Approach to Cardiovascular Autonomic Dysfunction in Patients with Synucleinopathies

Autonomic dysfunction is a common feature of synucleinopathies such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and pure autonomic failure (PAF). Orthostatic hypotension (OH) and supine hypertension (SH) are hallmark manifestations of cardiovascular autonomic dysfunction that are increasingly recognized as contributors to long-term adverse clinical outcomes such as accelerated cognitive decline, motor symptom exacerbation, and end-organ damage. Several atypical presentations of OH, including coat-hanger pain, cognitive fluctuation, postural instability, fatigue, exertional dyspnea, and falls, commonly overlap with motor and non-motor features of synucleinopathies. This clinical overlap highlights the need for heightened awareness of the diverse and often subtle manifestations of OH in affected individuals. Although the general management of OH has been addressed in prior literature, a dedicated framework tailored to the pathophysiological and clinical nuances specific to synucleinopathies remains lacking. SH, despite its high prevalence and significant prognostic implications, has received minimal attention in existing reviews and is often overlooked in clinical practice. Given the growing recognition of cardiovascular autonomic dysfunction as a potentially modifiable contributor to disease progression and patient quality of life, a focused updated review is warranted to inform clinical decision-making and guide future research in this evolving area. This narrative review comprehensively discusses the approach to OH and SH in the context of synucleinopathies. The key topics addressed are the pathophysiology of OH and SH in synucleinopathies, diagnostic criteria and types of OH, diagnostic criteria of SH, and management strategies (non-pharmacological, pharmacological, and novel/experimental).