Autonomic Dysfunction in Parkinson's Disease.
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ABSTRACT:
SUBMITTER: Pfeiffer RF
PROVIDER: S-EPMC7851208 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAutonomic dysfunction is common in the later stages of Parkinson's disease (PD), but less is known about its presence and severity in early disease.ObjectiveTo analyze features of autonomic dysfunction in recent onset PD cases, and their relationship to motor severity, medication use, other nonmotor symptoms (NMS), and quality-of-life scores.MethodsDetailed patient-reported symptoms of autonomic dysfunction were assessed in a multicenter cohort study in PD cases that had been diagnosed within the preceding 3.5 years.ResultsThere were 1746 patients (1132 males, 65.2%), mean age 67.6 years (SD 9.3), mean disease duration 1.3 years (SD 0.9), mean Movement Disorder Society Unified Parkinson's Disease Rating Scale motor score 22.5 (SD 12.1). Orthostatic symptoms were reported by 39.6%, male erectile dysfunction by 56.1%, and female anorgasmia by 57.4%. Sialorrhea was an issue in 51.4% of patients, constipation in 43.6%, and dysphagia in 20.1%. Autonomic features increased with higher modified Hoehn and Yahr stages (P < 0.001). The severity of autonomic dysfunction was associated with the postural instability gait difficulty motor phenotype [?-coefficient 1.7, 95% confidence interval (CI) 0.7, 2.6, P < 0.001], depression (?-coefficient 4.1, CI 3.0, 5.2, P < 0.001), and excess daytime sleepiness (?-coefficient 3.1, CI 1.9, 4.2, P < 0.001). Dopamine agonists were the only drug class associated with greater autonomic dysfunction (P = 0.019). The severity of autonomic dysfunction strongly correlated with the presence of other NMS (? = 0.717, P < 0.001), and with poorer quality-of-life scores (? = 0.483, P < 0.001).ConclusionsAutonomic dysfunction is common in early PD. Autonomic dysfunction correlates with the presence of other NMS, and with worse quality of life.
| S-EPMC6174464 | biostudies-literature
Project description:Autonomic dysfunction (AutD) is one of the non-motor symptoms (NMSs) in Parkinson's disease (PD). To investigate the prevalence and clinical features of AutD in Chinese patients with PD, a large multicenter cohort of 2,556 individuals with PD were consecutively involved in the Parkinson's Disease and Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) between January 1, 2017, and December 31, 2019. The assessment of AutD was performed using the Scale for Outcomes in Parkinson's Disease for Autonomic Symptoms (SCOPA-AUT). The evaluation of motor symptoms and other NMSs were performed using well-established scales recommended by the Movement Disorder Society. We found that out of 2,556 patients with PD, 2,333 patients with PD (91.28%) had AutD. Compared with the group of patients with PD without AutD, the group of patients with PD with AutD had older age, older age of onset, longer disease duration, more severe motor symptoms, motor complications, and more frequent NMSs. As for partial correlation analysis, the total SCOPA-AUT score was significantly and positively associated with motor severity scales [Unified Parkinson's Disease Rating Scale (UPDRS) total score] and some of the NMSs [Rapid Eye Movement Sleep Behavior Disorder Questionnaire (RBD), Epworth Sleepiness Scale, Hamilton Depression Scale], Fatigue Severity Scale, and Parkinson's disease questionnaire. PD Sleep Scale was significantly and negatively correlated with AutD. With logistic regression analysis for potentially related factors, age, UPDRS total score, RBD, hyposmia, depression, and fatigue may be associated with PD with AutD. In conclusion, our multicenter cohort study reported the high prevalence of AutD in Chinese PD and revealed the associated factors of PD with AutD.
| S-EPMC8670376 | biostudies-literature
Project description:BackgroundAutonomic dysfunction (AD) is one of the non-motor features of Parkinson's disease (PD). Some symptoms tend to occur in the early stages of PD. AD also has a great impact on patient's quality of life. In this study, we aimed to discover the association between AD (Scales for Outcomes in Parkinson's disease-Autonomic, SCOPA-AUT) and microstructural changes in white matter tracts in drug-naïve early PD patients to elucidate the central effects of autonomic nervous system impairments.MethodIn total, this study included 85 subjects with PD recruited from the Parkinson's Progression Markers Initiative (PPMI) database. Among the 85 PD patients, 38 were in Hoehn & Yahr stage 1 (HY1PD) and 47 were in stage 2 (HY2PD). Diffusion magnetic resonance imaging (DMRI) data were reconstructed in the MNI space using q-space diffeomorphic reconstruction to obtain the spin distribution function. The spin distribution function (SDF) values were used in DMRI connectometry analysis. We investigated through diffusion MRI connectometry the structural correlates of white matter tracts with SCOPA-AUT subscores and total score.ResultsConnectometry analysis also revealed positive association with white matter density in bilateral corticospinal tract in HY1PD patients and negative association in genu of corpus callosum (CC) and, bilateral cingulum in both groups. In addition, there were associations between gastrointestinal, sexual, thermoregulatory and urinary items and structural brain connectivity in PD.ConclusionOur study reveals positive correlation, suggesting neural compensations in early PD. Cingulum and CC tracts have well-known roles in PD pathology, compatible with our findings that bring new insights to specific areas of AD and its role in central nervous system (CNS) neurodegeneration, paving the way for using prodromal makers in the diagnosis and treatment of PD.
| S-EPMC6139241 | biostudies-literature
Project description:Introduction: Autonomic dysfunction is a common and disabling non-motor symptom of Parkinson's disease (PD). We aimed to understand autonomic dysfunction in PD motor subtypes, the pattern of sympathetic skin response (SSR) to motor asymmetry, and the association of SSR with autonomic and motor dysfunctions. Methods: A total of 101 PD patients of Han Chinese were included. Unified PD rating scale (UPDRS), scales for outcomes in PD-autonomic symptoms (SCOPA-AUT), orthostatic hypotension, and SSR were evaluated. Results: SCOPA-AUT and incidences of orthostatic hypotension and absent SSR were worse in the subtype of postural instability gait disorder (PIGD) than the subtypes of tremor dominant and intermediate. SSR latency and amplitude were asymmetrical corresponding to the accentuation of motor severity. Patients with absent SSR had worse UPDRS and SCOPA-AUT scores. SSR parameters of the severe side in patients with SSR showed no independent association with the scores. Conclusion: Our results support that autonomic dysfunction is more severe in the PIGD than other subtypes and demonstrate an asymmetry of SSR in PD patients. Absent SSR may indicate worse autonomic and motor symptoms, but SSR parameters are not sufficient to evaluate the severity of the dysfunctions.
| S-EPMC7669620 | biostudies-literature
Project description:Cardiovascular autonomic dysfunctions (CAD) are prevalent in Parkinson's disease (PD). It contributes to the development of cognitive dysfunction, falls and even mortality. Significant progress has been achieved in the last decade. However, the underlying mechanisms and effective treatments for CAD have not been established yet. This review aims to help clinicians to better understand the pathogenesis and therapeutic strategies. The literatures about CAD in patients with PD were reviewed. References for this review were identified by searches of PubMed between 1972 and March 2021, with the search term "cardiovascular autonomic dysfunctions, postural hypotension, orthostatic hypotension (OH), supine hypertension (SH), postprandial hypotension, and nondipping". The pathogenesis, including the neurogenic and non-neurogenic mechanisms, and the current pharmaceutical and non-pharmaceutical treatment for CAD, were analyzed. CAD mainly includes four aspects, which are OH, SH, postprandial hypotension and nondipping, among them, OH is the main component. Both non-neurogenic and neurogenic mechanisms are involved in CAD. Failure of the baroreflex circulate, which includes the lesions at the afferent, efferent or central components, is an important pathogenesis of CAD. Both non-pharmacological and pharmacological treatment alleviate CAD-related symptoms by acting on the baroreflex reflex circulate. However, pharmacological strategy has the limitation of failing to enhance baroreflex sensitivity and life quality. Novel OH treatment drugs, such as pyridostigmine and atomoxetine, can effectively improve OH-related symptoms via enhancing residual sympathetic tone, without adverse reactions of supine hypertension. Baroreflex impairment is a crucial pathological mechanism associated with CAD in PD. Currently, non-pharmacological strategy was the preferred option for its advantage of enhancing baroreflex sensitivity. Pharmacological treatment is a second-line option. Therefore, to find drugs that can enhance baroreflex sensitivity, especially via acting on its central components, is urgently needed in the scientific research and clinical practice.
| S-EPMC8460297 | biostudies-literature
Project description:Cardiovascular autonomic dysfunctions, including neurogenic orthostatic hypotension, supine hypertension and post-prandial hypotension, are relatively common in patients with Parkinson disease. Recent evidence suggests that early autonomic impairment such as cardiac autonomic denervation and even neurogenic orthostatic hypotension occur prior to the appearance of the typical motor deficits associated with the disease. When neurogenic orthostatic hypotension develops, patients with Parkinson disease have an increased risk of mortality, falls, and trauma-related to falls. Neurogenic orthostatic hypotension reduces quality of life and contributes to cognitive decline and physical deconditioning. The co-existence of supine hypertension complicates the treatment of neurogenic orthostatic hypotension because it involves the use of drugs with opposing effects. Furthermore, treatment of neurogenic orthostatic hypotension is challenging because of few therapeutic options; in the past 20 years, the US Food and Drug Administration approved only two drugs for the treatment of this condition. Small, open-label or randomized studies using acute doses of different pharmacologic probes suggest benefit of other drugs as well, which could be used in individual patients under close monitoring. This review describes the pathophysiology of neurogenic orthostatic hypotension and supine hypertension in Parkinson disease. We discuss the mode of action and therapeutic efficacy of different pharmacologic agents used in the treatment of patients with cardiovascular autonomic failure.
| S-EPMC5809001 | biostudies-literature
Project description: Not available
| S-EPMC7396847 | biostudies-literature
Project description:Fatigue is a disabling non-motor symptom in Parkinson disease (PD). We investigated the relationship between autonomic dysfunction and fatigue in PD while accounting for possible confounding factors.29 subjects with PD (8F/21M; mean age 61.6±5.9; mean disease duration 4.8±3.0years), underwent clinical assessment and completed several non-motor symptom questionnaires, including a modified version of the Mayo Clinic Composite Autonomic Symptom Score (COMPASS) scale and the Fatigue Severity Scale (FSS).The mean modified COMPASS was 21.6±14.2 (range 1.7-44.2) and the mean FSS score was 3.3±1.6 (range 1.0-6.7). There was a significant bivariate relationship between the modified COMPASS and FSS scores (R=0.69, P<0.0001). Stepwise regression analysis was used to assess the specificity of the association between the modified COMPASS and FSS scores while accounting for possible confounder effects from other variables that were significantly associated with autonomic dysfunction. Results showed that the modified COMPASS (R2=0.52, F=28.4, P<0.0001) was highly associated with fatigue, followed by ESS (R2=0.13, F=8.4, P=0.008) but no other co-variates. Post-hoc analysis exploring the association between the different modified COMPASS autonomic sub-domain scores and FSS scores found significant regressor effects for the orthostatic intolerance (R2=0.45, F=21.2, P<0.0001) and secretomotor sub-domains (R2=0.09, F=4.8, P=0.04) but not for other autonomic sub-domains.Autonomic dysfunction, in particular orthostatic intolerance, is highly associated with fatigue in PD.
| S-EPMC5536106 | biostudies-literature
Project description:INTRODUCTION:Autonomic disorders have been recognized as important Parkinson's disease (PD) components. Some vulnerable structures are related to the central autonomic network and have also been linked to autonomic function alterations. The aims of the study are to evaluate the severity of the autonomic dysfunction and the cortical hypoperfusion using arterial spin labeling (ASL) MRI. And then, possible relationships of significant between-group differences in perfusion pattern to clinical variables and autonomic functions were examined to determine the pharmaceutical effects of dopaminergic treatment on cerebral blood flow (CBF) in patients with PD. METHODS:Brain ASL MRI was carried out in 20 patients with PD (6 men and 14 women, mean age: 63.3?±?6.4?years) and 22 sex- and age-matched healthy volunteers to assess whole-brain CBF and the effects of dopaminergic therapy on perfusion. All subjects underwent a standardized evaluation of cardiovagal and adrenergic function including a deep breathing, Valsalva maneuver, and 5-min head-up tilt test. Perfusion MRI data were acquired on a 3.0?T scanner with a pulsed continuous ASL technique. The CBF, autonomic parameters, and clinical data were analyzed after adjusting for age and sex. RESULTS:Patients exhibited a decline in autonomic function (rapid heart rate in response to deep breathing, low baroreflex sensitivity, high systolic and diastolic pressure, and altered tilting test response), widespread low CBF, and robust response to dopaminergic therapy. Lower perfusion in the middle frontal gyrus was associated with increased clinical disease severity (Unified Parkinson's Disease Rating Scale I score, P?<?0.001). Lower perfusion in autonomic control areas, such as the frontal lobe and insula, were significantly associated with autonomic impairment (P?<?0.001). CONCLUSIONS:Our study indicates that PD is a progressive neurodegenerative disorder that changes the perfusion of central nervous system and is associated with variable autonomic dysfunctions. Neuronal loss and sympathetic activation may explain the interaction between cortical autonomic region perfusion and cardiovascular autonomic function.
| S-EPMC5462903 | biostudies-literature
Project description:Importance:Evidence suggests that development of autonomic dysfunction (AutD) may negatively affect disease course and survival in patients with synucleinopathies. However, the few available studies on Parkinson disease (PD) have conflicting results, comprise a small number of patients, have short follow-up periods, and lack pathologic confirmation of the diagnosis. Objective:To examine the association of time of onset of AutD with disease progression and survival in PD. Design, Setting, and Participants:This retrospective review of clinical data from 100 consecutive patients with an autopsy-confirmed diagnosis of PD from the archives of the Queen Square Brain Bank in London, United Kingdom, from January 1, 2006, to June 3, 2016, included patients with PD regularly seen by hospital specialists (neurologists or geriatricians) in the United Kingdom throughout their disease until death. Patients with dementia before or within 1 year after onset of motor symptoms, monogenic forms of PD, comorbidities that affect autonomic function, a coexisting neuropathologic diagnosis, or insufficient clinical information were excluded. Main Outcomes and Measures:Survival and time from diagnosis to specific disease milestones were calculated to assess disease progression. Autonomic dysfunction was defined as autonomic failure at autonomic function testing or 2 of the following symptoms: urinary symptoms, constipation, upper gastrointestinal tract dysfunction, orthostatic hypotension, sweating abnormalities, or erectile dysfunction. Multivariable Cox proportional hazards regression models on the risk of a disease milestone and death were used. Results:A total of 100 patients (60 [60.0%] male; mean [SD] age at diagnosis, 63.9?[10.3] years; mean [SD] disease duration, 14.6?[7.7] years) were studied. Autonomic dysfunction developed in 85 patients (mean [SD] time from diagnosis, 6.7?[7.7] years) and was associated with older age at diagnosis, male sex, poor initial levodopa treatment response, and postural instability and gait difficulty motor PD subtype in linear regression analysis, but staging of ?-synuclein pathologic changes was unrelated. Earlier AutD increased the risk of reaching the first milestone (hazard ratio, 0.86; 95% CI, 0.83-0.89; P?<?.001) and shortened survival (hazard ratio, 0.92; 95% CI, 0.88-0.96; P?<?.001). Older age at diagnosis and poorer levodopa treatment response were the other factors associated with shorter survival in adjusted multivariate analysis. Conclusions and Relevance:Earlier AutD is associated with a more rapid development of disease milestones and shorter survival in patients with PD.
| S-EPMC5710320 | biostudies-literature