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J Neurosonol Neuroimag > Volume 16(2); 2024 > Article
Cho: The Pathophysiology of Syncope and the Role of Transcranial Doppler in its Diagnostic Evaluation

Abstract

Syncope, defined as the transient loss of consciousness due to reduced cerebral blood flow, is a common clinical presentation across patients of all age groups; however, it poses diagnostic challenges owing to its varied etiologies, ranging from benign reflex-mediated mechanisms to more severe cardiac or autonomic dysfunctions. Traditionally, the head-up tilt (HUT) test is applied to assess syncope by simulating orthostatic stress; however, its diagnostic yield is limited, particularly in cases lacking obvious systemic hypotension. Transcranial Doppler (TCD) ultrasonography, a noninvasive tool for measuring cerebral blood flow velocity, provides critical insights into cerebrovascular dynamics during syncope episodes and enhances diagnostic accuracy, particularly when combined with the HUT test. TCD allows for the real-time monitoring of cerebral autoregulation and blood flow changes, and can be used to identify cerebral hypoperfusion patterns in patients with neurocardiogenic syncope, orthostatic hypotension, and orthostatic cerebral hypoperfusion syndrome. Despite the diagnostic value of TCD, challenges such as technical operator dependency, interpretation variability, and the need for standardized protocols persist. Future research directions include the integration of TCD with advanced imaging modalities, leveraging artificial intelligence and machine learning for data interpretation, and refining personalized diagnostic approaches. Standardization and technological enhancements of TCD applications further hold promise for improving syncope management by providing a nuanced understanding of cerebral hemodynamics. This review explores the pathophysiology of syncope, focusing on the reflex and orthostatic forms, and highlighting the role of TCD in syncope evaluation.

INTRODUCTION

Syncope, defined as a transient loss of consciousness, is caused by a temporary reduction in cerebral blood flow, and can be triggered by a variety of underlying mechanisms and etiologies.1-4 It is a relatively common clinical symptom in emergency departments and outpatient clinics, affecting a wide age range of patients, from adolescents to the elderly.5 Failure to identify the cause of syncope can result in physical injury due to recurrent episodes, and may increase the risk of sudden cardiac death or other cardiovascular events associated with underlying cardiac conditions. Among other diagnostic tools, the head-up tilt (HUT) test is widely recommended and applied to assist in differentiating the causes of syncope.1
Transcranial Doppler (TCD) ultrasonography, which allows for the direct assessment of cerebral blood flow dynamics, provides valuable insights into the pathophysiology and mechanisms of syncope, particularly when used in conjunction with the HUT test.6,7 The use of TCD in syncope evaluation can enhance understanding of underlying cerebrovascular changes, facilitating more accurate diagnosis and targeted management.
This review examines the pathophysiology of syncope and explores the role of TCD in its evaluation, placing a particular focus on reflex syncope and syncope due to orthostatic hypotension. In addition, future directions for the application of TCD in syncope assessment are discussed.

1. Definition of syncope

Syncope, a common and diverse clinical syndrome encountered in everyday medical practice,2,5 is defined as a temporary loss of consciousness due to a sudden decrease in cerebral blood flow.1,7 An abrupt decrease in blood flow results in impaired brain perfusion, triggering a transient episode in which the individual loses consciousness, which is generally rapidly recovered without intervention.8,9 Prior to this loss of consciousness, patients commonly experience a range of warning symptoms, collectively referred to as prodromal symptoms,10 including lightheadedness, nausea, sweating, generalized weakness, and visual disturbances. Presyncope is defined as the sensation of imminent loss of consciousness, often marked by a reduction in muscle tone that induces a feeling of impending faintness or collapse without actual syncope. This phenomenon is typically accompanied by autonomic symptoms, such as sweating, nausea, and pallor, resembling those observed in complete syncopal episodes. Recognizing these prodromal manifestations is essential in clinical practice, as they frequently offer valuable diagnostic clues regarding the underlying etiology of syncope, aiding in differentiating between neurogenic, orthostatic, and cardiac origins of the condition.10 The prodromal phase of syncope can last from seconds to minutes, and may resolve if the individual reclines quickly. During loss of consciousness, the skeletal muscles relax, while sphincter control is maintained, subsequently, the pupils dilate, heart rate slows, systolic blood pressure falls below 60 mmHg, and breathing may be difficult to detect. Upon lying down, the pulse strengthens, circulation recovers, and the facial color normalizes. If unconsciousness persists for 15–20 seconds or longer, clonic jerks, facial contractions, or tonic extension may occur, making this condition susceptible to misdiagnosis as an epileptic seizure.10

2. Prevalence of syncope

Syncope is a relatively common symptom, with a lifetime prevalence of 3–3.5% among adults, accounting for approximately 1% of emergency department visits.2,11 Initial episodes frequently occur between the ages of 10 and 30 years, while incidence rates increase sharply with advancing age.5 In cases where syncope is associated with neurological or cardiovascular comorbidities, mortality rates tend to increase. Patients with unexplained syncope typically exhibit a benign clinical course.12,13

3. Clinical importance of syncope

Other conditions that may present with transient loss of consciousness include epilepsy; metabolic disorders, such as hypoglycemia or hypocapnia; vertebrobasilar insufficiency; drug intoxication; psychogenic pseudosyncope; subclavian steal syndrome; subarachnoid hemorrhage; and cyanotic breath-holding spells.1,3,10 These conditions exhibit unique pathophysiological mechanisms that differentiate them from syncope, and require targeted diagnostic approaches to ensure accurate identification and management.3

CLASSIFICATION OF SYNCOPE

As mentioned previously, syncope occurs when cerebral blood flow is suddenly interrupted for approximately 6-8 seconds, or if systemic blood pressure drops below 60 mmHg, resulting in a transient loss of consciousness. As such, the fundamental pathophysiology, or the “final common pathway,” of syncope is a critical reduction in cerebral blood flow due to a significant decrease in blood pressure.14 The blood pressure itself is regulated by two primary factors: cardiac output and total peripheral vascular resistance,15 which form the basis of syncope pathophysiology, and are influenced by the underlying cause of blood pressure dysregulation, classifying syncope into three main types: (1) reflex (neurally mediated) syncope, (2) syncope due to orthostatic hypotension, and (3) cardiac syncope (Table 1).1,4 It is also worth noting that terms such as (1) reflex/neurally mediated syncope and (2) vasovagal/neurocardiogenic syncope are often used interchangeably in the literature, although they may emphasize slightly different aspects of similar underlying mechanisms.

1. Reflex (neurally mediated) syncope

Reflex syncope, also known as neurally mediated syncope, is a form of syncope characterized by dysregulation of the autonomic nervous system that leads to transient hypotension or bradycardia.14 This type is common in younger individuals, but can occur at any age. Risk factors for reflex syncope include a family history of syncope, dehydration, prolonged standing, and exposure to stressors that can provoke autonomic reflexes.16,17 Certain medications, such as antihypertensives, may also increase susceptibility.
The central nervous control for blood pressure and vascular regulation is located in the nucleus tractus solitarius (NTS) of the medulla, in which neural signals are transmitted via the sympathetic and vagal nerves to the heart and blood vessels.18 In reflex syncope, an impairment in normal blood pressure regulation occurring in response to a trigger results in bradycardia and vasodilation, triggering a drop in blood pressure and subsequent cerebral hypoperfusion, which leads to syncope.19
Reflex syncope is categorized into the vasodepressor, cardioinhibitory, and mixed types, based on the mechanisms underlying blood pressure and heart rate regulation.1,20 Vasodepressor syncope predominantly leads to hypotension without significant bradycardia, cardioinhibitory syncope is characterized by pronounced bradycardia or asystole with minimal vasodilation, and the mixed type involves both significant hypotension and bradycardia.1,19 However, in clinical practice, it is more meaningful to identify the cause of syncope; thus, classification according to the type of trigger that stimulates the medulla-based reflex arc is deemed more practical.1,3 Classifications based on the type of trigger includes: (1) vasovagal (neurocardiogenic) syncope, (2) situational syncope, and (3) carotid sinus syndrome (carotid sinus hypersensitivity, carotid sinus syncope).1,21

1) Vasovagal (neurocardiogenic) syncope

Vasovagal syncope occurs when heightened vagal tone or reduced sympathetic tone decreases cerebral blood flow. This reduction can be triggered by specific circumstances or stimuli, leading to a sudden drop in blood pressure.7,15 Prolonged standing or exposure to intense emotional stimuli activates the sympathetic nervous system and increases cardiac contractility. This heightened cardiac output stimulates C fibers in the heart, which in turn activates the vasodepressor region in the medulla.22 This response ultimately leads to vagal activation, resulting in bradycardia and hypotension. Although bradycardia can be addressed with medications or pacemakers, such interventions do not effectively prevent syncope, as hypotension typically precedes the onset of bradycardia, indicating that peripheral vasodilation is the primary underlying mechanism. Additionally, hyperventilation-induced hypocapnia commonly accompanies reflex syncope, and is thought to contribute to peripheral vasodilation and cerebral vasoconstriction.23 Individual sensitivity to carbon dioxide likely varies, influencing susceptibility to these effects.24 While most episodes resolve within 20 s, symptoms may persist for several minutes in rare cases.

2) Situational syncope

Situational syncope refers to syncopal episodes triggered by specific actions, such as coughing, swallowing, urination, or defecation.23 These activities increase intrathoracic or abdominal pressure and decrease venous return to the heart, triggering a reflex-mediated drop in heart rate or blood pressure.21 This can be exacerbated in patients with heightened vagal tone or diminished compensatory sympathetic responses, resulting in transient cerebral hypoperfusion.

3) Carotid sinus syndrome (carotid sinus hypersensitivity, carotid sinus syncope)

Carotid sinus syndrome occurs when the mechanical stimulation of the carotid sinus, such as by wearing a tight collar or head rotation, triggers a strong vagal response.1,25,26 This can result in sudden bradycardia or hypotension, causing syncope. Carotid sinus syndrome is more common in older adults, and its prevalence thus increases with age. This condition represents is an important diagnostic consideration for unexplained syncope, particularly in patients with repeated episodes triggered by neck manipulation.

2. Syncope due to orthostatic hypotension or orthostatic intolerance

The maintenance of blood pressure during various physical activities or postural changes relies on normal cardiovascular and autonomic responses. The autonomic sensory nerve endings of the glossopharyngeal and vagus nerves respond sensitively to pressure via mechanoreceptors located in the aortic arch, carotid sinus, and cardiac wall. Afferent neural stimuli from such receptors are transmitted to the vasomotor center in the medulla, particularly the nucleus tractus solitarius (NTS).27 Efferent signals from the NTS are relayed through the reticular formation of the ventrolateral medulla to the intermediolateral cell column of the spinal cord’s sympathetic nervous system, ultimately determining the vascular tone in skeletal muscle, skin, and visceral vascular beds. When the neural input from these baroreceptors decreases, an increase in excitatory output subsequently increases blood pressure and cardiac output, thus maintaining cerebral blood flow. The autonomic nervous system response is immediate, typically stabilizing systolic pressure with a slight drop (5–10 mmHg) and a slight increase in diastolic pressure (5–10 mmHg), along with an increase in the heart rate of 10–25 beats per minute, helping maintain stable cerebral blood flow.28,29
Orthostatic hypotension (OH) is defined as a drop in systolic blood pressure of 20 mmHg or more upon standing from a seated or lying position.1 OH typically occurs due to delayed vasoconstriction in the lower extremities, resulting in approximately 0.5–1 liter of blood pooling in the legs and reduced venous return, ultimately leading to decreased cardiac output.30 In older adults, orthostatic intolerance, which includes OH, is one of the primary causes of dizziness. The timing of the blood pressure drop allows for the classification of OH into three types: initial OH (within 15 seconds), classic OH (within 3 minutes), and delayed OH (after 3 minutes).1,3
OH arises from the failure of the ANS to adequately adjust to changes in posture. In neurogenic OH, this impairment is commonly caused by underlying autonomic failure, in which sympathetic tone does not sufficiently increase, leading to inadequate vasoconstriction and decreased cardiac output.6,8 Disorders such as Parkinson’s disease, multiple system atrophy, and diabetes can lead to neurogenic OH. Non-neurogenic OH may result from hypovolemia, endocrine dysfunction, or pharmacological influences (e.g., diuretics and antihypertensives) that impair blood pressure maintenance.31
In the broader category of orthostatic intolerance syndromes, OH, postural orthostatic tachycardia syndrome (POTS), and orthostatic cerebral hypoperfusion syndrome (OCHOS) are included.

1) Postural Orthostatic Tachycardia Syndrome (POTS)

Postural Orthostatic Tachycardia Syndrome (POTS) is a form of orthostatic intolerance leading to syncope. POTS is characterized by an increase in the heart rate of 30 beats per minute or more within 10 min of standing, without any corresponding drop in blood pressure.1,4,32 POTS commonly affects women aged between 15 and 50 years, and presents with symptoms such as dizziness, tachycardia, sweating abnormalities, and sometimes hypovolemia or elevated norepinephrine levels. Familial predisposition was noted in approximately one in eight cases, suggesting a genetic component, and approximately half of the cases reported a recent infection, indicating potential autonomic nervous system involvement.33

2) Orthostatic cerebral hypoperfusion syndrome (OCHOS)

Orthostatic cerebral hypoperfusion syndrome (OCHOS) is a recently identified condition previously described as cerebral syncope. OCHOS is characterized by a reduction in cerebral blood flow velocity (CBFv) during standing, without concurrent orthostatic (systemic) hypotension, bradycardia, or excessive tachycardia.33 Patients with OCHOS typically exhibits stable orthostatic blood pressure, heart rate, and respiratory patterns despite reduced orthostatic CBFv. This syndrome is a common cause of orthostatic dizziness. One study reported that 102/1,279 patients (7.9%) with unexplained orthostatic dizziness were ultimately diagnosed with orthostatic cerebral hypoperfusion syndrome (OCHOS).32

3. Cardiac syncope

Cardiac or cardiogenic syncope, commonly caused by paroxysmal arrhythmias, valvular stenosis, or intracardiac masses, occurs when the blood flow from the heart is temporarily obstructed, leading to an abrupt reduction in cerebral perfusion.17 This form of syncope is associated with a poorer prognosis compared to other forms, owing to the underlying cardiac pathology and its potential to cause sudden cardiac death if left untreated. It is widely recognized as the most serious form of syncope owing to its high mortality risk.19,34

ROLE OF TRANSCRANIAL DOPPLER IN DIAGNOSTIC EVALUATION OF SYNCOPE

1. Application of transcranial Doppler ultrasonography in evaluation of syncope

TCD ultrasonography is a noninvasive tool used to measure CBFv, allowing the real-time monitoring of its changes during syncope episodes.6,7,35 TCD is used to identify abnormalities in cerebral autoregulation and blood flow dynamics that can contribute to syncope, particularly in cases where cardiac causes are not evident. TCD combined with the HUT test is a valuable method for identifying the underlying causes of syncope.7 Monitoring cerebral blood flow (CBF) via TCD during the HUT test can help to establish whether syncope results from cerebral hypoperfusion, thereby providing key diagnostic insights. TCD also allows the assessment of cerebral autoregulation, which is crucial for distinguishing syncope caused by autoregulatory failure from other forms, such as cardiac-related syncope. The ability to continuously monitor and quantify CBF changes makes TCD an indispensable tool for understanding the dynamic vascular responses during syncope episodes. Integration of TCD into the syncope evaluation protocol can significantly enhance diagnostic accuracy, particularly in cases where conventional methods, such as electrocardiography or basic cardiovascular evaluation, fail to explain the patient’s symptoms. The noninvasive and portable nature of TCD allows its use in outpatient settings, making it a practical choice for continuous monitoring during syncope episodes.
One of the key advantages of TCD in this setting is its ability to detect OCHOS, in which CBF decreases without accompanying blood pressure changes, providing a unique diagnostic edge.32,36 Studies have demonstrated that TCD monitoring during HUT test shows significant drops in middle cerebral artery blood flow velocity (MCA-BFV) prior to syncope onset in patients with neurocardiogenic syncope, even without major systemic hypotension.8 This finding underscores the value of TCD in assessing cerebrovascular autoregulation and detecting early cerebral hypoperfusion in real-time, which standard HUT test alone might miss.

2. Procedure for performing TCD with Tilt Table Testing36,37 (Fig. 1)

• Preparation: The patient is placed in the supine position on a tilt table for at least 5 min. The baseline blood pressure and heart rate are measured. For TCD integration, a 2 MHz Doppler probe is placed in the temporal window to measure the middle cerebral artery blood flow velocity (CBFv) and pulsatility index.
• Tilting: The table is raised to 60–70 degrees to optimize venous pooling in the lower extremities, which reduces lower-limb muscle tension and suppresses sympathetic activation, enhancing test sensitivity.
• Monitoring: Changes in blood pressure, heart rate, and CBFv are monitored for 20–45 minutes. If symptoms such as dizziness, weakness, or syncope appear, the timing and symptoms can be documented. A positive result includes symptom reproduction with a CBFv drop or hypotension, necessitating immediate table descent for recovery.
• Use of Pharmacologic Provocation: For patients with negative responses to passive tilting, pharmacological agents such isoproterenol (1–3 μg/min, with heart rate increasing by 20–25%) or sublingual nitroglycerine (300–400 μg) can be administered to enhance test sensitivity. However, isoproterenol use is contraindicated in patients with coronary artery disease, severe aortic stenosis, or uncontrolled hypertension owing to the risk of arrhythmia.

3. Interpretation of Test Results36

Interpretation relies on the combined assessment of blood-, heart-, and TCD-measured CBFv changes during the HUT. The symptoms presented by patients during testing are essential to ensure an accurate interpretation.
 1) Normal Response: If the blood pressure, heart rate, and CBFv remained stable without symptom provocation, the result is interpreted as normal.
 2) Vasodepressive and Cardioinhibitory Responses:
o A vasodepressive response is diagnosed when blood pressure drops significantly without a corresponding decrease in heart rate. This pattern indicates that a vasodepressant reaction is often linked to excessive vasodilation triggered by autonomic dysregulation.
o A cardioinhibitory response is diagnosed when both blood pressure and heart rate decrease. Heart rate decreases prior to the onset of a syncopal episode, followed by a subsequent decline in blood pressure. This response is commonly observed in neurocardiogenic (vasovagal) syncope and indicates increased vagal activity leading to bradycardia.
 3) OH:
o OH is defined as a blood pressure decrease by ≥20 mmHg systolic or ≥10 mmHg diastolic within 3 min of tilting, with little or no change in heart rate. TCD often shows decreased CBFv in the middle cerebral artery owing to diminished cerebral perfusion.
o Early OH occurs within 15 s of tilting, and is related to an immediate imbalance between the cardiac output and total peripheral resistance.
o Classic OH occurs within 3 min of tilting, and typically results from a failure of compensatory autonomic responses.
o Delayed OH manifests after 3 min without significant bradycardia, which helps to differentiate it from vasovagal syncope.

4. Patterns of TCD findings on syncope patients in the HUT test

The patterns of heart rate, blood pressure, and CBFv for various types of syncope are presented in Table 1 and Fig. 2.
 1) Vasovagal syncope38,39
o Initially, blood pressure may remain stable because of compensatory mechanisms. However, after a delay, the blood pressure drops significantly (≥20 mmHg systolic or ≥10 mmHg diastolic), commonly accompanied by bradycardia. Presyncope symptoms and actual syncope may also follow.
o Significant reductions in middle cerebral artery blood flow velocity (MCA-BFV) occur immediately before the syncopal episode. This decrease in diastolic blood flow is critical for distinguishing VVS from other forms of syncope. The MCA-BFV score decreased sharply before loss of consciousness.
o TCD findings indicate a decrease in MCA blood flow velocity by approximately 30%, with a greater reduction in diastolic than systolic flow, leading to a pronounced dicrotic notch (suggesting paradoxical cerebral vasoconstriction).
o Prolonged Recovery Time: Research combining TCD with EEG recordings has indicated that patients with vasovagal syncope tend to have a prolonged recovery time for cerebral blood flow normalization following a syncopal event. This slow recovery is associated with persistent cerebral hypoperfusion, further contributing to the diagnostic value of TCD in vasovagal syncope.
 2) OH7
o Patients with OH commonly experience impaired cerebral autoregulation, leading to significant reductions in middle cerebral artery blood flow velocity (MCA-BFV) during orthostatic stress.
o Combining TCD with the HUT offers a powerful method for assessing how blood flow in the brain responds to hypotensive episodes that occur during OH. In prior studies, patients with OH exhibited a marked decline in diastolic MCA-BFV during HUT, indicating that the cerebral circulation fails to maintain adequate perfusion under orthostatic stress.
o The typical pattern detected by TCD in patients with OH involves a progressive decrease in both systolic and diastolic blood flow velocities in an upright posture, often accompanied by dizziness or presyncope. Such findings are especially valuable when assessing patients with delayed orthostatic hypotension, in whom traditional diagnostic methods may miss early signs of cerebral hypoperfusion.
 3) POTS40,41
o POTS is characterized by an increase in heart rate of ≥30 bpm, or a heart rate exceeding 120 bpm within 10 min of tilt without any significant blood pressure drop.
o When combined with TCD, POTS is diagnosed if there is a ≥30% decrease in MCA CBFV without marked blood pressure changes. This pattern, indicated by an increased pulsatility index, likely results from distal cerebral vasoconstriction due to heightened sympathetic activity.
 4) OCHOS32
o During the tilt test, patients with OCHOS typically display a marked reduction in CBFv when transitioning to an upright position, without concurrent hypotension or arrhythmias, which are often associated with orthostatic intolerance syndromes such as OH or POTS.
o Research has indicated that while blood pressure remains stable during tilting in OCHOS, CBFv drops significantly, suggesting that impaired cerebral autoregulation rather than systemic cardiovascular dysfunction is the underlying mechanism. This pattern helps distinguish OCHOS from other types of syncope and conditions involving blood pressure variability.

CLINICAL UTILITY OF TCD IN DIAGNOSTIC EVALUATION OF SYNCOPE

1. Diagnostic accuracy improvement in syncope patients

TCD has shown significant utility in improving the accuracy of syncope diagnosis. For example, among patients with neurocardiogenic syncope, TCD can detect paradoxical cerebral vasoconstriction preceding systemic hypotension.7,42,43 Studies using the HUT test combined with TCD have indicated that blood flow reduction in the middle cerebral artery (MCA) precedes changes in heart rate and blood pressure.43 This early detection can help clinicians to predict the onset of syncope, and offers a more precise diagnosis than standard cardiovascular evaluations alone.

2. Differential diagnosis of syncope using TCD

TCD is useful in differentiating between various types of syncope.6,7 For example, vasovagal syncope shows a characteristic decrease in diastolic blood flow velocity prior to loss of consciousness, whereas cardiac syncope involves more abrupt changes in cerebral blood flow due to compromised cardiac output. TCD also aids in distinguishing neurogenic syncope from cardiac causes such as arrhythmias by analyzing the temporal profile of blood flow changes.

3. Comparison with other non-invasive diagnostic methods

Compared to other non-invasive methods, such as the HUT test alone, TCD provides a deeper understanding of the cerebral aspects of syncope.1,6,7 The HUT test is effective at diagnosing reflex syncope in approximately 50% of cases; however, the diagnostic yield increases when combined with TCD, especially in detecting cerebral hypoperfusion prior to systemic changes.1,43 In addition, it is useful in detecting orthostatic cerebral hypoperfusion syndrome, which could be revealed only in TCD-HUT.

LIMITATIONS AND CONSIDERATIONS ON USAGE OF TCD IN EVALUATION OF SYNCOPE

1. Technical limitations of TCD

TCD is highly operator-dependent, meaning that the accuracy of the results varies significantly based on the skill and experience of the technician performing the examination. 6,44 This presents a major limitation, as less-experienced operators may produce less reliable results, particularly in more complex cases, such as syncope. Additionally, the acoustic window used for TCD, typically the temporal bone, can be challenging to penetrate in certain patients, especially elderly women with thicker skull bones, reducing the reliability of the test in these populations.

2. Interpretation challenges

The interpretation of TCD results in patients with syncope may be complicated by factors such as varying hemodynamic responses and baseline conditions. TCD measures the CBFv in the large basal arteries, which may not reflect local blood flow variations, particularly in microcirculatory regions.45 For example, changes in diastolic flow velocity can indicate different underlying mechanisms in vasovagal versus cardiac syncope, requiring a nuanced understanding of the waveform patterns. Misinterpretation may further lead to incorrect diagnoses, particularly when differentiating between types of syncope.

3. Need for standardized protocols

A major limitation of the clinical use of TCD for syncope is the lack of standardized protocols. Variations in the administration and interpretation of tests across clinical settings can also affect diagnostic consistency. As such, establishing standardized protocols is essential to ensure the reliability of data collection, accurate interpretation, and reproducibility. The development of these standards will improve TCD’s effectiveness of TCD as a diagnostic tool and enable its broader application in syncope evaluation.

FUTURE DIRECTIONS OF TCD IN DIAGNOSTIC EVALUATION OF SYNCOPE

1. TCD integration with new imaging technologies

Although powerful, TCD is commonly limited by its ability to only measure blood flow velocity in the major basal arteries.45 However, advancements in imaging technology offer the potential to integrate TCD with other imaging modalities, such as MRI, CT, and advanced ultrasound techniques. Such integration could enhance the spatial resolution and provide more comprehensive data on cerebral hemodynamics during syncope evaluation. For example, combining TCD with 3D or 4D imaging modalities may facilitate the real-time monitoring of cerebral perfusion and vessel structure, thereby enhancing the diagnostic precision for different syncope types.

2. The need for further research in syncope evaluation using TCD

Although TCD has been validated in many cerebrovascular applications, its use in syncope, particularly in distinguishing between different etiologies, requires further investigation. Future research should therefore focus on standardizing TCD protocols, specifically for syncope evaluation, and refining the technology to enhance its utility in various patient populations. For example, more studies are required to evaluate the role of TCD in detecting early cerebral blood flow reduction before syncopal events, as observed in neurocardiogenic and orthostatic syncope.

3. Artificial intelligence and machine learning for TCD data analysis

The integration of artificial intelligence (AI) and machine learning (ML) into TCD data analysis is considered a promising area of research.46 AI can help to overcome one of the major limitations of TCD—its operator dependency—by automating the interpretation of complex waveforms and patterns. Machine learning algorithms can also be used to detect subtle changes in the cerebral blood flow that may not be easily recognizable by humans, leading to more accurate diagnoses and personalized treatment plans.

4. TCD’s role in personalized diagnostic approaches

In the era of personalized medicine, TCD play a critical role in offering tailored diagnostics based on individual cerebral hemodynamic responses. AI-enhanced TCD can process large datasets from diverse patient groups and identify unique cerebral blood flow patterns linked to specific syncopal episodes. This allows clinicians to develop customized management strategies for patients based on specific cerebrovascular responses.

CONCLUSION

Syncope represents a complex clinical challenge, characterized by heterogeneous etiologies that require an integrative diagnostic approach. Although the HUT has traditionally been employed in the evaluation of syncope, its combination with TCD ultrasonography significantly enhances diagnostic accuracy by providing real-time insights into cerebral blood flow dynamics. In particular, the combination of TCD and HUT facilitates the early detection of cerebral hypoperfusion in conditions such as neurocardiogenic syncope, OH, and OCHOS, making TCD an invaluable tool for identifying subtle cerebrovascular changes that may elude standard cardiovascular evaluations. However, the use of TCD is challenging; operator dependency, variability in interpretation, and the absence of standardized protocols limit its broader clinical application. Addressing these limitations through the implementation of standardized procedures and improved operator training, and the integration of advanced imaging technologies will be crucial for unlocking TCD’s full diagnostic potential of TCD. The introduction of artificial intelligence and machine learning also presents promising avenues for automating TCD data analysis, potentially reducing operator variability, and enhancing the detection of nuanced hemodynamic patterns associated with syncope.
Future research should prioritize the refinement of TCD protocols for syncope assessment and explore their role in personalized diagnostics. By customizing evaluations based on individual cerebrovascular responses, TCD may play a pivotal role in precision medicine for syncope management. As research and technological advances progress, TCD has become a cornerstone in the diagnostic arsenal for syncope, providing deeper insights into the cerebrovascular mechanisms underlying this condition, and facilitating the development of more targeted and effective treatment strategies.

NOTES

Ethics Statement
The Institutional Review Board process and patient consent were not obtained because this is a review article.
Availability of Data and Material
This is not applicable to this type of manuscript as it does not contain raw data.
Sources of Funding
None.
Conflicts of Interest
No potential conflicts of interest relevant to this article was reported.

Acknowledgments

I extend my sincere gratitude to technicians Lee Jung Hun, Jeon Nam Joon, and Yoon Seok Hwi from the Neurophysiology Laboratory for their invaluable assistance and collaboration.

Fig. 1.
Transcranial Doppler (TCD) monitoring during the head-up tilt test. (A) Placement of the TCD device on the head. (B) Monitoring heart rate, blood pressure and cerebral blood flow during the supine phase of the head-up tilt test. (C) Tilting to approximately 70 degrees during the head-up tilt test. Monitoring was also applied.
jnn-2024-00160f1.jpg
Fig. 2.
A schematic representation of the Transcranial Doppler (TCD) during the head-up tilt test. Examples for reflex syncope, orthostatic hypotension, orthostatic cerebral hypoperfusion syndrome, and postural orthostatic tachycardia syndrome are shown. BP, blood pressure; HR, heart rate; mCBFv, mean cerebral blood flow velocity.
jnn-2024-00160f2.jpg
Table 1.
Different patterns of syncope in heart rate, blood pressure, and cerebral blood flow velocity during the head-up tilt test
HR BP CBFv
Reflex syncope
 Syncope, cardiovagal Decline before syncope Profound decline Vasodilation pattern*
 Syncope, vasodepressor No decline Profound decline Vasodilation pattern*
 Syncope, mixed Decline simultaneously Decline simultaneously Vasodilation pattern*
Orthostatic syndrome
 Orthostatic hypotension Normal HR increment (>10 and <30 bpm) Reduced Reduced
 OCHOS Normal HR increment (>10 and <30 bpm) Stable Reduced
Tachycardia syndrome
 POTS Sustained increment (>30 bpm or to >120 bpm) Stable Reduced

OCHOS, orthostatic cerebral hypoperfusion syndrome; POTS, postural orthostatic tachycardia syndrome; HR, heart rate; bpm, beats per minute; BP, blood pressure; CBFv, cerebral blood flow velocity.

* Vasodilation pattern indicates a decline in diastolic blood flow and an increase in systolic cerebral blood flow velocity.

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