Female sexual dysfunction in multiple system atrophy: a prospective cohort study.

PURPOSE: The diagnosis of probable multiple system atrophy relies on the presence of severe cardiovascular or urogenital autonomic failure. Erectile dysfunction is required to fulfil the latter criterion in men, whereas no corresponding item is established for women. In this study, we aimed to investigate sexual dysfunction in women with multiple system atrophy. METHODS: We administered the Female Sexual Function Index questionnaire and interviewed women with multiple system atrophy and age-matched controls regarding the presence of "genital hyposensitivity." RESULTS: We recruited 25 women with multiple system atrophy and 42 controls. Female Sexual Function Index scores in sexually active women with multiple system atrophy were significantly lower (multiple system atrophy = 10; 15.4, 95% CI [10.1, 22.1], controls = 37; 26.1 [24.1, 28.1], p = 0.0004). The lowest scores concerned the domains of desire, arousal and lubrication. Genital hyposensitivity was reported by 56% of the patients with multiple system atrophy and 9% controls (p < 0.0001). CONCLUSIONS: Sexual dysfunction is highly prevalent in women with multiple system atrophy. Screening for disturbances in specific sexual domains should be implemented in the clinical evaluation of women with suggestive motor symptoms.

Consensus statement on the definition of neurogenic supine hypertension in cardiovascular autonomic failure by the American Autonomic Society (AAS) and the European Federation of Autonomic Societies (EFAS) : Endorsed by the European Academy of Neurology (EAN) and the European Society of Hypertension (ESH).

PURPOSE: Patients suffering from cardiovascular autonomic failure often develop neurogenic supine hypertension (nSH), i.e., high blood pressure (BP) in the supine position, which falls in the upright position owing to impaired autonomic regulation. A committee was formed to reach consensus among experts on the definition and diagnosis of nSH in the context of cardiovascular autonomic failure. METHODS: As a first and preparatory step, a systematic search of PubMed-indexed literature on nSH up to January 2017 was performed. Available evidence derived from this search was discussed in a consensus expert round table meeting in Innsbruck on February 16, 2017. Statements originating from this meeting were further discussed by representatives of the American Autonomic Society and the European Federation of Autonomic Societies and are summarized in the document presented here. The final version received the endorsement of the European Academy of Neurology and the European Society of Hypertension. RESULTS: In patients with neurogenic orthostatic hypotension, nSH is defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, measured after at least 5 min of rest in the supine position. Three severity degrees are recommended: mild, moderate and severe. nSH may also be present during nocturnal sleep, with reduced-dipping, non-dipping or rising nocturnal BP profiles with respect to mean daytime BP values. Home BP monitoring and 24-h-ambulatory BP monitoring provide relevant information for a customized clinical management. CONCLUSIONS: The establishment of expert-based criteria to define nSH should standardize diagnosis and allow a better understanding of its epidemiology, prognosis and, ultimately, treatment.

Development and Validation of a Prognostic Model to Predict Overall Survival in Multiple System Atrophy.

Background: Multiple system atrophy (MSA) is a devastating disease characterized by a variable combination of motor and autonomic symptoms. Previous studies identified numerous clinical factors to be associated with shorter survival. Objective: To enable personalized patient counseling, we aimed at developing a risk model of survival based on baseline clinical symptoms. Methods: MSA patients referred to the Movement Disorders Unit in Innsbruck, Austria, between 1999 and 2016 were retrospectively analyzed. Kaplan-Meier curves and multivariate Cox regression analysis with least absolute shrinkage and selection operator penalty for variable selection were performed to identify prognostic factors. A nomogram was developed to estimate the 7 years overall survival probability. The performance of the predictive model was validated and calibrated internally using bootstrap resampling and externally using data from the prospective European MSA Study Group Natural History Study. Results: A total of 210 MSA patients were included in this analysis, of which 124 patients died. The median survival was 7 years. The following clinical variables were found to significantly affect overall survival and were included in the nomogram: age at symptom onset, falls within 3 years of onset, early autonomic failure including orthostatic hypotension and urogenital failure, and lacking levodopa response. The time-dependent area under curve for internal and external validation was >0.7 within the first 7 years of the disease course. The model was well calibrated showing good overlap between predicted and actual survival probability at 7 years. Conclusion: The nomogram is a simple tool to predict survival on an individual basis and may help to improve counseling and treatment of MSA patients.

Characterization of gait variability in multiple system atrophy and Parkinson's disease.

BACKGROUND: Gait impairment is a pivotal feature of parkinsonian syndromes and increased gait variability is associated with postural instability and a higher risk of falls. OBJECTIVES: We compared gait variability at different walking velocities between and within groups of patients with Parkinson-variant multiple system atrophy, idiopathic Parkinson's disease, and a control group of older adults. METHODS: Gait metrics were recorded in 11 multiple system atrophy, 12 Parkinson's disease patients, and 18 controls using sensor-based gait analysis. Gait variability was analyzed for stride, swing and stance time, stride length and gait velocity. Values were compared between and within the groups at self-paced comfortable, fast and slow walking speed. RESULTS: Multiple system atrophy patients displayed higher gait variability except for stride time at all velocities compared with controls, while Parkinson's patients did not. Compared with Parkinson's disease, multiple system atrophy patients displayed higher variability of swing time, stride length and gait velocity at comfortable speed and at slow speed for swing and stance time, stride length and gait velocity (all P < 0.05). Stride time variability was significantly higher in slow compared to comfortable walking in patients with multiple system atrophy (P = 0.014). Variability parameters significantly correlated with the postural instability/gait difficulty subscore in both disease groups. Conversely, significant correlations between variability parameters and MDS-UPDRS III score was observed only for multiple system atrophy patients. CONCLUSION: This analysis suggests that gait variability parameters reflect the major axial impairment and postural instability displayed by multiple system atrophy patients compared with Parkinson's disease patients and controls.

Association of transient orthostatic hypotension with falls and syncope in patients with Parkinson disease.

OBJECTIVES: To assess the frequency of transient orthostatic hypotension (tOH) and its clinical impact in Parkinson disease (PD), we retrospectively studied 173 patients with PD and 173 age- and sex-matched controls with orthostatic intolerance, who underwent cardiovascular autonomic function testing under continuous noninvasive blood pressure (BP) monitoring. METHODS: We screened for tOH (systolic BP fall ≥20 mm Hg or diastolic ≥10 mm Hg resolving within the first minute upon standing) and classic OH (cOH, sustained systolic BP fall ≥20 mm Hg or diastolic ≥10 mm Hg within 3 minutes upon standing). In patients with PD, we reviewed the medical records of the 6 months preceding and following autonomic testing for history of falls, syncope, and orthostatic intolerance. RESULTS: tOH occurred in 24% of patients with PD and 21% of controls, cOH in 19% of patients with PD and in none of the controls, independently of any clinical-demographic or PD-specific characteristic. Forty percent of patients with PD had a history of falls, in 29% of cases due to syncope. Patients with PD with history of orthostatic intolerance and syncope had a more severe systolic BP fall and lower diastolic BP rise upon standing, most pronounced in the first 30-60 seconds. CONCLUSIONS: tOH is an age-dependent phenomenon, which is at least as common as cOH in PD. Transient BP falls when changing to the upright position may be overlooked with bedside BP measurements, but contribute to orthostatic intolerance and syncope in PD. Continuous noninvasive BP monitoring upon standing may help identify a modifiable risk factor for syncope-related falls in parkinsonian patients.

Physiotherapy improves motor function in patients with the Parkinson variant of multiple system atrophy: A prospective trial.

BACKGROUND AND OBJECTIVES: Gait impairment and reduced mobility are disabling symptoms of multiple system atrophy. While physiotherapy is increasingly recognized as a valuable supplement to pharmacotherapy for patients with Parkinson's disease, data on the efficacy of physiotherapy for multiple system atrophy are lacking. This study aimed to explore the feasibility of two consecutive exercise-based interventions in patients with multiple system atrophy. SUBJECTS AND METHODS: We included 10 patients with the parkinsonian variant of multiple system atrophy and 10 patients with Parkinson's disease, matched for gender and Hoehn & Yahr stage (≤3). Interventions consisted of a five-day inpatient physiotherapy program followed by a five-week unsupervised home-based exercise program. Outcomes included instrumented gait analysis, patient questionnaires, clinical rating scales and physical tests. Patients were examined at baseline, after the first inpatient treatment and again after the home-based intervention. Additionally, a structured telephone interview was performed immediately after the second intervention period. RESULTS: Both patient groups exhibited a similar improvement of gait after the interventions, as measured by instrumented gait analysis. These effects reached their maximum level after inpatient physiotherapy and remained stable following the home-based exercise program. Patient questionnaires also showed improvements after the interventions, but motor clinical rating scales did not. CONCLUSION: Our pilot results suggest that a short-term bout of physiotherapy is feasible, safe and improves gait performance in patients with multiple system atrophy. This highlights the potential of physiotherapy for this disabling condition where pharmacotherapy typically achieves poor effects. The present findings warrant a larger controlled study.

Management of supine hypertension in patients with neurogenic orthostatic hypotension: scientific statement of the American Autonomic Society, European Federation of Autonomic Societies, and the European Society of Hypertension.

: Supine hypertension commonly occurs in patients with neurogenic orthostatic hypotension due to autonomic failure. Supine hypertension promotes nocturnal sodium excretion and orthostatic hypotension, thus, interfering with quality of life. Perusal of the literature on essential hypertension and smaller scale investigations in autonomic failure patients also suggest that supine hypertension may predispose to cardiovascular and renal disease. These reasons provide a rationale for treating supine hypertension. Yet, treatment of supine hypertension, be it through nonpharmacological or pharmacological approaches, may exacerbate orthostatic hypotension when patients get up during the night. Fall-related complications may occur. More research is needed to define the magnitude of the deleterious effects of supine hypertension on cardiovascular, cerebrovascular, and renal morbidity and mortality. Integration of more precise cardiovascular risk assessment, efficacy, and safety data, and the prognosis of the underlying condition causing autonomic failure is required for individualized management recommendations.

Sensor-based gait analysis in atypical parkinsonian disorders.

BACKGROUND AND OBJECTIVES: Gait impairment and reduced mobility are typical features of idiopathic Parkinson's disease (iPD) and atypical parkinsonian disorders (APD). Quantitative gait assessment may have value in the diagnostic workup of parkinsonian patients and as endpoint in clinical trials. The study aimed to identify quantitative gait parameter differences in iPD and APD patients using sensor-based gait analysis and to correlate gait parameters with clinical rating scales. SUBJECTS AND METHODS: Patients with iPD and APD including Parkinson variant multiple system atrophy and progressive supranuclear palsy matched for age, gender, and Hoehn and Yahr (≤3) were recruited at two Movement Disorder Units and assessed using standardized clinical rating scales (MDS-UPDRS-3, UMSARS, PSP-RS). Gait analysis consisted of inertial sensor units laterally attached to shoes, generating as objective targets spatiotemporal gait parameters from 4 × 10 m walk tests. RESULTS: Objective sensor-based gait analysis showed that gait speed and stride length were markedly reduced in APD compared to iPD patients. Moreover, clinical ratings significantly correlated with gait speed and stride length in APD patients. CONCLUSION: Our findings suggest that patients with APD had more severely impaired gait parameters than iPD patients despite similar disease severity. Instrumented gait analysis provides complementary rater independent, quantitative parameters that can be exploited for clinical trials and care.