Bladder dysfunction as the initial presentation of multiple system atrophy: a prospective cohort study.

OBJECTIVES: Multiple system atrophy (MSA) is a disease that combines autonomic (orthostatic or bladder) with motor [parkinsonian (MSA-P) or cerebellar (MSA-C)] dysfunction. While bladder dysfunction may occur earlier than motor disorders, thus far no prospective study has been available to determine how often and how early bladder autonomic dysfunction predates motor dysfunction in MSA. Therefore, we present data from detailed history-taking in patients with MSA. METHODS: This is a prospective cohort study. Detailed history-taking was performed and a questionnaire administered in 121 MSA patients (73 MSA-C, 48 MSA-P; 74 men, 47 women; age, 58 ± 8.0 years; initial recruitment period, 5 years; follow-up, 6.5 ± 4.0 years). RESULTS: Among the patients with MSA-C, 40 patients (55%) suffered motor dysfunction first, 22 (30%) suffered autonomic dysfunction first, and 11 (15%) initially suffered both simultaneously. Among the patients with MSA-P, 22 patients (46%) suffered motor dysfunction first, 22 (46%) suffered autonomic dysfunction first, and two (8%) initially suffered both simultaneously. Among the 'autonomic-first' subgroup of MSA-C patients, five suffered orthostatic dysfunction first, 13 suffered urinary dysfunction first, and four initially suffered both simultaneously. Among the 'autonomic-first' subgroup of MSA-P patients, six suffered orthostatic dysfunction first, nine suffered urinary dysfunction first, and seven initially suffered both simultaneously. Urinary symptoms were further preceded by erectile dysfunction in men. Overall, 18.2% of patients suffered only urinary symptoms initially, and the mean interval from the onset of urinary to the onset of motor symptoms was 2.8 years (range 1-7 years). CONCLUSION: In MSA patients, 18.2% presented with bladder dysfunction as the sole initial manifestation, and the mean interval from the onset of urinary to the onset of motor symptoms was 2.8 years. It is clinically important to avoid unnecessary prostatic surgery when MSA patients see urologists before neurologists.

Gastrointestinal function in dementia with Lewy bodies: a comparison with Parkinson disease.

PURPOSE: To investigate gastrointestinal function in dementia with Lewy bodies and Parkinson disease. METHODS: We examined gastric emptying and colonic transit time in 19 dementia with Lewy bodies and 46 Parkinson disease patients. RESULTS: Gastric emptying was longer in dementia with Lewy bodies than in Parkinson disease (p = 0.014). Colonic transit time tended to be longer in dementia with Lewy bodies than in Parkinson disease. There was no relationship between gastric emptying and colonic transit time, nor between gastric emptying, colonic transit time and age. CONCLUSION: Gastric emptying was prolonged in dementia with Lewy bodies compared to Parkinson disease.

Lower Urinary Tract Function in Familial Spastic Paraplegia.

In order to investigate lower urinary tract function in hereditary spastic paraplegia (HSP), we recruited 12 HSP patients: 8 men, 4 women; mean age, 64.6 years; mean disease duration, 18.9 years; walk without cane, 2, walk with cane, 6, wheelchair bound, 3. We performed urinary symptom questionnaires and a urodynamic testing in all patients. As a result, urinary symptoms were observed in all but 3, including urinary urgency/frequency (also called overactive bladder) in 9 and hesitancy/poor stream in 6. Urodynamic abnormalities included detrusor overactivity during bladder filling in 10, underactive detrusor on voiding in 8 (detrusor hyperactivity with impaired contraction [DHIC] in 5), detrusor-sphincter dyssynergia (DSD) on voiding in 3, and post-void residual in 5. Sphincter electromyography showed neurogenic motor unit potential in 4. In conclusion, we observed high frequency of urinary symptoms in HSP. Urodynamics indicated that the main mechanism is DHIC with/without DSD for their urinary symptom, and sacral cord involvement in some cases. These findings facilitate patients' care including clean, intermittent catheterization.

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.

Antibodies against muscle-specific kinase impair both presynaptic and postsynaptic functions in a murine model of myasthenia gravis.

Antibodies against acetylcholine receptors (AChRs) cause pathogenicity in myasthenia gravis (MG) patients through complement pathway-mediated destruction of postsynaptic membranes at neuromuscular junctions (NMJs). However, antibodies against muscle-specific kinase (MuSK), which constitute a major subclass of antibodies found in MG patients, do not activate the complement pathway. To investigate the pathophysiology of MuSK-MG and establish an experimental autoimmune MG (EAMG) model, we injected MuSK protein into mice deficient in complement component five (C5). MuSK-injected mice simultaneously developed severe muscle weakness, accompanied by an electromyographic pattern such as is typically observed in MG patients. In addition, we observed morphological and functional defects in the NMJs of EAMG mice, demonstrating that complement activation is not necessary for the onset of MuSK-MG. Furthermore, MuSK-injected mice exhibited acetylcholinesterase (AChE) inhibitor-evoked cholinergic hypersensitivity, as is observed in MuSK-MG patients, and a decrease in both AChE and the AChE-anchoring protein collagen Q at postsynaptic membranes. These findings suggest that MuSK is indispensable for the maintenance of NMJ structure and function, and that disruption of MuSK activity by autoantibodies causes MG. This mouse model of EAMG could be used to develop appropriate medications for the treatment of MuSK-MG in humans.

"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.

Stroke and cardio-ankle vascular stiffness index.

BACKGROUND: We investigated the relationship between stroke and cardio-ankle vascular stiffness index (CAVI), a novel noninvasive measure of vascular stiffness. METHODS: Eighty-five patients with cerebrovascular disease who underwent CAVI were enrolled in the current study. They were 63 men and 22 women with a mean age of 70.0 ± 10.8 years. They were divided into 4 groups according to neurologic abnormalities and magnetic resonance imaging (MRI) findings: 12 with transient ischemic attack (TIA), 26 with white matter ischemic lesions (WMLs), 17 with large artery atherosclerosis, and 30 with small vessel occlusion. Eight hundred fifty-four healthy patients (487 men and 367 women; mean age 65.1 ± 9.4 years) served as controls. The results were stratified by gender and age and statistically analyzed using the Fisher, Bonferroni-Dunn, and Scheffe tests. RESULTS: The average of CAVI was as follows: control males 60 to 69 years of age, 9.05 ± 0.82 (as a representative value); TIA, 9.3 ± 1.5; WML, 10.3 ± 1.3; large artery atherosclerosis, 10.2 ± 1.2; and small vessel occlusion, 10.0 ± 1.6, respectively. The difference in CAVI between each group and age- and gender-matched controls was 0.492 for TIA (no statistical significance); WML, 0.733 (P < .001, and P = .002 Scheffe); large artery atherosclerosis, 0.838 (P < .001, and P = .005 Scheffe); and small vessel occlusion, 1.034 (P < .001), respectively. Linear regression analysis of CAVI and plaque score revealed a significant relationship in patients with ischemic cerebrovascular disease (P < .05). CONCLUSIONS: Compared with healthy control subjects, CAVI is statistically greater in patients with ischemic cerebrovascular diseases, particularly with WML, large artery atherosclerosis, and small vessel occlusion, but not in patients with TIA. CAVI had a clear relationship with carotid ultrasound plaque score. It appears that CAVI is a simple and noninvasive test for indicating atherosclerosis in patients with stroke.

Proteolytic ectodomain shedding of muscle-specific tyrosine kinase in myasthenia gravis.

Autoantibodies to muscle-specific tyrosine kinase (MuSK) proteins at the neuromuscular junction (NMJ) cause refractory generalized myasthenia gravis (MG) with dyspnea more frequently than other MG subtypes. However, the mechanisms via which MuSK, a membrane protein locally expressed on the NMJ of skeletal muscle, is supplied to the immune system as an autoantigen remains unknown. Here, we identified MuSK in both mouse and human serum, with the amount of MuSK dramatically increasing in mice with motor nerve denervation and in MG model mice. Peptide analysis by liquid chromatography-tandem-mass spectrometry (LC-MS/MS) confirmed the presence of MuSK in both human and mouse serum. Furthermore, some patients with MG have significantly higher amounts of MuSK in serum than healthy controls. Our results indicated that the secretion of MuSK proteins from muscles into the bloodstream was induced by ectodomain shedding triggered by neuromuscular junction failure. The results may explain why MuSK-MG is refractory to treatments and causes rapid muscle atrophy in some patients due to the denervation associated with Ab-induced disruption of neuromuscular transmission at the NMJ. Such discoveries pave the way for new MG treatments, and MuSK may be used as a biomarker for other neuromuscular diseases in preclinical studies, clinical diagnostics, therapeutics, and drug discovery.

Pathophysiology of bladder dysfunction in Parkinson's disease.

Bladder dysfunction (urinary urgency/frequency) is a common non-motor disorder in Parkinson's disease (PD). In contrast to motor disorders, bladder dysfunction is sometimes non-responsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine basal ganglia-frontal circuit, which normally suppresses the micturition reflex. The pathophysiology of the bladder dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. These treatments might be beneficial in maximizing the patients' quality of life.

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.

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 α-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.