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 Parkinson's 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.

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.

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.

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.

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.

Selection of genetically distinct, rapidly proliferating clones does not contribute to repopulation during fractionated irradiation in FaDu squamous cell carcinoma.

Acceleration of clonogen repopulation during fractionated irradiation after about 3 weeks has been demonstrated previously in FaDu human squamous cell carcinoma in nude mice (Petersen et al., Int. J. Radiat. Oncol. Biol. Phys. 51, 483-493, 2001). Selection of genetically distinct, rapidly proliferating clones might contribute to this phenomenon. To address this question, three sublines (R1-R3) were established from FaDu tumors that recurred locally after fractionated irradiation. The tumors were retransplanted and irradiated under clamp hypoxia with single doses or with 18 x 3 Gy within 18 days or 36 days, followed by graded top-up doses. The results were compared with data obtained after the same treatment schedules in the parental tumor line. Histologies, tumor volume doubling times, and potential doubling times of FaDu sublines R1-R3 were not different from those of the parental line. The radiation dose required to control 50% of the tumors (TCD(50)) after single-dose irradiation of 37-38 Gy was the same for the FaDu sublines R1-R3 and the parental tumor. The top-up TCD(50) values for the FaDu sublines R1-R3 after 18 fractions within 36 days were 14-17 Gy higher than those after 18 fractions within 18 days, indicating significant repopulation. The magnitude of this effect was not significantly different between the sublines R1-R3 or between these sublines and the parental FaDu tumors. The results indicate that selection of genetically distinct, rapidly proliferating clones does not contribute to the acceleration of repopulation during fractionated irradiation in poorly differentiated FaDu tumors.

Switching and combining of dopamine agonists.

Dopamine agonists have been proved safe and effective as initial therapy in early stages of Parkinson's disease. Prospective long-term clinical trials demonstrated that initial symptomatic treatment with a dopamine agonist is associated with a significantly reduced risk for motor complications in comparison with levodopa therapy. Switching from one dopamine agonist to another has become a common clinical practice in the treatment of patients with Parkinson's disease. Moreover, the combination of two dopamine agonists seems to be an attractive alternative to delay initiation of levodopa therapy. This article explores some more motives for switching and combining of dopamine agonists in consideration of practical aspects and very recently published data.

Olfactory loss may be a first sign of idiopathic Parkinson's disease.

Recent studies support the idea of olfactory dysfunction as a very early sign of idiopathic Parkinson's disease (IPD). Aim of the present study was to clinically follow-up patients with idiopathic hyposmia to find out the percentage of patients developing IPD after 4 years time. At baseline, olfactory tests had been combined with transcranial sonography of the substantia nigra and (123)I-FP-CIT SPECT imaging. At the present neurological examination, 7% of the individuals with idiopathic hyposmia had developed clinical IPD. Altogether, 13% presented with abnormalities of the motor system. Our data suggest that a combination of olfactory testing and other tests may constitute a screening tool for the risk to develop IPD.

Valvular heart disease in Parkinson's disease patients treated with dopamine agonists: a reader-blinded monocenter echocardiography study.

Fibrotic valvular heart disease (VHD) has been reported in association with ergot dopamine agonists (DAs), but the current database is insufficient regarding clinical relevance and comparison to data on non-ergot DAs. We evaluated the effects of four DAs (pergolide, cabergoline, ropinirole, pramipexole) on morphology and function of heart valves in patients with Parkinson's disease (PD) to determine the frequency and clinical relevance of DA-induced VHD. A total of 85 patients treated with ergot or non-ergot DAs and 38 age-matched controls were evaluated by transthoracic echocardiography. Valvular pathology was assessed by established criteria of valvular regurgitation and a VHD scoring system. Both grading systems revealed increased frequency of VHD in ergot DA patients compared to both non-ergot DA patients and controls with 22% of ergot DA patients having moderate VHD versus 3% of non-ergot DA patients and none of controls (P = 0.001). We did not find correlations of echocardiographic findings with duration/cumulative dose of treatment, age, or vascular risk factors. Our data suggest that ergot DAs are associated with higher prevalence of VHD compared to non-ergot DAs and controls. Standard echocardiography seems sufficient to detect VHD in PD patients treated with DAs.

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 Parkinson's 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.