Comprehensive autonomic assessment does not differentiate between Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy

Differential diagnosis of parkinsonian syndromes is a major challenge in movement disorders. Dysautonomia is a common feature but may vary in clinical severity and onset. The study attempted to find a pattern of autonomic abnormalities discriminative for patients with different parkinsonian syndromes. The cross-sectional study included 38 patients with multiple system atrophy (MSA), 32 patients with progressive supranuclear palsy (PSP), 26 patients with idiopathic Parkinson’s disease (IPD) and 27 age-matched healthy controls. Autonomic symptoms were evaluated by a standardized questionnaire. The performance of patients and controls was compared on five autonomic function tests: deep breathing, Valsalva manoeuvre, tilt-table testing, sympathetic skin response, pupillography, and 24-h ambulatory blood pressure monitoring (ABPM). Disease severity was significantly lower in IPD than PSP and MSA. Except for pupillography, none of the laboratory autonomic tests distinguished one patient group from the other alone or in combination. The same was observed on the questionnaire. Receiver operating characteristic curve revealed discriminating performance of pupil diameter in darkness and nocturnal blood pressure change. The composite score of urogenital and vasomotor domains significantly distinguished MSA from IPD patients but not from PSP. Our study supports the observation that even mild IPD is frequently indistinguishable from more severe MSA and PSP. Thus, clinical combination of motor and non-motor symptoms does not exclusively point at MSA. Pupillography, ABPM and the questionnaire may assist in delineating the three syndromes when applied in combination.     

Baroreflex sensitivity and power spectral analysis in different extrapyramidal syndromes

Cardiac autonomic abnormalities have been described in Parkinson’s disease and other extrapyramidal syndromes. To investigate baroreflex sensitivity as an important risk marker of cardiovascular mortality in patients with Parkinson’s disease and other extrapyramidal syndromes. We recorded continuously blood pressure, ECG and respiration in 35 patients with multiple system atrophy (MSA), 32 patients with progressive supranuclear palsy (PSP), 46 patients with idiopathic Parkinson’s disease (PD) and in 27 corresponding healthy subjects (Con). Recordings of 2 min at rest were used to calculate baroreflex and spectral analysis of heart rate and systolic blood pressure. Resting baroreflex sensitivity (BRS) was significantly lower in the MSA and the PSP group but not in the PD group in comparison to the Con group. With increasing Hoehn & Yahr stage, BRS significantly decreased in all patient groups. In spectral analysis, all patient groups had a significantly lower relative low frequency (LF)-band power than the healthy controls. Patients with extrapyramidal disorders frequently demonstrate pathologically decreased BRS values and abnormalities of spectral analysis. This may have fundamental impact on the cardiovascular prognosis of patients with extrapyramidal disease.     

Detecting nocturnal hypertension in Parkinson’s disease and multiple system atrophy: proposal of a decision-support algorithm

A pathological nocturnal blood pressure (BP) profile, either non-dipping or reverse dipping, occurs in more than 50 % of subjects diagnosed with multiple system atrophy (MSA) or Parkinson’s disease (PD). This may play a negative prognostic role in α-synucleinopathies, but, being mostly asymptomatic, remains largely underdiagnosed. In this proof-of-concept study, we aimed at developing a decision-support algorithm to predict pathological nocturnal BP profiles during a standard tilt-table examination in PD and MSA. Sixteen MSA and 16 PD patients underwent standard tilt-table examination and 24-h ambulatory BP monitoring (24-h ABPM). Clinical and tilt test differences between patients with a normal and a pathological nocturnal BP profile at 24-h ABPM were assessed, and a decision-support algorithm was developed accordingly. 75 % of MSA and 31 % of PD patients showed a pathological nocturnal BP profile. This was associated with more pronounced orthostatic BP drop (p = 0.03), joint occurrence of orthostatic hypotension and supine hypertension (p = 0.046), and lack of BP overshoot in the late phase II (II_L, p = 0.002) and in the phase IV (p = 0.007) of the Valsalva manoeuvre. Combined ?BP ≤0.5 mmHg in the II_L and ≤?7 mmHg in the IV phase of Valsalva manoeuvre correctly predicted a pathological nocturnal BP profile with 87.5 % sensitivity and 85.7 % specificity. Pathological nocturnal BP profiles are associated with evidence of cardiovascular noradrenergic failure in PD and MSA. The Valsalva manoeuvre is routinely performed during standard tilt-table examinations. We propose the naked-eye evaluation of Valsalva phase II_L and phase IV BP behaviour as time-sparing screening tool for pathological nocturnal BP profiles in PD and MSA.     

Valsalva manoeuvre in patients with different Parkinsonian disorders

The valsalva manoeuvre (VM), used as an autonomic function test, can detect sympathetic and/or parasympathetic autonomic dysfunction. This study investigated the value of VM in patients with different Parkinsonian syndromes (PS). We continuously recorded blood pressure, ECG and respiration among 38 patients with multiple system atrophy (MSA), 32 patients with progressive supranuclear palsy (PSP), 26 patients with idiopathic Parkinson’s disease (PD) and in 27 healthy subjects matched in age and sex (Con). VM was performed in addition to metronomic breathing and tilt-table testing. VM could not be analysed in 26% of the ES patients. Valsalva ratio (VR), as a parameter of cardiovagal function, was pathologically decreased in all patient groups. Valsalva ratio (VR) was not able to discriminate parasympathetic dysfunction between patients and controls as well as E/I ratio of metronomic breathing. As a parameter of sympathetic dysfunction during VM, the physiological increase of blood pressure was more often missing during phase IV than phase II especially in PD and MSA patients. Correlation with orthostatic hypotension during tilt-table testing was only moderate. Although VM can demonstrate sympathetic and parasympathetic autonomic dysfunction, we cannot recommend VM as a first line autonomic test in PS patients. Metronomic breathing and tilt-table test seem more capable as parasympathetic resp. and sympathetic function tests to identify cardiovascular abnormalities in PS patients.     

Cardiovascular reflex testing contributes to clinical evaluation and differential diagnosis of Parkinsonian syndromes.

The differentiation between Parkinson's disease (PD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA) may be difficult but is important for prognostic and therapeutic purposes. Varying degrees of autonomic failure have been described in PD and MSA, whereas its involvement in PSP remains controversial. The aim of this study was to investigate autonomic function in patients fulfilling strict clinical diagnostic criteria for the disorders above, to evaluate the diagnostic capacity of laboratory autonomic tests. The study group was consecutively recruited among patients referred to a movement disorder unit. Thirty-four patients with PD, 15 patients with PSP, and 47 patients with MSA were compared with 18 healthy age-matched controls. Autonomic tests included analysis of heart rate variability (HRV) in temporal domain, at rest and during forced respiration, as well as blood pressure (BP) changes during 75 degrees head-up tilt. HRV did not differ between groups during quiet breathing but was significantly reduced during forced respiration in MSA (P < 0.01), while PD and PSP groups did not differ from controls. Hypotensive responses during orthostatic provocation were seen in PD (P < 0.01) and MSA (P < 0.001), whereas BP remained stable in most PSP patients, not differing from the healthy control group. On an individual basis, decreased HRV and severe hypotensive responses were seen in MSA patients regardless of age and disease duration, whereas PD patients showed this combination only at high age and long duration. In PSP, only a few cases with decreased HRV and limited hypotensive responses were found. We conclude that cardiovascular reflex tests can supplement the clinical differentiation of Parkinsonian syndromes.     

Abnormalities of rate-corrected QT intervals in Parkinson's disease-a comparison with multiple system atrophy and progressive supranuclear palsy

A number of patients with Parkinson's disease (PD) and multiple system atrophy (MSA), in whom sudden death does occur occasionally, have QT or rate-corrected QT (QTc) interval prolongation on electrocardiogram (ECG). Although these QT or QTc interval abnormalities are likely related to autonomic dysfunction, the pathophysiology remains unknown. The aim of this study was to compare the degree of QTc interval prolongation among akinetic-rigid syndromes, namely PD and related disorders, and to evaluate the relationship between QTc prolongation and severity of autonomic dysfunction. Thirty-four patients with PD, 22 with MSA, 11 with progressive supranuclear palsy (PSP) and 30 healthy controls underwent standard autonomic function tests, and electrocardiography variables (RR, QT and QTc intervals) were measured by an ECG recorder with an automated analyzer. The relationship between QTc interval and cardiovascular reflex tests were also analyzed. Orthostatic hypotension and decreased heart rate in response to respiratory stimuli were prominent in MSA, while these were relatively mild in PD. Unlike the RR and QT intervals, the QTc interval significantly differed among all groups (p<0.01). The QTc interval was significantly prolonged in PD (409+/-17 ms; p<0.001) and MSA (404+/-14 ms; p<0.05) compared with healthy controls (394+/-19 ms). Neither autonomic dysfunction nor QTc interval prolongation was evident in PSP. QTc intervals and cardiovascular reflexes did not correlate, except for Valsalva ratio. The QTc interval was obviously prolonged in PD patients to an extent that could not be accounted for simply by autonomic dysfunction levels. MSA patients showed slightly prolonged QTc intervals in spite of marked cardiovascular autonomic dysfunction. Abnormalities of the QTc may reflect the degeneration of cardioselective sympathetic and parasympathetic neurons that cannot be fully captured by cardiovascular autonomic function tests.     

Ambulatory blood pressure monitoring in patients with spinocerebellar degeneration

OBJECTIVES: The aim of this study was to demonstrate circadian blood pressure trends and to evaluate autonomic function in patients with spinocerebellar degeneration (SCD). MATERIALS AND METHODS: We performed 24-h ambulatory blood pressure monitoring (ABPM) on 10 patients from seven Japanese families with spinocerebellar ataxia type 6 (SCA6), 10 patients with idiopathic cerebellar ataxia (ICA), eight patients with multiple system atrophy (MSA) suffering from cerebellar MSA (MSA-C), and 12 age- and gender-matched normal subjects. We also evaluated autonomic function in these patients. RESULTS: Three SCA6 patients (30%), six ICA patients (60%), eight MSA-C patients (100%) and four normal subjects (33%) were non-dippers. The nocturnal reduction rate of blood pressure in MSA patients was significantly less than those in normal subjects, SCA6 patients and ICA patients. There were no abnormal findings in any patient with SCA6 in autonomic function tests. All dipper patients exhibited normal findings on autonomic function tests. This is the first report of ABPM in patients with SCD. CONCLUSIONS: Blunted reduction of nocturnal blood pressure may be associated with autonomic dysfunction in patients with SCD.     

Autonomic dysfunction in patients with progressive supranuclear palsy

The most important features that characterize and differentiate progressive supranuclear palsy (PSP) from other parkinsonian syndromes are postural instability, supranuclear gaze palsy, pseudobulbar palsy, and cognitive disturbances. Although it has been reported that significant autonomic dysfunction is an exclusionary feature for PSP diagnosis, we could demonstrate in this study using semiquantitative clinical interview and cardiovascular testing that both PSP and idiopathic Parkinson's disease (PD) patients can present with significant autonomic dysfunction. The parasympathetic cardiovascular system seems to be involved to a similar extent in PD and PSP patients, whereas sympathetic cardiovascular dysfunction is more frequent and severe in PD patients, but can also be found in PSP patients. Our findings have a profound implication on the diagnosis and treatment of PSP patients. © 2008 Movement Disorder Society     

Predictors of falls and fractures in bradykinetic rigid syndromes: a retrospective study

BACKGROUND: Falls and fractures contribute to morbidity and mortality in bradykinetic rigid syndromes. METHODS: The authors performed a retrospective case notes review at the Queen Square Brain Bank for Neurological Disorders and systematically explored the relation between clinical features and falls and fractures in 782 pathologically diagnosed cases (474 with Parkinson's disease (PD); 127 progressive supranuclear palsy (PSP); 91 multiple system atrophy (MSA); 46 dementia with Lewy bodies (DLB); 27 vascular parkinsonism; nine Alzheimer's disease; eight corticobasal degeneration). RESULTS: Falls were recorded in 606 (77.5%) and fractures in 134 (17.1%). In PD, female gender, symmetrical onset, postural instability, and autonomic instability all independently predicted time to first fall. In PD, PSP, and MSA latency to first fall was shortest in those with older age of onset of disease. Median latency from disease onset to first fall was shortest in Richardson's syndrome (12 months), MSA (42), and PSP-parkinsonism (47), and longest in PD (108). In all patients fractures of the hip were more than twice as common as wrist and forearm fractures. Fractures of the skull, ribs, and vertebrae occurred more frequently in PSP than in other diseases. CONCLUSION: Measures to prevent the morbidity associated with falls and fractures in bradykinetic rigid syndromes may be best directed at patients with the risk factors identified in this study.     

Cardiovascular autonomic testing in extrapyramidal disorders

Various diagnostic tests are available to demonstrate autonomic failure in extrapyramidal disease. Autonomic function tests can identify parasympathetic and sympathetic dysfunction. While specialized tests are only available in autonomic labs, routine tests such as 24h ambulatory blood pressure measurements can be broadly used in clinical practice eg. as screening tests. In this review, we briefly introduce functional cardiovascular autonomic testing and propose a workup plan for patients with extrapyramidal disease. In all patients with extrapyramidal disease, screening for autonomic dysfunction should be performed. In the case of pathological findings, detailed autonomic testing should be considered with repeated measurements at follow up visits.     

Heart rate circadian profile in the differential diagnosis between Parkinson disease and multiple system atrophy

Clinical diagnostic criteria indicate presence of autonomic features as the primary hallmark of Multiple System Atrophy (MSA). However involvement of the autonomic system is also a recognized feature of Parkinson's Disease (PD), yielding a broad clinical overlap between the two diseases. Laboratory assessments may help in the differential diagnosis between PD and MSA. Ambulatory Monitoring of Blood Pressure (AMBP) is a suitable tool to study the circadian rhythm of blood pressure (BP) and heart rate (HR). Different studies reported a reduction of physiological BP nocturnal dipping in PD and MSA patients, but failed to identify a distinctive pattern discriminating the two diseases. On the other hand, HR nocturnal behavior has not been exhaustively analyzed. In the present study we compared the profiles of HR circadian rhythm in 61 PD and 19 MSA patients who underwent 24 h AMBP.We found higher nocturnal HR (nHR) (71.5 beats/min ± 7.4) in MSA compared with PD (63.8 beats/min ± 9.6) as well as significantly lower nocturnal decline of HR (ndHR) in MSA (7.3% ± 8.2) vs. PD (14% ± 7.5). At a Receiver Operating Curve analysis nHR and ndHR significantly discriminated MSA from PD. nHR showed a sensitivity of 84.2% and a specificity of 62.3% (AUC 0.76; 95% IC 0.65–0.85); ndHR showed a sensitivity of 68% of and a specificity of 77% (AUC 0.72; 95% IC 0.61–0.82).According to our findings, nHR is increased and ndHR is reduced in MSA compared to PD. Moreover, these two indices discriminate between the two diseases with acceptable accuracy.     

What features improve the accuracy of the clinical diagnosis of progressive supranuclear palsy‐parkinsonism (PSP‐P)?

Progressive supranuclear palsy‐parkinsonism (PSP‐P) is a primary tauopathy characterised by neurofibrillary degeneration, which is frequently mistaken for Parkinson's disease (PD), multiple system atrophy (MSA), and vascular parkinsonism (VP) at presentation. The aim of this study was to identify particular clinical features (green flags) that may be helpful in differentiating PSP‐P from these other disorders. We identified 37 patients with PSP‐P from 726 patients archived at the Queen Square Brain Bank. Using a retrospective case notes review the clinical features were compared between the PSP‐P group and Lewy body associated parkinsonism (PD, n = 444 and dementia with Lewy bodies (DLB), n = 46), MSA (n = 90), and VP (n = 19), using the χ²‐test for proportions for a two‐by‐two contingency table. The sensitivity, specificity, and positive predictive values (PPV) and negative predictive values (NPV) were calculated for individual clinical features. A specificity of >0.85 or a PPV of >0.85 were considered reliable discriminators. No clinical features were predictive of PSP‐P, but late drug induced dyskinesias (specificity 0.92, PPV 0.99), late autonomic dysfunction (specificity 0.94, PPV 0.99) and any visual hallucinations (specificity 0.94, PPV 0.99) were better in distinguishing PD and PSP‐P than predicted using operational diagnostic criteria for PD. PSP‐P shares many clinical features with PD and DLB, MSA and VP, but visual hallucinations, drug induced dyskinesias and autonomic dysfunction are very uncommon and may be helpful exclusion criteria. © 2010 Movement Disorder Society     

Assessment of cardiovascular autonomic dysfunction in multiple system atrophy

Because heart rate is controlled mainly by the autonomic nervous system, cardiovascular autonimic dysfunction may contribute to the prognosis of patients with multiple system atrophy (MSA). To clarify cardiovascular autonomic dysfunctions in MSA, the authors investigated the relation between blood pressure (BP) and pulse rate (PR), and assessed a power spectral analysis of heart rate variability (HRV) during the clinical course using ambulatory BP and a heart rate monitor for 24 hours. The authors studied seven patients with MSA (five men and two women, aged 61.0±5.8 years) and seven healthy volunteers (four men and three women, aged 58.0±6.6 years) without hypertension, heart disease, or intracranial lesions. The MSA group showed abnormal circadian variations of BP and PR and a significantly decreased correlation coefficient between BP and PR. A significant decrease and altered circadian variation also existed in the number of changes in successive R-R intervals greater than 50 msec (RR50) and in the power of the high- and low-frequency component of HRV. The authors observed a significant negative correlation between the duration of illness and the number of changes in successive R-R intervals greater than 50 msec. The characteristic dysautonomia in MSA was a decrease in sympathetic and parasympathetic activity, with an abnormal circadian rhythm of BP and HRV. The balance between sympathetic and parasympathetic activity was also impaired. The parasympathetic modulation represented by RR50 worsened according to the development of the illness. Those autonomic dysfunctions may have affected the cardiovascular systems, which may indicate a poor prognosis in patients with MSA. An analysis of HRV and the circadian rhythm of BP and HRV are useful in evaluating cardiac autonomic dysfunctions in MSA.     

Diurnal Blood Pressure and Heart Rate Variability in Hypertensive Patients with Cerebral Small Vessel Disease: A Case-Control Study

BackgroundWhether autonomic dysfunction contributes to cerebral small vessel disease (CSVD) remains unclear. This study aimed to explore the relationship between CSVD and blood pressure variability (BPV) and heart rate variability (HRV).MethodsThis case-control study recruited 50 patients with CSVD and 50 non-CSVD hypertensive age- and gender-matched controls. All participants completed a 24-h ambulatory electrocardiogram recording and ambulatory BP monitoring (ABPM). Differences in HRV and BPV between the two groups were examined. BPV indices assessed by ABPM included mean systolic BP (SBP), mean diastolic BP (DBP), coefficient of variation and weighted standard deviation of SBP and DBP.ResultsCSVD patients had significant higher 24-h mean systolic BP (SBP), 24-h mean diastolic BP (DBP), daytime mean SBP, nocturnal mean SBP, and nocturnal mean DBP (P < .05 for all). CSVD patients had a significant lower nocturnal SBP fall rate compared with controls (median: 1.0 versus 6.2, respectively; P < .001) and were more likely to be non-dippers and reverse dippers. There were no differences in HRV variables between the two groups. Five logistic models were built to explore the correlations between BPV indices and CSVD. BPV indices were separately entered into the logistic regression models, together with hyperlipidemia, ischemic stroke history, current use of anti-hypertensive agents, and serum blood urea nitrogen. In models 1?3, 24-h mean SBP and nocturnal mean SBP and DBP were significantly correlated with CSVD (r² = 0.308?0.340). In model 4, the nocturnal SBP fall rate was negatively correlated with CSVD (odds ratio [OR] = 0.871, 95% confidence interval [CI] = 0.804?0.943; P = .001), with r² = 0.415 fitting the model. In model 5, the pattern of SBP dipping was significantly associated with CSVD, with non-dipper (OR = 8.389, 95%CI = 1.489?47.254; P = .016) and reverse dipper (OR = 27.008, 95%CI = 3.709?196.660; P = .001) having the highest risks of CSVD (r² = 0.413).ConclusionsLower nocturnal SBP fall rate is associated with CSVD. Non-dipper and reverse dipper hypertensive patients have a higher risk of CSVD.     

Twenty-four-hour blood pressure profile,orthostatic hypotension,and cardiac dysautonomia in elderly type 2 diabetic hypertensive patients

Purpose

The aim of this study was to evaluate the relationship between orthostatic hypotension (OH), defined as a decrease in systolic blood pressure (SBP) ≥20 mmHg and/or a decrease in diastolic blood pressure (DBP) ≥10 mmHg, and 24-h ambulatory BP profile in elderly hypertensive type 2 diabetic patients.

Methods

After a 2-week antihypertensive wash-out period, 200 hypertensive well-controlled diabetic outpatients, aged 65–75 years, underwent a clinical examination, including BP measurements, ECG, 24-h ABP monitoring (ABPM), an orthostatic test, and three tests for cardiovascular autonomic function assessment [deep breathing, heart rate (HR) variability, resting HR].

Results

According to their nighttime BP profile, patients were divided into three groups: dippers (n = 86) (BP fall during nighttime ≥10 %), non-dippers (n = 80) (BP fall during nighttime 0–10 %), and reverse dippers (n = 34) (nighttime BP > daytime BP). Orthostatic test produced a significantly greater orthostatic SBP fall in dippers and even more in reverse dippers. In these latter, a significant fall was observed also in DBP. Prevalence of OH was 9.3 % in dippers, 30 % in non-dippers, and 79.4 % in reverse dippers.

Conclusions

In elderly hypertensive type 2 diabetics, a blunted nocturnal BP fall is associated with OH and autonomic dysfunction. These data suggest that ABPM should be performed in the assessment of hypertensive diabetic patients in whom the cardiovascular dysautonomia is suspected or the signs of it are present (such as OH).

     

Screening For Mutations In The Peripheral Myelin Genes PMP22, MPZ AND CX32 (GJB1) in Russian Charcot-Marie-Tooth Neuropathy Patients

OBJECTIVE—To examine the relationship between 24-h blood pressure (BP) measurements, urinary albumin excretion rates, and autonomic neuropathy (AN) in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS—A total of 31 patients with microalbuminuria (MA), 20 patients with intermittent MA (I-MA) and 11 patients with persistent MA (P-MA) were identified from the diabetes clinics at two major Australian tertiary care pediatric hospitals. Two control groups were used, one consisted of 19 age-, sex-, and diabetes duration-matched adolescents with normoalbuminuria (NA), and the other consisted of 46 age and sex-matched nondiabetic control subjects. A medical history and physical examination were followed by a series of noninvasive tests of cardiovascular and pupillary autonomic function and then by 24-h ambulatory blood pressure monitoring (ABPM). RESULTS—ABPM showed an incremental increase in all BP parameters from nondiabetic control subjects through subjects with NA. A parallel incremental increase in diurnal and nocturnal ambulatory heart rates was also evident. Subjects with MA had significantly reduced pupillary adaptation to darkness compared with nondiabetic subjects and subjects with NA. The above results paralleled an incremental increase in HbA(1c) levels in adolescents with type 1 diabetes from subjects with NA to subjects with P-MA. CONCLUSIONS—Higher 24-h BP values and evidence of subclinical signs of AN are present before P-MA develops and may have important implications for timing the introduction of treatments designed to prevent or retard the microvascular complications of type 1 diabetes in adolescents.     

Nocturnal body core temperature falls in Parkinson's disease but not in Multiple-System Atrophy.

OBJECTIVE: To evaluate whether the circadian rhythm of body core temperature (CRT degrees ) can differentiate Multiple-System Atrophy (MSA) from Idiopathic Parkinson's disease (IPD). METHODS: We evaluated 14 patients with probable MSA, seven with IPD, and eight controls. After a preliminary evaluation of cardiovascular autonomic function, rectal temperature and sleep-wake cycle were monitored continuously for 48 hours in a temperature-controlled room, at constant bed rest with controlled food intake and fixed light-dark schedule. RESULTS: MSA patients showed cardiovascular autonomic sympathetic and parasympathetic failure. IPD had normal cardiovascular autonomic function. A 24-hour rhythm of body core temperature (BcT degrees ) was present in all subjects. IPD had CRT degrees comparable to controls. In MSA the mesor was higher and mean BcT degrees of each hour was significantly higher from 11 p.m. to 7 a.m. The analysis of mean BcT degrees during the different sleep phases showed significantly higher values during both NREM (1--2, 3--4) and REM sleep stages in MSA. CONCLUSIONS: The physiological nocturnal fall of BcT degrees is blunted in MSA patients mainly because BcT degrees did not decrease during sleep. This CRT degrees pattern is not justified by differences in sleep structure and may reflect an impairment of central sympathetic nervous system function.     

Can the frontal assessment battery (FAB) differentiate bradykinetic rigid syndromes? Relation of the FAB to formal neuropsychological testing

The frontal assessment battery (FAB) is a bedside test of executive function. It takes less than 10 minutes to administer and a low score indicates executive dysfunction. To determine whether the FAB could detect the more severe subcortical dementia that is a feature of PSP and differentiate it from other bradykinetic rigid syndromes, we studied 17 patients with progressive supranuclear palsy (PSP); 11 with multiple system atrophy (MSA) and 12 with Parkinson's disease (PD). We compared FAB scores with the results of more detailed tests of executive and general cognitive function.FAB scores were significantly lower in PSP than in MSA or PD (p=0.02 and p<0.001) and were also found to be significantly lower in MSA than in PD (p=0.047). We divided the study group into those with an FAB score <15 and those with an FAB score>/=5, regardless of the clinical diagnosis. While 82% of the PSP group had FAB scores of <15, such scores were recorded in only 36% of the MSA and 8% of the PD groups. The lexical fluency and motor series subscores of the FAB discriminated 70% of the PSP, MSA and PD patients. The FAB scores correlated with tests of executive function, as well as with scores on the Mattis Dementia Rating Scale, the Mini Mental State Examination and other tests of general cognitive function. A stepwise regression analysis revealed that across the groups, among the variables that correlated with FAB scores, alternating semantic fluency accounted for 80% of FAB variance.These results suggest that the FAB is a valid and easily applicable bedside test to discriminate executive dysfunction in these three frequently confused bradykinetic rigid syndromes.     

Autonomic dysfunction in different subtypes of multiple system atrophy

Multiple system atrophy (MSA) can clinically be divided into the cerebellar (MSA‐C) and the parkinsonian (MSA‐P) variant. However, till now, it is unknown whether autonomic dysfunction in these two entities differs regarding severity and profile. We compared the pattern of autonomic dysfunction in 12 patients with MSA‐C and 26 with MSA‐P in comparison with 27 age‐ and sex‐matched healthy controls using a standard battery of autonomic function tests and a structured anamnesis of the autonomic nervous system. MSA‐P patients complained significantly more often about the symptoms of autonomic dysfunctions than MSA‐C patients, especially regarding vasomotor, secretomotor, and gastrointestinal subsystems. However, regarding cardiovascular, sudomotor pupil, urogenital, and sleep subsystems, there were no significant quantitative or qualitative differences as analyzed by autonomic anamnesis and testing. Our results suggest that there are only minor differences in the pattern of autonomic dysfunction between the two clinical MSA phenotypes. © 2008 Movement Disorder Society     

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