Standardized Autonomic Testing in Patients With Probable Radiation-Induced Afferent Baroreflex Failure

Injury of the afferent limb of the baroreflex from neck radiation causes radiation-induced afferent baroreflex failure (R-ABF). Identification and management of R-ABF is challenging. We aimed to investigate the pattern of autonomic dysfunction on standardized autonomic testing in patients with probable R-ABF. We retrospectively analyzed all autonomic reflex screens performed at Mayo Clinic in Rochester, MN, between 2000 and 2020 in patients with probable R-ABF. Additional tests reviewed included ambulatory blood pressure monitoring, plasma norepinephrine, and thermoregulatory sweat test. We identified 90 patients with probable R-ABF. Median total composite autonomic severity score (range, 0–10) was 7 (interquartile range, 6–7). Cardiovascular adrenergic impairment was seen in 85 patients (94.4%), increased blood pressure recovery time after Valsalva maneuver in 71 patients (78.9%; median 17.4 seconds), and orthostatic hypotension in 68 patients (75.6%). Cardiovagal impairment was demonstrated by abnormal heart rate responses to deep breathing (79.5%), Valsalva ratio (87.2%), and vagal baroreflex sensitivity (57.9%). Plasma norepinephrine was elevated and rose appropriately upon standing (722–1207 pg/mL). Ambulatory blood pressure monitoring revealed hypertension, postural hypotension, hypertensive surges, tachycardia, and absence of nocturnal dipping. Blood pressure lability correlated with impaired vagal baroreflex function. Postganglionic sympathetic sudomotor function was normal in most cases; the most frequent thermoregulatory sweat test finding was focal neck anhidrosis (78.9%). Standardized autonomic testing in R-ABF demonstrates cardiovascular adrenergic impairment with orthostatic hypotension, blood pressure lability, and elevated plasma norepinephrine. Cardiovagal impairment is common, while sudomotor deficits are limited to direct radiation effects.

603 CHALLENGES IN THE MANAGEMENT OF SEVERE ORTHOSTATIC HYPOTENSION ASSOCIATED WITH SUPINE HYPERTENSION IN A PATIENT WITH AUTONOMIC DYSFUNCTION ON BACKGROUND OF NASOPHARYNGEAL CARCINOMA AND TYPE II DIABETES MELLITUS

Introduction Combined chemotherapy and radiotherapy increases long term survival in patients with nasopharyngeal carcinoma. However, radiotherapy of the carotid sinus or brain stem can evolve labile hypertension and orthostatic intolerance from chronic baroreflex failure. Diabetes would also cause this neuropathy. Management of patients with Supine hypertension-Orthostatic hypotension can be very challenging. Methods A case report was done on a 71-year-old man with metastatic nasopharyngeal carcinoma status post radiation therapy who was admitted with severe supine hypertension-orthostatic hypotension. Patient was managed with both non-pharmacological and pharmacological methods, and monitored for postural symptoms, complications of severe supine hypertension—which has been linked to left ventricular hypertrophy and kidney dysfunction, and placed on 24 hour ambulatory blood pressure monitoring to aid in management so as to prevent hypertension induced organ damage. Results This review outlines the pathophysiology of Supine hypertension-Orthostatic hypotension, treatment complications and potential management strategies recommendations for this group of patients. It revealed the benefit of having a 24 hour ambulatory blood pressure monitoring, which provides insight on the timing and magnitude of an individual’s blood pressure fluctuations throughout the day so as to further guide management. Conclusion Chronic baroreflex failure is a late sequela of neck irradiation for naso-pharyngeal carcinoma due to accelerated atherosclerosis in the region of the carotid sinus baroreceptor. Treatment goal is achieved with adequate control of pre-syncopal symptoms and prevention of long term complications. Non-pharmacological interventions remain the first line of therapy, followed by pharmacological interventions as necessary. Nonetheless, management of blood pressure in these elderly patients with baroreflex dysfunction remains challenging and should be individualized. Moving forward, a prospective study on the incidence of late onset, iatrogenic baroreflex failure as a late complication of neck irradiation and its particular relationship to carotid arterial rigidity should be conducted to increase awareness, timely diagnosis and management of the condition among physicians.

Hyperperfusion Syndrome and Baroreflex Failure following Carotid Artery Angioplasty and Stenting for Symptomatic Radiation-Associated Carotid Artery Stenosis

Cerebrovascular manifestations of radiotherapy for head and neck cancers are well described. In Southeast Asia, because nasopharyngeal cancer is common, patients with late cerebrovascular consequences are encountered regularly. This case report describes the long-term follow-up of a Chinese male patient with symptomatic severe radiation-associated atherosclerosis, who had carotid artery angioplasty and stenting performed, and the subsequent complications encountered: cerebral hyperperfusion syndrome, baroreflex failure, and progressive carotid artery stenosis.

Afferent Baroreflex Dysfunction: Decreased or Excessive Signaling Results in Distinct Phenotypes

Head and neck tumors can affect afferent baroreceptor neurons and either interrupt or intermittently increase their signaling, causing blood pressure to become erratic. When the afferent fibers of the baroreflex are injured by surgery or radiotherapy or fail to develop as in familial dysautonomia, their sensory information is no longer present to regulate arterial blood pressure, resulting in afferent baroreflex failure. When the baroreflex afferents are abnormally activated, such as by paragangliomas in the neck, presumably by direct compression, they trigger acute hypotension and bradycardia and frequently syncope, by a mechanism similar to the carotid sinus syndrome. We describe our observations in a large series of 23 patients with afferent baroreflex dysfunction and the cardiovascular autonomic features that arise when the sensory baroreceptor neurons are injured or compressed. The management of afferent baroreceptor dysfunction is limited, but pharmacological strategies can mitigate blood pressure swings, improve symptoms, and may reduce hypertensive organ damage. Although rare, the prevalence of afferent baroreflex dysfunction appears to be increasing in middle-aged men due to human papillomavirus related oropharyngeal cancer.

Carbidopa for Afferent Baroreflex Failure in Familial Dysautonomia

Afferent lesions of the arterial baroreflex occur in familial dysautonomia. This leads to excessive blood pressure variability with falls and frequent surges that damage the organs. These hypertensive surges are the result of excess peripheral catecholamine release and have no adequate treatment. Carbidopa is a selective DOPA-decarboxylase inhibitor that suppresses catecholamines production outside the brain. To learn whether carbidopa can inhibit catecholamine-induced hypertensive surges in patients with severe afferent baroreflex failure, we conducted a double-blind randomized crossover trial in which patients with familial dysautonomia received high dose carbidopa (600 mg/day), low-dose carbidopa (300 mg/day), or matching placebo in 3 4-week treatment periods. Among the 22 patients enrolled (13 females/8 males), the median age was 26 (range, 12–59 years). At enrollment, patients had hypertensive peaks to 164/116 (range, 144/92 to 213/150 mm Hg). Twenty-four hour urinary norepinephrine excretion, a marker of peripheral catecholamine release, was significantly suppressed on both high dose and low dose carbidopa, compared with placebo ( P =0.0075). The 2 co-primary end points of the trial were met. The SD of systolic BP variability was reduced at both carbidopa doses (low dose: 17±4; high dose: 18±5 mm Hg) compared with placebo (23±7 mm Hg; P =0.0013), and there was a significant reduction in the systolic BP peaks on active treatment ( P =0.0015). High- and low-dose carbidopa were similarly effective and well tolerated. This study provides class Ib evidence that carbidopa can reduce blood pressure variability in patients with congenital afferent baroreflex failure. Similar beneficial effects are observed in patients with acquired baroreflex lesions.