study of silodosin monotherapy for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia for more than 6 years.

Characterizing restless legs syndrome and leg motor restlessness in patients with Parkinson's disease: A multicenter case-controlled study

BACKGROUNDnWe investigated the prevalence and impact of restless legs syndrome (RLS) and leg motor restlessness (LMR) in patients with Parkinsons disease (PD) in a multicenter study.nnnMETHODSnA total of 436 PD patients and 401 age- and sex-matched controls were included in this study. RLS was diagnosed based on four essential features. LMR was diagnosed when a participant exhibited the urge to move his or her legs but did not meet the four essential features of RLS.nnnRESULTSnThe RLS prevalence did not differ between PD patients and controls (3.4% vs. 2.7%), while LMR prevalence was significantly higher in PD patients than in controls (12.8% vs. 4.5%). PD patients with RLS or LMR had a higher prevalence of excessive daytime sleepiness (EDS) (50.7%, vs. 6.9%), probable REM sleep behavior disorder (38.0% vs. 3.4%) and PD-related sleep problems (49.3% vs. 20.7%) than controls with RLS or LMR. RLS/LMR preceding PD onset was related to an older age of PD onset.nnnCONCLUSIONnOur study revealed an increased prevalence of LMR but not RLS in PD patients. LMR could be an early manifestation of PD; however, whether LMR is within the range of RLS or whether LMR and RLS constitute different entities in PD requires further studies.

Could istradefylline be a treatment option for postural abnormalities in mid-stage Parkinson's disease?

BASEGROUNDnPostural abnormalities are refractory complications observed in mid- to late-stage Parkinsons disease (PD).nnnMETHODSnWe analyzed the effects of istradefylline, a selective adenosine A2A receptor antagonist, on posture in 21 levodopa-treated PD patients from the subanalysis of a three-month open-label study.nnnRESULTSnThe subitem score of posture (3.13) on the Movement Disorder Society revision of the Unified Parkinsons Disease Rating Scale (MDS-UPDRS) part III significantly improved following istradefylline treatment (baseline, 1.3±1.0 points vs 3months, 0.9±0.9 points; p<0.05). Among 18 patients who had postural abnormalities at baseline, defined as 1 point or greater on MDS-UPDRS part III subitem 3.13, posture improved in 9 (50%) and was unchanged in 9 (50%) patients after istradefylline treatment. Improved and unchanged groups did not show differences in baseline characteristics, except for tendency for a higher rate of Hoehn and Yahr stage IV and V (Off state) observed in the improved group. Changes in scores of posture (3.13) did not correlate with those of other MDS-UPDRS part III items, PD Questionnaire-8, PD Sleep Scale-2 and Epworth Sleepiness Scale.nnnCONCLUSIONnBased on our preliminary findings, istradefylline could be an effective treatment option for postural abnormalities in mid-stage PD patients.

Nocturia Quality-of-Life questionnaire is a useful tool to predict nocturia and a risk of falling in Japanese outpatients: A cross-sectional survey

To evaluate the Japanese version of the Nocturia Quality‐of‐Life questionnaire for prediction of night‐time voiding and risk of falling.

A Card-type Odor Identification Test for Japanese Patients with Parkinson's Disease and Related Disorders

Objective The characteristics of olfactory impairment in Parkinsons disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) have not been determined in detail. We assessed the olfactory function among PD, MSA and PSP patients. Methods A card-type odor identification test, Open Essence (OE, Wako, Japan), which consists of 12 different odorants familiar to Japanese subjects, was administered to 98 PD patients, 32 MSA patients, 17 PSP patients and 96 control subjects ≥50 years of age. Results The PD patients had significantly lower OE scores than the other groups. The OE scores of the MSA and PSP patients fell between those of the PD patients and the control subjects. A cut-off OE score of 6 was beneficial for differentiating PD patients from controls with 84.7% sensitivity and 85.4% specificity. A cut-off OE score of 4 had 60.2% sensitivity and 77.6% specificity for differentiating PD patients from MSA and PSP patients. The correct answer rates for the curry, Japanese orange and perfume odorants in the PD patients were lower than those in the MSA and PSP patients and controls. The PD patients also had the highest ratio of “not detected” choices across the 12 odors. Conclusion Marked olfactory impairment was a feature of the patients with PD, while mild olfactory impairment was observed in those with MSA or PSP. The answer patterns and the specific odorants may also be useful in differentiating PD from related disorders.

Randomized, Single-Blind, Parallel Study of the Effectiveness and Safety of Solifenacin versus Propiverine in the Treatment of Overactive Bladder

Objectives: To compare the effectiveness and safety of solifenacin versus propiverine in the treatment of overactive bladder (OAB), in a single‐blind, randomized parallel study.