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Neurobiology of Disease Feb 2020Parkinson's disease (PD) is a neurodegenerative disease with a 200 year-long research history. Our understanding about its clinical phenotype and pathogenesis remains... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disease with a 200 year-long research history. Our understanding about its clinical phenotype and pathogenesis remains limited, although dopaminergic replacement therapy has significantly improved patient outcomes. Autonomic dysfunction is an essential category of non-motor phenotypes that has recently become a cutting edge field that directs frontier research in PD. In this review, we initially describe the epidemiology of dysautonomic symptoms in PD. Then, we perform a meticulous analysis of the pathophysiology of autonomic dysfunction in PD and propose that the peripheral autonomic nervous system may be a key route for α-synuclein pathology propagation from the periphery to the central nervous system. In addition, we recommend that constipation, orthostatic hypotension, urinary dysfunction, erectile dysfunction, and pure autonomic failure should be viewed as prodromal dysautonomic markers in PD prediction and diagnosis. Finally, we summarize the strategies currently available for the treatment of autonomic dysfunction in PD and suggest that high-quality, better-designed, randomized clinical trials should be conducted in the future.
Topics: Animals; Autonomic Nervous System; Autonomic Nervous System Diseases; Humans; Mice; Parkinson Disease
PubMed: 31809788
DOI: 10.1016/j.nbd.2019.104700 -
Muscle & Nerve Jan 2021Autonomic neuropathies represent a complex group of disorders that preferentially target autonomic fibers and can be classified as either acute/subacute or chronic in... (Review)
Review
Autonomic neuropathies represent a complex group of disorders that preferentially target autonomic fibers and can be classified as either acute/subacute or chronic in onset. Acute-onset autonomic neuropathies manifest with such conditions as paraneoplastic syndromes, Guillain-Barre syndrome, Sjögren syndrome, infection, or toxins/chemotherapy. When the presentation is acute, immune-mediated, and without a secondary cause, autoimmune autonomic ganglionopathy is likely, and should be considered for immunotherapy. Of the chronic-onset forms, diabetes is the most widespread and disabling, with autonomic impairment portending increased mortality and cardiac wall remodeling risk. Acquired light chain (AL) and transthyretin (TTR) amyloidosis represent two other key etiologies, with TTR amyloidosis now amenable to newly-approved gene-modifying therapies. The COMPASS-31 questionnaire is a validated outcome measure that can be used to monitor autonomic severity and track treatment response. Symptomatic treatments targeting orthostatic hypotension, among other symptoms, should be individualized and complement disease-modifying therapy, when possible.
Topics: Amyloid Neuropathies, Familial; Autoimmune Diseases of the Nervous System; Autonomic Nervous System; Autonomic Nervous System Diseases; Humans; Peripheral Nervous System Diseases; Prealbumin
PubMed: 32926436
DOI: 10.1002/mus.27048 -
Journal of the American College of... Mar 2019Autonomic nervous system control of the heart is a dynamic process in both health and disease. A multilevel neural network is responsible for control of chronotropy,... (Review)
Review
Autonomic nervous system control of the heart is a dynamic process in both health and disease. A multilevel neural network is responsible for control of chronotropy, lusitropy, dromotropy, and inotropy. Intrinsic autonomic dysfunction arises from diseases that directly affect the autonomic nerves, such as diabetes mellitus and the syndromes of primary autonomic failure. Extrinsic autonomic dysfunction reflects the changes in autonomic function that are secondarily induced by cardiac or other disease. An array of tests interrogate various aspects of cardiac autonomic control in either resting conditions or with physiological perturbations from resting conditions. The prognostic significance of these assessments have been well established. Clinical usefulness has not been established, and the precise mechanistic link to mortality is less well established. Further efforts are required to develop optimal approaches to delineate cardiac autonomic dysfunction and its adverse effects to develop tools that can be used to guide clinical decision-making.
Topics: Autonomic Nervous System; Autonomic Nervous System Diseases; Heart; Heart Diseases; Heart Rate; Humans; Myocardial Contraction
PubMed: 30871703
DOI: 10.1016/j.jacc.2018.12.064 -
The Lancet. Neurology Sep 2017A substantial minority of patients who survive an acquired brain injury develop a state of sympathetic hyperactivity that can persist for weeks or months, consisting of... (Review)
Review
A substantial minority of patients who survive an acquired brain injury develop a state of sympathetic hyperactivity that can persist for weeks or months, consisting of periodic episodes of increased heart rate and blood pressure, sweating, hyperthermia, and motor posturing, often in response to external stimuli. The unifying term for the syndrome-paroxysmal sympathetic hyperactivity (PSH)-and clear diagnostic criteria defined by expert consensus were only recently established. PSH has predominantly been described after traumatic brain injury (TBI), in which it is associated with worse outcomes. The pathophysiology of the condition is not completely understood, although most researchers consider it to be a disconnection syndrome with paroxysms driven by a loss of inhibitory control over excitatory autonomic centres. Although therapeutic strategies to alleviate sympathetic outbursts have been proposed, their effects on PSH are inconsistent between patients and their influence on outcome is unknown. Combinations of drugs are frequently used and are chosen on the basis of local custom, rather than on objective evidence. New rigorous tools for diagnosis could allow better characterisation of PSH to enable stratification of patients for future therapeutic trials.
Topics: Autonomic Nervous System Diseases; Brain Injuries; Humans; Sympathetic Nervous System
PubMed: 28816118
DOI: 10.1016/S1474-4422(17)30259-4 -
Methodist DeBakey Cardiovascular Journal 2018Cardiovascular autonomic neuropathy (CAN) is a severely debilitating yet underdiagnosed condition in patients with diabetes. The prevalence can range from 2.5% (based on... (Review)
Review
Cardiovascular autonomic neuropathy (CAN) is a severely debilitating yet underdiagnosed condition in patients with diabetes. The prevalence can range from 2.5% (based on the primary prevention cohort in the Diabetes Control and Complications Trial) to as high as 90% of patients with type 1 diabetes. Clinical manifestations range from orthostasis to myocardial infarction. The diagnosis is made using multiple autonomic function tests to assess both sympathetic and parasympathetic function. The pathophysiology of CAN is complex, likely multifactorial, and not completely understood. Treatment is limited to symptomatic control of orthostatic hypotension, which is a late complication, and current strategies to reverse CAN are limited. This review explores the epidemiology, pathophysiology, clinical manifestations, diagnosis, and complications of CAN as well as current treatment options.
Topics: Autonomic Nervous System; Autonomic Nervous System Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Heart; Humans; Predictive Value of Tests; Risk Factors; Treatment Outcome
PubMed: 30788010
DOI: 10.14797/mdcj-14-4-251 -
Movement Disorders : Official Journal... Mar 2018Dysfunction of the autonomic nervous system afflicts most patients with Parkinson disease and other synucleinopathies such as dementia with Lewy bodies, multiple system... (Review)
Review
Dysfunction of the autonomic nervous system afflicts most patients with Parkinson disease and other synucleinopathies such as dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure, reducing quality of life and increasing mortality. For example, gastrointestinal dysfunction can lead to impaired drug pharmacodynamics causing a worsening in motor symptoms, and neurogenic orthostatic hypotension can cause syncope, falls, and fractures. When recognized, autonomic problems can be treated, sometimes successfully. Discontinuation of potentially causative/aggravating drugs, patient education, and nonpharmacological approaches are useful and should be tried first. Pathophysiology-based pharmacological treatments that have shown efficacy in controlled trials of patients with synucleinopathies have been approved in many countries and are key to an effective management. Here, we review the treatment of autonomic dysfunction in patients with Parkinson disease and other synucleinopathies, summarize the nonpharmacological and current pharmacological therapeutic strategies including recently approved drugs, and provide practical advice and management algorithms for clinicians, with focus on neurogenic orthostatic hypotension, supine hypertension, dysphagia, sialorrhea, gastroparesis, constipation, neurogenic overactive bladder, underactive bladder, and sexual dysfunction. © 2018 International Parkinson and Movement Disorder Society.
Topics: Autonomic Nervous System Diseases; Humans; Parkinson Disease; Synucleins
PubMed: 29508455
DOI: 10.1002/mds.27344 -
Journal of the American College of... Sep 2018Neurogenic orthostatic hypotension is a highly prevalent and disabling feature of autonomic failure due to both peripheral and central neurodegenerative diseases.... (Review)
Review
Neurogenic orthostatic hypotension is a highly prevalent and disabling feature of autonomic failure due to both peripheral and central neurodegenerative diseases. Community-based epidemiological studies have demonstrated a high morbidity and mortality associated with neurogenic orthostatic hypotension. It is due to impairment of baroreflex-mediated vasoconstriction of the skeletal muscle and splanchnic circulation and is caused by damage or dysfunction at central and/or peripheral sites in the baroreflex efferent pathway. Nonpharmacological and pharmacological interventions may be implemented to ameliorate the symptoms of orthostatic intolerance and improve quality of life. Many patients will be adequately treated by education, counseling, removal of hypotensive medications, and other nonpharmacological interventions, whereas more severely afflicted patients require pharmacological interventions. The first stage of pharmacological treatment involves repletion of central blood volume. If unsuccessful, this should be followed by treatment with sympathomimetic agents.
Topics: Algorithms; Autonomic Nervous System Diseases; Baroreflex; Blood Volume; Humans; Hypotension, Orthostatic; Lewy Body Disease; Multiple System Atrophy; Parkinson Disease; Patient Education as Topic; Pure Autonomic Failure; Vasoconstriction
PubMed: 30190008
DOI: 10.1016/j.jacc.2018.05.079 -
Neurotherapeutics : the Journal of the... Oct 2020Recognition of the importance of nonmotor dysfunction as a component of Parkinson's disease has exploded over the past three decades. Autonomic dysfunction is a frequent... (Review)
Review
Recognition of the importance of nonmotor dysfunction as a component of Parkinson's disease has exploded over the past three decades. Autonomic dysfunction is a frequent and particularly important nonmotor feature because of the broad clinical spectrum it covers. Cardiovascular, gastrointestinal, urinary, sexual, and thermoregulatory abnormalities all can appear in the setting of Parkinson's disease. Cardiovascular dysfunction is characterized most prominently by orthostatic hypotension. Gastrointestinal dysfunction can involve virtually all levels of the gastrointestinal tract. Urinary dysfunction can entail either too frequent voiding or difficulty voiding. Sexual dysfunction is frequent and frustrating for both patient and partner. Alterations in sweating and body temperature are not widely recognized but often are present. Autonomic dysfunction can significantly and deleteriously impact quality of life for individuals with Parkinson's disease. Because effective treatment for many aspects of autonomic dysfunction is available, it is vitally important that assessment of autonomic dysfunction be a regular component of the neurologic history and exam and that appropriate treatment be initiated and maintained.
Topics: Autonomic Nervous System Diseases; Cardiovascular Diseases; Gastrointestinal Diseases; Humans; Hypotension, Orthostatic; Parkinson Disease; Sexual Dysfunction, Physiological
PubMed: 32789741
DOI: 10.1007/s13311-020-00897-4 -
Chest Aug 2017Insomnia is the most prevalent sleep disorder in the United States and has high comorbidity with a number of cardiovascular diseases (CVDs). In the past decade, a number... (Review)
Review
Insomnia is the most prevalent sleep disorder in the United States and has high comorbidity with a number of cardiovascular diseases (CVDs). In the past decade, a number of observational studies have demonstrated an association between insomnia and incident cardiovascular disease (CVD) morbidity and mortality, including hypertension (HTN), coronary heart disease (CHD), and heart failure (HF). Despite some inconsistencies in the literature, likely due to variations in how insomnia is defined and measured, the existing data suggest that insomnia, especially when accompanied by short sleep duration, is associated with increased risk for HTN, CHD and recurrent acute coronary syndrome, and HF. Purported mechanisms likely relate to dysregulation of the hypothalamic-pituitary axis, increased sympathetic nervous system activity, and increased inflammation. This paper reviews the most recent studies of insomnia and CVD and the potential pathophysiological mechanisms underlying this relationship and highlights the need for randomized trials to further elucidate the nature of the relationship between insomnia and CVD.
Topics: Autonomic Nervous System Diseases; C-Reactive Protein; Cardiovascular Diseases; Coronary Disease; Heart Failure; Humans; Hypertension; Hypothalamo-Hypophyseal System; Observational Studies as Topic; Pituitary-Adrenal System; Risk Factors; Sleep Initiation and Maintenance Disorders
PubMed: 28153671
DOI: 10.1016/j.chest.2017.01.026 -
Journal of Internal Medicine Apr 2019Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular autonomic disorder characterized by an excessive heart rate increase on standing and... (Review)
Review
Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular autonomic disorder characterized by an excessive heart rate increase on standing and orthostatic intolerance. POTS affects younger individuals 15-45 years old with a distinct female predominance (≈80%). The prevalence ranges between 0.2% and 1.0% in developed countries. The onset of POTS is typically precipitated by immunological stressors such as viral infection, vaccination, trauma, pregnancy, surgery or psychosocial stress. The most common complaints are dizziness, weakness, rapid heartbeat and palpitation on standing. Moreover, patients often report physical deconditioning and reduced exercise capacity as well as headache, 'brain fog', dyspnoea, gastrointestinal disorders and musculoskeletal pain. The aetiology of POTS is largely unknown and three main hypotheses include an autoimmune disorder, abnormally increased sympathetic activity and catecholamine excess, and sympathetic denervation leading to central hypovolaemia and reflex tachycardia. The golden standard for POTS diagnosis is head-up tilt test with a non-invasive beat-to-beat haemodynamic monitoring. Although long-term prognosis of POTS is poorly explored, around 50% of patients spontaneously recover within 1-3 years. After the diagnosis has been established, patient should be thoroughly educated about non-pharmacological measures alleviating the symptoms. Exercise training may be very effective and counteract deconditioning. In more symptomatic patients, different drugs directed at controlling heart rate, increasing peripheral vasoconstriction and intravascular volume can be tested. However, the overall effects of pharmacological therapy are modest and the most affected patients remain handicapped. Future efforts should focus on better understanding of POTS pathophysiology and designing randomized controlled trials for selection of more effective therapy.
Topics: Cardiovascular System; Humans; Postural Orthostatic Tachycardia Syndrome
PubMed: 30372565
DOI: 10.1111/joim.12852