Article type: Narrative Review
Article title: Intersection of Autonomic Dysfunction and Parkinson’s Disease: Insights Into Neurogenic and Classical Orthostatic Hypotension
Journal: Cureus
Year: 2025
Authors: Jamir Pitton Rissardo, Masoumeh Rashidi, Fatemeh Rashidi, Khalil I. Hmedat, Ibrahim Khalil, Hania Moharam, Mallak Bahar, Ali Dway, Omesh Prathiraja, Ana Leticia Fornari Caprara, Maleesha Jayasinghe
E-mail: jamirrissardo@gmail.com
ABSTRACT
Neurogenic orthostatic hypotension (nOH) and classical orthostatic hypotension (OH) are prevalent non-motor manifestations of Parkinson’s disease (PD). They can significantly impact quality of life, increasing the risk of falls, cognitive decline, and functional impairment. Despite the high prevalence and clinical impact of neurogenic orthostatic hypotension and OH in PD, no comprehensive consensus integrates recent advances in pathophysiology, diagnostic tools, and personalized treatment. This review synthesizes current evidence to bridge this gap, offering a practical framework for clinicians to improve patient outcomes. Neurogenic orthostatic hypotension in PD results from complex interactions between central and peripheral autonomic dysfunction, alpha-synuclein accumulation, baroreflex failure, and medication effects. Its prevalence increases with disease progression and age. Clinical evaluation remains the cornerstone of diagnosis, supported by specialized testing such as the active standing test, ambulatory blood pressure monitoring, and autonomic function assessments. Management requires a tailored approach, combining non-pharmacologic strategies, such as fluid and salt intake optimization, compression garments, and physical counter-maneuvers, with pharmacological treatments, including midodrine, droxidopa, and fludrocortisone. Emerging therapies and ongoing clinical trials offer promising avenues for future interventions. Early recognition and individualized management of OH are critical in PD care.
Keywords: autonomic failure; baroreflex dysfunction; dysautonomia; neurogenic orthostatic hypotension; nocturnal hypertension; non-motor symptom; parkinson’s disease; postprandial hypotension; prodromal; supine hypertension.
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Citation
Pitton Rissardo J, Rashidi M, Rashidi F, Hmedat KI, Khalil I, Moharam H, Bahar M, Dway A, Prathiraja O, Fornari Caprara AL, Jayasinghe M. Intersection of Autonomic Dysfunction and Parkinson’s Disease: Insights Into Neurogenic and Classical Orthostatic Hypotension. Cureus 2025;17: e88487. doi:10.7759/cureus.88487
Table 1. Epidemiological studies on the incidence and prevalence of orthostatic hypotension in Parkinson's disease. BP: blood pressure; OH: orthostatic hypotension; PD Parkinson’s disease; PPMI: Parkinson’s progression markers initiative; nOH: neurogenic orthostatic hypotension; RR: relative risk; IV: intravenous; MIBG: meta-iodobenzylguanidine.
Table 2. Key distinguishing features of neurogenic versus non-neurogenic orthostatic hypotension. ADH: anti-diuretic hormone (vasopressin); ANS: autonomic nervous system; BP: blood pressure; MSA: multiple system atrophy; NE: norepinephrine; PAF: pure autonomic failure; PD: Parkinson’s disease; RAAS: renin-angiotensin-aldosterone system; SBP: systolic blood pressure; OH: orthostatic hypotension.
Table 3. Diagnostic tests to evaluate orthostatic hypotension. ABPM: ambulatory blood pressure monitoring; ANS: autonomic nervous system; BP: blood pressure; ECG: electrocardiogram; HR: heart rate; nOH: neurogenic orthostatic hypotension; OH: orthostatic hypotension; QST: quantitative sudomotor axon reflex test.
Table 4. Management of orthostatic hypotension in Parkinson’s disease. BP: blood pressure; DBP: diastolic blood pressure; FC: fludrocortisone; MBP: mean blood pressure; OH: orthostatic hypotension; PD: Parkinson’s disease; SBP: systolic blood pressure; TID: three times a day; NA: not applicable.
Figure 1. Diagnosis of orthostatic hypotension in Parkinson's disease. OH: orthostatic hypotension; PD: Parkinson's disease; BP: blood pressure; SCOPA-AUT: Scales for Outcomes in Parkinson's disease - Autonomic Dysfunction; COMPASS: Composite Autonomic Symptom Scale; OHQ: Orthostatic Hypotension Questionnaire; OGS: Orthostatic Grading Scale.
Figure 2. Four-phase treatment strategy of orthostatic hypotension in Parkinson's disease. BP: blood pressure.
Figure 3. Complex factors underpinning orthostatic hypotension in Parkinson's disease. OH: orthostatic hypotension.