The neurally mediated syncopal syndromes (Table 71.2) comprise a variety of pathophysiologically related conditions. For the most part, clinical distinctions are based on the source of the trigger for the episodes (e.g., pain, carotid sinus stimulation, cough, micturition). In this regard, the presumed triggering neural signals may arise within the central nervous system (CNS) itself (e.g., syncope associated with fear or anxiety), or from any of a number of peripheral receptors that respond to stimuli of various types (e.g., mechanical, chemical, pain). Thus, by way of example, in carotid sinus syndrome, the afferent aspect of the reflex loop is typically believed to arise from stimulation of autonomic receptors in the cervical region. However, it now seems likely that carotid sinus stimulation may need to interact with failure of parallel CNS inputs from the ipsilateral neck muscles to trigger the syndrome (19). In typical vasovagal syncope (Fig. 71.1), the location and nature of the trigger sites are usually less certain (20,21,22,23,24,25,26).

Vasovagal syncope may be triggered by any of a variety of situational factors. Some of the latter include unpleasant sights
(e.g., sight of blood), pain, and extreme emotion. Common venues for fainting are churches, hospitals, queues, and restaurants. In many but not all cases, this type of faint is easy to diagnose because a clear history of preceding dizziness together with other typical phenomena is obtained (1). The patient may reports feelings of lack of air, a change in breathing pattern, sweating, loss of hearing, and nausea before partial or total loss of consciousness. Pallor is a common physical finding in association with these faints, and witnesses to the event should be queried directly regard recollection of this finding. During the recovery phase there is rapid return of orientation. However, fatigue, weakness, nausea, and headache may last from minutes to hours. Often, in older individuals, warning symptoms may be of very brief duration or nonexistent, thereby complicating establishment of the diagnosis.

When vasovagal syncope is suspected by clinical history but uncertainty remains, tilt-table testing diagnostic techniques have been of value (1,23,24,25,26,27,28,29,30,31,32,33,34,35,36). Tilt-table testing has a specificity of approximately 90% and an approximate reproducibility in the short term of 80% to 90% and in the longer term (over more than 1 year) around 60% (35). Tilt-table testing is the only investigation that provides the opportunity to precipitate a typical attack under the eyes of the investigator and allows the victim to confirm the associated symptoms.

Carotid sinus syndrome is the second most common form of the neurally mediated syncopal syndromes (1,37,38,39,40). In this setting, syncope often presents without warning (i.e., absence of premonitory symptoms). Although rare, a history suggesting that head movements trigger dizziness or syncope supports this diagnosis. As a rule, the condition almost exclusively afflicts older people, especially men.

In clinical practice, carotid sinus syndrome is often overlooked. The reasons for this include failure to perform carotid sinus massage routinely in patients with syncope and/or failure to record both blood pressure and heart rate responses when carotid massage is undertaken. Carotid massage resulting in dizziness or syncope owing to hypotension with or without bradycardia is the key diagnostic finding in patients suspected of having carotid sinus syndrome. Testing is best conducted with the patient upright on a tilt table, with continuous digital plethysmography or intraarterial pressure measurements used to record beat-to-beat arterial pressure changes (39). Firm carotid sinus massage for 5 to 10 seconds is recommended. A cardioinhibitory response is presumed to predominate when carotid sinus massage is associated with symptom reproduction in conjunction with asystole or paroxysmal atrioventricular (AV) block (37,38,39,40). However, the vasodepressor component must be assessed separately during the maneuver by beat-to-beat arterial pressure monitoring while preventing bradycardia using a temporary dual-chamber pacing system. The magnitude of this latter part of the reflex can also be estimated by examining the rate of blood pressure recovery after resumption of the native heart rate. In the absence of symptom reproduction, the demonstration of a pause of 5 seconds or longer, and/or a systolic blood pressure fall of at least 50 mmHg, is probably relevant and can be considered to support a presumptive diagnosis (1).

Among the other forms of neurally mediated reflex syncope, postmicturition syncope, swallow syncope, and cough syncope are probably the next most frequent. The medical history associated with these situational faints provides the diagnosis. The remaining conditions (Table 71.2) are only rarely encountered.

Orthostatic syncope is the result of postural hypotension or orthostatic hypotension (Table 71.3). The term orthostatic intolerance has also come to be widely used as a descriptor of patients susceptible to recurring orthostatic syncope. Presyncopal or syncopal symptoms associated with abrupt assumption of upright posture are common occurrences (Table 71.3). Elderly persons, less physically fit individuals, or patients who are for whatever reason dehydrated or volume depleted are at greatest risk. Iatrogenic factors such as excessive diuresis or overly aggressive use of certain antihypertensive agents are important contributors. Environmental factors (e.g., excessive heat) and complications associated with certain medical conditions (e.g., hemorrhage) or diseases (e.g., diabetes insipidus, adrenal insufficiency) may also play a role in specific cases. Volume depletion (often iatrogenic) (27,28,41,42,43,44), exposure to vasodilator drugs, and neurologic disturbances of vascular control resulting from concomitant disease are the most frequent causes of orthostatic syncope. In certain cases, however, patients may be manifesting a form of primary autonomic failure with inadequate reflex adaptations to upright posture. The most important of the primary autonomic disturbances encountered in practice are pure autonomic failure, multisystem atrophy, and Parkinson disease with autonomic failure.

Specific primary autonomic nervous system dysfunctions leading to disturbances of vascular control are currently considered to be relatively infrequent causes of syncope in general medical practice. Nevertheless, as the broad spectrum of these disturbances and their potentially subtle manifestations become more widely appreciated by physicians, these diagnoses will be made more often (45,46,47,48,49,50,51). More commonly, neuropathies associated with chronic diseases (e.g., diabetes) or toxic agents (e.g., alcohol) are the source of the problem.

In a review of 155 patients referred to a center specialized in autonomic system evaluation for assessment of suspected orthostatic hypotension, Low and colleagues (48) found that among the most severely affected symptomatic patients (n = 90; mean age, 64 years), pure autonomic failure accounted for 33%, multisystem atrophy accounted for 26%, and autonomic/diabetic neuropathy accounted for 31%. The most frequently reported symptoms in these individuals were lightheadedness (88%), weakness or tiredness (72%), cognitive difficulties (47%), blurred vision (47%), tremulousness (38%), and vertigo (37%). Patients with postural orthostatic tachycardia syndrome (POTS), conversely, tended to be symptomatic during upright posture, but they did not typically manifest sufficient hypotension to result in syncope or marked hypotension.

Primary cardiac arrhythmias as the cause of syncope encompass those rhythm disturbances associated with intrinsic cardiac disease (e.g., sinus node dysfunction [SND], AV conduction system disease), accessory conduction pathways, or other structural abnormalities (e.g., congenital anomalies, postoperative disturbances), as well as those resulting from proarrhythmic effects of cardioactive drugs (e.g., cardiac glycosides, positive inotropic agents, antiarrhythmic drugs).

Arrhythmias resulting from intrinsic conduction system disturbances (usually acquired but occasionally congenital) are important causes of syncope. However, it is often difficult to substantiate the relationship between syncope and a suspected arrhythmia in free-living individuals (e.g., by ambulatory electrocardiographic [ECG] monitoring) resulting from the unpredictable occurrence of symptomatic events. Thus, implantable long-term loop recorders (ILRs) and mobile cardiac outpatient telemetry (MCOT) are becoming more widely applied (see later). In some cases, invasive electrophysiologic testing may be indicated (52,53,54,55,56).