Claudia Schmidt

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 Parkinsons 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.

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.

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.

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 During Autonomic Testing in Different Extrapyramidal Syndromes

Autonomic dysfunction has been frequently demonstrated in patients with extrapyramidal diseases by cardiovascular autonomic testing. In addition to classical testing, we applied the more detailed baroreflex and spectral analysis on three traditional cardiovascular tests in this study to get additional information on autonomic outflow. We recorded continuously blood pressure, electrocardiogram, and respiration in 35 patients with multiple system atrophy, 32 patients with progressive supranuclear palsy, 46 patients with idiopathic Parkinsons disease and in 27 corresponding healthy subjects during cardiovascular autonomic testing (metronomic breathing, Valsalva manoeuvre, head‐up tilt). Baroreflex and spectral analyses were performed by using trigonometric regressive spectral analysis between and during the manoeuvres. Consistent with previous interpretations, our data showed an increase of sympathetic activity in head‐up tilt and Valsalva test in healthy controls. This sympathetic activity was significantly decreased in patients with typical and atypical Parkinson syndromes. Significant modulation of baroreflex activity could be observed especially during metronomic breathing; again it was significantly lower in all patient groups. Baroreflex and spectral parameters could not only differentiate between patients and healthy controls, but also differentiate between clinically symptomatic (with autonomic dysfunction as eg. orthostatic hypotension) and asymptomatic patients. In conclusion, our approach allows the evaluation of autonomic variability during short and nonstationary periods of time and may constitute a useful advance in the assessment of autonomic function in both physiological and pathological conditions.

Pupil diameter in darkness differentiates progressive supranuclear palsy (PSP) from other extrapyramidal syndromes

The most important features that characterize and differentiate progressive supranuclear palsy from other Parkinsonian syndromes are postural instability, supranuclear gaze palsy, pseudobulbar palsy, parkinsonism, and cognitive disturbances. In this article, we demonstrate that progressive supranuclear palsy patients exhibit pathologically decreased pupil diameters after dark adaptation recorded by TV pupillography. A cut off value of 3.99 mm was defined to differentiate progressive supranuclear palsy patients from patients with other extrapyramidal disorders like Parkinsons disease and multiple system atrophy with a specificity of 86.4% and a sensitivity of 70.8%. Other pupil abnormalities could not be described in patients with extrapyramidal syndromes.

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 Parkinsons 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.