Fuyuki Tateno

Alpha-synuclein in the cerebrospinal fluid differentiates synucleinopathies (Parkinson Disease, dementia with Lewy bodies, multiple system atrophy) from Alzheimer disease.

Background:We examined the utility of quantification of &agr;-synuclein (SNCA) in the cerebrospinal fluid (CSF) to differentiate patients with Alzheimer disease (AD), dementia with Lewy bodies (DLB), Parkinson disease (PD), and multiple system atrophy (MSA). Methods:Thirty-seven patients were divided into 4 age-matched and sex-matched clinical groups: AD (n=9), DLB (n=6), PD (n=11), and MSA (n=11). Eleven subjects served as neurological disease controls. The total of 48 subjects included 27 men and 21 women, aged 66.5±11.4 years. We performed a solid-phase sandwich enzyme-linked immunosorbent assay, which enables the sensitive quantification of CSF SNCA. Results:In comparison with controls, CSF SNCA levels in AD were significantly higher (P<0.05). CSF SNCA levels in PD (P<0.001), DLB (P<0.01), and MSA (P<0.05) were all significantly lower than those in AD. However, CSF SNCA levels did not differ significantly among the 3 synucleinopathies. Conclusions:The results of the present study suggest that quantification of CSF SNCA helps in the differentiation of synucleinopathies (PD, DLB, and MSA) from AD. However, CSF SNCA levels did not differ significantly among the 3 synucleinopathies.

MIBG myocardial scintigraphy in pre-motor Parkinson's disease: A review

OBJECTIVES Detecting very early markers of neurodegeneration that predate the diagnosis of idiopathic Parkinsons disease (PD) is a crucial research topic for the development of disease-modifying therapeutic interventions. Recently (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy has become widely used for this purpose, since this test shows high sensitivity and specificity in the diagnosis of PD, based on evidence that cardiac sympathetic nerve fibers are affected early and commonly in PD. We reviewed the literature to determine the role of MIBG myocardial scintigraphy for diagnosing pre-motor PD. METHODS We performed a systematic review of the literature to identify the use of MIBG myocardial scintigraphy in relation to the constellation of pre-motor symptoms in PD. RESULTS Mild memory disorder, autonomic failure (constipation and postural hypotension), depression/anxiety, visual hallucination/psychosis (in the elderly), sleep disorder (REM sleep behavior disorder), and impaired olfaction are reported to appear as sole initial symptoms of PD. All clinical features except for impaired olfaction are accompanied by low MIBG uptake, suggestive of very early PD in situ. CONCLUSION Identifying persons with mild memory disorder, constipation/postural hypotension, depression/anxiety, visual hallucination/psychosis (in the elderly), and REM sleep behavior disorder associated with low MIBG uptake may provide a unique opportunity to detect very early PD in situ within a pre-clinical window. Future prospective studies to investigate further the findings of these early cases are warranted.

Plasma levodopa peak delay and impaired gastric emptying in Parkinson's disease

OBJECTIVES Whereas delayed gastric emptying is believed to be a causative factor for producing delayed-on and motor fluctuation in Parkinsons disease (PD), few studies have directly measured levodopa pharmacodynamics and gastric emptying together. In order to determine the relationship, we measured these two parameters in a single PD patients cohort. METHODS Thirty-one patients with PD were enrolled in the study. They were 11 men and 20 women; age, 68.1 ± 7.8 years; disease duration, 4.2 ± 3.8 years; Unified Parkinsons Disease Rating Scale Part 3 Motor Score 18.37 ± 8.60; bowel movement <3 times a week in 20; all taking 301 mg ± 94 mg/day levodopa/carbidopa. All patients underwent levodopa pharmacokinetic study and the gastric emptying study using (13)C-octanoic acid expiration breath test. Statistical analysis was performed by Students t-test and Mann-Whitneys U test. RESULTS Pharmacokinetic study showed that the plasma levodopa peak was at 2 hours in 42% (13/31 patients) whereas at 1 hour in 58% (18/31 patients), total of 50.7 ± 16.4 min (mean ± standard deviation) in all 31 patients. The gastric emptying study showed that T(max) ((13)C)>60 min was more common in patients with a plasma levodopa peak at 2 hours (14/18, 69%) than in those with a plasma levodopa peak at 1 hour (4/13, 22%) (p<0.05), total of 50.7 ± 16.4 min in all 31 patients. CONCLUSION We found a significant relationship between levodopa pharmacokinetics and gastric emptying in PD patients, suggesting that delayed gastric emptying is a causative factor for producing delayed-on in PD. Therefore, studies of improved gastric emptying in order to ameliorate delayed-on in PD are warranted.

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.

Vascular incontinence: incontinence in the elderly due to ischemic white matter changes

This review article introduces the new concept of vascular incontinence, a disorder of bladder control resulting from cerebral white matter disease (WMD). The concept is based on the original observation in 1999 of a correlation between the severity of leukoareosis or WMD, urinary symptoms, gait disorder and cognitive impairment. Over the last 20 years, the realization that WMD is not a benign incidental finding in the elderly has become generally accepted and several studies have pointed to an association between geriatric syndromes and this type of pathology. The main brunt of WMD is in the frontal regions, a region recognized to be crucial for bladder control. Other disorders should be excluded, both neurological and urological, such as normal-pressure hydrocephalus, progressive supranuclear palsy, etc., and prostatic hyperplasia, physical stress incontinence, nocturnal polyuria, etc. Treatment involves management of small vessel disease risk factors and anticholinergic drugs that do not easily penetrate the blood brain barrier to improve bladder control.

Correlation of right frontal hypoperfusion and urinary dysfunction in iNPH: A SPECT study

To elucidate the pathophysiology of urinary dysfunction in idiopathic normal‐pressure hydrocephalus (iNPH) by single‐photon emission computed tomography (SPECT) and statistical brain mapping.

Sensitivity and specificity of metaiodobenzylguanidine (MIBG) myocardial accumulation in the diagnosis of Lewy body diseases in a movement disorder clinic

Cardiac scintigraphy with metaiodobenzylguanidine (MIBG), an analog of norepinephrine (NE), is now widely performed in Lewy body diseases (Parkinson’s disease (PD), dementia with Lewy bodies (DLB), pure autonomic failure (PAF), and REM sleep-related behavioral disorder (RBD)) to assess function of the sympathetic nerve endings in the heart. Monitoring of this function is considered important because cardiac sympathetic denervation has been documented in Lewy body diseases by scintigraphy as well as by pathology [1]. However, sensitivity and specificity of MIBG myocardial scintigraphy in the diagnosis of Lewy body diseases has not fully been established. The objective of this study was to determine sensitivity and specificity of MIBG myocardial scintigraphy in the diagnosis of Lewy body diseases in a movement disorder clinic. The study enrolled 182 new patients who visited our movement disorder clinic in a period of 15 months, most of whom were referred patients. They comprised Lewy body diseases in 127 (90 PD, 34 DLB, one PAF, and 2 RBD; 53 men, 74 women; mean age 73 years (range 51–85 years); mean disease duration 6.0 years (range 1–18 years); median Hohen Yahr stage 3 (range 1–4) in PD, DLB), and neurologic diseases control in 62 (parkinsonian gait disorder, cognitive decline, or autonomic dysfunction; including 21 Alzheimer’s disease [AD], 9 progressive supranuclear palsy [PSP], etc.) (Fig. 1). All patients fulfilled the ‘probable’ diagnostic consensus criteria for degenerative neurological disorders, which were confirmed again during a 3-year follow-up period. In order to confirm the diagnosis, in addition to standard neurological and cognitive examination, we performed brain magnetic resonance imaging (MRI) and brain single-photon emission computed tomography (SPECT) imaging using 99mTclabeled L,L-ethyl cysteinate dimer (ECD) in all patients. The methods of MIBG scintigraphy are based on evidence that NE and MIBG have the same mechanisms for uptake, storage, and release. The cut-off value of delayed images of the heart versus mediastinum (HM) ratio was 2.0. Statistical analysis was

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 Parkinsons disease (PD) patients, using objective parameters given by the 13C-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 Parkinsons 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 Students 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 13C-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.

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 Parkinsons 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‐Whitneys U‐test for analyzing the relation between detrusor overactivity and gait as well as Spearmans 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.

White Matter Lesions or Alzheimer's Disease:: Which Contributes More to Overactive Bladder and Incontinence in Elderly Adults with Dementia?

Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Boureau: acquisition of participants, interpretation of data, preparation of manuscript. Bourbouloux: analysis of data. Retornaz: study concept and design. Berrut: study concept and design, interpretation of data. de Decker: study concept and design, preparation of manuscript. Sponsor’s Role: No sponsor.