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

OBJECTIVES: Urinary dysfunction is a prominent autonomic feature in Parkinson's 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.     

Clinical features of autopsy-confirmed multiple system atrophy in the Mayo Clinic Florida brain bank

BackgroundMultiple system atrophy (MSA) presents with various combinations of autonomic dysfunction, parkinsonism, and cerebellar ataxia. Although clinical diagnostic criteria have been widely used, the sensitivity and specificity are suboptimal. This study aims to provide evidence supporting the revision of the current diagnostic criteria for MSA.MethodsMedical records of 171 patients with autopsy-confirmed MSA in the Mayo Clinic brain bank were reviewed with regard to their clinical features and diagnoses. Pathologic features, including concomitant pathologies (i.e., Alzheimer-related and Lewy-related pathologies), were also assessed.ResultsThe cohort included 133 MSA-parkinsonian type, 36 MSA-cerebellar type, and 2 unclassified MSA patients who did not show significant motor symptoms. Twenty-three patients (13%) were not clinically diagnosed with MSA, but instead with progressive supranuclear palsy, Parkinson's disease (PD), PD with dementia (PDD), or dementia with Lewy bodies (DLB). Three patients with PDD and DLB also had concomitant Lewy body pathology. Six patients had late-onset MSA, with an age of onset greater than 75 years. Erectile dysfunction was frequent in male patients (60/63; 95%) in all age ranges. REM sleep behavior disorder (RBD) was present in 82 patients (48%) and was the initial symptom in 13 patients. Cognitive impairment was present in 60 patients (35%), but was an initial symptom in only two patients.ConclusionsOur findings support the conclusion that late-onset presentation should not exclude MSA. The findings of this large autopsy-based cohort provides valuable insights for improving clinical criteria for MSA.     

What clinical features are most useful to distinguish definite multiple system atrophy from Parkinson's disease?

OBJECTIVES: Few studies have attempted to identify what premortem features best differentiate multiple system atrophy (MSA) from Parkinson's disease (PD). These studies are limited by small sample size, clinical heterogeneity, or lack of postmortem validation. We evaluated the sensitivity and specificity of different clinical features in distinguishing pathologically established MSA from PD. METHODS: One hundred consecutive cases of pathologically confirmed PD and 38 cases of pathologically confirmed MSA in one Parkinson's disease brain bank were included. All cases had their clinical notes reviewed by one observer (AH). Clinical features were divided into two groups: those occurring up to 5 years after onset of disease and those occurring up to death. Statistical analysis comprised multivariate logistic regression analysis to choose and weight key variables for the optimum predictive model. RESULTS: The selected early features and their weightings were: autonomic features (2), poor initial levodopa response (2), early motor fluctuations (2), and initial rigidity (2). A cut off of 4 or more on the ROC curve resulted in a sensitivity of 87.1% and specificity of 70.5%. A better predictive model occurred if the following features up to death were included: poor response to levodopa (2), autonomic features (2), speech or bulbar dysfunction (3), absence of dementia (2), absence of levodopa induced confusion (4), and falls (4). The resulting ROC curve based on individual scores showed a best cut off score of at least 11 of 17 (sensitivity 90.3%, specificity 92.6%). CONCLUSIONS: Predictive models may help differentiate MSA and PD premortem. Hitherto poorly recognised features, suggestive of MSA, included preserved cognitive function and absence of psychiatric effects from antiparkinsonian medication. Diagnostic accuracy was higher in those models taking into account all clinical features occurring up to death. Further studies need to be based on new incident cohorts of parkinsonian patients with subsequent neuropathological evaluation.     

Diagnostic performance of iodine-123-metaiodobenzylguanidine scintigraphy in differential diagnosis between Parkinson's disease and multiple-system atrophy: a systematic review and a meta-analysis

Background and purpose

This study was designed to review the diagnostic performance of iodine-123-metaiodobenzylguanidine (MIBG) scintigraphy in differential diagnosis between Parkinson's disease (PD) and multiple-system atrophy (MSA).

Methods

A comprehensive computer literature search of studies published through March 2011 regarding MIBG scintigraphy in patients with PD and MSA was performed in PubMed/MEDLINE and Embase databases. Only studies in which MIBG scintigraphy was performed for differential diagnosis between PD and MSA were selected. Pooled sensitivity and specificity of MIBG scintigraphy were presented with a 95% confidence interval (CI). The area under the ROC curve was calculated to measure the accuracy of MIBG scintigraphy in differential diagnosis between PD and MSA.

Results

Ultimately, we identified 12 studies comprising a total of 1226 patients (593 patients with PD, 117 patients with other Lewy body disease, 129 patients with MSA, and 387 patients with other diseases). The pooled sensitivity of MIBG scintigraphy to detect PD was 89% (95% CI: 86-91%); the pooled specificity of MIBG scintigraphy to discriminate between PD and MSA was 77% (95% CI: 68-84%). The area under the ROC curve was 0.93.

Conclusions

MIBG scintigraphy is an accurate test for PD detection and differential diagnosis between PD and MSA; this method shows high sensitivity and adequate specificity in this field. Nevertheless, possible causes of false negative and false positive findings should be considered when interpreting the scintigraphic results.     

Urodynamic analysis in multiple system atrophy: characterisation of detrusor-sphincter dyssynergia

In multiple system atrophy (MSA), parkinsonism and a cerebellar syndrome are associated with autonomic dysfunction. Both bladder neck dysfunction and external sphincter denervation have been implicated in detrusor-sphincter dyssynergia. However, urethral dysfunction may not be adequately reflected by a single global measurement of urethral pressure. Pressure assessment at several levels of the urethra is needed to unravel the mechanisms of bladder-urethra dysfunction. Here, we evaluated the use of multiple sensor pressure transducers to assess bladder-sphincter function in 52 patients with MSA in comparison to patients with Parkinson’s disease (PD) who were matched for age and severity in the “off” condition. Urinary dysfunction appeared significantly earlier in MSA (<2 years) than in PD (>5 years). Detrusor under-activity with dysuria was observed in 58% of MSA patients within 4 years and in 76% of patients thereafter. Detrusor-urethral dyssynergia in MSA patients was always better characterized by multiple sensor pressure transducer measurement of bladder and urethral pressure than by a single global measurement. This new approach may prove useful for differential diagnosis of parkinsonian syndromes, and especially MSA.     

Multiple system atrophy is distinguished from idiopathic Parkinson's disease by the arginine growth hormone stimulation test

OBJECTIVE: Multiple system atrophy (MSA) may be difficult to distinguish from idiopathic Parkinson's disease (PD). Our aim was to evaluate the accuracy of the arginine growth hormone (GH) stimulation test in distinguishing between MSA and PD in large populations of patients. METHODS: We measured the GH response to arginine in 69 MSA (43 MSAp [parkinsonism as the main motor feature] and 26 MSAc [cerebellar features predominated]) patients, 35 PD patients, and 90 healthy control subjects. We used receiver-operating curve analysis to establish the arginine cutoff value that best differentiated between MSA and PD. RESULTS: The GH response to arginine was significantly lower (p < 0.01) in MSA than in either PD patients or control subjects. At a cutoff level of 4 microg/L, arginine distinguished MSAp from PD with a sensitivity and specificity of 91% and MSAc from PD with a sensitivity of 96% and specificity of 91%. The arginine test had a positive predictive value for MSA of 95%. The GH response to arginine was not affected by disease duration or severity, MSA motor subtype, pyramidal signs, response to dopaminergic therapy, or magnetic resonance imaging findings. INTERPRETATION: The GH response to arginine differentiates MSA from PD with a high diagnostic accuracy. The results suggest an impairment of cholinergic central systems modulating GH release in MSA.     

Comparaison de la qualité de vie de patients atteints d’atrophie multisystématisée et de maladie de Parkinson

Purpose

Quality of life (QoL) in multiple system atrophy (MSA) is thought to be poorer than in Parkinson's disease (PD), primarily because of motor impairment, autonomic dysfunction and depression. The aim of the study was to investigate QoL in 10 patients with probable MSA (parkinsonian subtype) compared with 10 PD patients matched for motor disability on UPDRS III motor score.

Methods

All patients were ambulatory and non-demented. Mean durations of disease in MSA and PD patients were respectively 3.6 and 9.0 years. QoL was assessed using the SF-36 health-related questionnaire and a life satisfaction visual analogue scale. Patients were also evaluated for cognitive function (Mattis Dementia Rating Scale [Mattis DRS], Wisconsin Card Sorting Test [WCST], Stroop, Fluencies), depression (Beck Depression Inventory-II [BDI-II]), apathy (Modified Apathy Evaluation Scale) and were screened for non-motor symptoms (NMS Quest).

Results

The only difference in QoL between MSA and PD patients matched for motor disability was that the SF-36 vitality subscore was more impaired in MSA and negatively correlated with interference index on Stroop word colour testing. Depression and non-motor symptoms were associated with poorer QoL in both groups. Among MSA patients, cognitive impairment (Stroop interference index) and apathy also had a negative impact.

Conclusion

There was no major difference in QoL between MSA and PD patients matched for motor disability with a disease duration about 5 years longer. The SF-36 vitality subscore was more impaired in MSA and associated with interference sensitivity.     

(123)I]beta-CIT SPECT imaging demonstrates reduced density of striatal dopamine transporters in Parkinson's disease and multiple system atrophy.

In vivo imaging of the dopamine transporter (DAT) with single photon emission computed tomography (SPECT) is a quantitative biomarker for Parkinson's disease (PD) onset and severity. This study has examined and compared the loss of striatal DAT in PD and multiple system atrophy (MSA) using [(123)I]beta-CIT SPECT imaging. One hundred and eighty-three patients (157 PD and 26 MSA) were studied. Clinical rating scales (Hoehn and Yahr stage and Unified Parkinson's Disease Rating Scale [UPDRS] scores) demonstrated that the MSA patients were more severely impaired than the PD patients. The striatal [(123)I]beta-CIT SPECT uptake was markedly reduced in both the PD and MSA groups. In addition, MSA patients showed more symmetric DAT loss compared with the PD patients, consistent with the more symmetric clinical motor dysfunction observed in MSA. While the loss of DAT was significantly reduced in all regions in both MSA and PD, comparison of the relative loss of the DAT did not significantly improve diagnostic accuracy in distinguishing between PD and MSA.     

123I]beta-CIT SPECT in multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration.

Differentiation between Parkinson's disease (PD) and other neurodegenerative disorders with parkinsonian features, such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), is difficult on clinical grounds. We studied the pattern of dopaminergic degeneration in 18 patients with probable MSA, 8 patients with PSP, 4 patients with CBD, 48 patients with PD and a similar degree of disability, and 14 control subjects performing single photon emission computed tomography (SPECT) 20 hours after injection of [123I]beta-CIT. Overall striatal binding was significantly reduced in MSA (-51% of normal mean), PSP (-60%), CBD (-35%), and PD (-58%), without overlap with control values. Asymmetry of striatal beta-CIT binding was significantly increased in patients with CBD and PD, as compared with control subjects. Although asymmetry seemed to be less pronounced in MSA and PSP than in PD, this was not statistically significant. Putamen-caudate nucleus ratios in patients with PD, MSA, and PSP, but not with CBD, were significantly reduced, as compared with control subjects. In conclusion, [123I]beta-CIT SPECT reliably enables the visualization of the presynaptic dopaminergic lesion in patients with MSA, PSP, and CBD. In most patients, however, it does not seem to be possible to differentiate these disorders from PD with this method.     

A comparison of auditory and vestibular dysfunction in Parkinson's disease and Multiple System Atrophy

IntroductionVertigo and disequilibrium are common symptoms in idiopathic Parkinson's disease (PD) and in Multiple System Atrophy (MSA). Hearing loss has been recently recognized as an additional non-motor feature in PD. The aim of this study is to evaluate audio-vestibular function in patients affected by PD and MSA.MethodsFifteen patients with PD, 16 patients with MSA and 20 age-matched healthy controls (HC) were enrolled. Audio-vestibular examination included pure-tone audiometry (PTA), vestibular bed-side examination, video Head Impulse Test (vHIT), and cervical Vestibular-Evoked Myogenic Potentials (cVEMPs).ResultsPD and MSA patients showed worse PTA thresholds compared to HC at high frequencies. MSA patients showed worse PTA thresholds at 125 Hz compared to HC. In patients with PD, a direct correlation between disease duration and PTA thresholds was found at 2000 Hz and 4000 Hz. In patients with MSA, disease duration was directly related to PTA thresholds at 125 Hz and 250 Hz. Among PD patients, cVEMPs were absent bilaterally in 46.7% and unilaterally in 13.3% of the subjects. Among MSA patients, cVEMPs were absent bilaterally in 26.7% and unilaterally in 40% of the subjects; p13 latency was significantly increased in PD patients as compared to HC. A significant inverse relationship was found between disease duration and cVEMP amplitude in MSA patients.ConclusionWe found that high-frequency hearing loss and cVEMP abnormalities are frequent features of both MSA and PD, suggesting that an audio-vestibular dysfunction may be present in these patients even in the absence of self-reported auditory or vestibular symptoms.     

CSF levels of DJ-1 and tau distinguish MSA patients from PD patients and controls

Differential diagnosis between Parkinson's disease (PD) and multiple system atrophy (MSA) is difficult, particularly at early disease stages, but is important for therapeutic management. The protein DJ-1 is implicated in the pathology of PD but little is known about its involvement in MSA. We aimed to determine the diagnostic value of CSF DJ-1 and tau proteins for discriminating PD and MSA. DJ-1 and total tau levels were quantified in the CSF of 43 PD patients, 23 MSA patients and 30 non-neurological controls matched for age and gender. Patients were part of a study with a 3-year prospective design with extended case-review follow-up of up to 9 years, ensuring maximum accuracy of the clinical diagnosis. Our results showed that CSF DJ-1 levels could distinguish MSA from PD with a 78% sensitivity and 78% specificity (AUC = 0.84). The combination of DJ-1 and tau proteins significantly improved this discrimination to 82% sensitivity and 81% specificity to identify MSA from PD (AUC = 0.92). Our results highlight the potential benefits of a combination of DJ-1 and total tau as biomarkers for differential diagnosis of MSA and PD.     

Cardiovascular autonomic nervous system evaluation in Parkinson disease and multiple system atrophy

BackgroundAutonomic nervous system dysfunction (ANSd) heralds or follows motor symptoms (MS) in Parkinson disease (PD), but may precede years and progress more rapidly in multiple system atrophy (MSA). Cardiac dysautonomia severity correlates with disabling symptoms thus a Cardiac Autonomic Nervous System Evaluation protocol (CANSEp) is useful to assess ANSd in PD and MSA patients.Methods and resultsConsecutive patients with PD or MSA were studied. The severity of MS was quantified with UPDR III and Hoehn/Yahr scales. CANSEp consisted of the 5-test Ewing protocol (EP) and Heart Rate Variability analysis (HRVa), in time-domain (TD) and frequency-domain (FD).36 patients with parkinsonian symptoms (23 PD, 13 MSA) and 40 healthy controls were studied. Parkinsonism was more severe in MSA, comparing UPDR III and Hoehn/Yahr scales (p < 0.0001). Higher EP's scores were found in MSA (mean 5.1 ± 1.98) compared to PD (mean 3.5 ± 2) and controls (score 0.25 ± 0.1). TD and FD-HRVa were abnormal in PD and MSA, compared to controls. In PD depression of vagal tone was predominant during sleep, whereas in MSA depression of sympathetic tone prevailed during daily activity.ConclusionsWhereas its specificity is very high, the sensitivity of the EP was only 43.5% in PD and 76.9% in MSA. HRVa improved diagnosis accuracy in 10 patients, unidentified by the EP alone, with overall sensitivity of 65.2% in PD and 92.3% in MSA. Thus CANSEp provides a better assessment of cardiovascular dysautonomia in parkinsonian syndromes, useful to differentiate PD from MSA and to address clinical and pharmacological management.     

Respiratory function impairment in patients with Parkinson's disease--a consideration on the possible pathogenetic relation to autonomic dysfunction]

To investigate the characteristics and clinical significance of respiratory function in patients with Parkinson's disease (PD), we studied 38 patients (male, 19; female, 19: mean age, 65.5 years: mean duration of disease, 6.7 years) who had no history of respiratory disease and smoking. Fifty three non-respiratory disease subjects (male, 26; female, 27: mean age, 67.6 years) were served as age-matched control. We measured spirometry and maximal expiratory flow-volume curve in all patients, and analyzed the relations between respiratory function variables and clinical profiles. The clinical disability of PD was indicated by Hoehn-Yahr (H-Y) scale. The number of PD patients was 15 in H-Y 2, 18 in H-Y 3 and 5 in H-Y 4, respectively. The values of % VC, %FEV 1, FEV 1/FVC, %PEFR, % V50 in H-Y 4 group were significantly smaller than those in H-Y 2 and 3 groups. Small airway dysfunction (SAD) was represented by abnormality of % V25, % V50/V25. The prevalence of impairment in % V25 and % V50/V25 was detected in 13 patients (34.2%) and 15 patients (39.5%), respectively, this was significantly higher than age-matched controls. However, the mean value and prevalence of impairment in % V25, % V50/V25 were not affected by H-Y scale and duration of disease or ideal body weight (%predicted value). Twenty seven patients showed normal ventilatory function based on % VC over 80% and FEV 1/FVC over 70%. The prevalence of impairment in % V25, % V50/V25 was detected in 8 patients (29.6%), 9 patients (33.3%), respectively, among 27 patients with normal ventilatory function. These results suggest that ventilatory dysfunction is concerned with clinical disability but SAD which is independent of clinical disability seen prevalently in patients with PD. It is widely accepted that patients with PD frequently have cardiac or bowel dysfunction based on the visceral autonomic dysfunction. We hypothesize that SAD may also be caused by possible autonomic dysfunction in patients with PD.     

Loss of nocturnal blood pressure fall in various extrapyramidal syndromes

Cardiovascular autonomic dysfunction has frequently been reported in some patients with extrapyramidal syndromes, especially multiple system atrophy (MSA) but also Parkinson's disease (PD). However, there are only few reports on the prevalence of cardiovascular autonomic dysfunction progressive in supranuclear palsy (PSP). Moreover, the relation of detailed cardiovascular testing and easy to assess 24‐hour ambulatory blood pressure (BP) is not known. Our study evaluates 24‐hour ambulatory BP monitoring in patients with PD, PSP, MSA, and corresponding controls (Con) and relates the findings to the results of comprehensive cardiovascular autonomic testing. Twenty‐three patients with PD, 25 patients with PSP, 25 patients with MSA, and 26 corresponding controls were studied by 24‐hour ambulatory BP monitoring (ABPM) in comparison to cardiovascular autonomic testing. Patients with PD, PSP, and MSA presented frequently with a pathological nocturnal BP regulation (no decrease or even an increase of nocturnal BP) in comparison to the control group (PD 48%, PSP 40%, MSA 68% vs. Con 8%). In MSA and PD patients, the frequent pathological BP increase during night was closely correlated to orthostatic hypotension. Since loss of nocturnal BP fall is frequent in patients with extrapyramidal syndromes, even if they are free of subjective autonomic dysfunction, we recommend 24‐hour ABPM as an easy to perform screening test, especially if detailed autonomic testing is not available. Pathological loss of nocturnal BP fall may account for increased cardiovascular mortality in extrapyramidal syndromes. © 2009 Movement Disorder Society     

Urological dysfunction in synucleinopathies: epidemiology,pathophysiology and management

Objective

Parkinson’s disease (PD) and multiple system atrophy (MSA) are major neurogenerative diseases characterized pathologically by abnormal alpha-synuclein aggregation. PD and MSA are clinically characterized by motor disorder and bladder dysfunction (mainly urinary urgency and frequency, also called overactive bladder). However, few literatures are available concerning bladder dysfunction in PD or MSA.

Method

A systematic review.

Results

The bladder dysfunction in MSA is more severe than that in PD for large post-void residual or urinary retention. These bladder dysfunctions presumably reflect the different nervous system pathologies. Overactive bladder in PD reflects lesions in the brain, e.g., in the prefrontal-nigrostriatal D1 dopaminergic bladder-inhibitory pathway. Overactive bladder in MSA reflects lesions similar to PD and the cerebellum (bladder-inhibitory), and the urinary retention in MSA presumably reflects lesions in the pontine micturition center and the sacral intermediolateral nucleus of the spinal cord (bladder-facilitatory). Bladder dysfunction not only impairs an individual’s quality of life, it can also cause emergency hospitalizations due to acute retention and early institutionalization. Anticholinergics are the first-line treatment for bladder dysfunction in PD and MSA patients, but care should be taken for the management of bladder dysfunction—particularly in MSA patients due to the high prevalence of difficult emptying, which needs clean, intermittent catheterization.

Conclusions

This review summarizes the epidemiology, pathophysiology, and management of bladder dysfunction in individuals with PD or MSA.

     

Sleep disorders and their determinants in multiple system atrophy

OBJECTIVES: To evaluate the incidence, types, determinants, and consequences of sleep disorders in patients with multiple system atrophy (MSA) and determine whether their characteristics are similar to those of patients with Parkinson's disease (PD). METHODS: Information about sleep disorders was collected using a standardised questionnaire in an unselected group of 57 patients with MSA and in 62 patients with PD matched as a group for age, sex distribution, and disease duration. RESULTS: Seventy percent of patients with MSA complained of sleep disorders compared with 51% of patients with PD (p=0.03). The most commonly reported sleep disorders were sleep fragmentation (52.5%), vocalisation (60%), REM sleep behaviour disorder (47.5%), and nocturnal stridor (19%). Except for sleep fragmentation, the incidence of these disorders was significantly higher than in PD. Sleep problems tended to be associated with more severe motor symptoms, longer disease duration, depression, and longer duration of levodopa treatment. Half of patients with MSA with sleep disorders complained of daytime somnolence compared with 30% of patients with PD. Daytime somnolence was significantly associated with disease severity in MSA. CONCLUSION: This study shows that sleep disorders are more common in patients with MSA than in those with PD after the same duration of the disease, reflecting the more diffuse underlying pathological process in MSA.     

Involvement of the ventrolateral medulla in parkinsonism with autonomic failure

OBJECTIVE: To determine whether patients with PD and autonomic failure (AF), manifested primarily with orthostatic hypotension (OH), have a consistent loss of tyrosine hydroxylase (TH) neurons in the rostral ventrolateral medulla (RVLM), similar to that occurring in patients with multiple system atrophy (MSA) and AF, and to determine whether there is loss of nicotinamide, adenine dinucleotide phosphate (NADPH) diaphorase (NADPH-d) RVLM neurons in both groups of patients. METHODS: The numbers of TH and NADPH-d neurons in the RVLM was assessed in brain sections obtained at autopsy from five patients with suspected PD and OH, six patients with MSA, two patients with corticobasal ganglionic degeneration and no AF, and 10 control subjects with no history of neurologic disease. Cell numbers were compared among groups and correlated with their final neuropathologic diagnosis. RESULTS: The number of TH neurons in the RVLM of patients with PD and OH were not significantly different from control subjects, and there were marked individual variations. The TH cell numbers in the RVLM were significantly higher (p < 0.06) in patients with PD than in patients with MSA, despite a similar degree of severity of OH. As a group, patients with PD and OH had reduced numbers of NADPH-d cells in the RVLM compared with control subjects, but again there were marked individual variations. NADPH-d cell numbers were reduced consistently and more markedly in patients with MSA. CONCLUSION: Unlike the case in patients with MSA, the number of TH neurons in the RVLM is highly variable in patients with PD and is unlikely to contribute significantly to the pathophysiology of OH. As a group, patients with PD have reduced numbers of NADPH-d neurons in the RVLM, but some patients had cell counts similar to control subjects. On the other hand, NADPH-d cell depletion in the RVLM is a consistent finding in MSA and may contribute to cardiorespiratory dysfunction in this disorder.     

The arginine growth hormone stimulation test in bradykinetic‐rigid parkinsonisms

The arginine growth hormone (GH) stimulation test differentiates the Parkinsonian variant of multiple system atrophy (MSA‐P) from idiopathic Parkinson's disease (PD). Our aim was to evaluate the accuracy of the arginine GH stimulation test in distinguishing between PSP, MSA‐P, and PD. We measured the GH response to arginine in serum samples of 26 MSA‐P, 23 PSP, and 26 PD patients, and in 80 healthy controls. We used ANOVA followed by the Bonferroni test to compare GH values and peaks among groups. We used receiver operating characteristic curve analysis to establish the arginine cut‐off level that best differentiated between MSA‐P, PSP, and PD. The GH peak was significantly lower (P < 0.01) in MSA‐P (1.46 ± 0.29 μg/L) than in both PD (8.74 ± 0.98 μg/L) and PSP (6.64 ± 0.82 μg/L) patients, and controls (8.59 ± 0.44 μg/L). Growth hormone peaked later in PSP patients than in PD patients and controls. At a cut‐off level of 4 μg/L, arginine test distinguished MSA‐P from PD with a sensitivity of 92% and a specificity of 96%, and MSA‐P from PSP with a sensitivity of 78% and a specificity of 96%. The GH response to arginine differentiates MSA‐P from PD and PSP with a good diagnostic accuracy. The neuroendocrine response to arginine of PSP patients differed from that of MSA‐P patients, but was not identical to that of normal controls and PD patients. Our results suggest that the impairment of the central mechanisms modulating GH release differs between PSP and MSA‐P. © 2007 Movement Disorder Society     

Parkinsonism in multiple system atrophy: natural history, severity (UPDRS-III), and disability assessment compared with Parkinson's disease.

We analyzed parkinsonian features in multiple system atrophy (MSA) compared with age- and disease duration-matched Parkinson's disease (PD) patients, and assessed the applicability of the Unified Parkinson's Disease Rating Scale (UPDRS) -III motor scale as a means of rating their severity. Cross-sectional analysis of parkinsonism was done using UPDRS-III, International Cerebellar Atatia Rating Scale, and disability scales (Hoehn and Yahr [H&A], Schwab and England, Katz and Lawton) in 50 unselected MSA patients and in 50 matched PD patients. At symptom onset, falls occurred 10 times more frequently in MSA, whereas limb tremor was 10 times more common in PD. At first visit (10.2 months), hemiparkinsonism and pill-rolling rest tremor were less common in MSA. Hypomimia, atypical rest, postural or action tremor, as well as postural instability were more frequent in MSA. At study examination (62.4 months), parkinsonian signs in MSA patients were more frequently symmetrical and associated with axial rigidity, antecollis and postural instability. A levodopa response of >50% was seen in <10% of MSA patients. Modified H&Y stages (3.2 +/- 1.3 vs. 2.2 +/- 0.78) and UPDRS-III scores (48.14 +/- 19.5 vs. 31.74 +/- 12.9) were significantly (P = 0.0001) higher in MSA. The internal consistency of the UPDRS-III was fair in MSA patients (Cronbach's alpha >0.90), and correlated well with marked dependency on the Schwab and England and Katz and Lawton scales. Factor structure analysis of UPDRS-III in MSA showed five clinically distinct subscores accounting for 74% of the variance, differing from PD by the dependency of the face-speech and limb bradykinesia items and independence of the postural-action tremor from the rest tremor items. There was a significant correlation (R(2) = 0.70, P = 0.001) between ICARS ataxia and UPDRS-III scores in MSA patients. Results confirm a distinct profile of parkinsonism in MSA and greater severity and disability compared with PD. It also indicates that the UPDRS-III provides a useful severity measure of parkinsonism in MSA, albeit contaminated by additional cerebellar dysfunction.     

Perverted head‐shaking and positional downbeat nystagmus in patients with multiple system atrophy

The diagnosis of multiple system atrophy (MSA) is mainly based on the clinical criteria, which are often of little assistance in the early stages of the disease. Positional downbeat nystagmus (pDBN) and perverted head‐shaking nystagmus (pHSN), possible signs of cerebellar dysfunction, may be useful in differentiating MSA from other parkinsonian disorders. To investigate the occurrences of pDBN and pHSN in patients with MSA compared with those in patients with Parkinson's disease (PD). A total of 127 consecutive patients with MSA and 274 patients with PD underwent a video‐oculographic recording of head‐shaking and positional nystagmus over a year. The occurrences of pDBN and pHSN were higher in MSA than in PD. pDBN was more frequently observed in MSA with overt cerebellar signs than in those without, but the occurrence of pHSN did not differ between the MSA groups. pHSN was more frequently observed in MSA‐p without overt cerebellar signs than in PD, but there was no difference in the occurrence of pDBN between them. The presence of pHSN and pDBN may be a clue for the diagnosis of MSA, and pHSN may be helpful in differentiating MSA‐p from PD when the patients do not have overt cerebellar features. © 2009 Movement Disorder Society