Diagnostic imaging of dementia with Lewy bodies by susceptibility-weighted imaging of nigrosomes versus striatal dopamine transporter single-photon emission computed tomography: a retrospective observational study.

INTRODUCTION: The characteristics of dementia with Lewy bodies (DLB), Alzheimer's disease (AD) and amnestic mild cognitive impairment (a-MCI) overlap but require different treatments; therefore, it is important to differentiate these pathologies. Assessment of dopamine uptake in the striatum using dopamine transporter (DaT) single-photon emission computed tomography (SPECT) is the gold standard for diagnosing DLB; however, this modality is expensive, time consuming and involves radiation exposure. Degeneration of the substantia nigra nigrosome-1, which occurs in DLB, but not in AD/a-MCI, can be identified by 3T susceptibility-weighted imaging (SWI). Therefore, the aim of this retrospective observational study was to compare SWI with DaT-SPECT for differentiation of DLB from AD/a-MCI. METHODS: SWI data were acquired for patients with clinically diagnosed DLB (n = 29), AD (n = 18), a-MCI (n = 13) and healthy controls (n = 26). Images were analysed for nigrosome-1 degeneration. Diagnostic accuracy was evaluated for DLB, AD and a-MCI compared with striatal dopamine uptake using DaT-SPECT. RESULTS: SWI achieved 90% diagnostic accuracy (93% sensitivity, 87% specificity) for the detection of nigrosome-1 degeneration in DLB and not in AD/a-MCI as compared with 88.3% accuracy (93% sensitivity, 84% specificity) using DaT-SPECT. CONCLUSIONS: SWI nigrosome-1 evaluation was useful in differentiating DLB from AD/a-MCI, with high accuracy. This less invasive and less expensive method is a potential alternative to DaT-SPECT for the diagnosis of DLB.

Lower urinary tract function in dementia with Lewy bodies (DLB).

OBJECTIVES: Dementia with Lewy bodies (DLB) is the second most common degenerative cause of dementia, whereas lower urinary tract (LUT) function in DLB patients has not been fully delineated. We investigated LUT function in DLB by clinical-urodynamic observations. METHODS: We examined 32 patients with DLB (23 men, 9 women; aged 59-86 [mean, 75.9] years; disease duration, 0.2-17 [3.3] years). All patients underwent an electromyography-cystometry, and 21 patients underwent the sphincter motor unit potential analysis. RESULTS: Ninety-one percent of patients had LUT symptoms: nighttime frequency (>8 times), 84%, and urinary incontinence (>1 per week), 50%. Detrusor overactivity was revealed in 87.1%, whereas postvoid residual was minimal. Neurogenic changes were shown in 50%. CONCLUSION: LUT dysfunction is a common feature in DLB, attributable not only to dementia and immobility, but also to central and peripheral types of somato-autonomic dysfunction.

Nizatidine ameliorates gastroparesis in Parkinson's disease: a pilot study.

BACKGROUND: The objective of this work was to perform an open trial of the effects of nizatidine (NZT), a selective histamine H2-receptor antagonist and a cholinomimetic, on gastroparesis in Parkinson's disease (PD) patients, using objective parameters given by a gastric emptying study using a (13) C-sodium acetate expiration breath test. METHODS: Twenty patients with PD were enrolled in the study. There were 13 men and 7 women; aged 68.0 ± 7.72 years; disease duration 5.50 ± 3.62 years. All patients underwent the breath test and a gastrointestinal questionnaire before and after 3 months of administration of NZT at 300 mg/day. Statistical analysis was performed by Student t test. RESULTS: NZT was well tolerated by all patients and none had abdominal pain or other adverse effects. NZT significantly shortened Tmax ((13) C) (the peak time of the (13) C-dose-excess curve) (P < 0.05). CONCLUSIONS: Although this is a pilot study, we found a significant shortening of gastric emptying time after administration of NZT in PD patients.

Tolterodine activates the prefrontal cortex during bladder filling in OAB patients: a real-time NIRS-urodynamics study.

AIMS: Studies of overactive bladder (OAB) have shown urothelial/suburothelial changes and increased bladder afferents, while in the brain the frontal micturition area that normally suppresses the bladder is deactivated. It has been unclear whether anticholinergic medication could reverse this suppression. To address this question, we performed a real-time NIRS (near-infrared spectroscopy)-urodynamic study in OAB patients before and after the administration of an anticholinergic agent, tolterodine. METHODS: We recruited 13 OAB patients in our outpatient clinic (9 males, 4 female; mean age 73 years). Before and after the administration of 4 mg/day tolterodine for 3 months, all patients completed the OAB-symptom scale and a NIRS-urodynamics examination. Cerebral changes in the oxy-hemoglobin concentration (oxy-Hb) were sampled. Concentration changes in oxy-Hb were calculated based on a modified Beer-Lambert approach. RESULTS: Tolterodine significantly reduced the OAB patients' nighttime frequency (P < 0.05) and increased their first-sensation volume (290-359 ml, P < 0.01). The number of patients with detrusor overactivity did not lessen significantly (11-9). The real-time NIRS-urodynamic study showed that, during slow bladder filling between start and bladder capacity, tolterodine significantly activated the right frontal micturition area of the OAB patients (P < 0.05). The activation was prominent in Brodmann's area 8, 9, 10 of the prefrontal cortex. CONCLUSIONS: Tolterodine reduced bladder sensation together with a significant activation of the frontal micturition area of OAB patients, particularly Brodmann's area 8, 9, 10 of the right prefrontal cortex. This activation seems to be a secondary phenomenon, since tolterodine does not easily penetrate the blood-brain barrier.

Dietary herb extract rikkunshi-to ameliorates gastroparesis in Parkinson's disease: a pilot study.

OBJECTIVE: To perform an open trial on the effects of the extract of the dietary herb Rikkunshi-to (RKT) on gastroparesis in Parkinson's disease (PD) patients, using objective parameters given by the (13)C-sodium acetate expiration breath test (gastric emptying study). METHODS: Twenty patients with PD were enrolled into this study. Eleven patients were male and 9 were female, with the following characteristics (mean ± SD): age, 69.4 ± 8.17 years; disease duration, 4.34 ± 4.03 years; modified Hoehn and Yahr stage, 2.37 ± 0.98, and Unified Parkinson's Disease Rating Scale Part 3 motor score, 16.6 ± 7.37. Fourteen patients came to the clinic due to constipation; 16 patients were taking 288 ± 72 mg/day levodopa/carbidopa, 2 were taking dopamine agonists, and the others were not treated yet. All patients underwent the breath test. Statistical analysis was performed using Student's t test. RESULTS: RKT was well tolerated by all patients and none experienced abdominal pain or other adverse effects, except for its bitter taste. RKT significantly reduced the peak time of the (13)C-dose-excess curve (p < 0.05). CONCLUSION: In this pilot trial, we found a significant shortening of the gastric emptying time after administration of the dietary herb extract RKT in PD patients. Further studies examining both gastric emptying and delayed-on in PD are warranted. .

Bladder function of patients with Parkinson's disease.

Bladder function of patients with Parkinson's disease alters significantly: the majority of patients have overactive bladder (urinary urgency/frequency) with little or no post-void residuals. This seems to be the result of an altered brain-bladder relationship, as in Parkinson's disease, the frontal-basal ganglia D1 dopaminergic circuit that normally suppresses the micturition reflex is altered. The pathophysiology of the bladder dysfunction in Parkinson's disease differs from that in multiple system atrophy; therefore, it might also aid in differential diagnosis. The effects of levodopa, the major drug to treat motor dysfunction, on the bladder in Parkinson's disease vary significantly; therefore, add-on therapy is often required. Anticholinergic drugs are the first-line treatment, with particular care for cognitive function in elderly patients. The second-line treatment includes serotonergics drug, desmopressin and others. Newer modalities include deep brain stimulation that improves the bladder in Parkinson's disease; and botulinum toxin is promising, particularly in difficult cases. These treatments might be beneficial in maximizing the patients' quality of life.

Is overactive bladder a brain disease? The pathophysiological role of cerebral white matter in the elderly.

Small-vessel disease of the brain affecting the deep white matter characteristically manifests with neurological syndromes, such as vascular dementia and vascular parkinsonism. There is, however, compelling evidence to suggest that white matter disease can cause overactive bladder and incontinence, and in some patients these might be the initial manifestation. As white matter disease increases significantly with age, and preferentially affects the prefrontal deep white matter, white matter disease becomes an anatomical substrate in the brain etiology of overactive bladder. Treatment entails the management of small-vessel disease risk factors and anticholinergic drugs that do not easily penetrate the blood-brain barrier, to improve bladder control. In short, when caring for elderly overactive-bladder patients, we should look at both the brain and the bladder.

"Invisible" brain stem infarction at the first day.

BACKGROUND: In specific stroke cases, serial diffusion-weighted magnetic resonance imaging (DW MRI) on day 1 was unable to show a lesion, whereas that on day 4 and later clearly revealed a lesion. However, clinical features of this phenomenon ("invisible" brain stem infarction [IBI] at the first day) have not been fully delineated. METHODS: We retrospectively recruited 212 stroke patients in the Emergency Unit and Neurology Department. Among these, we studied patients with IBI. Definition of IBI is that acute and clear brain stem symptoms/signs on arrival were ameliorated at discharge and appearance of high signal intensity on serial DW images with low apparent diffusion coefficient (ADC) by 1.5 T MRI with 2-mm slices. RESULTS: IBI were found in only 6 patients. Day 1 invisible stroke was found only in the brain stem (17%, 6 of 35) but none (0 of 177) in the hemispheric infarction (P < .05). In most patients with IBI, DW MRI turned out visible at the third/fourth day. Before the fourth day, DW/ADC signal changes in patients with IBI were minimal. In IBI, lesion size (mean 2.7 mm(2)) was smaller than that of visible cases (mean 7.3 mm(2)). In IBI, lesion location was mostly at the dorsolateral medulla. In IBI, sensory disturbance was significantly more common (67%) than visible cases (24%; P < .05), whereas dysarthria was less common (0%; P < .01) than visible cases (66%; P < .01). CONCLUSIONS: It is likely that patients with smaller stroke volume, sensory disturbance, and medullary location are prone to develop IBI. When evaluating stroke using MRI criteria, recognition of IBI is important to start early management.

"Meningitis-retention syndrome": a review.

AIMS: A peculiar combination of acute urinary retention and aseptic meningitis has been described. This combination is referred to as meningitis-retention syndrome (MRS), since patients with this syndrome exhibited no other abnormalities, except for mild pyramidal involvement. We aimed to delineate this syndrome by reviewing literatures. METHODS: We performed a systematic review of the literature to identify the frequency, clinical symptoms, urodynamic findings, putrative underlying pathology, and management of this syndrome. RESULTS: Patients with MRS have typical symptoms of fever, headache, stiff neck, and minor pyramidal signs, together with acute urinary retention. The bladder is initially areflexic, but soon becomes either normal or overactive in the repeated urodynamics during the course of the disorder. MRS is thought to be a very mild form of acute disseminated encephalomyelopathy (ADEM), with increased cell count, total protein, and occasional myelin basic protein in the cerebrospinal fluid. Proper management of the acute urinary retention is necessary to avoid bladder injury due to overdistension. The effectiveness of immune treatments (e.g., steroid pulse therapy) in shortening the urinary retention period awaits further study. CONCLUSIONS: Although rare, MRS is a disorder that both urologists and neurologists may encounter. MRS should be listed in the differential diagnosis of acute urinary retention.

Inhibitory control task is decreased in vascular incontinence patients.

OBJECTIVE: 'Vascular incontinence' is a part of elderly incontinence due to cerebral white matter change (WMC). We studied the relationship between performance on several cognitive tasks and urodynamic detrusor overactivity (DO) in patients with vascular incontinence. METHODS: We recruited 40 patients with lower urinary tract symptoms due to WMC [20 male, 20 female; mean age 77 years (60-89 years)]. Other neurologic, urologic, and systemic causes of LUT dysfunction were excluded. All patients underwent urodynamics tests and two sets of cognitive tasks, i.e., the Mini-Mental State Examination (MMSE) (general cognitive tasks), and the Frontal Assessment Battery (FAB) (frontal lobe tasks). RESULTS: The most common urinary symptom was urinary urgency (27 patients), followed by urinary incontinence (26) and nocturnal urinary frequency (25). The urodynamic testing revealed DO in 22 patients. The cognitive testing revealed that the patients' mean MMSE score was 25.8 (range 15-30), and their mean FAB score was 13.6 (4-18). There was no relationship between DO and the total MMSE or FAB score, but our analysis of the relationship between DO and the six subdomains of the FAB (conceptualization, mental flexibility, programming, sensitivity to interference, inhibitory control, and environmental autonomy) revealed a significant relationship between DO and the inhibitory control task (p < 0.005). CONCLUSIONS: The results of the present study showed that performance on an inhibitory control task is decreased in vascular incontinence patients with DO.

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.

Weak detrusor contractility correlates with motor disorders in Parkinson's disease.

Limited attention has been paid to the relationship between urinary symptoms or urodynamic findings and motor disorders in Parkinson's disease (PD). We aimed to correlate pressure-flow urodynamic parameters with video-gait analysis parameters in PD. We recruited 41 patients with PD (25 men and 16 women; age, 70.6 ± 8.5 years; H & Y motor grading: 2 [range, 1-3]; disease duration: 4 years [range, 1-7]; taking levodopa 300 mg/day [range, 100-400]). All patients underwent pressure-flow urodynamics (parameters: first sensation, bladder capacity, detrusor overactivity [noted in 24 patients], and Watts factor [WF]) and video-gait analysis (parameters: time and number of strides for 5-m gait [simple task] and time for timed up and go [complex task]). Statistical analysis was made by Mann-Whitney's U-test for analyzing the relation between detrusor overactivity and gait as well as Spearman's rank-correlation coefficient test for analyzing the relation between the remaining parameters and gait. We found no relation between filling-phase urodynamics (detrusor overactivity, first sensation, and bladder capacity) and video-gait analysis parameters. By contrast, we found a significant relation between voiding-phase urodynamics (WF, reflecting detrusor power) and all three video-gait analysis parameters (reflecting lower-half bradykinesia and loss of postural reflex) in our PD patients (P < 0.01). The close relation between the WF and motor disorders in the present study suggests that, though clinically mild, a weak detrusor in PD might have a central origin. We should follow postvoid residual volume carefully in PD patients with advanced gait disorder, because postvoid residual volume might increase in such patients.

The Relationship between Bladder, Periarterial and Somatic Neuropathy in Diabetes.

Objective Diabetes commonly affects the bladder nerves. However, the relationship among bladder, periarterial and somatic neuropathy in diabetes is not well known. In the present study we investigated these relationships. Methods A total of 110 diabetic subjects were enrolled in the study. All were referred for screening for diabetic neuropathy, irrespective of their symptoms. The patients included 61 men and 49 women; the mean age was 59.3 years (31-85 years); the mean disease duration was 14.0 years (5-30 years); and the mean HbA1c value was 10.1% (5.1-16.3%). We performed a nerve conduction study (NCS, A-alpha/beta and B fiber), ultrasound-based measurement of the post-void residual (PVR) volume (abnormal, >50 mL, mainly A-delta/C fiber) and postural blood pressure measurement (abnormal, >-20 mmHg, A-delta/C fiber). Fisher's exact probability test and Student's t-test were used to analyze the significance of differences. Results NCS abnormality, an abnormal PVR volume, and postural hypotension were noted in 74, 19, and 36 of the subjects, respectively. There were clear relationships between NCS and an abnormal PVR volume (p<0.05), postural hypotension and an abnormal PVR volume (p<0.05), or NCS and postural hypotension (p<0.01). There were also subjects who had NCS abnormality alone, a high PVR volume alone or postural hypotension alone. An abnormal PVR volume was not associated with the HbA1c value, but was clearly related to the duration of diabetes (p<0.05). Conclusion Bladder dysfunction was correlated with somatic and periarterial neuropathy. On the other hand, 16% of the cases of bladder dysfunction occurred in patients without somatic or periarterial neuropathy; thus, the regular measurement of the PVR volume is necessary.

Genetic Screening for Spinocerebellar Ataxia Genes in a Japanese Single-Hospital Cohort.

OBJECTIVE: Diagnosis of sporadic cerebellar ataxia is a challenge for neurologists. A wide range of potential causes exist, including chronic alcohol use, multiple system atrophy of cerebellar type (MSA-C), and sporadic late cortical cerebellar atrophy. Recently, an autosomal-dominant spinocerebellar ataxia (SCA) mutation was identified in a cohort of patients with non-MSA-C sporadic cerebellar ataxia. The aim of this study is to genetically screen genes involved in SCA in a Japanese single-hospital cohort. METHODS: Over an 8-year period, 140 patients with cerebellar ataxia were observed. There were 109 patients with sporadic cerebellar ataxia (no family history for at least four generations, 73 patients with MSA-C, and 36 patients with non-MSA-C sporadic cerebellar ataxia) and 31 patients with familial cerebellar ataxia. We performed gene analysis comprising SCA1, 2, 3, 6, 7, 8, 12, 17, 31, and dentatorubro-pallidoluysian atrophy (DRPLA) in 28 of 31 non-MSA-C sporadic patients who requested the test. Familial patients served as a control. RESULTS: Gene abnormalities were found in 57% of non-MSA-C sporadic cerebellar ataxia cases. Among patients with sporadic cerebellar ataxia, abnormalities in SCA6 were the most common (36%), followed by abnormalities in SCA1 (7.1%), SCA2 (3.6%), SCA3 (3.6%), SCA8 (3.6%), and DRPLA (3.6%). In contrast, gene abnormalities were found in 75% of familial cerebellar ataxia cases, with abnormalities in SCA6 being the most common (29%). For sporadic versus familial cases for those with SCA6 abnormalities, the age of onset was older (69 years vs. 59 years, respectively), and CAG repeat length was shorter (23 vs. 25, respectively) in the former than in the latter (not statistically significant). CONCLUSION: Autosomal-dominant mutations in SCA genes, particularly in SCA6, are not rare in sporadic cerebellar ataxia. The reason for the frequency of mutations in SCA6 remains unclear; however, the reason may reflect a higher age at onset and variable penetrance of SCA6 mutations.

Bladder recovery relates with increased mid-cingulate perfusion after shunt surgery in idiopathic normal-pressure hydrocephalus: a single-photon emission tomography study.

AIMS OF STUDY: It is reported that severe bladder disorder in idiopathic normal-pressure hydrocephalus (iNPH) is predicted by right frontal hypoperfusion. However, it is not known whether bladder recovery is predicted by brain perfusion change after shunt surgery. To address this issue, we compared bladder and brain function before and after shunt surgery in iNPH. METHODS: We enrolled 75 patients in the study. Before and 12 months after shunt surgery, we analyzed brain perfusion by SPECT and bladder disorder by a specialized grading scale. The scale consisted of grade 0, none; grade 1, urinary urgency and frequency; grade 2, urinary incontinence 1-3 times a week; grade 3, urinary incontinence >daily; and grade 4, loss of bladder control. More than one grade improvement is defined as improvement, and more than one grade decrement as worsening; otherwise no changes. RESULTS: Comparing before and after surgery, in the bladder-no-change group (32 cases) there was an increase in blood flow which is regarded as reversal of enlargement in the Sylvian fissure and lateral ventricles (served as control). In contrast, in the bladder-improved group (32 cases) there was an increase in bilateral mid-cingulate, parietal, and left frontal blood flow (p < 0.05). In the bladder-worsened group (11 cases) no significant blood flow change was observed. CONCLUSION: The present study showed that after shunt surgery, bladder recovery is related with mid-cingulate perfusion increase in patients with iNPH. The underlying mechanism might be functional restoration of the mid-cingulate that normally inhibits the micturition reflex.