神经介导性晕厥

晕厥包括神经介导性晕厥、直立性低血压晕厥、心源性晕厥、脑源性晕厥及不明原因的晕厥。其中神经介导性晕厥是最常见的晕厥,包括血管迷走性晕厥、情景性晕厥、颈动脉窦晕厥和精神性晕厥。本文阐述了神经介导性晕厥发病机制及其治疗,对神经介导性晕厥有更深入的了解。     

A Patient Responding to Combined Therapy with Pirmenol and Midodrine for Refractory Neurally Mediated Syncope Complicated by Prostatic Hypertrophy

A 67-year-old man with neurally mediated syncope (NMS) complicated by prostatic hypertrophy responded well to combined therapy with pirmenol and midodrine. In 2003, syncope occurred while the patient was driving a car. Results of head-up tilt-table testing (HUT) suggested a mixed type of NMS. Oral administration of disopyramide provided severe urinary obstruction. Pirmenol treatment was not associated with syncope during ordinary HUT, but nausea, sweating, and syncope occurred during HUT with provocative administration of isosorbide dinitrate. Combined therapy with pirmenol and midodrine avoided syncope during HUT, and has prevented attacks since discharge from the hospital.     

Management of Vasovagal Syncope

Vasovagal syncope is a common disorder of autonomic cardiovascular regulation that can be very disabling and result in a significant level of psychosocial and physical limitations. The optimal approach to treatment of patients with vasovagal syncope remains uncertain. Although many different types of treatment have been proposed and appear effective based largely on small nonrandomized studies and clinical series, there is a remarkable absence of data from large prospective clinical trials. However, based on currently available data, the pharmacologic agents most likely to be effective in the treatment of patients with vasovagal syncope include beta blockers, fludrocortisone, and alpha-adrenergic agonists. In this article, we provide a summary of the various therapeutic options that have been proposed for vasovagal syncope and review the clinical studies that form the basis of present therapy for this relatively common entity.     

Selective Vagal Denervation of the Sinus and Atrioventricular Nodes, Guided by Vagal Reflexes Induced by High Frequency Stimulation, to Treat Refractory Neurally Mediated Syncope

A 15-year-old female patient presented with frequent episodes of vasovagal syncope refractory to non-pharmacological and pharmacological measures. Two tilt-table tests performed before and after conventional therapy were positive and reproduced the patient's clinical symptoms. Selective vagal denervation, guided by HFS, was performed. Six radiofrequency pulses were applied on the left and right sides of the interatrial septum, abolishing vagal responses at these locations. Basal sinus node and Wenckebach cycle lengths changed significantly following ablation. A tilt test performed after denervation was negative and revealed autonomic tone modification. The patient reported significant improvement in quality of life and remained asymptomatic for 9 months after denervation. After this period, three episodes of NMS occurred during a 4-month interval and a tilt test performed 11 months after the procedure demonstrated vagal activity recovery.     

Recurrent Supine Syncope:

Supine Syncope. Introduction : Syncope occasionally may occur in the supine patient due to severe brady- or tachyarrhythmia. However, recurrent syncope upon assumption of the supine position as a result of a neurally mediated reflex mechanism has not been reported previously.
Methods and Results : Two young patients, both of whom had significant systemic illnesses, experienced recurrent episodes of presyncope and/or syncope shortly after assuming the supine position. During ambulatory ECG monitoring, symptoms were provoked only by lying down and were associated with transient bradycardia. Head-up tilt table testing was undertaken as part of the syncope evaluation and was nondiagnostic in both cases. However, both patients exhibited a transient cardioinhibitory response with reproduction of typical symptoms upon return of the table to the supine position ("reverse tilt"). During follow-up (8 and 14 months), both patients improved with pharmacologic treatment (disopyramide in one case and midodrine in the other).
Conclusion : Presyncope or syncope upon lying down can he an unusual manifestation of the neurally mediated faint.     

Orthostatic Versus Electrophysiologic Testing in Unexplained Syncope in Children and Adolescents

Orthostatic vs EP Testing in Pediatric Unexplained Syncope. Introduction: Unexplained syncope in the pediatric age group is a common problem that often requires cardiac evaluation. This work-up is expensive and frequently unrevealing. Electrophysiologic and, more recently, tilt table or orthostatic testing have been used in the evaluation of unexplained syncope. Methods and Results: We undertook to compare the results of these two forms of evaluation in a group of 26 young patients less than 19 years of age with episodes of unexplained syncope. Sixteen of the 26 patients (62%) had an abnormal electrophysiologic study with the majority having either mild sinus node dysfunction or inducible atrial flutter. Four of the 26 patients (16%) were thought to have an abnormality found that was clinically significant (sustained ventricular tachycardia [2], nonsustained ventricular tachycardia/polymorphic premature ventricular contractions [1], and high-degree atrioventricular block [1]). An abnormal response to orthostatic testing was found in 14 of 26 patients (56%) with 13 of 14 developing syncope at an average standing time of 6.5 minutes. Sixteen patients underwent treatment based on the study findings and follow-up with an average time of 1.6 years is available on 13 of 16 patients who underwent treatment. Of the nine patients treated for neurally mediated syncope (fludrocortisone [7], beta blocker [1], theophylline [1]), all are asymptomatic. The four patients with an arrhythmic cause of syncope found by electrophysiologic testing are asymptomatic on treatment (antiarrhythmic drug [3], permanent pacing [1]). Conclusion: Orthostatic testing has a higher positive yield than electrophysiologic testing in the evaluation of unexplained syncope in young patients. Orthostatic or tilt table testing should be considered early on in the cardiovascular evaluations of these patients. (J Cardiovasc Electrophysiol, Vol. 3, pp. 418–422, October 1992)     

Clinical recognition of neurally mediated syncope

BACKGROUND: Most cases of syncope are due to hypotension, with a vasovagal response the commonest single mechanism. Neurally mediated syncope (NMS) is a vasovagal response evoked by common physical or psychological stress factors in susceptible individuals. Although upright tilt table testing (TTT) has been developed to diagnose this condition, the clinical recognition of this common syndrome in the general community remains poor. AIMS: To evaluate the clinical presentation of patients with NMS and pre-syncope, proven by TTT, and compare them to patients with syncope that have a low probability of having NMS (e.g. older patients with cardiac disease and negative TTT). METHODS: Prospective evaluation by questionnaire at the time of TTT, including documentation of presenting symptoms and signs, and provoking factors in consecutive patients. Comparisons between patient groups analyzed using chi-squared tests and logistic regression. RESULTS: Neurally mediated syncope patients were more likely to present with both syncope and pre-syncope, often with prolonged histories of pre-syncope. Certain provoking stress factors were more common in NMS, with multiple factors often present. Most NMS patients had a hypotensive prodrome before syncope, whereas control patients had a higher incidence of syncope without warning. CONCLUSION: Neurally mediated syncope patients present with situational syncope that is not only stereotypical for the individual, but shares common features with other similar patients. While none of the clinical observations is unique to NMS, a carefully detailed history can elicit a convincing diagnostic pattern that can often obviate the need for extensive and expensive investigation, and in younger patients a TTT may not be required to make the diagnosis.     

Recent History of Vasovagal Syncope in a Young,Referral‐Based Population Is a Stronger Predictor of Recurrent Syncope Than Lifetime Syncope Burden

Syncope Prediction. Introduction: Accurate selection of patients for vasovagal syncope studies requires strong risk stratification and knowledge of the natural history of syncope. We aimed to test the hypothesis that recent history of vasovagal syncope compared to distant history better predicts subsequent recurrence of syncope. Methods and Results: In all, 208 subjects with a positive tilt test and ≥3 lifetime syncope spells were followed for 1 year. Syncope episodes in the preceding year and total historical spells were compared for their ability to predict a syncope recurrence using the criteria of optimal statistical significance, best linear separation of risk populations, and impact on power calculations. The number of vasovagal syncope spells in the preceding year better predicted syncope recurrence when compared to total number of historical spells (likelihood ratio statistic 28.4, P < 0.0001; versus 20.4, P = 0.001), and showed a substantial effect as the number of syncope events increased. For example, syncope recurred in 22% of those with <2 spells in the previous year compared to 69% in those with >6 spells. A history of no syncope compared to any syncope in the preceding year was associated with a 1‐year probability of 7% versus 46% for syncope recurrence. A study designed to detect a 50% decrease in syncope recurrence at P = 0.05 with 80% power would require 159 patients with at least 3 lifetime spells, and only 108 patients with at least 3 spells in the previous year. Conclusions: The number of syncope events in the year preceding clinical evaluation is the best predictor of syncope recurrence. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1375‐1380, December 2010)     

Neurally Mediated Syncope as a Cause of Syncope in Patients with Brugada Electrocardiogram

Neurally Mediated Syncope in Brugada Syndrome. Introduction: Patients with type 1 Brugada electrocardiogram (ECG) and an episode of syncope are diagnosed as symptomatic Brugada syndrome; however, all episodes of syncope may not be due to ventricular tachyarrhythmia. Methods and Results: Forty‐six patients with type 1 Brugada ECG (all males, 51 ± 13 years, 29 spontaneous, 17 Ic‐drug induced), 20 healthy control subjects (all males, 35 ± 11 years), and 15 patients with suspected neurally mediated syncope (NMS; 9 males, 54 ± 22 years) underwent the head‐up tilt (HUT) test. During the HUT test, 12‐lead ECGs were recorded in all patients, and the heart rate variability was investigated in some patients. Sixteen (35%) of 46 patients with Brugada ECG, 2 (10%) of 20 control subjects, and 10 (67%) of 15 patients with suspected NMS showed positive responses to the HUT test. Although no significant differences were observed in HUT‐positive rate among Brugada patients with documented VT (7/14; 50%), syncope (5/19; 26%) and asymptomatic patients (4/13; 31%), the HUT‐positive rate was significantly higher in patients with documented VT (50%) and those with VT or no symptoms (11/27, 41%) compared to that in control subjects (10%) (P < 0.05). Augmentation of ST‐segment amplitude (≥0.05 mV) in leads V1‐V3 was observed in 11 (69%) of 16 HUT‐positive patients with Brugada ECG during vasovagal responses, and was associated with augmentation of parasympathetic tone following sympathetic withdrawal. Conclusion: Thirty‐five percent of patients with Brugada ECG showed vasovagal responses during the HUT test, suggesting that some Brugada patients have impaired balance of autonomic nervous system, which may relate to their syncopal episodes. (J Cardiovasc Electrophysiol, Vol. 21, pp. 186‐192, February 2010)     

Neurally mediated syncope and unexplained or nonaccidental falls in the elderly

Falls and syncope are among the leading causes for which older patients seek hospital admissions. The prevalence of unexplained or nonaccidental falls is high in this group. The clinical spectrum of falls and syncope has been shown to overlap significantly in the elderly. Carotid sinus syndrome and vasovagal syncope, the two common examples of neurally mediated syncope (NMS), have been increasingly recognised as important attributable causes for unexplained falls and syncope. However, in clinical practice NMS is not widely investigated as a cause of fall and is likely to be underdiagnosed.     

Clinical spectrum of neurally mediated reflex syncopes.

AIMS: The clinical features of the various types of neurally mediated reflex syncope have not been systematically investigated and compared. We sought to assess and compare the clinical spectrum of neurally mediated reflex syncopes. METHODS AND RESULTS: Four hundred sixty-one patients with syncope were prospectively evaluated and 280 had neurally mediated reflex syncope. Each patient was interviewed using a standard questionnaire. A cause of syncope was assigned using standardized diagnostic criteria. Typical vasovagal syncope was diagnosed in 39 patients, situational syncope in 34, carotid sinus syncope in 34, tilt-induced syncope in 142 and complex neurally mediated syncope (positive response to both carotid sinus massage and tilt test) in 31. The clinical features of situational, carotid sinus, tilt-induced and complex neurally mediated syncope were very similar. By contrast, typical vasovagal syncope differed from other neurally mediated syncopes not only in terms of its precipitating factors (fear, strong emotion, etc.), which constituted predefined diagnostic criteria, but also in the variety of its clinical features (lower age and prevalence of organic heart disease, higher prevalence of prodromal symptoms, and of autonomic prodromes, longer duration of prodromes, higher prevalence of symptoms during the recovery phase and lower prevalence of trauma). CONCLUSION: The clinical spectrum of neurally mediated reflex syncopes demonstrates much overlap between them. However, when the afferent neural signals are localized in cortical sites, as in typical vasovagal syncope, symptoms are more frequent and of longer duration.     

International Study on Syncope of Uncertain Etiology 2: the management of patients with suspected or certain neurally mediated syncope after the initial evaluation Rationale and study design

STUDY DESIGN: Multi-centre, prospective observational study. OBJECTIVES: Main objective is to verify the value of implantable loop recorder(ILR) in assessing the mechanism of syncope and the efficacyof the ILR-guided therapy after syncope recurrence. INCLUSION CRITERIA: Patients who met the following criteria are included: suspectedor definite neurally mediated syncope based on initial evaluation;3 syncope episodes in the last 2 years; severe clinical presentationof syncope requiring treatment initiation in the judgement ofthe investigator and age >30 years. EXCLUSION CRITERIA: Patients with one or more of the following are excluded: carotidsinus syndrome; suspected or definite heart disease and highlikelihood of cardiac syncope; symptomatic orthostatic hypotensiondiagnosed by standing blood pressure measurement; loss of consciousnessdifferent from syncope (e.g. epilepsy, psychiatric, metabolic,drop-attack, TIA, intoxication, cataplexy) and subclavian stealsyndrome. END-POINTS: The primary end-points are the ECG-documented syncopal eventsand the syncope recurrences after application of ILR-guidedtherapy. SAMPLE SIZE AND DURATION: A minimum of 400 patients will be enrolled during an anticipatedperiod of 3 years.     

How and When to Pace in Vasovagal Syncope

Pacing in Vasovagal Syncope. This article discusses the indications for pacing in vasovagal syncope. It also reviews the literature on pacing results; notably, there are two small randomized controlled trials of pacing versus no therapy (or continued nondevice therapy) that show a clear benefit for pacing. The mode of benefit is, as yet, unclear. Pacing has to be dual chamber with some form of rate hysteresis. Ways of improving pacemaker therapy delivery in vasovagal syncope are anticipated.     

Single-stage adenosine tilt testing in patients with unexplained syncope

INTRODUCTION: We previously have shown that a 3-minute single-stage adenosine tilt test has a diagnostic yield comparable to a two-stage protocol consisting of a 30-minute drug-free tilt followed by a 15-minute isoproterenol tilt. In this study, we sought to further define the clinical utility of adenosine tilt testing in patients with unexplained syncope by prospectively evaluating test specificity and determining predictors of a positive test response. METHODS AND RESULTS: The specificity of single-stage adenosine tilt testing was determined using 30 control subjects. To determine the diagnostic yield of this protocol, adenosine tilts were performed in 129 patients with unexplained syncope. The adenosine tilt test protocol had high specificity (100%) but a low overall diagnostic yield (18%). However, the yield was affected significantly by age. In patients /=65 years of age (2/41 patients [5%], P < 0.0001). CONCLUSION: These data support single-stage adenosine tilt testing in patients 40 years of age is low, suggesting that the clinical utility of this protocol is limited in these patients.     

Different mechanisms of isoproterenol-induced and nitroglycerin-induced syncope during head-up tilt in patients with unexplained syncope: important role of epinephrine in nitroglycerin-induced syncope

INTRODUCTION: A reduction in left ventricular volume and an increase in epinephrine levels have been reported in tilt-induced neurally mediated syncope. To compare the mechanisms of isoproterenol-induced and nitroglycerin-induced syncope during head-up tilt and to investigate the role of catecholamines, the temporal changes in plasma levels of norepinephrine and epinephrine and in left ventricular volume were measured. METHODS AND RESULTS: The first study population consisted of 90 patients with syncope of unknown etiology and 12 control subjects. The second study population consisted of 43 patients with unexplained syncope. In the first study, head-up tilt (80 degree angle) was conducted for 40 minutes, and norepinephrine and epinephrine levels were measured. In the second study, all patients were randomly allocated to either isoproterenol test (20 patients) or nitroglycerin test (23 patients) for 20-minute head-up tilt. Isoproterenol infusion was given at a rate of 1 to 3 microg/min. Intravenous infusion of nitroglycerin was started at 250 microg/hour with increasing dosages up to 1,500 microg/hour. Norepinephrine and epinephrine were measured in peripheral venous blood. Left ventricular volumes were measured by echocardiography with patients in the supine position and during head-up tilt every 1 minute. End-diastolic volume and end-systolic volume were calculated. In the first study, 61 patients demonstrated a positive response and 29 patients demonstrated a negative response. Plasma norepinephrine changes during head-up tilt were not significantly different, whereas epinephrine levels were significantly higher in the positive patients than in the negative and control subjects (148 +/- 118 pg/mL vs 66 +/- 31 pg/mL and 55 +/- 27 pg/mL). Thirteen of the 20 patients given isoproterenol and 15 of the 23 patients given nitroglycerin showed a positive head-up tilt (65.0% vs 65.2%; P = NS). During isoproterenol and nitroglycerin infusion head-up tilt, epinephrine in the positive group determined by the nitroglycerin test was significantly higher than that in the other three groups (103 +/- 38 pg/mL vs 60 +/- 33 pg/mL, 31 +/- 21 pg/mL, and 50 +/- 52 pg/mL). In contrast, end-systolic volume was significantly smaller in the positive group than in the other three groups based on findings of the isoproterenol test. CONCLUSION: The findings suggest that nitroglycerin triggers head-up tilt-induced syncope by increasing epinephrine levels, whereas isoproterenol induces syncope by decreasing left ventricular volume.     

Endothelial function and peripheral vasomotion in the brachial artery in neurally mediated syncope

BACKGROUND: Paradoxical peripheral vasodilation is one of the suspected mechanisms of neurally mediated syncope. Parasympathetic stimulation following sympathetic activation during orthostatic stress mainly contributes to this vasodilation. HYPOTHESIS: Since endothelial function modulates peripheral vascular tone, this study aimed to determine whether endothelial function and inappropriate peripheral vasomotion has a significant role in the pathogenesis of neurally mediated syncope. METHODS: To investigate whether endothelial function is augmented or whether abnormal peripheral vasomotion exits, flow-mediated dilation (FMD, endothelium-dependent vasodilation) and sublingual glyceryl trinitrate-induced dilation (0.3 mg, GTN-D, endothelium-independent vasodilation) were measured in the brachial artery in 16 patients with neurally mediated syncope, aged 33 +/- 10 years, by using high-resolution ultrasound. All patients underwent positive head-up tilt testing. These measures were compared with those in 16 control subjects matched with the patients by age, gender, and coronary risk factors. For FMD, percent diameter changes were obtained from baseline to hyperemic conditions (1 min after 5 min occlusion of the forearm artery). There were five smokers in both the patient and the control groups, but there was no structural heart disease in either group. RESULTS: Baseline brachial artery diameters were comparable (3.8 +/- 0.6 vs. 3.8 +/- 0.7 mm, NS). Flow-mediated dilation in patients with neurally mediated syncope had a normal value of 9.8 +/- 5.0% despite the inclusion of five smokers. Flow-mediated dilation and GTN-D in patients with neurally mediated syncope were significantly greater than those in controls (9.0 +/- 5.0 vs. 3.0 +/- 3.5%, p<0.05; 18.4 +/- 5.5 vs. 14.1 +/- 4.4%, p<0.05). CONCLUSIONS: Augmented endothelial function and/or abnormal peripheral vasomotion in peripheral arteries are important in patients with neurally mediated syncope in selected populations.     

The Clinical Spectrum of Neurocardiogenic Syncope

Neurocardiogenic Syncope. Neurocardiogenic syncope is a collective term used to describe the clinical syndromes of syncope that result from inappropriate, and often excessive, autonomic reflex activity, and manifest as abnormalities in the control of vascular tone and heart rate. These include carotid sinus syndrome, vasovagal syncope, and the syndromes of cough, deglutition, and micturition syncope. Orthostatic hypotension, which, in contrast, results from a failure of autonomic reflexes, is not considered part of this family of closely related syndromes. This review will focus on vasovagal and carotid sinus syndromes.