Head impulse, nystagmus, and test of skew examination for diagnosing central causes of acute vestibular syndrome

Michael Gottlieb; Gary D Peksa; Jestin N Carlson

doi:10.1002/14651858.CD015089.pub2

. 2023 Nov 2;2023(11):CD015089. doi: 10.1002/14651858.CD015089.pub2

Head impulse, nystagmus, and test of skew examination for diagnosing central causes of acute vestibular syndrome

Michael Gottlieb ^1,^✉, Gary D Peksa ¹, Jestin N Carlson ²

Editor: Cochrane Stroke Group

PMCID: PMC10620998 PMID: 37916744

Abstract

Background

Dizziness is a common reason for people to seek medical care. Acute vestibular syndrome (AVS) is a specific type of dizziness, which can include severe vertigo, nausea and vomiting, nystagmus, or unsteadiness. Acute vestibular syndrome can be due to peripheral or central causes. It is important to determine the cause, as the intervention and outcomes differ if it is from a peripheral or central cause. Clinicians can assess for the cause using risk factors, patient history, examination findings, or advanced imaging, such as a magnetic resonance imaging (MRI). The head impulse, nystagmus, test of skew (HINTS) examination is a three‐part examination performed by clinicians to determine if AVS is due to a peripheral or central cause. This includes assessing how the eyes move in response to rapidly turning a person's head (head impulse), assessing the direction of involuntary eye movements (nystagmus), and assessing whether the eyes are aligned or misaligned (test of skew). The HINTS Plus examination includes an additional assessment of auditory function.

Objectives

To assess the diagnostic accuracy of the HINTS and HINTS Plus examinations, with or without video assistance, for identifying a central etiology for AVS.

Search methods

We searched CENTRAL, MEDLINE, Embase, Google Scholar, the International HTA database, and two trials registers to September 2022.

Selection criteria

We included all retrospective and prospective diagnostic test accuracy studies that evaluated the HINTS or HINTS Plus test used in a primary care clinic, an urgent care clinic, the emergency department, or during inpatient hospitalization against a final diagnosis of a central etiology of AVS, as defined by the reference standard of advanced imaging or final diagnosis by a neurologist.

Data collection and analysis

Two review authors independently determined eligibility of each study according to eligibility criteria, extracted data, assessed the risk of bias, and determined the certainty of evidence. Disagreements were adjudicated by consensus or a third review author if needed.

The primary outcome was the diagnostic accuracy of the HINTS and HINTS Plus examinations for identifying a central etiology for AVS, conducted clinically (clinician visual assessment) or with video assistance (e.g. video recording with goggles); we independently assessed the clinical and video‐assisted examinations.

Subgroup analyses were performed by provider type (e.g. physicians, non‐physicians), time from symptom onset to presentation (e.g. less than 24 hours, longer than 24 hours), reference standard (e.g. advanced imaging, discharge diagnosis), underlying etiology (e.g. ischemic stroke, alternative etiologies [hemorrhagic stroke, intracranial mass]), study setting (e.g. outpatient [outpatient clinic, urgent care clinic, emergency department], inpatient), physician level of training (e.g. resident, fellow/attending), physician specialty (e.g. otolaryngology, emergency medicine, neurology, and neurologic subspecialist [e.g. neuro‐ophthalmology, neuro‐otology]), and individual diagnostic accuracy of each component of the examination (e.g. head impulse, direction‐changing nystagmus, test of skew).

We created 2 x 2 tables of the true positives, true negatives, false positives, and false negatives and used these data to calculate the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio with 95% confidence intervals (95% CI) for each outcome.

Main results

We included 16 studies with a total of 2024 participants (981 women and 1043 men) with a mean age of 60 years. Twelve studies assessed the HINTS examination; five assessed the HINTS Plus examination. Thirteen studies were performed in the emergency department; half were performed by neurologists.

The clinical HINTS examination (12 studies, 1890 participants) was 94.0% (95% confidence interval [CI] 82.0% to 98.2%) sensitive, and 86.9% (95% CI 75.3% to 93.6%) specific (low‐certainty evidence). The video‐assisted HINTS examination (3 studies, 199 participants) was 85.0% to 100% sensitive (low‐certainty evidence), and 38.9% to 100% specific (very low‐certainty evidence).

The clinical HINTS Plus examination (5 studies, 451 participants) was 95.3% (95% CI 78.4% to 99.1%) sensitive, and 72.9% (95% CI 44.4% to 90.1%) specific (low‐certainty evidence). The video‐assisted HINTS Plus examination (2 studies, 163 participants) was 85.0% to 93.8% sensitive, and 28.6% to 38.9% specific (moderate‐certainty evidence).

Subgroup analyses were limited, as most studies were conducted in the emergency department, by physicians, and with MRI as a reference standard. Time from symptom onset to presentation varied across studies.

Three studies were at high risk of bias and three studies were at unclear risk of bias for participant selection. Three studies were at unclear risk of bias for the index test. Four studies were at unclear risk of bias for the reference standard. Two studies were at unclear risk of bias for flow and timing. One study had unclear applicability concerns for participant selection. Two studies had high applicability concerns for the index test and two studies had unclear applicability concerns for the index test. No studies had applicability concerns for the reference standard.

Authors' conclusions

The HINTS and HINTS Plus examinations had good sensitivity and reasonable specificity for diagnosing a central cause for AVS in the emergency department when performed by trained clinicians. Overall, the evidence was of low certainty. There were limited data for the role of video‐assistance or specific subgroups.

Future research should include more high‐quality studies of the HINTS and HINTS Plus examination; assessment of inter‐rater reliability across users; accuracy across different providers, specialties, and experience; and direct comparison with no HINTS or MRI to assess the effect on clinical care.

Keywords: Female; Humans; Male; Middle Aged; Dizziness; Dizziness/diagnosis; Dizziness/etiology; Nausea; Nausea/etiology; Nystagmus, Pathologic; Nystagmus, Pathologic/diagnosis; Nystagmus, Pathologic/etiology; Prospective Studies; Reproducibility of Results; Retrospective Studies; Vertigo; Vertigo/diagnosis; Vertigo/etiology; Vomiting; Vomiting/etiology

Plain language summary

Head impulse, nystagmus, and test of skew (HINTS) examination for causes in the brain of acute dizziness

Key Messages

The HINTS and HINTS Plus examinations were reasonably accurate for diagnosing a central cause for acute vestibular syndrome (AVS).

What is acute vestibular syndrome?

Acute vestibular syndrome is a specific type of dizziness, which can include severe vertigo (spinning sensation), nausea and vomiting, nystagmus (involuntary eye movements), or unsteadiness. Acute vestibular syndrome can be due to peripheral causes (those within the ear canal) or central causes (those within the brain). Clinicians can assess for the cause using risk factors, personal history, examination findings, or advanced imaging, such as magnetic resonance imaging (MRI).

What are the HINTS and HINTS Plus examinations?

The head impulse, nystagmus, test of skew (HINTS) examination is a three‐step examination performed by clinicians to determine if AVS is due to a peripheral or central cause. This includes assessing how the eyes move in response to rapidly turning a person's head (head impulse), assessing the direction of involuntary eye movements (nystagmus), and assessing whether the eyes are aligned or misaligned (test of skew). The HINTS Plus examination includes an assessment of auditory function (hearing).

What did we want to find out?

This review looked at how accurate the HINTS or HINTS Plus examination is in determining if a person's AVS is due to a central cause.

What did we do?

We looked for studies of adults (aged 16 years or older) that assessed the diagnostic accuracy of the HINTS or HINTS Plus examination compared with a gold standard of advanced imaging or final diagnosis by a neurologist.

What did we find?

We found 16 studies with a total of 2024 participants. Twelve studies assessed the HINTS examination; five assessed the HINTS Plus examination. Most studies were performed in the emergency department; half were performed by neurologists. The HINTS and HINTS Plus examinations had good sensitivity and reasonable specificity for diagnosing a central cause for AVS.

What are the limitations of the evidence?

The included participants, clinician training, clinician specialty, and clinician experience varied across studies. Study outcomes focused primarily on a single central cause (stroke), while only a few assessed for broader causes, such as intracranial bleeding, intracranial mass, or multiple sclerosis.

How up to date is this evidence?

This evidence is up‐to‐date to 26 September 2022.

Summary of findings

Summary of findings 1. What is the diagnostic accuracy of HINTS and HINTS Plus for diagnosing a central cause of acute vestibular syndrome?

What is the diagnostic accuracy of HINTS and HINTS Plus for diagnosing a central cause of acute vestibular syndrome?
Patient population	Adults with symptoms of acute vestibular syndrome
Settings	Emergency department in 13 studies (Carmona 2016; Choi 2017; Dmitriew 2021; Filippopulos 2022; Gerlier 2021; Kmetonyova 2022; Korda 2022a; Korda 2022b; Newman‐Toker 2013a; Saber Tehrani 2013a; Salim 2022; Siepmann 2021a; Thomas 2022); emergency department and outpatient clinic in 1 study (Wang 2021); outpatients and inpatients in 1 study (Sankalia 2021); and only inpatients in 1 study (Batuecas‐Caletrio 2014).
Clinician performing exam	Neurologist in 7 studies (Carmona 2016; Filippopulos 2022; Kmetonyova 2022; Saber Tehrani 2013a; Siepmann 2021a; Thomas 2022; Wang 2021); neuro‐otologist in 3 studies (Choi 2017; Korda 2022a; Korda 2022b); emergency medicine physician in 2 studies (Dmitriew 2021; Gerlier 2021); neuro‐ophthalmologist in 1 study (Newman‐Toker 2013a); and otolaryngologist in 1 study (Batuecas‐Caletrio 2014). The clinician specialty was not reported in 2 studies (Salim 2022; Sankalia 2021).
Index test	Clinical HINTS was evaluated in 12 studies (Batuecas‐Caletrio 2014; Carmona 2016; Dmitriew 2021; Filippopulos 2022; Gerlier 2021; Kmetonyova 2022; Korda 2022b; Newman‐Toker 2013a; Salim 2022; Sankalia 2021; Thomas 2022; Wang 2021); video‐assisted HINTS was evaluated in 3 studies (Korda 2022a; Saber Tehrani 2013a; Thomas 2022); clinical HINTS Plus was evaluated in 5 studies (Choi 2017; Newman‐Toker 2013a; Sankalia 2021; Siepmann 2021a; Thomas 2022); and video‐assisted HINTS Plus was evaluated in 2 studies (Siepmann 2021a; Thomas 2022).
Reference standard	MRI was used in 13 studies (Batuecas‐Caletrio 2014; Carmona 2016; Choi 2017; Gerlier 2021; Kmetonyova 2022; Korda 2022a; Korda 2022b; Newman‐Toker 2013a; Saber Tehrani 2013a; Salim 2022; Sankalia 2021; Siepmann 2021a; Wang 2021); MRI or clinical diagnosis was used in 2 studies (Filippopulos 2022; Thomas 2022); and MRI, CT, or clinical diagnosis was used in 1 study (Dmitriew 2021).
Target condition	The target condition was acute ischemic stroke in 8 studies (Carmona 2016; Choi 2017; Kmetonyova 2022; Korda 2022a; Korda 2022b; Saber Tehrani 2013a; Sankalia 2021; Thomas 2022); ischemic or hemorrhagic stroke in 3 studies (Batuecas‐Caletrio 2014; Salim 2022; Wang 2021); stroke or transient ischemic attack in 2 studies (Filippopulos 2022; Siepmann 2021a); any acute brain process in the posterior fossa in 2 studies (Gerlier 2021; Newman‐Toker 2013a); and stroke, transient ischemic attack, or multiple sclerosis in 1 study (Dmitriew 2021).
Included studies	14 prospective and 2 retrospective studies; 14 full text and 2 abstract only; 2024 total participants
Limitations	Differences in inclusion and exclusion criteria; variation in clinician training, experience, and specialty; differences in specific target condition assessed; variation in MRI timing
Objective	Numberof studies (participants)	Pooled sensitivity; % (95% CI)	Pooled specificity; % (95% CI)	Prevalence with effect per 100 participants^a	True positives: people in whom the index test will correctly identify disease	False negatives: people in whom the index test will miss identifying disease	True negatives: people in whom the index test will correctly identify absence of disease	False positives: people in whom the index test will incorrectly identify disease	Certainty of the evidence (GRADE)
Clinical HINTS	12 (1890)	94.0 (82.0 to 98.2) Index test will correctly identify disease in 94 out of 100 people with the disease (6 missed)	86.9 (75.3 to 93.6) Index test will correctly identify absence of disease in 87 out of 100 people without the disease (13 missed)	20%	19	1	70	10	⨁⨁◯◯ Low^b,c
				30%	28	2	61	9
				40%	38	2	52	8
Video‐assisted HINTS	3 (199)	Range: 85.0 to 100; 96.3 (87.6 to 100.0)	Range: 38.9 to 100.0; 75.7 (37.1 to 100.0)	20%	19	1	61	19	⨁⨁◯◯ Low (sensitivity)^c,d ⨁◯◯◯ Very low (specificity)^b,c,d
				30%	29	1	53	17
				40%	39	1	45	15
Clinical HINTS Plus	5 (451)	95.3 (78.4 to 99.1)	72.9 (44.4 to 90.1)	20%	19	1	58	22	⨁⨁◯◯ Low^b,c
				30%	29	1	51	19
				40%	38	2	44	16
Video‐assisted HINTS Plus	2 (163)	Range: 85.0 to 93.8; 90.6 (81.1 to 100.0)	Range: 28.6 to 38.9; 37.6 (29.2 to 46.0)	20%	18	2	30	50	⨁⨁⨁◯ Moderate^d
				30%	27	3	26	44
				40%	36	4	23	37
Secondary objectives for HINTS subcomponents
Head impulse	9 (905)	68.8 (42.0 to 87.1)	92.5 (75.8 to 98.0)	20%	14	6	74	6	⨁⨁◯◯ Low^b,c
				30%	21	9	65	5
				40%	28	12	56	4
Video head impulse	3 (239)	Range: 18.2 to 82.6; 61.1 (24.7 to 97.5)	Range: 45.1 to 86.8; 66.7 (36.7 to 96.7)	20%	12	8	53	27	⨁◯◯◯ Very low^b,c,d
				30%	18	12	47	23
				40%	24	16	40	20
Nystagmus	9 (1128)	56.8 (40.2 to 71.9)	98.8 (96.0 to 99.7)	20%	11	9	79	1	⨁⨁◯◯ Low (sensitivity)^b,c ⨁⨁⨁◯ Moderate (specificity)^b
				30%	17	13	69	1
				40%	23	17	59	1
Test of skew	10 (1313)	15.0 (6.6 to 30.5)	98.7 (97.1 to 99.4)	20%	3	17	79	1	⨁⨁◯◯ Low (sensitivity)^b,c ⨁⨁⨁◯ Moderate (specificity)^b
				30%	5	25	69	1
				40%	6	34	59	1
Investigation of heterogeneity and sensitivity analyses	Heterogeneity was deemed high for the clinical HINTS examination; supported by moderately wide confidence intervals for the summary estimates of sensitivity (95% CI 82.0% to 98.2%) and specificity (95% CI 75.3% to 93.6%); and an SROC curve with a 95% prediction region that visually appeared to encompass a majority of the plot area. Subgroup analyses yielded similar summary sensitivity and specificity estimates as the primary analysis, without meaningful impact on heterogeneity. Sensitivity analyses, including only prospective study designs, studies deemed to be at low risk of bias, and excluding studies that were outliers in sensitivity, specificity, or both, provided summary estimates similar to the primary analysis.
Conclusions	The clinical HINTS examination has good sensitivity (94.0%, 95% CI 82.0% to 98.2%) to help rule out a central cause for acute vestibular syndrome, and reasonable specificity (86.9%, 95% CI 75.3% to 93.6%) to help rule in a central cause. The clinical HINTS Plus examination has good sensitivity (95.3%, 95% CI 78.4% to 99.1%) to help rule out a central cause for acute vestibular syndrome, and reasonable specificity (72.9%, 95% CI 44.4% to 90.1%) to help rule in a central cause. There are insufficient data on video‐assisted HINTS and HINTS Plus; more data are needed for these applications.

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^aWe chose 3 values of disease prevalence based on the median prevalence from included studies of 30%, the first quartile of 20%, and the third quartile of 40%. ^bWe downgraded the certainty of evidence due to inconsistency (wide variance of point estimates across studies). ^cWe downgraded the certainty of evidence due to imprecision (wide confidence intervals of the summary estimates). ^dWe downgraded the certainty of evidence due to imprecision (low information size).

CI: confidence interval; CT: computed tomography; MRI: magnetic resonance imaging.

GRADE Working Group certainty of evidence grades.

High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

Background

Target condition being diagnosed

Dizziness and vertigo are common reasons for people to present for medical care, and account for approximately 3% of emergency department (ED) visits and 6% of general medicine clinic visits (Kroenke 1998; Newman‐Toker 2008a). This corresponds to over 3.9 million ED visits per year, with an annual cost exceeding USD 4 billion in the USA (Saber Tehrani 2013B).

Acute vestibular syndrome (AVS) is a subset of dizziness and vertigo consisting of a constellation of symptoms, which can include severe vertigo, nausea and vomiting, spontaneous nystagmus (involuntary rhythmic side‐to‐side, up‐and‐down or circular movement of the eyes), and postural instability/imbalance (Hotson 1998). The etiology of AVS can include peripheral causes (e.g. vestibular neuronitis, neurolabrynthitis, Meniere's syndrome) or central causes (e.g. ischemic stroke, intracerebral hemorrhage, intracranial mass, bulbar ischemia [Hotson 1998]). Most people with AVS will have a benign peripheral etiology (i.e. a non‐dangerous cause, which can often be managed symptomatically [Hotson 1998]). However, dangerous central causes, such as cerebellar infarction and cerebellar hemorrhage, can mimic peripheral causes. Studies report that up to 25% of people presenting to an ED with AVS may have a cerebellar infarction (Cnyrim 2008; Duncan 1975; Kerber 2006; Lee 2006; Norrving 1995). These central causes are more time‐sensitive, often requiring admission, serial neurologic assessments, and additional acute evaluation and management, depending upon the specific cause. For example, an acute stroke may necessitate thrombolysis or endovascular thrombectomy in the context of acute symptoms.

It is critically important to identify people with cerebellar infarction because it may produce significant cerebellar edema (swelling), leading to compression of the brainstem and death without neurosurgical intervention (Hornig 1994; Hotson 1998; Sypert 1975). People with cerebellar infarction are also at increased risk of recurrent stroke, so it is important to diagnose this, in order to reduce the probability of recurrent stroke (Amarenco 1994; Duncan 1975; Hotson 1998; Norrving 1995).

Index test(s)

The head impulse, nystagmus, test of skew (HINTS) examination consists of three individual examination components: head impulse, nystagmus, and test of skew. The head impulse test is a measure of the vestibulo‐ocular reflex (VOR), and is performed by having the person focus their eyes on a single central target, while their head is rapidly rotated side‐to‐side in a horizontal direction (Halmagyi 1988; Newman‐Toker 2008b). A normal VOR response for this test is for the person to generate an equal and opposite eye movement, such that their eyes appear stationary in space while their head moves (Black 2005). An abnormal VOR response occurs when the eyes are unable to maintain the fixation in one direction due to loss of the vestibular afferent input, causing the person to develop a corrective gaze shift (i.e. their eyes must correct back to the center instead of remaining stationary [Newman‐Toker 2008b]).

Nystagmus (i.e. rapid, involuntary eye movements in a horizontal, vertical, or rotatory direction) is often present in people with AVS, from both a central and peripheral etiology (Newman‐Toker 2008b). When AVS is due to a peripheral etiology, the nystagmus is predominately horizontal, and beats only in a single direction, with the intensity increasing when the person looks in the direction of the nystagmus fast phase, also known as Alexander's Law (Cnyrim 2008; Newman‐Toker 2009B). An abnormal finding (suggestive of a central cause of AVS) includes vertical nystagmus, torsion nystagmus, or nystagmus that changes in direction on eccentric gaze (i.e. does not localize in a single direction [Cnyrim 2008; Kattah 2009; Newman‐Toker 2009B]). The latter finding is often referred to as direction‐changing, gaze‐evoked nystagmus.

Skew deviation consists of a vertical misalignment of the eyes, due to an imbalance of vestibular tone in the oculomotor system (Brodsky 2006). This is typically assessed by performing an alternate cover test, wherein the clinician covers each eye in isolation, assessing for vertical correction of the eye position (Kattah 2009). A vertical correction would be abnormal, and suggestive of a central cause (Cnyrim 2008).

A 'central HINTS' examination is suggestive of a central cause, and occurs when there is a normal head impulse test (i.e. normal VOR), direction‐changing nystagmus, or vertical correction on test of skew. This can be recalled using the mnemonic INFARCT (Impulse Normal, Fast‐phase Alternating, or Refixation on Cover Test). In contrast, a 'peripheral HINTS' examination is suggestive of a peripheral etiology, and requires that the person have an abnormal head impulse test, unilateral nystagmus, and no evidence of vertical correction on test of skew. The HINTS examination was first described in 2009, and since then, a number of studies have evaluated the accuracy of this test (Kattah 2009). In fact, some research has suggested that the HINTS examination may even outperform early magnetic resonance imaging (MRI [Kattah 2009]).

The 'HINTS Plus' examination is an expansion of the HINTS examination, which includes a fourth step that assesses for the presence of new hearing loss, which is generally unilateral and on the same side as the abnormal head impulse test (i.e. the side opposite the fast phase of the nystagmus [Newman‐Toker 2013a]). This is used to assess for an inner ear or cochlear nucleus stroke, and is frequently assessed by the clinician rubbing their fingers together next to each of the patient's ears to identify a new asymmetry in the patient's hearing (Newman‐Toker 2013a; Häusler 2000; Lee 2012; Lin 2008).

Clinical pathway

The traditional approach to people presenting with AVS begins with a thorough history and physical examination. Depending upon the findings and the person's risk of a central cause, clinicians may obtain additional blood testing, an electrocardiogram, or advanced imaging (e.g. ultrasound, computed tomography (CT), MRI). The approach to testing can vary. Some institutions perform routine MRI on all people with AVS, while others may only perform MRI for those deemed at higher risk using the aforementioned criteria, which can include the HINTS or HINTS Plus examination. However, when compared with a control population, those with AVS are generally more likely to receive additional testing and hospital admission, with overall admission rates ranging from 19% to 46% (Chase 2014; Dallara 1994; Newman‐Toker 2008a).

Alternative test(s)

Studies have demonstrated that individual history and physical examination features are poorly predictive in isolation. Traditional risk factors, such as hypertension, diabetes mellitus, or history of ischemic stroke have minimal impact on the post‐test probability of a central cause (Chase 2014; Chen 2018; Machner 2020). The description of the symptoms and chronicity have limited diagnostic utility (Chase 2014; Machner 2020), while the physical examination findings are more variable (Chase 2014; Chen 2018; Machner 2020). This has prompted many to rely more heavily on imaging.

The imaging test of choice for cerebellar and bulbar infarction is MRI with diffusion‐weighted imaging (DWI). While CT is often ordered, studies have demonstrated that the diagnostic accuracy of CT is substantially lower than MRI when assessing for ischemic stroke (Chalela 2007). This is even more limited when evaluating the posterior fossa, where CT is known to perform worse due to the bone‐related artifacts (Simmons 1986).

Despite the overall increased accuracy compared with CT, MRI has reduced accuracy within the first 48 hours. In fact, studies have reported false negative rates of 5% to 12% among early MRI compared to MRI obtained later than 48 hours after symptom onset (Kattah 2009; Oppenheim 2000).

Rationale

While most people with AVS have a benign etiology, it is important to accurately identify the more dangerous central causes. However, individual history and physical examination findings are of limited diagnostic utility, leading to increased use of resources and greater likelihood of hospitalization (Dallara 1994; Newman‐Toker 2008a). Therefore, there is a need to identify an accurate tool for detecting and excluding central causes of AVS.

Objectives

The primary aim of this review was to assess the diagnostic accuracy of the head impulse, nystagmus, test of skew (HINTS) and HINTS Plus (HINTS combined with hearing loss) examinations for identifying a central etiology for acute vestibular syndrome. As the HINTS examination can be conducted clinically (clinician visual assessment) or with video assistance (e.g. video‐recording with goggles), we independently assessed the clinical and video‐assisted examinations.

Secondary objectives

Secondary objectives include assessing the diagnostic accuracy of HINTS and HINTS Plus among the following subgroups:

provider type (e.g. physicians, non‐physicians)
time from symptom onset to presentation (e.g. less than 24 hours, longer than 24 hours)
reference standard (e.g. advanced imaging, discharge diagnosis)
underlying etiology (e.g. ischemic stroke, alternative etiologies [hemorrhagic stroke, intracranial mass])
study setting (e.g. outpatient [outpatient clinic, urgent care clinic, ED], hospitalized patients)
provider level of training (e.g. resident, fellow/attending)
provider specialty (e.g. otolaryngology, emergency medicine, neurology, and neurologic subspecialist [e.g. neuro‐ophthalmology, neuro‐otology])
individual diagnostic accuracy of each component of the examination (e.g. head impulse, direction‐changing nystagmus, test of skew).

Methods

Criteria for considering studies for this review

Types of studies

We considered all primary diagnostic test accuracy studies if they evaluated the head impulse, nystagmus, test of skew (HINTS) or HINTS Plus test in a primary care clinic, an urgent care clinic, the emergency department (ED), or during inpatient hospitalization, against a final diagnosis of a central etiology of acute vestibular syndrome (AVS), as defined by the reference standard of advanced imaging or final diagnosis by a neurologist, and that provided sufficient data to create the 2 × 2 tables to calculate sensitivity, specificity, and negative and positive likelihood ratios. A central etiology comprised causes involving the central nervous system (e.g. ischemic stroke, hemorrhagic stroke, intracranial mass). We included prospective and retrospective studies, provided that the HINTS or HINTS Plus test was applied directly to participants. We excluded retrospective studies in which the tool was applied to records as opposed to actual people. We also excluded case‐control studies, case series, and case reports.

Participants

We included adults (aged ≥ 16 years) with symptoms of AVS, who were evaluated in a primary care clinic, an urgent care clinic, the ED, or during inpatient hospitalization. If studies provided data on a mixed population (i.e. pediatric and adult participants), we included the adult population if the adult data were presented separately. We did not include studies with mixed populations in which adult‐only cohort data were not available.

Index tests

The index test is the HINTS examination, which comprises head impulse, nystagmus, and test of skew deviation. We considered any of the following findings as evidence of a central etiology: normal head impulse test, direction‐changing horizontal nystagmus, or skew deviation for the HINTS examination. For the HINTS Plus, we considered any of the previously mentioned HINTS findings or hearing loss to be evidence of a central etiology. The index test could be administered by a paramedic, emergency medicine technician, nurse, physician assistant, nurse practitioner, or physician (regardless of specialty). While we collected data on the diagnostic accuracy of individual subcomponents of the HINTS examination when available, we did not include studies that only assessed a single component in the absence of the full HINTS examination (e.g. isolated head impulse testing without a HINTS examination performed).

Target conditions

The target condition was a central etiology for the AVS symptoms, which was defined as any cause involving the central nervous system (e.g. ischemic stroke, hemorrhagic stroke, intracranial mass).

Reference standards

The reference standard for ischemic stroke, hemorrhagic stroke, or intracranial mass could include advanced imaging (e.g. magnetic resonance imaging (MRI), positron emission tomography) or final diagnosis by a neurologist.

Search methods for identification of studies

Electronic searches

The Cochrane Stroke Review Group's Information Specialist searched the following electronic databases for retrospective and prospective studies of the HINTS examination. There were no restrictions on language or year of publication.

Cochrane Central Register of Controlled Trials (CENTRAL, 2022, issue 9) in the Cochrane Library (searched 26 September 2022; Appendix 1)
Cochrane Database of Systematic Reviews (CDSR) in the Cochrane Library (searched 26 September 2022)
MEDLINE Ovid (1946 to 26 September 2022; Appendix 2)
Embase Ovid (1980 to 26 September 2022; Appendix 3)

Searching other resources

We searched ClinicalTrials.gov (www.clinicaltrials.gov; Appendix 4), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; apps.who.int/trialsearch/; Appendix 5) for ongoing trials. We also searched the International Health Technology Assessment (HTA) Database (database.inahta.org/; Appendix 6) for published international health technology assessments. In addition, we checked reference lists of reviews and retrieved articles for additional studies, and performed citation searches on key articles. We searched Google Scholar, limited to the first 200 references, as recommended in Bramer 2017 (Appendix 7). We contacted all study authors for additional information, if it was not available in the published manuscript.

Data collection and analysis

Selection of studies

Two review authors (MG, JNC) independently determined eligibility of each study identified by the search. They excluded studies that clearly did not satisfy the inclusion criteria, and obtained full copies of the remaining studies. Two review authors (MG, JNC) independently read these studies to select relevant studies. In the event of disagreement, the authors resolved by consensus or the addition of a third review author (GDP), if needed.

We did not anonymize the studies in any way before assessment. We included a PRISMA flowchart to show the status of identified studies (Page 2021). We included studies in the review regardless of whether they reported measured outcome data in a 'usable' way.

Data extraction and management

Two review authors (MG, JNC) independently extracted data, using a standard piloted form, and checked for agreement before entry into Review Manager (RevMan Web 2023). In the event of disagreement, the authors resolved by consensus, or the addition of a third review author (GDP), if needed. When the same study was published in multiple reports, we included only the largest study sample for the given outcome, so that each study, rather than report was the unit of interest in the review. If multiple reports included overlapping but distinct data, we collated the multiple reports as a single study. We extracted the following information.

Study characteristics

Study date
Study design
Study setting
Study country
Study duration
Provider type and specialty
Details of blinding and allocation concealment
Follow‐up duration
Publication type
Study funding source
Study author conflicts of interest

Participants

Total number of participants
Inclusion criteria
Exclusion criteria
Mean or median age
Gender distribution
Existing comorbidities
Time from symptom onset to presentation

Index test

Number of central findings for the head impulse test component
Number of central findings for the direction‐changing nystagmus component
Number of central findings for the test of skew component
Number of total 'central clinical HINTS' examinations
Number of total 'central video‐assisted HINTS' examinations
Number of total 'central clinical HINTS Plus' examinations
Number of total 'central video‐assisted HINTS Plus' examinations

Outcomes

True positive (TP), true negative (TN), false positive (FP), and false negative (FN) results for the clinical HINTS examination
TP, TN, FP, and FN results for the video‐assisted HINTS examination
TP, TN, FP, and FN results for the clinical HINTS Plus examination
TP, TN, FP, and FN results for the video‐assisted HINTS Plus examination
TP, TN, FP, and FN results for each individual component of the HINTS examination
TP, TN, FP, and FN results for the HINTS examination when performed by physicians only, and when performed by non‐physicians only
TP, TN, FP, and FN results for the HINTS examination when performed less than 24 hours after symptom onset versus longer than 24 hours after symptom onset
TP, TN, FP, and FN results for the HINTS examination when the reference standard was advanced imaging versus discharge diagnosis
TP, TN, FP, and FN results for the HINTS examination when the etiology was ischemic stroke versus alternative etiologies
TP, TN, FP, and FN results for the HINTS examination when performed in the hospital setting versus the outpatient setting
TP, TN, FP, and FN results for the HINTS examination when performed by a resident versus fellow or attending
TP, TN, FP, and FN results for the HINTS examination by physician specialty (e.g. otolaryngology, emergency medicine, neurology, and neurologic subspecialist [e.g. neuro‐ophthalmology, neuro‐otology])

Analysis

Statistical techniques used
Subgroup analyses
Number and percentage lost to follow‐up

Assessment of methodological quality

Two review authors (MG, JNC) independently assessed methodological quality using the Quality Assessment of Diagnostic Accuracy Studies version 2 (QUADAS‐2) tool (Whiting 2011). We applied the QUADAS‐2 tool in four phases: 1) summarized the review question; 2) tailored the tool to the review and produced review‐specific guidance; 3) constructed a flow diagram for the primary study; and 4) assessed risk of bias and concerns regarding applicability. The tool provides evaluation across four domains, including patient selection, index test, reference standard, and flow and timing. All domains allow judgment for risk of bias with ratings of low, high, or unclear. In addition, the domains of patient selection, index test, and reference standard allow the evaluation of concerns of applicability, with ratings of low, high, or unclear. We classified studies as overall low risk of bias when judged as low across all four domains, or low across three domains with one unclear domain. We used a pre‐determined tool (Appendix 8). Any disagreements between review authors were resolved through discussion with a third review author (GDP).

Statistical analysis and data synthesis

The HINTS index test comprises three components: 1) head impulse test; 2) direction‐changing nystagmus; and 3) test of skew. The HINTS Plus index test comprises four components: 1) head impulse test; 2) direction‐changing nystagmus; 3) test of skew; and 4) hearing loss. We classified a central finding in any of these components as a 'central HINTS' or 'central HINTS Plus' result for overall evaluation. We generated 2 x 2 tables of TP, TN, FP, and FN, and used these data to estimate summary sensitivities and specificities with 95% confidence intervals (95% CI) for the HINTS examination, as well as each of the individual components. We calculated positive and negative likelihood ratios from the summary sensitivity and specificity data. Data were visually depicted using forest plots and a summary receiver operating characteristic (SROC) curve with 95% confidence region.

We completed statistical analyses using a bivariate, generalized linear mixed model (Chu 2006). The parameters of the bivariate distribution were used to create SROC curves (Reitsma 2005). We calculated the summary estimates via the MIDAS, METANDI, or METAN modules (or a combination) for StataMP (Stata). We transcribed the summary estimates to generate forest plots and SROC plots in Review Manager (RevMan Web 2023). For instances when a bivariate mixed‐effects regression model was not feasible due to low study inclusion, we described the study results and performed a univariate random‐effects model (Takwoingi 2017).

Investigations of heterogeneity

We investigated heterogeneity for diagnostic tests when data were sufficient (more than 10 included studies). We investigated heterogeneity between studies by visually examining forest plots in subgroup analyses. We investigated heterogeneity by meta‐regression, considering specific providers (physician versus non‐physician), time from symptom onset to presentation (less than 24 hours versus longer than 24 hours), reference standard (advanced imaging versus discharge diagnosis), underlying etiology (ischemic stroke versus alternative etiology), study setting (outpatient versus inpatient), physician level of training (resident versus fellow/attending), and physician specialty (e.g. otolaryngology, emergency medicine, neurology, and neurologic subspecialist [e.g. neuro‐ophthalmology, neuro‐otology]).

We also investigated heterogeneity via sensitivity analyses, based on study quality and time of completion for the index test. We selected physician versus non‐physician providers, given the differences in training. We selected time from symptom onset to presentation to account for the potential of different diagnostic accuracy among early versus delayed presentations. While both reference standards are acceptable, there remains no perfect gold standard, so we subgrouped, based upon reference standard. We selected underlying etiology, given the potential that ischemic stroke may differ from a non‐ischemic stroke etiology. We selected study setting, given potential differences in populations leading to spectrum bias. We selected physician level of training and specialty given that experience may impact exam execution.

Sensitivity analyses

We performed a sensitivity analysis of only prospective studies, due to the greater potential for confounding among retrospective studies. We also performed a sensitivity analysis based on methodological quality. We included studies classified as overall low risk of bias from the QUADAS‐2 assessment. We further performed post‐hoc sensitivity analysis by excluding the studies by Filippopulos 2022 and Thomas 2022, given their outlier results compared to other included studies.

Assessment of reporting bias

We did not conduct an assessment of reporting bias, because no standard approach is currently available for diagnostic test accuracy reviews.

Summary of findings and assessment of the certainty of the evidence

We created a summary of findings (SoF) table and assessed the certainty of evidence for the diagnostic test studies according to GRADE criteria (GRADEpro GDT; Schünemann 2020a; Schünemann 2020b). Two review authors (MG, GDP) independently rated the certainty of the body of evidence for the outcomes, with discrepancies resolved by consensus or addition of a third reviewer (JNC), if needed. GRADE considers the following factors that may decrease the certainty of evidence for systematic reviews of diagnostic studies: risk of bias, indirectness, inconsistency, imprecision, and publication bias. We rated each domain as not serious, serious, or very serious. Imprecision could also receive a rating of extremely serious. The final certainty of evidence was rated as one of four grades.

High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

Results

Results of the search

Our search identified a total of 23,705 records. After removing duplicates, we reviewed 20,472 unique records. Of those, 20,434 were not relevant to the review, so we excluded them during the initial screening stage. We reviewed 38 full‐text articles and excluded 22 records for specific reasons (Characteristics of excluded studies). We selected 16 studies for inclusion in this review (Characteristics of included studies and Figure 1). We did not identify any ongoing trials.

Characteristics of the included studies

For the quantitative synthesis, we included 16 studies with 2024 participants. Of these, 569 (28.1%) had a central etiology for their symptoms. The mean age of participants was 60 years. There were 981 women and 1043 men in the studies.

Fourteen studies were published as full text (Batuecas‐Caletrio 2014; Carmona 2016; Choi 2017; Dmitriew 2021; Filippopulos 2022; Gerlier 2021; Kmetonyova 2022; Korda 2022a; Korda 2022b; Newman‐Toker 2013a; Sankalia 2021; Siepmann 2021a; Thomas 2022; Wang 2021), while two were abstracts (Saber Tehrani 2013a; Salim 2022).

Fourteen were prospective studies (Batuecas‐Caletrio 2014; Choi 2017; Filippopulos 2022; Gerlier 2021; Kmetonyova 2022; Korda 2022a; Korda 2022b; Newman‐Toker 2013a; Saber Tehrani 2013a; Salim 2022; Sankalia 2021; Siepmann 2021a; Thomas 2022; Wang 2021). Two studies were retrospective (Carmona 2016; Dmitriew 2021).

Studies were conducted across multiple countries, including Germany (Filippopulos 2022; Siepmann 2021a), India (Salim 2022; Sankalia 2021), Switzerland (Korda 2022a; Korda 2022b), the United States (Newman‐Toker 2013a; Saber Tehrani 2013a), Argentina (Carmona 2016) Australia (Thomas 2022), Canada (Dmitriew 2021), China (Wang 2021), Czech Republic (Kmetonyova 2022), France (Gerlier 2021), Spain (Batuecas‐Caletrio 2014), and South Korea (Choi 2017).

Thirteen studies were conducted in the emergency department (ED [Carmona 2016; Choi 2017; Dmitriew 2021; Filippopulos 2022; Gerlier 2021; Kmetonyova 2022; Korda 2022a; Korda 2022b; Newman‐Toker 2013a; Saber Tehrani 2013a; Salim 2022; Siepmann 2021a; Thomas 2022]). One was conducted in the ED and outpatient clinic (Wang 2021), one in outpatients and hospitalized participants (Sankalia 2021), and one included only hospitalized participants (Batuecas‐Caletrio 2014).

The HINTS exam was performed by a neurologist in seven studies (Carmona 2016; Filippopulos 2022; Kmetonyova 2022; Saber Tehrani 2013a; Siepmann 2021a; Thomas 2022; Wang 2021), a neuro‐otologist in three studies (Choi 2017; Korda 2022a; Korda 2022b), an emergency medicine physician in two studies (Dmitriew 2021; Gerlier 2021), a neuro‐ophthalmologist in one study (Newman‐Toker 2013a), and an otolaryngologist in one study (Batuecas‐Caletrio 2014). The clinician specialty was not reported in two studies (Salim 2022; Sankalia 2021). The exam was performed by attending physicians in six studies (Choi 2017; Gerlier 2021; Korda 2022a; Korda 2022b; Newman‐Toker 2013a; Siepmann 2021a), resident physicians in four studies (Carmona 2016; Filippopulos 2022; Kmetonyova 2022; Thomas 2022), and a combination of resident and attending physicians in four studies (Batuecas‐Caletrio 2014; Dmitriew 2021; Saber Tehrani 2013a; Wang 2021). The physician experience level was not reported in two studies (Salim 2022; Sankalia 2021).

Methodological quality of included studies

The results of our risk of bias assessment are summarized in Figure 2 and Figure 3.

Risk of bias and applicability concerns graph: review authors' judgments about each domain presented as percentages across included studies.

Risk of bias and applicability concerns summary: review authors' judgments about each domain for each included study.

Patient selection

Ten studies were at low risk of bias for patient selection (Batuecas‐Caletrio 2014; Choi 2017; Filippopulos 2022; Kmetonyova 2022; Newman‐Toker 2013a; Saber Tehrani 2013a; Sankalia 2021; Siepmann 2021a; Thomas 2022; Wang 2021). Three studies were at unclear risk of bias due to insufficient information to determine if enrollment was consecutive (Carmona 2016; Dmitriew 2021; Salim 2022), while three studies were at high risk of bias due to reliance on a convenience sample for enrollment (Gerlier 2021; Korda 2022a; Korda 2022b). Applicability concerns were low for all studies except one, which included transferred patients and those with a stroke risk factor of ≥ 1 (Newman‐Toker 2013a).

Index test

Thirteen studies were at low risk of bias for the index test (Batuecas‐Caletrio 2014; Carmona 2016; Choi 2017; Filippopulos 2022; Gerlier 2021; Kmetonyova 2022; Korda 2022a; Korda 2022b; Newman‐Toker 2013a; Saber Tehrani 2013a; Siepmann 2021a; Thomas 2022; Wang 2021). Three studies were at unclear risk of bias due to insufficient information to determine if the clinicians performing the HINTS examination were blinded to the reference standard (Dmitriew 2021; Salim 2022; Sankalia 2021). Applicability concerns were low for 12 studies (Batuecas‐Caletrio 2014; Carmona 2016; Choi 2017; Gerlier 2021; Kmetonyova 2022; Korda 2022a; Korda 2022b; Newman‐Toker 2013a; Saber Tehrani 2013a; Siepmann 2021a; Thomas 2022; Wang 2021). Two studies had unclear applicability concerns due to insufficient information about clinician training (Salim 2022; Sankalia 2021), while another two studies had high applicability concerns because the clinicians performing the HINTS examination did not receive any specific training, which could result in misapplication of the tool (Dmitriew 2021; Filippopulos 2022).

Reference standard

Twelve studies were at low risk of bias for the reference standard (Carmona 2016; Choi 2017; Filippopulos 2022; Gerlier 2021; Kmetonyova 2022; Korda 2022a; Korda 2022b; Newman‐Toker 2013a; Saber Tehrani 2013a; Siepmann 2021a; Thomas 2022; Wang 2021). Four studies were at unclear risk of bias due to insufficient information to determine if the clinicians completing the reference standard were blinded to the findings from the HINTS examination (Batuecas‐Caletrio 2014; Dmitriew 2021; Salim 2022; Sankalia 2021). All studies had low applicability concerns for the reference standard.

Flow and timing

Fourteen studies were at low risk of bias for flow and timing (Batuecas‐Caletrio 2014; Carmona 2016; Choi 2017; Filippopulos 2022; Kmetonyova 2022; Korda 2022a; Korda 2022b; Newman‐Toker 2013a; Saber Tehrani 2013a; Salim 2022; Sankalia 2021; Siepmann 2021a; Thomas 2022; Wang 2021). Two studies were at unclear risk of bias because the timing between the initial test and reference standard was not available (Dmitriew 2021; Gerlier 2021).

Findings

Of the 16 studies included, 12 studies evaluated the clinical HINTS examination (Batuecas‐Caletrio 2014; Carmona 2016; Dmitriew 2021; Filippopulos 2022; Gerlier 2021; Kmetonyova 2022; Korda 2022b; Newman‐Toker 2013a; Salim 2022; Sankalia 2021; Thomas 2022; Wang 2021), three studies evaluated the video‐assisted HINTS examination (Korda 2022a; Saber Tehrani 2013a; Thomas 2022), five studies evaluated the clinical HINTS Plus examination (Choi 2017; Newman‐Toker 2013a; Sankalia 2021; Siepmann 2021a; Thomas 2022), and two studies evaluated the video‐assisted HINTS Plus examination (Siepmann 2021a; Thomas 2022). The results are presented in the Table 1 and summary of analyses table (Table 2), with the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for each evaluated objective.

1. Summary of analyses of test accuracy.

Objective	Numberof studies (participants)	Sensitivity; % (95% CI)	Specificity; % (95% CI)	Positive likelihood ratio; n (95% CI)	Negative likelihood ratio; n (95% CI)
Primary objectives
Clinical HINTS	12 (1890)	94.0 (82.0 to 98.2)	86.9 (75.3 to 93.6)	7.2 (3.7 to 14.2)	0.1 (< 0.1 to 0.2)
Video‐assisted HINTS	3 (199)	range: 85.0 to 100; 96.3 (87.6 to 100)	range: 38.9 to 100.0; 75.7 (37.1 to 100)	range: 1.4 to 8.8 4.0; (1.4 to inestimable)	range: 0 to 0.4; 0.1 (< 0.1 to 0.3)
Clinical HINTS Plus	5 (451)	95.3 (78.4 to 99.1)	72.9 (44.4 to 90.1)	3.5 (1.4 to 9.1)	0.1 (< 0.1 to 0.4)
Video‐assisted HINTS Plus	2 (163)	range: 85.0 to 93.8; 90.6 (81.1 to 100)	range: 28.6 to 38.9; 37.6 (29.2 to 46.0)	range: 1.3 to 1.4; 1.5 (1.1 to 1.9)	range: 0.2 to 0.4; 0.3 (< 0.1 to 0.6)
Secondary objectives for HINTS subcomponents
Head impulse	9 (905)	68.8 (42.0 to 87.1)	92.5 (75.8 to 98.0)	9.2 (2.5 to 33.4)	0.3 (0.2 to 0.7)
Video head impulse	3 (239)	range: 18.2 to 82.6; 61.1 (24.7 to 97.5)	range: 45.1 to 86.8; 66.7 (36.7 to 96.7)	range: 0.6 to 6.3; 1.8 (0.4 to 29.5)	range: 0.2 to 1.2; 0.6 (< 0.1 to 2.1)
Nystagmus	9 (1128)	56.8 (40.2 to 71.9)	98.8 (96.0 to 99.7)	49.1 (13.8 to 174.6)	0.4 (0.3 to 0.6)
Test of skew	10 (1313)	15.0 (6.6 to 30.5)	98.7 (97.1 to 99.4)	11.6 (5.3 to 25.3)	0.9 (0.8 to 1.0)
Secondary objectives for clinical HINTS
Providers − physicians	10 (1515)	90.6 (75.3 to 96.8)	87.3 (72.3 to 94.8)	7.2 (3.1 to 16.7)	0.1 (<0.1 to 0.3)
Providers − non‐physicians	0	‐	‐	‐	‐
Time from symptom onset to presentation − less than 24 hours	1 (71)	70.8 (48.9 to 87.4)	100 (92.5 to 100)	cannot be estimated	0.3 (0.2 to 0.5)
Time from symptom onset to presentation − longer than 24 hours	2 (209)	range: 23.9 to 82.6; 52.9 (0 to 100)	range: 6.1 to 83.0; 44.4 (0 to 100)	range: 0.3 to 4.9; cannot be estimated	range: 0.2 to 12.6; cannot be estimated
Reference standard − advanced imaging	8 (1146)	95.7 (87.7 to 98.6)	89.1 (76.5 to 95.4)	8.8 (3.9 to 19.8)	< 0.1 (< 0.1 to 0.1)
Reference standard − discharge diagnosis	0	‐	‐	‐	‐
Underlying etiology − ischemic stroke	6 (924)	91.3 (66.8 to 98.2)	79.9 (63.2 to 90.2)	4.5 (2.3 to 9.1)	0.1 (< 0.1 to 0.5)
Underlying etiology − alternative	0	‐	‐	‐	‐
Study setting − outpatient	11 (1799)	94.4 (81.0 to 98.6)	85.4 (72.7 to 92.8)	6.5 (3.3 to 12.7)	0.1 (< 0.1 to 0.2)
Study setting − inpatient	1 (91)	87.5 (47.3 to 99.7)	96.4 (89.8 to 99.2)	24.2 (7.7 to 75.8)	0.1 (< 0.1 to 0.8)
Provider level of training − resident	4 (773)	91.3 (45.8 to 99.2)	79.1 (52.3 to 92.9)	4.4 (1.6 to 12.3)	0.1 (< 0.1 to 1.2)
Provider level of training − fellow/attending	3 (566)	range: 82.6 to 96.8; 96.0 (92.3 to 99.7)	range: 67.5 to 97.0; 82.6 (62.3 to 100)	range: 3.0 to 31.9; 5.5 (2.4 to inestimable)	range: < 0.1 to 0.2; < 0.1 (< 0.1 to 0.1)
Provider specialty − otolaryngology	1 (91)	87.5 (47.3 to 99.7)	96.4 (89.8 to 99.2)	24.2 (7.7 to 75.8)	0.1 (< 0.1 to 0.8)
Provider specialty − emergency medicine	2 (314)	96.8 (88.8 to 99.6)^a	range: 64.3 to 67.6; 67.5 (61.7 to 73.3)	3.0 (2.5 to 3.6)^a	0.1 (< 0.1 to 0.2)^a
Provider specialty − neurology	5 (844)	87.2 (53.0 to 97.6)	88.0 (58.3 to 97.4)	7.2 (1.7 to 30.8)	0.1 (< 0.1 to 0.7)
Provider specialty − neuro‐otology/neuro‐opthalmology	2 (266)	range: 82.6 to 96.8; 91.8 (78.6 to 100)	range: 83.0 to 97.0; 90.8 (77.2 to 100)	range: 4.9 to 31.9; 10.0 (3.5 to inestimable)	range: < 0.1 to 0.2; 0.1 (< 0.1 to 0.3)
Secondary objectives for video‐assisted HINTS
Providers − physicians	3 (199)	range: 85.0 to 100; 96.3 (87.6 to 100)	range: 38.9 to 100.0; 75.7 (37.1 to 100)	range: 1.4 to 8.8; 4.0 (1.4 to inestimable)	range: 0 to 0.4; 0.1 (< 0.1 to 0.3)
Providers − non‐physicians	0	‐	‐	‐	‐
Time from symptom onset to presentation − less than 24 hours	0	‐	‐	‐	‐
Time from symptom onset to presentation − longer than 24 hours	2 (179)	range: 85.0 to 100; 93.5 (79.0 to 100)	range: 38.9 to 88.6; 63.7 (15.0 to 100)	range: 1.4 to 8.8; 2.6 (0.9 to inestimable)	range: < 0.1 to 0.4; 0.1 (<0.1 to 1.4)
Reference standard − advanced imaging	2 (66)	range: 100 to 100; 99.9 (97.1 to 100)	range: 88.6 to 100; 93.8 (82.7 to 100)	8.8 (3.5 to 22.0)^a; 16.1 (5.6 to inestimable)	cannot be estimated
Reference standard − discharge diagnosis	0	‐	‐	‐	‐
Underlying etiology − ischemic stroke	3 (199)	range: 85.0 to 100; 96.3 (87.6 to 100)	range: 38.9 to 100.0; 75.7 (37.1 to 100)	range: 1.4 to 8.8; 4.0 (1.4 to inestimable)	range: 0 to 0.4; 0.1 (< 0.1 to 0.3)
Underlying etiology − alternative	0	‐	‐	‐	‐
Study setting − outpatient	3 (199)	range: 85.0 to 100; 96.3 (87.6 to 100)	range: 38.9 to 100.0; 75.7 (37.1 to 100)	range: 1.4 to 8.8; 4.0 (1.4 to inestimable)	range: 0 to 0.4; 0.1 (< 0.1 to 0.3)
Study setting − inpatient	0	‐	‐	‐	‐
Provider level of training − resident	1 (133)	85.0 (62.1 to 96.8)	38.9 (29.9 to 48.6)	1.4 (1.1 to 1.8)	0.4 (0.1 to 1.1)
Provider level of training − fellow/attending	1 (46)	100 (71.5 to 100)	88.6 (73.3 to 96.8)	8.8 (3.5 to 22.0)	cannot be estimated
Provider specialty − otolaryngology	0	‐	‐	‐	‐
Provider specialty − emergency medicine	0	‐	‐	‐	‐
Provider specialty − neurology	2 (153)	range: 85.0 to 100; 93.3 (78.7 to 100)	range: 38.9 to 100; 69.3 (9.5 to 100)	range: cannot be estimated; 3.0 (0.9 to inestimable)	range: cannot be estimated; 0.1 (< 0.1 to 2.2)
Provider specialty − neuro‐otology/neuro‐opthalmology	1 (46)	100 (71.5 to 100)	88.6 (73.3 to 96.8)	8.8 (3.5 to 22.0)	cannot be estimated
Secondary objectives for clinical HINTS Plus
Providers − physicians	4 (376)	92.8 (69.1 to 98.7)	71.3 (34.2 to 92.2)	3.2 (1.0 to 10.9)	0.1 (< 0.1 to 0.8)
Providers − non‐physicians	0	‐	‐	‐	‐
Time from symptom onset to presentation − less than 24 hours	1 (23)	100 (29.2 to 100)	75.0 (50.9 to 91.3)	4.0 (1.9 to 8.6)	cannot be estimated
Time from symptom onset to presentation − longer than 24 hours	1 (133)	80.0 (56.3 to 94.3)	43.4 (34.1 to 53.0)	1.4 (1.1 to 1.9)	0.5 (0.2 to 1.1)
Reference standard − advanced imaging	3 (128)	range: 72.7 to 100; 93.6 (77.3 to 100)	range: 43.4 to 80.0; 65.1 (40.7 to 86.5)	range: 1.4 to 5.0; 2.7 (1.3 to 7.4)	0.5 (0.2 to 1.1)^a; 0.1 (< 0.1 to 0.6)
Reference standard − discharge diagnosis	0	‐	‐	‐	‐
Underlying etiology − ischemic stroke	4 (261)	95.4 (57.9 to 99.7)	60.0 (39.1 to 77.9)	3.4 (1.3 to 4.4)	0.1 (< 0.1 to 1.3)
Underlying etiology − alternative	0	‐	‐	‐	‐
Study setting − outpatient	4 (376)	92.8 (69.1 to 98.7)	71.3 (34.2 to 92.2)	3.2 (1.0 to 10.9)	0.1 (< 0.1 to 0.8)
Study setting − inpatient	0	‐	‐	‐	‐
Provider level of training − resident	1 (133)	80.0 (56.3 to 94.3)	43.4 (34.1 to 53.0)	1.4 (1.1 to 1.9)	0.5 (0.2 to 1.1)
Provider level of training − fellow/attending	3 (243)	range: 72.3 to 100; 93.4 (77.9 to 100)	range: 36.8 to 97.0; 70.8 (36.3 to 100)	range: 1.2 to 32.7; 3.2 (1.2 to inestimable)	range: < 0.1 to 0.7; 0.1 (< 0.1 to 0.6)
Provider specialty − otolaryngology	0	‐	‐	‐	‐
Provider specialty − emergency medicine	0	‐	‐	‐	‐
Provider specialty − neurology	2 (163)	range: 72.7 to 80.0; 77.8 (63.2 to 92.4)	range: 36.8 to 43.3; 42.4 (34.0 to 50.8)	range: 1.2 to 1.4; 1.4 (1.0 to 1.9)	range: 0.5 to 07; 0.5 (0.1 to 1.1)
Provider specialty − neuro‐otology/neuro‐opthalmology	2 (213)	range: 99.2 to 100; 99.2 (97.6 to 100)	range: 75.0 to 97.0; 88.0 (66.9 to 100)	range: 4.0 to 32.7; 8.3 (2.9 to inestimable)	range: < 0.1 to < 0.1; < 0.1 (< 0.1 to < 0.1)
Secondary objectives for video‐assisted HINTS Plus
Providers − physicians	2 (163)	range: 85.0 to 93.8; 90.6 (81.1 to 100)	range: 28.6 to 38.9; 37.6 (29.2 to 46.0)	range: 1.3 to 1.4; 1.5 (1.1 to 1.9)	range: 0.2 to 0.4; 0.3 (< 0.1 to 0.6)
Providers − non‐physicians	0	‐	‐	‐	‐
Time from symptom onset to presentation − less than 24 hours	0	‐	‐	‐	‐
Time from symptom onset to presentation − longer than 24 hours	1 (133)	85.0 (62.1 to 96.8)	38.9 (29.9 to 48.6)	1.4 (1.1 to 1.8)	0.4 (0.1 to 1.1)
Reference standard − advanced imaging	1 (30)	93.8 (69.8 to 99.8)	28.6 (8.4 to 58.1)	1.3 (0.9 to 1.9)	0.2 (< 0.1 to 1.7)
Reference standard − discharge diagnosis	0	‐	‐	‐	‐
Underlying etiology − ischemic stroke	2 (163)	range: 85.0 to 93.8; 90.6 (81.1 to 100)	range: 28.6 to 38.9; 37.6 (29.2 to 46.0)	range: 1.3 to 1.4; 1.5 (1.1 to 1.9)	range: 0.2 to 0.4; 0.3 (< 0.1 to 0.6)
Underlying etiology − alternative	0	‐	‐	‐	‐
Study setting − outpatient	2 (163)	range: 85.0 to 93.8; 90.6 (81.1 to 100)	range: 28.6 to 38.9; 37.6 (29.2 to 46.0)	range: 1.3 to 1.4; 1.5 (1.1 to 1.9)	range: 0.2 to 0.4; 0.3 (< 0.1 to 0.6)
Study setting − inpatient	0	‐	‐	‐	‐
Provider level of training − resident	1 (133)	85.0 (62.1 to 96.8)	38.9 (29.9 to 48.6)	1.4 (1.1 to 1.8)	0.4 (0.1 to 1.1)
Provider level of training − fellow/attending	1 (30)	93.8 (69.8 to 99.8)	28.6 (8.4 to 58.1)	1.3 (0.9 to 1.9)	0.2 (< 0.1 to 1.7)
Provider specialty − otolaryngology	0	‐	‐	‐	‐
Provider specialty − emergency medicine	0	‐	‐	‐	‐
Provider specialty − neurology	2 (163)	range: 85.0 to 93.8; 90.6 (81.1 to 100)	range: 28.6 to 38.9; 37.6 (29.2 to 46.0)	range: 1.3 to 1.4; 1.5 (1.1 to 1.9)	range: 0.2 to 0.4; 0.3 (< 0.1 to 0.6)
Provider specialty − neuro‐otology/neuro‐opthalmology	0	‐	‐	‐	‐

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For objectives with fewer than 4 studies included, data are presented as the range of individual study estimates and meta‐analyses.

^aData are from a single study; data for the other included studies cannot be estimated.

CI: confidence interval.

Primary objectives

Accuracy of HINTS

Twelve studies (1890 participants) evaluated the clinical HINTS examination (Batuecas‐Caletrio 2014; Carmona 2016; Dmitriew 2021; Filippopulos 2022; Gerlier 2021; Kmetonyova 2022; Korda 2022b; Newman‐Toker 2013a; Salim 2022; Sankalia 2021; Thomas 2022; Wang 2021).

We calculated a summary sensitivity of 94.0% (95% confidence interval (CI) 82.0% to 98.2%) and specificity of 86.9% (75.3% to 93.6%; low‐certainty evidence; Data table 1). While sensitivity and specificity estimates indicated a high level of accuracy, the confidence intervals were wide and certainty of the evidence was low. The SROC curve with 95% confidence region and 95% prediction region is shown in Figure 5, and indicates high heterogeneity.

Three studies (199 participants) evaluated the video‐assisted HINTS examination (Korda 2022a; Saber Tehrani 2013a; Thomas 2022).

We calculated a summary sensitivity of 96.3% (95% CI 87.6% to 100%; low‐certainty evidence), and specificity of 75.7% (37.1% to 100%; very low‐certainty evidence; Data table 2). Visual inspection of the forest plot and range of estimates indicated a high level of heterogeneity.

Accuracy of HINTS Plus

Five studies (451 participants) evaluated the clinical HINTS Plus examination (Choi 2017; Newman‐Toker 2013a; Sankalia 2021; Siepmann 2021a; Thomas 2022).

The pooled sensitivity was 95.3% (95% CI 78.4% to 99.1%); specificity was 72.9% (95% CI 44.4% to 90.1%; low‐certainty evidence; Data table 3). Given the low number of studies, we did not develop an SROC curve.

Two studies (163 participants) evaluated the video‐assisted HINTS Plus examination (Siepmann 2021a; Thomas 2022).

The studies ranged in sensitivity from 85.0% to 93.8% and in specificity from 28.6% to 38.9%, with a summary sensitivity of 90.6% (95% CI 81.1% to 100%) and a summary specificity was 37.6% (95% CI 29.2% to 46.0%; moderate‐certainty evidence; Data table 4).

Secondary objectives

Accuracy of HINTS subcomponents

We pooled results of the individual HINTS examination subcomponents across all included studies. Nine studies (905 participants) reported data for the subcomponent head impulse (Batuecas‐Caletrio 2014; Carmona 2016; Kmetonyova 2022; Korda 2022b; Newman‐Toker 2013a; Sankalia 2021; Siepmann 2021a; Thomas 2022; Wang 2021), three studies (239 participants) reported on video head impulse (Korda 2022b; Siepmann 2021a; Thomas 2022), nine studies (1128 participants) reported on clinical nystagmus (Batuecas‐Caletrio 2014; Carmona 2016; Kmetonyova 2022; Korda 2022b; Newman‐Toker 2013a; Salim 2022; Sankalia 2021; Thomas 2022; Wang 2021), and 10 studies (1313 participants) reported on the clinical test of skew (Batuecas‐Caletrio 2014; Carmona 2016; Filippopulos 2022; Kmetonyova 2022; Korda 2022b; Newman‐Toker 2013a; Sankalia 2021; Siepmann 2021a; Thomas 2022; Wang 2021).

We found a high degree of statistical uncertainty due to wide confidence intervals around the summary estimates for the HINTS subcomponent, head impulse (sensitivity 68.8%, 95% CI 42.0% to 87.1%; and specificity 92.5%, 95% CI 75.8% to 98.0%; low‐certainty evidence; Data table 5). Video head impulse had a sensitivity of 61.1% (95% CI 24.7% to 97.5) and a specificity of 66.7% (95% CI 36.7% to 96.7%; very low‐certainty evidence; Data table 6).

For nystagmus, we calculated a sensitivity of 56.8% with a fairly wide 95% CI (40.2% to 71.9%; low‐certainty evidence); and a specificity of 98.8% with a narrow 95% CI (96.0% to 99.7%; moderate‐certainty evidence; Data table 7).

We also calculated a low sensitivity for the test of skew (15.0% with a wide 95% CI of 6.6% to 30.5%; low‐certainty evidence) and a specificity of 98.7% with a narrow 95% CI (97.1% to 99.4%; moderate‐certainty evidence; Data table 8).

Accuracy of clinical HINTS by subgroup

Type of provider ‐ physicians

Ten of 12 studies reported that physicians were the providers (Batuecas‐Caletrio 2014; Carmona 2016; Dmitriew 2021; Filippopulos 2022; Gerlier 2021; Kmetonyova 2022; Korda 2022b; Newman‐Toker 2013a; Thomas 2022; Wang 2021); the other two studies did not report provider type (Salim 2022; Sankalia 2021).

The accuracy of the clinical HINTS examination performed by physicians yielded a sensitivity of 90.6% (95% CI 75.3% to 96.8%); and a specificity of 87.3% (95% CI 72.3% to 94.8%; Data table 9). We did not develop an SROC curve because the results were similar to the overall accuracy estimates for the clinical HINTS examination.

Time from symptom onset to presentation

Three studies reported time from symptom onset to presentation (Korda 2022b; Thomas 2022; Wang 2021).

One study (71 participants) reported a time frame of less than 24 hours from symptom onset to presentation (Data table 10).

Clinical HINTS ‐ time from symptom onset to presentation − less than 24 hours

Two studies (209 participants) with a longer than 24‐hour time frame reported a sensitivity range of 23.9% to 82.6% and specificity range of 6.1% to 83.0%, with a pooled sensitivity of 52.9% (95% CI 0 to 100%) and a pooled specificity of 44.4 (95% CI 0 to 100%; Data table 11).

Clinical HINTS ‐ time from symptom onset to presentation − longer than 24 hours

Reference standard ‐ advanced imaging

Eight studies used a reference standard of advanced imaging; no studies used discharge diagnoses in isolation (Batuecas‐Caletrio 2014; Carmona 2016; Gerlier 2021; Kmetonyova 2022; Korda 2022b; Salim 2022; Sankalia 2021; Wang 2021).

Pooled analysis of eight studies (1146 participants) found a sensitivity of 95.7% (95% CI 87.7% to 98.6%) and specificity of 89.1% (95% CI 76.5% to 95.4%; Data table 12).

Etiology

Six studies (924 participants) reported a target condition of ischemic stroke (Carmona 2016; Filippopulos 2022; Kmetonyova 2022; Korda 2022b; Sankalia 2021; Thomas 2022).

Calculations found a pooled sensitivity of 91.3% (95% CI 66.8% to 98.2%) and a specificity of 79.9% (95% CI 63.2% to 90.2%; Data table 13).

Clinical HINTS ‐ etiology − ischemic stroke

No studies met our definition of an alternative etiology (hemorrhagic stroke or intracranial mass).

Study setting

Eleven of 12 studies reported outpatient study settings (Carmona 2016; Dmitriew 2021; Filippopulos 2022; Gerlier 2021; Kmetonyova 2022; Korda 2022b; Newman‐Toker 2013a; Salim 2022; Sankalia 2021; Thomas 2022; Wang 2021). Batuecas‐Caletrio 2014 (91 participants) reported an inpatient setting.

The meta‐analysis for the outpatient setting (1799 participants) found a sensitivity of 94.4% (95% CI 81.0% to 98.6%) and a specificity of 85.4% (95% CI 72.7% to 92.8%; Data table 14). We did not develop an SROC curve because the results were similar to the overall accuracy estimates for the clinical HINTS examination.

Clinical HINTS ‐ study setting − outpatient

Level of clinician training

Four of 12 studies (773 participants) reported resident as the level of clinical training (Carmona 2016; Filippopulos 2022; Kmetonyova 2022; Thomas 2022), three studies (566 participants) reported it was fellow or attending physician (Gerlier 2021; Korda 2022b; Newman‐Toker 2013a). The remaining studies either did not specify or did not provide level of training.

For residents, we calculated a sensitivity of 91.3% (95% CI 45.8% to 99.2%) and a specificity of 79.1% (95% CI 52.3% to 92.9%; Data table 16); fellows or attending physicians resulted in a sensitivity of 96.0% (95% CI 92.3% to 99.7%) and a specificity of 82.6% (95% CI 62.3% to 100%; Data table 17).

Clinical HINTS ‐ level of training − resident

Clinical HINTS ‐ level of training − fellow/attending

Clinical specialty

One study (91 participants) reported that the clinicians were otolaryngologists (Batuecas‐Caletrio 2014), two studies (314 participants) reported a specialty of emergency medicine (Dmitriew 2021; Gerlier 2021), five studies (844 participants) reported a specialty of neurology (Carmona 2016; Filippopulos 2022; Kmetonyova 2022; Thomas 2022; Wang 2021), and two studies (266 participants) reported a specialty of neuro‐otology or neuro‐opthalmology (Korda 2022b; Newman‐Toker 2013a).

The sensitivity across provider specialties were similar, but specificity was lower for emergency medicine (67.5%, 95% CI 61.7% to 73.3%; Data table 19) compared to otolaryngology (96.4%, 95% CI 89.8% to 99.2%; Data table 18) and neuro‐otology or neuro‐opthalmology (90.8%, 95% CI 77.2% to 100%; Data table 21).

Clinical HINTS ‐ provider specialty − emergency medicine

Clinical HINTS ‐ provider specialty − otolaryngology

Clinical HINTS ‐ provider specialty − neuro‐otology/neuro‐opthalmology

Accuracy of video‐assisted HINTS by subgroup

Three studies evaluated the video‐assisted HINTS examination (Korda 2022a; Saber Tehrani 2013a; Thomas 2022).

All studies used physicians only, only involved ischemic stroke as the underlying etiology, and occurred exclusively in the outpatient setting. We did not develop new forest plots, as the results were the same as Data table 2.

Time from symptom onset to presentation

Two studies (179 participants) measured time from symptom onset to presentation longer than 24 hours (Korda 2022a; Thomas 2022); one study did not clearly describe a time frame (Saber Tehrani 2013a). The sensitivity was 93.5% (95% CI 79.0% to 100%) and the specificity was 63.7% (95% CI 15.0% to 100%; 2 studies; Data table 23).

Reference standard ‐ advanced imaging

Two studies (66 participants) used advanced imaging as the reference standard (Korda 2022a; Saber Tehrani 2013a). Both studies reported a sensitivity of 100%; the calculated summary specificity was 93.8% (95% CI 82.7% to 100%; Data table 24).

One study used a combination of advanced imaging and clinical course. We were unable to accurately extract the data specifically for advanced imaging (Thomas 2022).

Level of clinician training

One study (133 participants) used residents (Thomas 2022), and one study (46 participants) used fellows or attending physicians (Korda 2022a). The sensitivity was similar between groups, but the specificity was lower for residents (38.9%, 95% CI 29.9% to 48.6%; Data table 27) versus fellows or attending physicians (88.6%, 95% CI 73.3% to 96.8%; Data table 28).

Video‐assisted HINTS ‐ level of training − resident

Video‐assisted HINTS ‐ level of training − fellow/attending

Clinical specialty

Two studies (153 participants) used neurologists (Saber Tehrani 2013a; Thomas 2022). The summary sensitivity was 93.3% (95% CI 78.7% to 100%); the summary specificity was 69.3% and had wide confidence intervals (95% CI 9.5% to 100%; Data table 29). One study (46 participants) used neuro‐otologists (Data table 30 [Korda 2022a]).

Video‐assisted HINTS ‐ provider specialty − neurology

Video‐assisted HINTS ‐ provider specialty − neuro‐otology/ neuro‐opthalmology

Accuracy of clinical HINTS Plus by subgroups

Five studies evaluated the clinical HINTS Plus examination (Choi 2017; Newman‐Toker 2013a; Sankalia 2021; Siepmann 2021a; Thomas 2022).

Four studies (376 participants) used physicians, in an outpatient study setting (Choi 2017; Newman‐Toker 2013a; Siepmann 2021a; Thomas 2022). Sankalia 2021 did not report provider type, and recruited a population from both outpatient and inpatient settings, which could not be separately extracted.

Type of provider ‐ physicians

The pooled sensitivity for physicians only was 92.8% (95% CI 69.1% to 98.7%); specificity was 71.3% (95% CI 34.2% to 92.2%; 4 studies, 376 participants; Data table 31).

Time from symptom onset to presentation

Two studies reported on the time from symptom onset to presentation; Choi 2017 reported on accuracy when presenting at less than 24 hours (Data table 32); Thomas 2022 reported on longer than 24 hours (Data table 33).

Clinical HINTS Plus ‐ time from symptom onset to presentation − longer than 24 hours

Reference standard ‐ advanced imaging

Three studies (128 participants) used a reference standard of advanced imaging (Choi 2017; Sankalia 2021; Siepmann 2021a). The sensitivity was 93.6% (95% CI 77.3% to 100%) and specificity was 65.1% (95% CI 40.7% to 86.5%; Data table 34). Two studies used a reference standard of advanced imaging and clinical course, from which we were unable to clearly extract separate data for the subgroups (Newman‐Toker 2013a; Thomas 2022).

Etiology

We were unable to extract data by underlying etiology from Newman‐Toker 2013a. The remaining four studies (261 participants) reported the underlying etiology as ischemic stroke (Choi 2017; Sankalia 2021; Siepmann 2021a; Thomas 2022).

The pooled sensitivity was 95.4% (95% CI 57.9% to 99.7%); specificity was 60.0% (95% CI 39.1% to 77.9%; Data table 35).

Clinical HINTS Plus ‐ etiology − ischemic stroke

Level of clinician training

One study (133 participants) used residents (Thomas 2022), and three studies (243 participants) used fellows or attending physicians (Choi 2017; Newman‐Toker 2013a; Siepmann 2021a). For fellows or attending physicians, the pooled sensitivity was 93.4% (95% CI 77.9% to 100%); specificity was 70.8% (95% CI 36.3% to 100%; Data table 38).

Clinical HINTS Plus ‐ level of training − fellow/attending

Clinical specialty

Two studies (163 participants) used neurologists (Siepmann 2021a; Thomas 2022); two studies (213 participants) used neuro‐otologists or neuro‐opthalmologists (Choi 2017; Newman‐Toker 2013a). The summary sensitivity for neurologists was 77.8% (95% CI 63.2% to 92.4%; Data table 39), and for neuro‐otologists or neuro‐opthalmologists, it was 99.2% (95% CI 97.6% to 100%; Data table 40). The summary specificity for neurologists (42.4%, 95% CI 34.0% to 50.8%) was lower than for neuro‐otologists or neuro‐opthalmologists (88.0%, 95% CI 66.9% to 100%).

Clinical HINTS Plus ‐ provider specialty − neurology

Clinical HINTS Plus ‐ provider specialty − neuro‐otology/neuro‐opthalmology

Accuracy of video‐assisted HINTS Plus subgroups

Two studies evaluated the video‐assisted HINTS Plus examination (Siepmann 2021a; Thomas 2022). All studies reported on physicians, an underlying etiology of ischemic stroke, study settings of outpatients, and a provider specialty of neurology. We did not create new forest plots for these subgroups, because the results were the same as previously described results (Data table 4).

A single study (133 participants) reported time from symptom onset to presentation longer than 24 hours, and a resident level of training (Thomas 2022). The sensitivity for this study was 85.0% (95% CI 62.1% to 96.8%) and specificity was 38.9% (95% CI 29.9% to 48.6%).

A single study (30 participants) reported a reference standard of advanced imaging, and a fellow or attending physician level of training (Siepmann 2021a). The sensitivity for this study was 93.8% (95% CI 69.8% to 99.8%) and specificity was 28.6% (95% CI 8.4% to 58.1%).

Investigation of heterogeneity

We formally investigated heterogeneity for the accuracy of the clinical HINTS examination because we included more than 10 studies. We did not formally investigate heterogeneity for the video‐assisted HINTS, clinical HINTS Plus, or video‐assisted HINTS Plus examinations, because we included fewer than 10 studies for each of these examinations.

Overall, we found high heterogeneity for the clinical HINTS examination. This was supported by moderately‐wide confidence intervals for the summary estimates of both sensitivity (95% CI 82.0% to 98.2%) and specificity (95% CI 75.3% to 93.6%), and an SROC curve with a 95% prediction region that visually appeared to encompass more than 50% of the plot area (Figure 5).

We also planned to evaluate heterogeneity for each subgroup; however, there was little variability in the subgroups. Despite the lack of variability, we calculated the sensitivity, specificity, positive and negative likelihood for each subgroup (Table 2). In our review of summary estimates and visual inspection of forest plots, no subgroup meaningfully impacted the accuracy of the clinical HINTS examination. We chose to forego meta‐regression analysis, based on a lack of variability in studies, no meaningful difference in subgroup accuracies, and the low number of studies in the subgroups.

In our statistical and visual inspections of Data table 1 and Figure 5, we judged that Filippopulos 2022 was an outlier due to its low sensitivity, and Thomas 2022 was an outlier due to its low specificity. We further reviewed these two studies, looking for factors that we did not consider a priori, which might affect their heterogeneity. We noted that Filippopulos 2022 did not specifically train personnel on the index test, but were unable to conclude if this was the reason for the low sensitivity. We obtained the study data directly from the study authors of Thomas 2022. We assessed risk of bias as low in all domains, and identified no applicability concerns.

We were unable to identify any post‐hoc factors that explained the outlier studies or provided greater insight into the high heterogeneity.

Sensitivity analyses

We undertook sensitivity analyses for the impact of study design (prospective studies), and risk of bias (studies with a low risk of bias). We also decided to undertake post‐hoc sensitivity analyses after visually identifying Filippopulos 2022 and Thomas 2022 as outliers. The sensitivity analyses results are provided in Table 3.

2. Sensitivity analyses.

Objective	Number of studies (participants)	Sensitivity; % (95% CI)	Specificity; % (95% CI)	Positive likelihood ratio; n (95% CI)	Negative likelihood ratio; n (95% CI)
Clinical HINTS
Study design − prospective	10 (1762)	92.0 (79.1 to 97.2)	87.3 (74.0 to 94.3)	7.2 (3.4 to 15.4)	0.1 (< 0.1 to 0.3)
Risk of bias − low	7 (1125)	89.8 (68.7 to 97.2)	91.7 (74.8 to 97.6)	10.8 (3.2 to 36.1)	0.1 (< 0.1 to 0.4)
Excluding Filippopulos 2022	11 (1483)	95.3 (88.4 to 98.2)	86.8 (73.4 to 94.0)	7.2 (3.4 to 15.2)	0.1 (< 0.1 to 0.1)
Excluding Thomas 2022	11 (1757)	94.9 (82.7 to 98.6)	88.8 (79.1 to 94.4)	8.5 (4.5 to 16.3)	0.1 (< 0.1 to 0.2)
Excluding Filippopulos 2022 and Thomas 2022	10 (1350)	96.1 (90.1 to 98.5)	89.1 (77.8 to 95.0)	8.9 (4.2 to 18.7)	< 0.1 (< 0.1 to 0.1)
Video‐assisted HINTS
Study design − prospective	not applicable
Risk of bias − low	2 (153)	range: 85.0 to 100; 93.3 (78.7 to 100)	range: 38.9 to 100; 69.3 (9.5 to 100)	range cannot be estimated; 3.0 (0.9 to inestimable)	range cannot be estimated; 0.1 (< 0.1 to 2.2)
Excluding Filippopulos 2022	not applicable
Excluding Thomas 2022	2 (66)	range: 100 to 100; 100.0 (91.7 to 100)	range: 88.6 to 100; 93.8 (82.7 to 100)	range cannot be estimated; 16.1 (5.3 to inestimable)	cannot be estimated
Excluding Filippopulos 2022 and Thomas 2022	not applicable
Clinical HINTS Plus
Study design − prospective	not applicable
Risk of bias − low	4 (376)	92.8 (69.1 to 98.7)	71.3 (34.2 to 92.2)	3.2 (1.0 to 10.9)	0.1 (< 0.1 to 0.8)
Excluding Filippopulos 2022	not applicable
Excluding Thomas 2022	4 (318)	97.0 (87.5 to 99.6)	79.2 (48.6 to 93.9)	4.7 (1.5 to 14.7)	< 0.1 (< 0.1 to 0.3)
Excluding Filippopulos 2022 and Thomas 2022	not applicable

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For objectives with fewer than 4 studies included, data are presented as the range of individual study estimates and meta‐analyses.

^aData are from a single study; data for the other included studies cannot be estimated.

CI: confidence interval.

Clinical HINTS examination

The first sensitivity analysis for the clinical HINTS examination included 10 prospective studies, with 1762 participants (Batuecas‐Caletrio 2014; Filippopulos 2022; Gerlier 2021; Kmetonyova 2022; Korda 2022b; Newman‐Toker 2013a; Salim 2022; Sankalia 2021; Thomas 2022; Wang 2021). We excluded the two retrospective studies (Carmona 2016; Dmitriew 2021). The summary sensitivity was 92.0% (95% CI 79.1% to 97.2%); specificity was 87.3% (95% CI 74.0% to 94.3%).

The second sensitivity analysis included seven studies (1125 participants) that were at an overall low risk of bias (Batuecas‐Caletrio 2014; Carmona 2016; Filippopulos 2022; Kmetonyova 2022; Newman‐Toker 2013a; Thomas 2022; Wang 2021). The summary sensitivity was 89.8% (95% CI 68.7% to 97.2%); specificity was 91.7% (95% CI 74.8% to 97.6%).

Overall, the sensitivity analyses yielded results similar to the overall results for the accuracy of the clinical HINTS examination (summary sensitivity 94.0%, 95% CI 82.0% to 98.2%; summary specificity 86.9%, 95% CI 75.3% to 93.6%). Excluding Filippopulos 2022 and Thomas 2022 did not impact summary estimates (Table 3).

Video‐assisted HINTS examination

For the video‐assisted HINTS examination, all studies were prospective, and did not include Filippopulos 2022.

We included two studies at low risk of bias in one analysis (Saber Tehrani 2013a; Thomas 2022); the analysis excluding Thomas 2022 also included two studies (Korda 2022a; Saber Tehrani 2013a).

Clinical HINTS Plus examination

All studies that assessed the clinical HINTS Plus examination were prospective, and did not include Filippopulos 2022.

We included four studies in the sensitivity analysis for low risk of bias (Choi 2017; Newman‐Toker 2013a; Siepmann 2021a; Thomas 2022); and four studies in the analysis excluding Thomas 2022 (Choi 2017; Newman‐Toker 2013a; Sankalia 2021; Siepmann 2021a).

Video‐assisted HINTS Plus examination

We did not undertake any sensitivity analyses for the video‐assisted HINTS Plus examination because there were only two studies for this examination (Siepmann 2021a; Thomas 2022). Both studies were prospective and at low risk of bias. Excluding Thomas 2022 left only one study.

Discussion

Summary of main results

In this systematic review, we identified 16 studies evaluating the HINTS or HINTS Plus examinations for identifying a central cause of acute vestibular syndrome. Overall, the HINTS examination had excellent sensitivity and good specificity for diagnosing a central etiology. When compared with the HINTS examination, the HINTS Plus examination had similar sensitivity but lower specificity.

Data on video‐assisted HINTS and HINTS Plus were limited by the small numbers of studies, but did not appear to improve the sensitivity or specificity over the clinical HINTS and HINTS Plus examinations.

Subgroup analyses for each examination were also limited, as most included studies involved physicians, occurred in the outpatient or emergency department setting, and used advanced imaging as the reference standard. When analyzed by specific subcomponents of the HINTS examination, the sensitivity was moderate‐to‐poor for each individual item, though the specificity for each was high.

Strengths and weaknesses of the review

This review has several strengths. We conducted a comprehensive search across multiple databases, with an expansive search strategy. We included studies regardless of language, and did not impose date restrictions. We also contacted experts and reviewed bibliographies of all included studies to identify any potentially missed studies. As a result, we were able to identify several studies not previously included in prior systematic reviews (Krishnan 2019; Ohle 2020). In addition, we included the HINTS Plus examination and separated out examinations conducted clinically versus those conducted with video assistance, which had not been undertaken in prior reviews (Krishnan 2019; Ohle 2020). We also contacted all study authors for clarification of study data and methodology. We received responses and individual data for all but three studies, which allowed us to ensure more accurate data on the true positive, true negative, false positive, and false negative, as well as to more accurately determine the risk of bias for each study.

This review is limited by differences between studies in inclusion and exclusion criteria, as well as the definition used, which varied from requiring that participants have a diagnosis of acute vestibular syndrome to a chief presenting symptom of dizziness. This may have led to the inclusion of some participants who did not actually have acute vestibular syndrome at the time of presentation. Studies included clinicians from multiple specialties and experience levels, which may have influenced the diagnostic accuracy. However, nearly all studies required specific training on performing the HINTS examination prior to enrollment. Most studies were conducted in the emergency department, and the applicability to other settings is more limited. Outcomes differed slightly across sites. The majority focused on ischemic strokes (Batuecas‐Caletrio 2014; Carmona 2016; Choi 2017; Filippopulos 2022; Kmetonyova 2022; Korda 2022a; Korda 2022b; Saber Tehrani 2013a; Salim 2022; Sankalia 2021; Thomas 2022; Wang 2021), while others defined central causes as those with any central etiology (e.g. stroke, transient ischemic attack, mass [Dmitriew 2021; Gerlier 2021; Newman‐Toker 2013a; Siepmann 2021a]). There was also variation in magnetic resonance imaging (MRI) timing, with some studies conducting the MRI in the first several days of participants' presentation, which may miss some strokes compared with delayed MRI (Kattah 2009; Oppenheim 2000; Sankalia 2021). Two studies had participants who were lost to follow‐up (combined total = 29 participants), which may have altered the diagnostic accuracy slightly (Gerlier 2021; Kmetonyova 2022). Many studies did not define the degree of skew deviation required to be considered abnormal, which would be important to report in future work, as small degrees of skew deviation (< 3.3 degrees) can be seen in peripheral etiologies (Korda 2022b). Of note, while we did separate out examination components to determine individual accuracy, the HINTS and HINTS Plus examinations are intended to be performed altogether.

Finally, despite a comprehensive search strategy, it is possible that relevant studies may have been missed due to publication bias or reporting bias. We sought to reduce this risk by consulting experts, including abstracts, and reviewing clinical trial registries.

Comparison with previous research

Two other recent meta‐analyses have evaluated the HINTS examination (Krishnan 2019; Ohle 2020). One review reported 96.7% sensitivity and 94.8% specificity among four studies, limited to only neurologists or otolaryngologists (Ohle 2020). Another review of six studies reported a pooled sensitivity of 95.5% and a specificity of 71.2% (Krishnan 2019).

Our review adds to these data by including twice the number of studies, with a four‐fold increase in participants, as well as subgroup analyses by type of provider, time from symptom onset, reference standard, underlying etiology, study setting, provider specialty, physician level of training, and examination subcomponents. When compared with prior reviews, we identified similar sensitivity to both prior reviews. However, we found a specificity of 86.9%, which is lower than Ohle 2020, but higher than Krishnan 2019.

Applicability of findings to the review question

Our review included studies conducted in 12 different countries, although most studies were limited to the emergency department. As such, there is limited data on the applicability to other settings, including people who are hospitalized or seen in outpatient clinics. The HINTS examination was performed by clinicians from multiple specialties and included both residents and attending physicians, which enhances the external validity of the findings for different physicians, provided they are adequately trained.

We did not identify any studies on the HINTS examination performed by non‐physicians, so it is unclear how these findings may differ when performed by other provider groups.

While this review sought to understand the diagnostic accuracy of HINTS for all central causes of acute vestibular syndrome, most studies focused only on strokes, with fewer data available for other central etiologies.

Authors' conclusions

Implications for practice.

The head impulse, nystagmus, and test of skew (HINTS) examination demonstrated a sensitivity of 94.0%, with some studies reporting higher sensitivity for stroke with the HINTS examination compared with early magnetic resonance imaging (MRI [Kattah 2009; Sankalia 2021]). However, MRI may be more specific, and is often used as the reference standard for diagnosing stroke and other central causes. Therefore, we believe the HINTS examination may be best suited as a triage tool to help determine the need for admission or further imaging. The specificity of 86.9% is insufficient to diagnose a central etiology in isolation, and advanced imaging (e.g. computed tomography, MRI) will likely be needed to further elucidate the specific etiology (e.g. ischemic or hemorrhagic stroke, intracranial mass, multiple sclerosis), as this will influence the subsequent management. Importantly, MRI is also an imperfect measure, and may have reduced sensitivity if performed too early (less than 48 to 72 hours after onset) or outside the diffusion‐weighted imaging time window (Grosse‐Dresselhaus 2014; Kattah 2009; Sankalia 2021).

The potential benefits of incorporating this into practice include a potential reduction in MRIs performed, which would improve resource utilization and reduce patient‐specific and overall healthcare costs. This may also reduce unintended consequences of MRI, including incidental findings leading to unnecessary downstream testing. Another benefit is reduced emergency department (ED) length of stay by avoiding the need to await an MRI or neurology consult prior to making a disposition decision. This can help improve resource utilization and reduce overall boarding in the ED. Finally, this could reduce the need for unnecessary admissions for stroke evaluation, which would help counteract hospital overcrowding and avoid potential iatrogenic complications from hospital admission.

The potential harms associated with this include false negatives (i.e. missed cases of central etiologies) due to either incorrect performance of the examination or the limitations of the exam sensitivity. This could lead to patients not receiving an intervention for the current central etiology, as well as risk reduction strategies for future strokes. Another potential harm is false positives (i.e. misidentification of a central etiology when one is not present), leading to unnecessary evaluations, imaging, and admissions, with the corresponding impact on iatrogenic complications, length of stay, and healthcare costs. Additional costs include the time needed to perform the examination, with one study reporting a mean of five minutes to complete the HINTS examination (Gerlier 2021). Moreover, the HINTS must be applied to the correct population and should not be used in people without symptoms or spontaneous nystagmus. Finally, HINTS requires adequate training and one must consider the costs associated with conducting and maintaining skills in this examination over time (Gerlier 2021).

Implications for research.

Based upon the data on our review, there are multiple areas in need of further research. More high‐quality studies are needed on the HINTS examination, which should include the inter‐rater reliability across users, as well as more data on the accuracy across different providers by field (e.g. physician, advanced practice providers, nursing) and by specialty. Studies should also determine the ideal training needed to ensure accurate performance and interpretation of the findings among end‐users. Data have demonstrated low rates of clinical use and reduced confidence in interpreting the HINTS examination among some users (Byworth 2022; Quimby 2018; Warner 2022). Future research should determine how to increase use and confidence with the HINTS examination.

As the literature on HINTS Plus was more limited, additional research is needed to better assess the sensitivity and specificity of this examination. More data are also needed to determine whether other additional exam components could be added to the HINTS examination to further augment the sensitivity or specificity. While a few studies have evaluated the role of video assistance, more data are needed to explore the role of video assistance for identifying subtle findings (particularly among non‐expert users), as well as the potential role for artificial intelligence. Further studies should also evaluate the role of Frenzel goggles for the detection of spontaneous nystagmus in the setting of removal of visual fixation, which may improve discovery of peripheral patterns of spontaneous nystagmus.

Finally, future research could include randomized controlled trials comparing the HINTS examination with either no HINTS examination or early MRI to better assess the effect of this examination on clinical care. Relevant outcomes to explore include the effect on admission, length of stay, healthcare utilization and costs, and patient experience.

History

Protocol first published: Issue 8, 2022

Acknowledgements

Editorial and peer‐reviewer contributions

Cochrane Stroke supported the authors in the development of this diagnostic test accuracy review.

The Cochrane Diagnostic Test Accuracy (DTA) editorial team and Central Editorial Service editorial team co‐ordinated a dual editorial process.

The following people conducted the editorial process for this article:

Sign‐off Editor (final editorial decision): Stefano Ricci, UO Neurologia, USL Umbria 1, Italy; and Cochrane DTA editorial team;
Managing Editor (selected peer reviewers, provided editorial guidance to authors, edited the article): Luisa Fernandez Mauleffinch, Cochrane Central Editorial Service;
Editorial Assistant (conducted editorial policy checks, collated peer‐reviewer comments and supported editorial team): Lisa Wydrzynski, Cochrane Central Editorial Service;
Copy Editor (copy editing and production): Victoria Pennick, Cochrane Central Production Service;
Peer‐reviewers (provided comments and recommended an editorial decision): Cochrane DTA editorial team (methods and search); Dr Benjamin Tsang, Sunshine Coast University Hospital, Australia (clinical); Justin L Hoskin, MD Barrow Neurological Institute Phoenix, AZ, USA (clinical); an additional peer reviewer provided clinical peer review but chose not to be publicly acknowledged.

Appendices

Appendix 1. CENTRAL search strategy

1. MeSH descriptor: [Sensitivity and Specificity] this term only 2. MeSH descriptor: [Point‐of‐Care Testing] this term only 3. ((point of care or bedside) NEAR/1 (test* or assessment* or exam* or measur* or procedure* or diagnos*)):ti,ab,kw 4. MeSH descriptor: [Neurologic Examination] this term only 5. MeSH descriptor: [Head Impulse Test] this term only 6. ((head NEAR/5 ((impulse or heave or thrust) NEAR/3 (test* or exam* or video* or assessment* or measur*))) or video‐oculograph*):ti,ab,kw 7. (HINTS or HITS or vHITS or v‐HITS or h‐HIT or video‐HIT or HITD or (HIT NEAR/3 devic*)):ti,ab,kw 8. (((oculo‐motor or oculomotor or (eye NEAR/2 movement*) or nystagmus) NEAR/3 (test* or assessment* or exam* or measur*)) or "test of skew"):ti,ab,kw 9. ((eye or vision or visual* or head* or saccad* or ocular or oculomotor or oculo‐motor) NEAR/3 (motion* or intoleranc* or movement* or function* or direction* or refixation or fixation or unidirection* or uni‐direction* or horizontal or vertical or torsional or bidirection* or bi‐direction*) NEAR/3 (diagnos* or test* or assessment* or exam* or measur*)):ti,ab,kw 10. (((eccentric NEAR/3 gaze) or ((skew or ocular) NEAR/3 (deviation* or misalign*)) or "vestibulo‐ocular reflex") NEAR/3 (diagnos* or test* or assessment* or exam* or measur*)):ti,ab,kw 11. {OR #1‐#10} 12. MeSH descriptor: [Vestibular Diseases] this term only

13. (acute NEAR/3 vestibular NEAR/3 (syndrome or disease or dysfunction* or disorder*)):ti,ab,kw 14. MeSH descriptor: [Vertigo] this term only and with qualifier(s): [diagnosis ‐ DI] 15. MeSH descriptor: [Dizziness] this term only and with qualifier(s): [diagnosis ‐ DI] 16. MeSH descriptor: [Nystagmus, Pathologic] explode all trees and with qualifier(s): [diagnosis ‐ DI] 17. MeSH descriptor: [Nausea] this term only and with qualifier(s): [diagnosis ‐ DI] 18. MeSH descriptor: [Vomiting] this term only and with qualifier(s): [diagnosis ‐ DI] 19. (dizz* or vertigo or nausea* or nauseous or vomit* or nystagmus or emesis or light‐headed* or ((walk or gait) NEAR/2 unstead*)):ti,ab,kw 20. {OR #12‐#19} 21. #11 AND #20 22. (NCT* or ISRCTN* or ChiCTR* or EUCTR* or JPRN‐UMIN* or ACTRN*):au 23. #21 and #22

Appendix 2. MEDLINE search strategy

1. "Sensitivity and Specificity"/ 2. Point‐of‐Care Testing/ 3. ((point of care or bedside) adj3 (test$ or assessment$ or exam$ or measur$ or procedure$ or diagnos$)).tw,kf. 4. Neurologic Examination/ or Head Impulse Test/ 5. ((head adj5 ((impulse or heave or thrust) adj3 (test$ or exam$ or video$ or assessment$ or measur$))) or video‐oculograph$).tw,kf. 6. (HINTS or HITS or vHITS or v‐HITS or h‐HIT or video‐HIT or HITD or (HIT adj3 devic$)).tw,kf. 7. (((oculo‐motor or oculomotor or (eye adj2 movement$) or nystagmus) adj3 (test$ or assessment$ or exam$ or measur$)) or "test of skew").tw,kf. 8. ((eye or vision or visual$ or head$ or saccad$ or ocular or oculomotor or oculo‐motor) adj3 (motion$ or intoleranc$ or movement$ or function$ or direction$ or refixation or fixation or unidirection$ or uni‐direction$ or horizontal or vertical or torsional or bidirection$ or bi‐direction$) adj3 (diagnos$ or test$ or assessment$ or exam$ or measur$)).tw,kf. 9. (((eccentric adj3 gaze) or ((skew or ocular) adj3 (deviation$ or misalign$)) or "vestibulo‐ocular reflex") adj3 (diagnos$ or test$ or assessment$ or exam$ or measur$)).tw,kf. 10. or/1‐9 11. Vestibular Diseases/ 12. (acute adj3 vestibular adj3 (syndrome or disease or dysfunction$ or disorder$)).tw,kf. 13. Vertigo/di, et [Diagnosis, Etiology] 14. Dizziness/di, et [Diagnosis, Etiology] 15. exp Nystagmus, Pathologic/di, et [Diagnosis, Etiology] 16. Nausea/di, et [Diagnosis, Etiology] 17. Vomiting/di, et [Diagnosis, Etiology] 18. (dizz$ or vertigo or nausea$ or nauseous or vomit$ or nystagmus or emesis or light‐headed$ or ((walk$ or gait) adj2 unstead$)).tw,kf. 19. or/11‐18 20. 10 and 19

Appendix 3. Embase search strategy

1. "sensitivity and specificity"/ 2. "point of care testing"/ 3. ((point of care or bedside) adj1 (test$ or assessment$ or exam$ or measur$ or procedure$ or diagnos$)).tw,kf. 4. neurologic examination/ or head impulse test/ 5. ((head adj5 ((impulse or heave or thrust) adj3 (test$ or exam$ or video$ or assessment$ or measur$))) or video‐oculograph$).tw,kf. 6. (HINTS or HITS or vHITS or v‐HITS or h‐HIT or video‐HIT or HITD or (HIT adj3 devic$)).tw,kf. 7. (((oculo‐motor or oculomotor or (eye adj2 movement$) or nystagmus) adj3 (test$ or assessment$ or exam$ or measur$)) or "test of skew").tw,kf. 8. ((eye or vision or visual$ or head$ or saccad$ or ocular or oculomotor or oculo‐motor) adj3 (motion$ or intoleranc$ or movement$ or function$ or direction$ or refixation or fixation or unidirection$ or uni‐direction$ or horizontal or vertical or torsional or bidirection$ or bi‐direction$) adj3 (diagnos$ or test$ or assessment$ or exam$ or measur$)).tw,kf. 9. (((eccentric adj3 gaze) or ((skew or ocular) adj3 (deviation$ or misalign$)) or "vestibulo‐ocular reflex") adj3 (diagnos$ or test$ or assessment$ or exam$ or measur$)).tw,kf. 10. or/1‐9 11. vestibular disorder/ or vestibular nystagmus/ 12. (acute adj3 vestibular adj3 (syndrome or disease or dysfunction$ or disorder$)).tw,kf. 13. vertigo/di [Diagnosis] 14. dizziness/di [Diagnosis] 15. nystagmus/di [Diagnosis] 16. nausea/di [Diagnosis] 17. "nausea and vomiting"/di [Diagnosis] 18. retching/di [Diagnosis] 19. vomiting/di [Diagnosis] 20. (dizz$ or vertigo or nausea$ or nauseous or vomit$ or nystagmus or emesis or light‐headed$ or ((walk$ or gait) adj2 unstead$)).tw,kf. 21. or/11‐20 22. 10 and 21

Appendix 4. Clinicaltrials.gov search strategy

Head Impulse Test OR HINTS OR HIT OR diagnostic OR examination OR measurement | Vestibular Diseases OR Vertigo OR Dizziness OR Nystagmus

Appendix 5. World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search strategy

Head Impulse Test OR HINTS OR HIT

Appendix 6. International HTA database search strategy

(((((HINTS or HITS or vHITS or v‐HITS or h‐HIT or video‐HIT or HITD)[Title]) OR ((((oculo‐motor or oculomotor or (eye AND movement*) or nystagmus) AND (test* or assessment* or exam* or measur*)) or "test of skew"))) OR ((eye or vision or visual* or head* or saccad* or ocular or oculomotor or oculo‐motor) AND (motion* or intoleranc* or movement* or function* or direction* or refixation or fixation or unidirection* or uni‐direction* or horizontal or vertical or torsional or bidirection* or bi‐direction*) AND (diagnos* or test* or assessment* or exam* or measur*))[Title]) OR (((eccentric AND gaze) or ((skew or ocular) AND (deviation* or misalign*)) or "vestibulo‐ocular reflex") AND (diagnos* or test* or assessment* or exam* or measur*))[Title])

Appendix 7. Google Scholar search strategy

Appendix 8. Quality Assessment Checklist (QUADAS‐2)

Domain 1: Patient selection

Was a consecutive or random sample of patients enrolled?

Yes ‐ Answer 'yes' if stated a consecutive or random sample was used.

No ‐ Answer 'no' if stated an enrollment method was used other than consecutive or random sampling.

Unclear ‐ Answer 'unclear' if there is no mention of the methods for sampling or enrollment.

Was a case–control design avoided?

Yes ‐ Answer 'yes' if case‐control design was avoided.

No ‐ Answer 'no' if case‐control design was not avoided. Study should be excluded from review.

Unclear ‐ Answer 'unclear' if there is insufficient detail to determine if a case‐control design was avoided.

Did the study avoid inappropriate exclusions?

Yes ‐ Answer 'yes' if there are no concerns regarding inappropriate exclusions.

No ‐ Answer 'no' if patients were excluded because they were difficult‐to‐diagnose or included while being easier to diagnose.

Unclear ‐ Answer 'unclear' if inappropriate exclusion criteria cannot be determined.

Risk of bias: could the selection of patients have introduced bias?

High ‐ If the answer to any of the signaling questions results in 'no', then rate as 'high'.

Low ‐ If the answer to all the signaling questions is 'yes', then rate as 'low'. Also, rate as 'low' if only one signaling question is 'unclear' while the remaining are 'yes'.

Unclear ‐ If two or more signaling questions are rated as 'unclear', then rate as 'unclear'.

Applicability: are there concerns that the included patients and setting do not match the review question?

High ‐ If study patients received extensive testing and risk stratification prior to entering the study, then rate as 'high'.

Low ‐ If study patients did not receive extensive testing and risk stratification prior to entering the study, then rate as 'low'.

Unclear ‐ If patient testing prior to enrollment was unclear (e.g. patients were transferred or referred from another center for evaluation of potential stroke), then rate as 'unclear'.

Domain 2: Index test

Were the index test results interpreted without knowledge of the results of the reference standard?

Yes ‐ Answer 'yes' if the results of the index test were blinded or completed by an independent party.

No ‐ Answer 'no' if the results were unblinded or the reference standard results were known prior to completion of the index test.

Unclear ‐ Answer 'unclear' if a determination cannot be made.

If a threshold was used, was it prespecified?

Yes ‐ Answer 'yes' if a prespecified threshold was used.

No ‐ Answer 'no' if a prespecified threshold was not used.

Unclear ‐ Answer 'unclear' if a determination cannot be made.

Risk of bias: could the conduct or interpretation of the index test have introduced bias?

High ‐ If the answer to any of the signaling questions results in 'no', then rate as 'high'.

Low ‐ If the answer to all the signaling questions is 'yes', then rate as 'low'.

Unclear ‐ If the answer to any of the signaling questions results in 'unclear', then rate as 'unclear'.

Applicability: are there concerns that the index test, its conduct, or its interpretation differ from the review question?

High ‐ If the providers performing the examination were not trained on how to perform the HINTS examination, then rate as 'high'.

Low ‐ If the providers received specific training on how to perform the HINTS examination, then rate as 'low'.

Unclear ‐ If the provider training for performing the HINTS examination is not described, then rate as 'unclear'.

Domain 3: Reference standard

Is the reference standard likely to correctly classify the target condition?

Yes ‐ Answer 'yes' if MRI, PET, or discharge diagnosis was used as the reference standard.

No ‐ Answer 'no' if a reference standard other than the criteria for 'yes' was used. The study should be excluded.

Unclear ‐ Answer 'unclear' if the advanced imaging modality is not appropriately described as the reference standard.

Were the reference standard results interpreted without knowledge of the results of the index test?

Yes ‐ Answer 'yes' if the clinician completing the reference standard was blinded to the index test result.

No ‐ Answer 'no' if the clinician completing the reference standard was aware of the index test result.

Unclear ‐ Answer 'unclear' if it cannot be determined whether the reference standard result was completed without knowledge of the index test. If it is not explicitly stated that advanced imaging or diagnosis was completed without knowledge of the HINTS exam result, then a rating of 'unclear' should be given.

Risk of bias: could the reference standard, its conduct, or its interpretation have introduced bias?

High ‐ If the answer to any of the signaling questions results in 'no', then rate as 'high'.

Low ‐ If the answer to all the signaling questions is 'yes', then rate as 'low'.

Unclear ‐ If the answer to any of the signaling questions results in 'unclear', then rate as 'unclear'.

Applicability: are there concerns that the target conditions defined by the reference standard do not match the question?

High ‐ If patients did not receive an accepted reference standard (defined as MRI, PET, or discharge diagnosis), then mark as 'high'.

Low ‐ If all patients received the accepted reference standard (defined as MRI, PET, or discharge diagnosis), then mark as 'low'.

Unclear ‐ If the reference standard is incompletely reported, then mark as 'unclear'.

Domain 4: Flow and timing

Was there an appropriate interval between index tests and reference standard?

Yes ‐ Answer 'yes' if the reference standard was completed at the time of the index test. For outpatients, this would be at the index clinic visit. For hospitalized patients, this would be diagnosis for the given admission.

No ‐ Answer 'no' if the reference standard was completed at a time following the index test. For example, the index test was completed during an outpatient visit, but the diagnosis used was from a later visit.

Unclear ‐ Answer 'unclear' if the time frame relation between the index test and the reference standard are not stated.

Did all patients receive a reference standard?

Yes ‐ Answer 'yes' for a reference standard of advanced imaging or discharge diagnosis.

No ‐ Answer 'no' if the reference standard was not applied to all patients.

Unclear ‐ Answer 'unclear' if the study does not mention whether all patients received the reference standard.

Did all patients receive the same reference standard?

Yes ‐ Answer 'yes' if the same reference standard was used for all patients.

No ‐ Answer 'no' if the same reference standard was not used for all patients.

Unclear ‐ Answer 'unclear' if this information cannot be determined.

Were all patients included in the analysis?

Yes ‐ Answer 'yes' if all participants enrolled were included in the accuracy assessment.

No ‐ Answer 'no' if the number of participants enrolled in the study differs from the number included in the accuracy assessment.

Unclear ‐ Answer 'unclear' if there is ambiguity in the number of enrolled and assessed patients.

Risk of bias: could the patient flow have introduced bias?

High ‐ If the answer to any of the signaling questions results in 'no', then rate as 'high'.

Low ‐ If the answer to all the signaling questions is 'yes', then rate as 'low'. Also, rate as 'low' if only one signaling question is 'unclear' while the remaining are 'yes'.

Unclear ‐ If two or more signaling questions are rated as 'unclear', then rate as 'unclear'.

Data

Presented below are all the data for all of the tests entered into the review.

Tests. Data tables by test.

Test	No. of studies	No. of participants
1 Clinical HINTS	12	1890
2 Video‐assisted HINTS	3	199
3 Clinical HINTS Plus	5	451
4 Video‐assisted HINTS Plus	2	163
5 HINTS ‐ subcomponent head impulse	9	905
6 HINTS ‐ subcomponent video head impulse	3	239
7 HINTS ‐ subcomponent nystagmus	9	1128
8 HINTS ‐ subcomponent test of skew	10	1313
9 Clinical HINTS ‐ physicians	10	1515
10 Clinical HINTS ‐ time from symptom onset to presentation − less than 24 hours	1	71
11 Clinical HINTS ‐ time from symptom onset to presentation − longer than 24 hours	2	209
12 Clinical HINTS ‐ advanced imaging	8	1146
13 Clinical HINTS ‐ etiology − ischemic stroke	6	924
14 Clinical HINTS ‐ study setting − outpatient	11	1799
15 Clinical HINTS ‐ study setting − inpatient	1	91
16 Clinical HINTS ‐ level of training − resident	4	773
17 Clinical HINTS ‐ level of training − fellow/attending	3	566
18 Clinical HINTS ‐ provider specialty − otolaryngology	1	91
19 Clinical HINTS ‐ provider specialty − emergency medicine	2	314
20 Clinical HINTS ‐ provider specialty − neurology	5	844
21 Clinical HINTS ‐ provider specialty − neuro‐otology/neuro‐opthalmology	2	266
22 Video‐assisted HINTS ‐ physicians	3	199
23 Video‐assisted HINTS ‐ time from symptom onset to presentation − longer than 24 hours	2	179
24 Video‐assisted HINTS ‐ advanced imaging	2	66
25 Video‐assisted HINTS ‐ etiology − ischemic stroke	3	199
26 Video‐assisted HINTS ‐ study setting − outpatient	3	199
27 Video‐assisted HINTS ‐ level of training − resident	1	133
28 Video‐assisted HINTS ‐ level of training − fellow/attending	1	46
29 Video‐assisted HINTS ‐ provider specialty − neurology	2	153
30 Video‐assisted HINTS ‐ provider specialty − neuro‐otology/ neuro‐opthalmology	1	46
31 Clinical HINTS Plus ‐ physicians	4	376
32 Clinical HINTS Plus ‐ time from symptom onset to presentation − less than 24 hours	1	23
33 Clinical HINTS Plus ‐ time from symptom onset to presentation − longer than 24 hours	1	133
34 Clinical HINTS Plus ‐ advanced imaging	3	128
35 Clinical HINTS Plus ‐ etiology − ischemic stroke	4	261
36 Clinical HINTS Plus ‐ study setting − outpatient	4	376
37 Clinical HINTS plus ‐ level of training − resident	1	133
38 Clinical HINTS Plus ‐ level of training − fellow/attending	3	243
39 Clinical HINTS Plus ‐ provider specialty − neurology	2	163
40 Clinical HINTS Plus ‐ provider specialty − neuro‐otology/neuro‐opthalmology	2	213
41 Video‐assisted HINTS Plus ‐ physicians	2	163
42 Video‐assisted HINTS Plus ‐ time from symptom onset to presentation − longer than 24 hours	1	133
43 Video‐assisted HINTS Plus ‐ advanced imaging	1	30
44 Video‐assisted HINTS Plus ‐ etiology − ischemic stroke	2	163
45 Video‐assisted HINTS Plus ‐ study setting − outpatient	2	163
46 Video‐assisted HINTS Plus ‐ level of training − resident	1	133
47 Video‐assisted HINTS Plus ‐ level of training − fellow/attending	1	30
48 Video‐assisted HINTS Plus ‐ provider specialty − neurology	2	163

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Clinical HINTS ‐ study setting − inpatient

Clinical HINTS ‐ provider specialty − neurology

Video‐assisted HINTS ‐ etiology − ischemic stroke

Video‐assisted HINTS ‐ study setting − outpatient

Clinical HINTS Plus ‐ study setting − outpatient

Clinical HINTS plus ‐ level of training − resident

Video‐assisted HINTS Plus ‐ time from symptom onset to presentation − longer than 24 hours

Video‐assisted HINTS Plus ‐ advanced imaging

Video‐assisted HINTS Plus ‐ etiology − ischemic stroke

Video‐assisted HINTS Plus ‐ study setting − outpatient

Video‐assisted HINTS Plus ‐ level of training − resident

Video‐assisted HINTS Plus ‐ level of training − fellow/attending

Video‐assisted HINTS Plus ‐ provider specialty − neurology

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Batuecas‐Caletrio 2014.

*Study characteristics*
Patient Sampling	Sampling: consecutive enrollment among hospitalized peoples with acute vestibular syndrome
Patient characteristics and setting	Country: Spain Time frame: January 2003 to December 2012 Location: Hospital (Otolaryngology Unit) Inclusion criteria: people admitted to the hospital with a diagnosis of acute vestibular syndrome Exclusion criteria: people with accompanying auditory symptoms or whose vestibular symptoms lasted less than 12 hours
Index tests	Index tests performed: clinical HINTS Clinician specialty: otolaryngology Clinician experience level: resident and attending physicians
Target condition and reference standard(s)	Target condition: CVA Reference standard: MRI
Flow and timing	Time from presentation to MRI: within first 4 days of admission Number of participants lost to follow‐up: 0
Comparative
Notes	Study authors were contacted and provided additional information.
*Methodological quality*
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Low risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

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Carmona 2016.

*Study characteristics*
Patient Sampling	Sampling: retrospective study of people presenting to ED with acute vestibular syndrome
Patient characteristics and setting	Country: Argentina Time frame: 2006 to 2012 Location: emergency department Inclusion criteria: people presenting to the ED with acute vestibular syndrome Exclusion criteria: none reported
Index tests	Index tests performed: Clinical HINTS Clinician specialty: neurology Clinician experience level: resident physicians
Target condition and reference standard(s)	Target condition: central vestibular syndrome (e.g. anterior inferior cerebellar artery or posterior inferior cerebellar artery lesion) Reference standard: MRI
Flow and timing	Time from presentation to MRI: 12 to 48 hours Number of participants lost to follow‐up: 0
Comparative
Notes	Study authors were contacted and provided additional information.
*Methodological quality*
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

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Choi 2017.

*Study characteristics*
Patient Sampling	Sampling: consecutive enrollment among people presenting to emergency department with acute vestibular syndrome
Patient characteristics and setting	Country: South Korea Time frame: January 2014 to December 2014 Location: emergency department Inclusion criteria: people presenting to the ED with acute vestibular syndrome, which included (1) rapid onset of vertigo/dizziness, gait unsteadiness, and head motion intolerance; (2) resolution of vestibular symptoms and signs within 24 hours after the onset of symptoms; and (3) no previous history of recurrent vertigo Exclusion criteria: dizziness due to benign paroxysmal positional vertigo, orthostatic hypotensions, medication/drug intoxication, cardiac arrhythmia, or a known medical or neurologic disorder; history of multiple sclerosis; inability to undergo MRIs; or a history of neurologic diseases that can influence cognitive function
Index tests	Index tests performed: clinical HINTS Plus Clinician specialty: neuro‐otolgy Clinician experience level: attending physicians
Target condition and reference standard(s)	Target condition: CVA Reference standard: MRI
Flow and timing	Time from presentation to MRI: within first 4 days of admission Number of participants lost to follow‐up: 0
Comparative
Notes	Study authors were contacted and provided additional information.
*Methodological quality*
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Low risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

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Dmitriew 2021.

*Study characteristics*
Patient Sampling	Sampling: retrospective study of people presenting to ED with dizziness, vertigo, lightheadedness, or unsteadiness
Patient characteristics and setting	Country: Canada Time frame: September 2014 to March 2018 Location: emergency department Inclusion criteria: all people presenting to the ED with a triage diagnosis of dizziness, vertigo, lightheadedness, and/or unsteadiness Exclusion criteria: people who left without being seen, had dizziness > 14 days, recent trauma, a Glasgow Coma Scale score of less than 15, or hypotension (systolic blood pressure < 90 mmHg), or reported syncope/loss of consciousness
Index tests	Index tests performed: clinical HINTS Clinician specialty: emergency medicine Clinician experience level: resident and attending physicians
Target condition and reference standard(s)	Target condition: central etiology (e.g. CVA, TIA, brain tumor, or multiple sclerosis) Reference standard: CT, MRI, neurology consultation, and discharge diagnosis codes
Flow and timing	Time from presentation to MRI: not reported Number of participants lost to follow‐up: 0
Comparative
Notes	Study authors were contacted and provided additional information.
*Methodological quality*
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Unclear
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Unclear
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Unclear risk

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Filippopulos 2022.

*Study characteristics*
Patient Sampling	Sampling: consecutive enrollment among people presenting to emergency department with acute onset of vertigo, dizziness, postural or gait instability, or double vision
Patient characteristics and setting	Country: Germany Time frame: 2016 to 2019 Location: emergency department Inclusion criteria: all people presenting to the ED with acute onset of vertigo, dizziness, postural or gait instability, or double vision. Symptoms had to be present for at least 10 min within the last 24 hours Exclusion criteria: none reported
Index tests	Index tests performed: clinical HINTS Clinician specialty: neurology Clinician experience level: resident physicians
Target condition and reference standard(s)	Target condition: CVA or TIA Reference standard: MRI or clinical diagnosis
Flow and timing	Time from presentation to MRI: within first 7 days of symptom onset Number of participants lost to follow‐up: 0
Comparative
Notes	Study authors were contacted and provided additional information.
*Methodological quality*
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Low risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

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Gerlier 2021.

*Study characteristics*
Patient Sampling	Sampling: convenience sample of people presenting to emergency department with acute vertigo or vestibulovisual symptoms
Patient characteristics and setting	Country: France Time frame: October 2019 to January 2021 Location: emergency department Inclusion criteria: adults presenting with acute vertigo (spinning or nonspinning quality) or vestibulovisual symptoms (spinning, flowing, or oscillating quality) and postural symptoms (an unsteadiness or an imbalance), as defined by the classification of the Barany Society for at least 1 hour and < 1 week Exclusion criteria: people with no symptoms at the time of the examination, having frank localizing neurologic signs, having another diagnosis on admission (hypotension, hypoglycemia, acute anemia, acute alcohol, or drug uses), those who could not be assessed (severe dementia, oculomotor nerve palsy), and those previously enrolled
Index tests	Index tests performed: clinical HINTS Clinician specialty: emergency medicine Clinician experience level: attending physicians
Target condition and reference standard(s)	Target condition: central etiology of vertigo Reference standard: MRI
Flow and timing	Time from presentation to MRI: at least 48 hours after symptom onset (median 4 days [Q1 to Q3 range: 3 to 9 days]) Number of participants lost to follow‐up: 20 out of 300
Comparative
Notes	Study authors were contacted and provided additional information.
*Methodological quality*
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Unclear
Did all patients receive the same reference standard?	Unclear
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Unclear risk

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Kmetonyova 2022.

*Study characteristics*
Patient Sampling	Sampling: consecutive enrollment among people presenting to emergency department with acute onset of dizziness and gait instability
Patient characteristics and setting	Country: Czech Republic Time frame: January 2020 to June 2021 Location: emergency department Inclusion criteria: adults with acute onset of dizziness and gait instability (either subjective or objective) with or without any other apparent focal neurological sign lasting less than 72 hours. Dizziness must be the chief symptom and present at the time of the examination Exclusion criteria: people with symptoms at admission lasting continually longer than 72 hours, peoples with a known history of Ménière’s disease, peoples with pre‐existing central nervous system disease, ocular palsy (nerve III, IV, VI), internuclear ophthalmoplegia, amaurosis or known congenital nystagmus, head trauma less than 48 hours prior to the onset of dizziness, or not cooperative to complete brain MRI
Index tests	Index tests performed: clinical HINTS Clinician specialty: neurology Clinician experience level: resident physicians
Target condition and reference standard(s)	Target condition: CVA Reference standard: MRI
Flow and timing	Time from presentation to MRI: at least 72 hours after symptom onset Number of participants lost to follow‐up: 9 out of 119
Comparative
Notes	Study authors were contacted and provided additional information.
*Methodological quality*
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Low risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

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Korda 2022a.

*Study characteristics*
Patient Sampling	Sampling: convenience sample of people presenting to emergency department with acute vestibular syndrome
Patient characteristics and setting	Country: Switzerland Time frame: July 2015 to April 2020 Location: emergency department Inclusion criteria: all people older than 18 years with acute, persistent dizziness fulfilling all criteria for an acute vestibular syndrome (new onset of continuous dizziness, nausea or vomiting, motion intolerance, spontaneous nystagmus in darkness) Exclusion criteria: people younger than 18 years, if symptoms lasted < 24 hours or if the index ED visit was > 72 hours after symptom onset, peoples with a history of previous dizziness, eye movement disorder, abnormal vision, or trauma or peoples not fit for the examination or not able to undergo neuroimaging
Index tests	Index tests performed: clinical and video‐assisted HINTS Clinician specialty: neuro‐otology Clinician experience level: attending physicians
Target condition and reference standard(s)	Target condition: CVA Reference standard: MRI
Flow and timing	Time from presentation to MRI: 3 to 10 days after symptom onset Number of participants lost to follow‐up: 0
Comparative
Notes	Study authors were contacted and provided additional information.
*Methodological quality*
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

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Korda 2022b.

*Study characteristics*
Patient Sampling	Sampling: convenience sample of people presenting to emergency department with acute vestibular syndrome
Patient characteristics and setting	Country: Switzerland Time frame: February 2015 to September 2020 Location: emergency department Inclusion criteria: all people older than 18 years with acute, persistent dizziness fulfilling all criteria for an acute vestibular syndrome (new onset of continuous dizziness, nausea or vomiting, motion intolerance, spontaneous nystagmus in darkness) Exclusion criteria: people younger than 18 years, if symptoms lasted < 24 hours or if the index ED visit was > 72 hours after symptom onset, peoples with a history of previous dizziness, eye movement disorder, abnormal vision, or trauma or peoples not fit for the examination or not able to undergo neuroimaging
Index tests	Index tests performed: clinical and video‐assisted HINTS Clinician specialty: neuro‐otology Clinician experience level: attending physicians
Target condition and reference standard(s)	Target condition: CVA Reference standard: MRI
Flow and timing	Time from presentation to MRI: 3 to 10 days after symptom onset Number of participants lost to follow‐up: 0
Comparative
Notes	Study authors were contacted and provided additional information.
*Methodological quality*
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

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Newman‐Toker 2013a.

*Study characteristics*
Patient Sampling	Sampling: consecutive enrollment among people presenting to emergency department with acute vestibular syndrome
Patient characteristics and setting	Country: United States Time frame: 1999 to 2012 Location: emergency department Inclusion criteria: people with acute vestibular syndrome (defined as at least 1 hour of acute, persistent, continuous vertigo or dizziness with spontaneous or gaze‐evoked nystagmus, Plus nausea or vomiting, head motion intolerance, and new gait unsteadiness) that presented within 1 week of symptom onset. Participants must also have at least one stroke risk factor (smoking, hypertension, diabetes, hyperlipidemia, atrial fibrillation, eclampsia, hypercoagulable state, recent cervical trauma, or prior stroke of myocardial infarction) Exclusion criteria: peoples were excluded if their symptoms abated prior to 24 hours; had a history of multiple attacks of recurrent vertigo or dizziness compatible with Meniere’s disease, vestibular migraine, or idiopathic recurrent vertigo; if they were successfully treated for benign paroxysmal positional vertigo by canalith repositioning; or were too lethargic to participate in the examination
Index tests	Index tests performed: clinical HINTS and clinical HINTS Plus Clinician specialty: neuro‐ophthalmology Clinician experience level: attending physicians
Target condition and reference standard(s)	Target condition: central etiology (e.g. CVA, demyelinating lesion) Reference standard: MRI plus clinical follow‐up
Flow and timing	Time from presentation to MRI: within 72 hours of symptoms Number of participants lost to follow‐up: 0
Comparative
Notes	Study authors were contacted and provided additional information.
*Methodological quality*
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Low risk
Are there concerns that the included patients and setting do not match the review question?			Unclear
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

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Saber Tehrani 2013a.

*Study characteristics*
Patient Sampling	Sampling: consecutive enrollment among people presenting to emergency department with acute vestibular syndrome
Patient characteristics and setting	Country: United States Time frame: August 2011 to June 2012 Location: emergency department Inclusion criteria: adults presenting to emergency department with acute vestibular syndrome defined as new, persistent dizziness/vertigo,nystagmus, plus one or more of the following: (1) nausea/vomiting, (2) head motionintolerance, (3) new gait unsteadiness Exclusion criteria: none reported
Index tests	Index tests performed: video‐assisted HINTS Clinician specialty: neurology Clinician experience level: residents and attending physicians
Target condition and reference standard(s)	Target condition: CVA Reference standard: MRI
Flow and timing	Time from presentation to MRI: 2 to 7 days after symptom onset Number of participants lost to follow‐up: not reported
Comparative
Notes	Study authors were contacted and provided additional information.
*Methodological quality*
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Low risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

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Salim 2022.

*Study characteristics*
Patient Sampling	Sampling: people presenting to the emergency department with vertigo, dizziness, nausea/vomiting, gait imbalance, or nystagmus
Patient characteristics and setting	Country: India Time frame: May 2018 to October 2019 Location: emergency department Inclusion criteria: people aged 18 to 75 years presenting with complaints of vertigo, dizziness, nausea/vomiting, gait imbalance, or nystagmus Exclusion criteria: none reported
Index tests	Index tests performed: clinical HINTS Clinician specialty: not reported Clinician experience level: not reported
Target condition and reference standard(s)	Target condition: CVA Reference standard: MRI
Flow and timing	Time from presentation to MRI: not reported Number of patients lost to follow‐up: not reported
Comparative
Notes
*Methodological quality*
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Unclear
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Unclear
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

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Sankalia 2021.

*Study characteristics*
Patient Sampling	Sampling: consecutive enrollment among outpatients and inpatients with spontaneous vertigo
Patient characteristics and setting	Country: India Time frame: August 2014 to April 2016 Location: outpatient and inpatient settings Inclusion criteria: people who presented with acute‐onset first episode of spontaneous vertigo aged > 18 years Exclusion criteria: people with a history of recurrent vertigo, chronic dizziness, only positional vertigo, and peoples who withdrew written informed consent
Index tests	Index tests performed: clinical HINTS and clinical HINTS Plus Clinician specialty: not reported Clinician experience level: not reported
Target condition and reference standard(s)	Target condition: CVA Reference standard: MRI
Flow and timing	Time from presentation to MRI: within 72 hours of presentation Number of participants lost to follow‐up: 0
Comparative
Notes
*Methodological quality*
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Low risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Unclear
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Unclear
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

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Siepmann 2021a.

*Study characteristics*
Patient Sampling	Sampling: consecutive enrollment among people presenting to emergency department with acute vestibular syndrome
Patient characteristics and setting	Country: Germany Time frame: July 2016 to July 2017 Location: emergency department Inclusion criteria: people with acute vestibular syndrome presenting to the emergency department within 7 days after onset of symptoms Exclusion criteria: people with postural vertigo defined as repeated, brief periods of spinning sensations following changes in the position of the head associated by nausea with positive Dix–Hallpike or roll test, visual impairment with inability of gaze stabilization, cervical spine impairment compromising conduction of head impulse test, history of psychogenic vertigo, consumption of alcohol or drugs, known ocular or vestibular disorder, or any other condition resulting in inability to participate in vertigo assessment
Index tests	Index tests performed: clinical HINTS Plus and video‐assisted HINTS Plus Clinician specialty: neurology Clinician experience level: attending physicians
Target condition and reference standard(s)	Target condition: CVA or TIA Reference standard: MRI
Flow and timing	Time from presentation to MRI: median of 1 day (interquartile range 2) Number of participants lost to follow‐up: 0
Comparative
Notes	Study authors were contacted and provided additional information.
*Methodological quality*
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Low risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

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Thomas 2022.

*Study characteristics*
Patient Sampling	Sampling: consecutive enrollment among people presenting to emergency department with acute vestibular syndrome
Patient characteristics and setting	Country: Australia Time frame: February 2018 to September 2021 Location: emergency department Inclusion criteria: people with symptoms of acute vestibular syndrome Exclusion criteria: people with acute focal neurologic deficits consistent with acute stroke
Index tests	Index tests performed: clinical HINTS, video‐assisted HINTS, clinical HINTS Plus, video‐assisted HINTS Plus Clinician specialty: neurology Clinician experience level: resident physicians
Target condition and reference standard(s)	Target condition: CVA Reference standard: MRI plus clinical diagnosis
Flow and timing	Time from presentation to MRI: at least 48 hours after symptom onset Number of participants lost to follow‐up: 0
Comparative
Notes	Study authors were contacted and provided additional information.
*Methodological quality*
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Low risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

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Wang 2021.

*Study characteristics*
Patient Sampling	Sampling: consecutive enrollment among people presenting to emergency department and outpatient clinic with vertigo or dizziness without an obvious cause
Patient characteristics and setting	Country: China Time frame: September 2016 to December 2018 Location: emergency department and outpatient clinic Inclusion criteria: people presenting for acute dizziness or vertigo without an obvious cause, such as trauma, where: (1) dizziness or vertigo was a chief symptom, (2) age ≥ 18 years, and (3) continuous dizziness or vertigo at the time of examination Exclusion criteria: peoples with: (1) age < 18 years; (2) continuous dizziness attributed to persistent postural‐perceptual dizziness; (3) recurrent dizziness or vertigo (defined as ≥ 5 prior similar episodes before examination and at least 1 episode within the past year); (4) dizziness or vertigo attributed to head trauma, orthostatic hypotension, or a known medical or neurologic disorder (e.g. hepatic encephalopathy, hydrocephalus); (5) benign paroxysmal positional vertigo; or (6) moderate‐to‐ severe, new‐onset, CNS examination abnormalities (e.g. hemiparesis, hemisensory loss, gaze palsy; mild abnormalities [e.g. small axial ataxia, mild dysarthria, or sensory symptoms] were not excluded in this study); (7) not cooperative to complete brain MRI; or (8) incomplete clinical data or not cooperative to neurological examination
Index tests	Index tests performed: clinical HINTS Clinician specialty: neurology Clinician experience level: residents and attending physicians
Target condition and reference standard(s)	Target condition: CVA Reference standard: MRI
Flow and timing	Time from presentation to MRI: 2 to 14 days after symptom onset Number of participants lost to follow‐up: 0
Comparative
Notes	Study authors were contacted and provided additional information.
*Methodological quality*
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Low risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

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CVA: cerebral vascular accident; CT: computed tomography; CNS: central nervous system; ED: emergency department; MRI: magnetic resonance imaging ; TIA: transient ischemic attack.

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Choi 2018	Ineligible population
Green 2021	Ineligible study design
Kattah 2009	Data were published as part of a data set in a larger study already selected for inclusion
Keene 2015	Ineligible study design
Kerber 2014	Ineligible outcome
Kohn 2014	Ineligible study design
Lee 2022	Ineligible population
Ljunggren 2018	Ineligible intervention
Nakatsuka 2022	Ineligible study design
Newman‐Toker 2009a	Abstract of an included study
Newman‐Toker 2013b	Abstract of an included study
Newman‐Toker 2013c	Abstract of an included study
Orinx 2022	Ineligible study design
Quimby 2018	Ineligible population
Rau 2020	Ineligible outcome
Regis 2019	Abstract of an included study
Siepmann 2021b	Abstract of an included study
Staibano 2019	Ineligible outcome
Tischer 2017	Abstract of an included study
Venhovens 2015	Ineligible study design
von Martial 2022	Ineligible outcome
Zwergal 2018	Abstract of an included study

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Differences between protocol and review

We expanded the HINTS examination to separate out video‐assisted from purely clinical assessment and reported them separately. We also added the HINTS Plus examination in addition to the HINTS examination. We added subgroup analyses by physician level of training and physician specialty. The CADTH gray matters tool was not used for unpublished/gray literature. We added measures of the certainty of evidence using the GRADE criteria.

Contributions of authors

Conception and design of the review: MG, GDP, JNC Co‐ordination of the review: MG Search and selection of studies for inclusion in the review: MG, GDP, JNC Collection of data for the review: MG, GDP, JNC Assessment of the risk of bias in the included studies: MG, GDP, JNC Analysis of data: GDP Assessment of the certainty in the body of evidence: MG, GDP Interpretation of data: MG, GDP, JNC Writing and revising the review: MG, GDP, JNC

Sources of support

Internal sources

Rush University Medical Center, USA

Salary support (MG, GDP)
United States Acute Care Solutions, USA

Salary support (JNC)

External sources

none, Other

nothing to declare

Declarations of interest

MG: receives grant funding from the Centers for Disease Control and Prevention, Rush Center for Emerging Infectious Diseases, Emergency Medicine Foundation, Society of Directors of Research in Medical Education, and Emergency Medicine: Reviews and Perspectives

GDP: none

JNC: serves as a consultant for the American Heart Association for team dynamics and resuscitation research

New

References

References to studies included in this review

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[CD015089-bib-0008] Korda A, Wimmer W, Zamaro E, Wagner F, Sauter TC, Caversaccio MD, et al. Videooculography "HINTS" in acute vestibular syndrome: a prospective study. Frontiers in Neurology 2022;13:920357. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD015089-bib-0009] Korda A, Zamaro E, Wagner F, Morrison M, Caversaccio MD, Sauter TC, et al. Acute vestibular syndrome: is skew deviation a central sign? Journal of Neurology 2022;269(3):1396-403. [DOI] [PMC free article] [PubMed] [Google Scholar]

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PERMALINK

Head impulse, nystagmus, and test of skew examination for diagnosing central causes of acute vestibular syndrome

Michael Gottlieb

Gary D Peksa

Jestin N Carlson

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Summary of findings 1. What is the diagnostic accuracy of HINTS and HINTS Plus for diagnosing a central cause of acute vestibular syndrome?

Background

Target condition being diagnosed

Index test(s)

Clinical pathway

Alternative test(s)

Rationale

Objectives

Secondary objectives

Methods

Criteria for considering studies for this review

Types of studies

Participants

Index tests

Target conditions

Reference standards

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Study characteristics

Participants

Index test

Outcomes

Analysis

Assessment of methodological quality

Statistical analysis and data synthesis

Investigations of heterogeneity

Sensitivity analyses

Assessment of reporting bias

Summary of findings and assessment of the certainty of the evidence

Results

Results of the search

1.

Characteristics of the included studies

Methodological quality of included studies

2.

3.

Patient selection

Index test

Reference standard

Flow and timing

Findings

1. Summary of analyses of test accuracy.

Primary objectives

Accuracy of HINTS

1. Test.

4.

2. Test.

Accuracy of HINTS Plus

3. Test.

4. Test.

Secondary objectives

Accuracy of HINTS subcomponents

5. Test.

6. Test.

7. Test.

8. Test.

Accuracy of clinical HINTS by subgroup

Type of provider ‐ physicians

9. Test.

Time from symptom onset to presentation

10. Test.