[Afferent baroreflex failure with hyponatremia: A case report].

Afferent baroreflex failure (ABF) is a rare disease. It refers to the clinical syndrome caused by the impairment of the afferent limb of the baroreflex or its central connections at the level of the medulla. The recognized causes include trauma, surgery in related areas (radical neck tumor surgery, carotid endarterectomy), neck radiotherapy, brain stem stroke, tumor growth paraganglioma and hereditary diseases, among which the most common cause is extensive neck surgery or radiotherapy for neck cancer. The main manifestations are fluctuating hypertension, orthostatic hypotension, paroxysmal tachycardia and bradycardia. This case is a young man, whose main feature is blood pressure fluctuation, accom-panied by neurogenic orthostatic hypotension (nOH). After examination, the common causes of hypertension and nOH were ruled out. Combined with the previous neck radiotherapy and neck lymph node dissection, it was considered that the blood pressure regulation was abnormal due to the damage of carotid sinus baroreceptor after radiotherapy for nasopharyngeal carcinoma and neck lymph node dissection, which was called ABF. At the same time, the patient was complicated with chronic hyponatremia. Combined with clinical and laboratory examination, the final consideration was caused by syndrome of in- appropriate antidiuretic hormone (SIADH). Baroreceptors controlled the secretion of heart rate, blood pressure and antidiuretic hormone through the mandatory "inhibition" signal. We speculate that the carotid sinus baroreceptor was damaged after neck radiotherapy and surgery, which leads to abnormal blood pressure regulation and nOH, while the function of inhibiting ADH secretion was weakened, resulting in higher ADH than normal level and mild hyponatremia. The goal of treating ABF patients was to reduce the frequency and amplitude of sudden changes in blood pressure and heart rate, and to alleviate the onset of symptomatic hypotension. At present, drug treatment is still controversial, and non-drug treatment may alleviate some patients' symptoms, but long-term effective treatment still needs further study. The incidence of ABF is not high, but it may lead to serious cardiovascular and cerebrovascular events, and the mechanism involved is extremely complicated, and there are few related studies. The reports of relevant medical records warn that patients undergoing neck radiotherapy or surgery should minimize the da-mage to the baroreceptor in the carotid sinus in order to reduce the adverse prognosis caused by complications.

[Differential Diagnostics of Vasovagal Fainting, Orthostatic Hypotension and Baroreflex Failure in a Patient With Syncope].

We present here a case report of recurring fainting due to orthostatic hypotension in a 45­year-old woman with Hodgkin's' disease, treated by radiation therapy and resection of cervical lymph node. We discuss difficulties of identification of etiology and mechanisms of orthostatic hypotension as well as possible role of baroreflex failure at the background of the Hodgkin's' disease treatment, and vasovagal syncope of which the patient suffered in her youth.

Baroreflex failure increases the risk of pulmonary edema in conscious rats with normal left ventricular function.

In heart failure with preserved ejection fraction (HFpEF), the complex pathogenesis hinders development of effective therapies. Since HFpEF and arteriosclerosis share common risk factors, it is conceivable that stiffened arterial wall in HFpEF impairs baroreflex function. Previous investigations have indicated that the baroreflex regulates intravascular stressed volume and arterial resistance in addition to cardiac contractility and heart rate. We hypothesized that baroreflex dysfunction impairs regulation of left atrial pressure (LAP) and increases the risk of pulmonary edema in freely moving rats. In 15-wk Sprague-Dawley male rats, we conducted sinoaortic denervation (SAD, n = 6) or sham surgery (Sham, n = 9), and telemetrically monitored ambulatory arterial pressure (AP) and LAP. We compared the mean and SD (lability) of AP and LAP between SAD and Sham under normal-salt diet (NS) or high-salt diet (HS). SAD did not increase mean AP but significantly increased AP lability under both NS (P = 0.001) and HS (P = 0.001). SAD did not change mean LAP but significantly increased LAP lability under both NS (SAD: 2.57 ± 0.43 vs. Sham: 1.73 ± 0.30 mmHg, P = 0.01) and HS (4.13 ± 1.18 vs. 2.45 ± 0.33 mmHg, P = 0.02). SAD markedly increased the frequency of high LAP, and SAD with HS prolonged the duration of LAP > 18 mmHg by nearly 20-fold compared with Sham (SAD + HS: 2,831 ± 2,366 vs. Sham + HS: 148 ± 248 s, P = 0.01). We conclude that baroreflex failure impairs volume tolerance and together with salt loading increases the risk of pulmonary edema even in the absence of left ventricular dysfunction. Baroreflex failure may contribute in part to the pathogenesis of HFpEF.

[Baroreflex failure syndrome after the resection of complex paragangliomas of head and neck: a case report].

Protection of cranial nerves is one of the major challenges in the resection of paragangliomas of head and neck, especially in complex paragangliomas. We report a case of bilateral jugular tumor with unilateral carotid body tumor. Baroreflex failure syndrome（BFS） occurred after staged resection of bilateral lesions. There is still a lack of effective treatment for this complication. More prudent and reasonable treatment strategy is important to reduce the incidence of BFS.

The unpredictability of labile blood pressure: Afferent baroreflex failure in a critical patient with multiple thyroid surgeries and COVID-19 infection.

The carotid sinus-arterial baroreflex is essential in maintaining blood pressure (BP) regulation. Afferent baroreflex failure (ABF) can present with labile changes in BP within seconds and can be secondary to neck surgery or radiation. We present here the first case, to our knowledge, of ABF precipitated by thyroidectomy, in a patient with active COVID-19 pneumonia, causing difficult control of severely labile BP in a critical care unit. Contributing factors included her critical illness state with upregulation of IL-6 leading to pituitary-adrenal axis alteration, her thyroidectomy further exacerbating autonomic dysfunction, as well as downregulation of ACE2 via COVID-19 infection. Management was achieved with a combination of midodrine and clonidine catered to specific BP thresholds. Additional research with a multidisciplinary approach is warranted to fully optimize the treatment of ABF in patients with neck surgery and or inflammatory conditions such as COVID-19.

Symptomatic use of carbidopa in autonomic disorders.

Carbidopa is being explored as a novel therapy for hyperadrenergic symptoms of autonomic disorders, due to its potential to decrease peripheral catecholamine levels. This study retrospectively characterized patients in our autonomic clinic who were prescribed carbidopa for open label treatment of autonomic symptoms. 23 patients were included; approximately half had postural orthostatic tachycardia syndrome. Those with documented plasma catecholamines had elevated standing norepinephrine. Patients typically had multiple comorbidities and multiple failed therapies. 19 took carbidopa (typically 25 mg three times daily); 12 continued it for longer than 3 months. 11 patients reported better symptom control with carbidopa, most commonly tremor and gastrointestinal dysfunction. 4 patients reported side effects. In this small retrospective study, carbidopa was well tolerated in patients with dysautonomia, and half reported symptomatic benefit. Larger, placebo-controlled trials are warranted for further investigation of this therapy.

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.

The Carotid Sinus Nerve-Structure, Function, and Clinical Implications.

Interest has been renewed in the anatomy and physiology of the carotid sinus nerve (CSN) and its targets (carotid sinus and carotid body, CB), due to recent proposals of surgical procedures for a series of common pathologies, such as carotid sinus syndrome, hypertension, heart failure, and insulin resistance. The CSN originates from the glossopharyngeal nerve soon after its appearance from the jugular foramen. It shows frequent communications with the sympathetic trunk (usually at the level of the superior cervical ganglion) and the vagal nerve (main trunk, pharyngeal branches, or superior laryngeal nerve). It courses on the anterior aspect of the internal carotid artery to reach the carotid sinus, CB, and/or intercarotid plexus. In the carotid sinus, type I (dynamic) carotid baroreceptors have larger myelinated A-fibers; type II (tonic) baroreceptors show smaller A- and unmyelinated C-fibers. In the CB, afferent fibers are mainly stimulated by acetylcholine and ATP, released by type I cells. The neurons are located in the petrosal ganglion, and centripetal fibers project on to the solitary tract nucleus: chemosensory inputs to the commissural subnucleus, and baroreceptor inputs to the commissural, medial, dorsomedial, and dorsolateral subnuclei. The baroreceptor component of the CSN elicits sympatho-inhibition and the chemoreceptor component stimulates sympatho-activation. Thus, in refractory hypertension and heart failure (characterized by increased sympathetic activity), baroreceptor electrical stimulation, and CB removal have been proposed. Instead, denervation of the carotid sinus has been proposed for the "carotid sinus syndrome." Anat Rec, 302:575-587, 2019. © 2018 Wiley Periodicals, Inc.

Afferent baroreflex failure with hyponatremia:A case report / 北京大学学报(医学版)

Afferent baroreflex failure(ABF)is a rare disease.It refers to the clinical syndrome caused by the impairment of the afferent limb of the baroreflex or its central connections at the level of the medul-la.The recognized causes include trauma,surgery in related areas(radical neck tumor surgery,carotid endarterectomy),neck radiotherapy,brain stem stroke,tumor growth paraganglioma and hereditary diseases,among which the most common cause is extensive neck surgery or radiotherapy for neck cancer.The main manifestations are fluctuating hypertension,orthostatic hypotension,paroxysmal tachycardia and bradycardia.This case is a young man,whose main feature is blood pressure fluctuation,accom-panied by neurogenic orthostatic hypotension(nOH).After examination,the common causes of hyper-tension and nOH were ruled out.Combined with the previous neck radiotherapy and neck lymph node dissection,it was considered that the blood pressure regulation was abnormal due to the damage of carotid sinus baroreceptor after radiotherapy for nasopharyngeal carcinoma and neck lymph node dissection,which was called ABF.At the same time,the patient was complicated with chronic hyponatremia.Com-bined with clinical and laboratory examination,the final consideration was caused by syndrome of in-appropriate antidiuretic hormone(SIADH).Baroreceptors controlled the secretion of heart rate,blood pres-sure and antidiuretic hormone through the mandatory"inhibition"signal.We speculate that the carotid sinus baroreceptor was damaged after neck radiotherapy and surgery,which leads to abnormal blood pres-sure regulation and nOH,while the function of inhibiting ADH secretion was weakened,resulting in higher ADH than normal level and mild hyponatremia.The goal of treating ABF patients was to reduce the frequency and amplitude of sudden changes in blood pressure and heart rate,and to alleviate the on-set of symptomatic hypotension.At present,drug treatment is still controversial,and non-drug treatment may alleviate some patients'symptoms,but long-term effective treatment still needs further study.The incidence of ABF is not high,but it may lead to serious cardiovascular and cerebrovascular events,and the mechanism involved is extremely complicated,and there are few related studies.The reports of rele-vant medical records warn that patients undergoing neck radiotherapy or surgery should minimize the da-mage to the baroreceptor in the carotid sinus in order to reduce the adverse prognosis caused by complica-tions.

Third-degree atrioventricular block followed by syncope, labile hypertension, and orthostatic hypotension in a patient with nasopharyngeal cancer: baroreflex failure.

Baroreflex failure is a rare cause of syncope and labile blood pressures. Here, we present a case of baroreflex failure in a patient with history of nasopharyngeal cancer, status-post neck radiation. A 76-year-old male presented from an outside facility for possible pacemaker placement as he was found to have symptomatic third-degree atrioventricular (AV) block. The AV block resolved following discontinuation of the patient's his verapamil. The patient then developed labile blood pressures. A work-up for secondary causes of hypertension was negative, but due to the patient's neck radiation history, it was suggested that the labile blood pressures were due to baroreflex failure. We then started the patient on clonidine and other nonpharmacological interventions. The blood pressure was maintained after these treatments and on follow-up, the labile blood pressures had resolved. Our case demonstrates that baroreflex failure can be managed without any invasive intervention by performing frequent blood pressure measurements along with medication management.

Overt and Subclinical Baroreflex Dysfunction After Bilateral Carotid Body Tumor Resection: Pathophysiology, Diagnosis, and Implications for Management.

BACKGROUND: Carotid body paragangliomas are rare, usually benign, tumors arising from glomus cells of the carotid body. Bilateral involvement is present in ∼5% of sporadic cases and up to one third of familial cases. In most patients undergoing bilateral resection of carotid body tumors, a condition known as baroreflex failure syndrome (BFS) develops after resection of the second tumor characterized by headache, anxiety, emotional lability, orthostatic lightheadedness, hypertension, and tachycardia. This condition is believed to result from damage to the carotid baroreceptor apparatus. Patients without overt cardiovascular abnormalities may have subclinical baroreceptor dysfunction evident only on specific testing, measuring heart rate and sympathetic nerve responses to baroloading (e.g., phenylephrine) and barounloading (e.g., Valsalva maneuver). Given the high incidence of BFS in patients undergoing bilateral resection of carotid body tumors, it is suggested that operation is limited to unilateral resection of the dominant/symptomatic lesion and nonsurgical intervention (i.e., embolization, radiotherapy) on the contralateral side. Alternatively, refinement of surgical technique to prevent injury to elements of the baroreceptor apparatus may prevent this complication of bilateral tumor resection. METHODS AND RESULTS: We present a case of a 16-year-old girl with bilateral jugular vagale and carotid body tumors who developed hypertension after surgical resection of her left jugular vagale tumor and worsening of hypertension concurrent with progression, requiring intensity-modulated radiation therapy and a resection for significant progression of her left jugular vagale tumor. Additional case studies and series of bilateral carotid body tumors and BFS were identified through a comprehensive literature search in the PubMed database. CONCLUSIONS: Our case shows the generalizability of BFS to patients with tumors involving the vagal baroafferent fibers.

Baroreceptor reflex failure: Review of the literature and the potential impact on patients with head and neck cancer.

BACKGROUND: Baroreceptor dysfunction and reflex failure may occur after surgery affecting the carotid artery. The implications for patients undergoing treatment for head and neck cancer are not well described. METHODS: A literature search of PubMed was performed between March 2016 and May 2016. Search terms used individually and in combination included: "baroreflex failure," "carotid sinus sensitivity," "carotid endarterectomy," "carotid body tumor," and "head and neck cancer." Bibliographies of included articles were also reviewed for additional pertinent articles. RESULTS: There is evidence of baroreceptor failure in certain patients after interventions associated with the carotid artery, including carotid endarterectomy and carotid body tumor excision. Few studies have been performed investigating the potential effect of head and neck surgery treatment, including surgery and/or radiation, on baroreflex function. CONCLUSION: Head and neck cancer treatment has the potential to cause baroreflex failure, and this is likely an underrecognized and underdiagnosed condition.

Cerebral autoregulation and symptoms of orthostatic hypotension in familial dysautonomia.

Familial dysautonomia is an inherited autonomic disorder with afferent baroreflex failure. We questioned why despite low blood pressure standing, surprisingly few familial dysautonomia patients complain of symptomatic hypotension or have syncope. Using transcranial Doppler ultrasonography of the middle cerebral artery, we measured flow velocity (mean, peak systolic, and diastolic), area under the curve, pulsatility index, and height of the dictrotic notch in 25 patients with familial dysautonomia and 15 controls. In patients, changing from sitting to a standing position, decreased BP from 124 ± 4/64 ± 3 to 82 ± 3/37 ± 2 mmHg (p < 0.0001, for both). Despite low BP, all patients denied orthostatic symptoms. Middle cerebral artery velocity fell minimally, and the magnitude of the reductions were similar to those observed in healthy controls, in whom BP upright did not fall. While standing, patients had a greater fall in cerebrovascular resistance (p < 0.0001), an increase in pulsatility (p < 0.0001), and a deepening of the dicrotic notch (p = 0.0010), findings all consistent with low cerebrovascular resistance. No significant changes occurred in controls. Patients born with baroreflex deafferentation retain the ability to buffer wide fluctuations in BP and auto-regulate cerebral blood flow. This explains how they can tolerate extremely low BPs standing that would otherwise induce syncope.

Carotid sinus malfunction presenting with presyncopal episodes during radiation therapy for head and neck cancer.

We report the case of a 67-year-old Caucasian man with unexplained presyncopal episodes during radiation therapy for oropharyngeal cancer.

Hemorrhagic onset of hemangioblastoma located in the dorsal medulla oblongata presenting with tako-tsubo cardiomyopathy and neurogenic pulmonary edema: a case report.

Here, we present a case of dorsal medulla oblongata hemangioblastoma with fourth ventricular hemorrhage. A 23-year-old female developed sudden consciousness disturbance, and CT revealed hemorrhage in all cerebral ventricles and a hyperdense mass in the cisterna magna. Although the reddish tumor located in the dorsal medulla oblongata was successfully removed, she suffered from severe tako-tsubo cardiomyopathy (TTC) and neurogenic pulmonary edema (NPE) because of baroreflex failure and damage to the solitary tract nuclei. After intensive care for 12 weeks following surgery, she was discharged without any neurological or radiological deficits. Pathogenesis of TTC/NPE is discussed in this paper.