Autonomic Dysfunction in α-Synucleinopathies

Abstract

The α-synucleinopathies are a group of neurodegenerative diseases characterized by abnormal accumulation of insoluble α-synuclein in neurons and glial cells, comprising Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Although varying in prevalence, symptom patterns, and severity among disorders, all α-synucleinopathies have in common autonomic nervous system dysfunctions, which reduce quality of life. Frequent symptoms among α-synucleinopathies include constipation, urinary and sexual dysfunction, and cardiovascular autonomic symptoms such as orthostatic hypotension, supine hypertension, and reduced heart rate variability. Symptoms due to autonomic dysfunction can appear before motor symptom onset, particularly in MSA and PD, hence, detection and quantitative analysis of these symptoms can enable early diagnosis and initiation of treatment, as well as identification of at-risk populations. While patients with PD, DLB, and MSA show both central and peripheral nervous system involvement of α-synuclein pathology, pure autonomic failure (PAF) is a condition characterized by generalized dysregulation of the autonomic nervous system with neuronal cytoplasmic α-synuclein inclusions in the peripheral autonomic small nerve fibers. Patients with PAF often present with orthostatic hypotension, reduced heart rate variability, anhydrosis, erectile dysfunction, and constipation, without motor or cognitive impairment. These patients also have an increased risk of developing an α-synucleinopathy with central involvement, such as PD, DLB, or MSA in later life, possibly indicating a pathophysiological disease continuum. Pathophysiological aspects, as well as developments in diagnosing and treating dysautonomic symptoms in patients with α-synucleinopathies are discussed in this review.

Obstructive Sleep Apnea in Neurodegenerative Disorders: Current Evidence in Support of Benefit from Sleep Apnea Treatment

“…However, treatment with dopaminergic agonists also influences sympathetic tone [160,161]. Conversely, dysregulation of the autonomic nervous system (ANS) is also found in OSA, as well as in neurodegenerative diseases [162]. Increase in sympathetic tone associated with baroreflex and chemoreflex changes has been observed in OSA and often persists beyond the sleep period [163,164].…”

Deep Brain Stimulation in Non-motor Symptoms of Neurodegenerative Diseases

“…Autonomic dysfunction develops as a consequence of progressive degeneration in neural pathways, mostly in diseases characterized by the accumulation of Lewy bodies or α-synuclein, and is much less pronounced in diseases such as Alzheimer's or frontotemporal lobar degeneration [43]. Three main symptoms of autonomic dysfunction are issues with bladder control, nocturia, and sexual dysfunction, all of which are linked to the dysfunction in the dopamine pathways and can somewhat improve with dopaminergic therapy [44].…”

“…Generally, there is a lack of extensive studies featuring a high number of patients, and studying the effects of DBS on autonomic dysfunction is usually not the main focus. Dysautonomia is more frequently found in movement disorders than other diseases in the neurodegeneration disease spectrum [43]. Early studies that focus on STN and GPi stimulation reveal that DBS has a beneficial effect on urinary symptoms, especially in reducing nocturia, frequency, and urgency [64].…”

Occurrence of internal diseases in the premotor phase of Parkinson’s disease by analyzing a large database covering a whole population

“…A szívbetegségek PK-ral összefüggő patomechanizmusában legjelentősebb faktor az autonóm diszfunkció. Több vizsgálat is alátámasztja, hogy a kardiovaszkuláris diszfunkció már a mozgászavar megjelenése és a PK diagnózisának felállítása előtt kialakul (26,27), melyet a perifériás noradrenerg innerváció csökkenésével magyaráznak. A kardiovaszkuláris autonóm diszfunkció részeként PK-ra elsősorban az orthostaticus hypotensio a jellemző (27), de a fekvő helyzetben jelentkező hypertensióval is találtak összefüggést (28,29).…”

“…Több vizsgálat is alátámasztja, hogy a kardiovaszkuláris diszfunkció már a mozgászavar megjelenése és a PK diagnózisának felállítása előtt kialakul (26,27), melyet a perifériás noradrenerg innerváció csökkenésével magyaráznak. A kardiovaszkuláris autonóm diszfunkció részeként PK-ra elsősorban az orthostaticus hypotensio a jellemző (27), de a fekvő helyzetben jelentkező hypertensióval is találtak összefüggést (28,29). Néhány epidemiológiai tanulmány azt találta, hogy a hypertonia (30) és az ischaemiás szívbetegség (31,32) fokozott PK megjelenést eredményeznek, előbbinél arra született evidencia, hogy PK kockázata 60%-kal nagyobb a kezeletlen, ellenőrizetlen magas vérnyomású nők körében.…”