Autonomic failure in neurodegenerative disorders

Area of Science:

• Neuroscience
• Autonomic Neurology
• Movement Disorders

Background:

• Autonomic failure, including orthostatic hypotension and dysfunction in bowel, bladder, and sexual function, is a common and disabling feature in Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).
• These Lewy body disorders share the presence of alpha-synuclein pathology in neurons or glia.
• Pure autonomic failure (PAF) is characterized by isolated severe autonomic failure, often presenting with disabling orthostatic hypotension, which can also be an initial symptom of MSA, complicating early diagnosis.

Purpose of the Study:

• To investigate the physiological underpinnings of autonomic dysfunction in neurodegenerative movement disorders.
• To highlight the diagnostic challenges and clinical differences between PD, MSA, and PAF.
• To explore previously unrecognized autonomic reflexes and their implications in patients with autonomic failure.

Main Methods:

• Clinical observation and characterization of patients with Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure.
• Assessment of autonomic responses to physiological stimuli such as meals and water intake.
• Evaluation of pressor effects of common medications (nasal decongestants) and the role of sympathetic tone in hypertension.

Main Results:

• Patients with autonomic failure exhibit profound hypotension after meals and unmasked sympathetic reflexes, such as blood pressure increase after water intake.
• Nasal decongestants can cause significant pressor effects in these individuals.
• Residual sympathetic tone contributes to sustained supine hypertension in MSA, which is abolished by ganglionic blockade, phenomena obscured by baroreflex buffering in healthy individuals.

Conclusions:

• Autonomic failure is a critical component of Lewy body disorders, presenting diagnostic challenges and impacting patient prognosis.
• Understanding these autonomic phenomena in patients with autonomic failure has revealed fundamental aspects of cardiovascular regulation previously unrecognized.
• While treatments for autonomic symptoms offer moderate efficacy, the management of associated movement disorders remains largely unsuccessful, underscoring the need for further research.