Afferent baroreflex failure (ABF) is an underrecognized but debilitating complication among head and neck cancer survivors, especially in oropharyngeal cancer (OPC), a malignancy with excellent prognosis. ABF is mainly caused by radiation therapy (RT), with neck surgery and some chemotherapies also contributing. It manifests as blood pressure lability, including severe hypertension or hypotension, syncope, and arrhythmias. To determine the prevalence and predictors of ABF-associated manifestations among OPC survivors treated with modern RT. We retrospectively studied OPC patients treated with RT at a tertiary cancer center between 2016-2019. Clinical data were collected from RT initiation to last follow-up or death. ABF-associated manifestations included new or worsening hypertension, hypotension requiring intervention, arrhythmias, and syncope. Secondary endpoints included new or worsened carotid artery atherosclerosis, stenosis, transient ischemic attack (TIA), stroke, and all-cause mortality. Among 393 patients (88% men, 91% White, mean age 61±10 years), 9.4% developed hypertension, 5.3% hypotension, 3.8% syncope, and 3.3% arrhythmias over median 6.3-year follow-up. Overall, 19.1% developed at least one ABF-associated manifestations. New or worsened carotid atherosclerosis occurred in 38.9%, with 7.1% developing >50% stenosis and 2.3% experiencing TIA or stroke. Mortality was 21.4%. On cause-specific multivariable Cox analysis, older age (adjusted hazard ratio [aHR] 1.03; 95% confidence interval [CI] 1.01-1.06), valvular disease (aHR 2.85; CI 1.03-7.92), T4 cancer (aHR 1.90; CI 1.10-3.27), and platinum-taxane chemotherapy (aHR 1.86; CI 1.13-3.05) independently increased risk of ABF-associated manifestations. Nearly 1 in 5 OPC survivors treated with RT develop ABF-associated manifestations, highlighting the need for early recognition and surveillance.

Baroreflex failure is an under-recognized and often overlooked cause of orthostatic hypotension, particularly following head and neck radiation therapy. We present an 88-year-old man who developed recurrent falls and a distinctive pattern of supine hypertension with systolic pressures reaching 235 mmHg and orthostatic hypotension as low as 66/44 mmHg three weeks after completing treatment for basal cell carcinoma. A comprehensive workup, including brain imaging, telemetry, serum catecholamines, thyroid function, and immunofixation electrophoresis, excluded structural, endocrine, and infiltrative causes of autonomic dysfunction. Radiation-induced baroreflex failure was inferred clinically based on pronounced positional blood pressure (BP) variability, lack of reciprocal heart rate changes, and the temporal relationship to recent therapy. Treatment with droxidopa, compression therapy, and a carefully titrated antihypertensive regimen led to improvement in orthostatic tolerance. Titration prioritized relief of symptomatic hypotension with droxidopa before addressing nocturnal hypertension, which was managed non-reactively using low-dose amlodipine. The patient remained stable throughout the 10-month follow-up with sustained symptom improvement. This case underscores the importance of recognizing radiation as a potential cause of baroreflex failure in patients with significant polyvascular disease, expanding the spectrum of presentations to include earlier onset than historically reported.

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.

Paroxysmal hypertension is characterized by a sudden and significant increase in blood pressure that may have coexisting hyperadrenergic symptoms (headache, palpitations, diaphoresis) with or without an obvious precipitating cause. Pheochromocytoma is suggested, although less than 1% of such patients have the tumor. Four syndromes should be considered, including labile hypertension, panic attacks, pseudopheochromocytoma, and baroreflex failure. Labile hypertension includes paroxysms that are provoked by obvious stress or anxiety; they may be asymptomatic or have hyperadrenergic symptoms. Similarly, panic attacks are precipitated by fear or anxiety. Pseudopheochromocytoma is characterized by paroxysms without obvious precipitating stress or anxiety, although anxiety may result from the paroxysm, and the paroxysms are invariably symptomatic; abnormal repression of emotions underlies most cases. Afferent baroreflex failure presents as symptomatic hypertensive paroxysms often precipitated by emotional or environmental stress alternating with periods of frank hypotension; orthostatic hypotension frequently coexists. No guidelines specify therapy of paroxysmal hypertension and no randomized controlled trials with hard endpoints exist for this syndrome. We discuss in detail the 4 pheochromocytoma mimics in the differential diagnosis of paroxysmal hypertension with recommendations on diagnosis and therapy.

To revisit the pharmacology and real-world use of carbidopa in the management of autonomic disorders. To identify articles suitable for this review, a search of the PubMed database was conducted in January 2025 using the keywords "Carbidopa," "MK-486," and "L-alpha-methyldopa hydrazine." The pharmacotherapeutic role of carbidopa extends beyond the management of Parkinson's disease. Our literature search revealed the use of carbidopa in three primary autonomic diseases to treat either nausea or symptoms of sympathetic hyperactivity: (1) familial dysautonomia, (2) hyperadrenergic postural orthostatic tachycardia syndrome (POTS), and (3) afferent baroreflex failure (familial or acquired). Even at a dose as high as 600 mg/day, carbidopa was not associated with bothersome side effects in some of the clinical trials on familial dysautonomia. Pre-clinical evidence also suggests in vitro and in vivo inhibition of T-cell activation by carbidopa and a potential therapeutic use in cytokine release syndrome. Current evidence, although limited, suggests that carbidopa has a favorable safety profile. While large, well-designed studies are warranted, observations from case series and small studies suggest that carbidopa could have utility in treating nausea in familial dysautonomia and symptoms of sympathetic hyperactivity in hyperadrenergic postural orthostatic tachycardia syndrome (POTS) and afferent baroreflex failure.