Can “HINTS” aid the Diagnosis of Posterior Circulation Stroke among patients with Acute Vestibular Syndrome?

Can “HINTS” aid the Diagnosis of Posterior Circulation Stroke among patients with Acute Vestibular Syndrome? Abstract Introduction: Identifying posterior circulation stroke in patients with AVS without obvious focal neurological deficits poses a difficult diagnostic challenge. It is estimated that about 10% to 20% of emergency department patients have acute dizziness with AVS7. About 25% have brainstem or cerebellar strokes, rest of AVS patients presented with benign peripheral vestibular causes 7, 9-10. Rapid, accurate diagnosis of posterior stroke is important for early management as well as prevention of devastating complications. HINTS is a clinical three-step bedside oculomotor exam, that has been suggested of high diagnostic accuracy in identifying posterior circulation stroke in patients with isolated continuous vertigo. Materials and Methods: A comprehensive systematic search of the literature was done using the NHS Evidence healthcare databases Medline, EMBASE, CLINIL, Google Scholar, and Cochrane. Results: 10 relevant articles were identified, combining the results of all six prospective studies showing a total of 338 patients on which the Clinical HINTS exam was performed. The overall Hints exam sensitivity was 96.86% 95%CI (92.8-99), specificity 96.09% 95%CI (92.1-98.4) and negative predictive value was 0.03 95%CI (0.01-0.08). ROC analysis was done in which the area under the curve was found to be 0.965. Conclusion: Delay in the diagnosis of posterior stroke can result in an 8-fold increase in mortality. 7 HINTS is a useful clinical bedside oculomotor exam, which if done appropriately by trained ED doctors, could aid in the early recognition of a subtly presenting posterior stroke with “acute isolated continuous vertigo”. Hence, will improve the overall diagnostic evaluation of acute vestibular syndrome.


Introduction
Dizziness is the commonly encountered chief presentation in Emergency departments. It accounts annually for about 4 million presented in the Emergency department and 160,000 to 240,000 (4% to 6%) have a cerebrovascular cause [1][2][3][4][5][6] in the United States. Dizziness is a broad term that encompasses vertigo, pre-syncope, unsteadiness, and other nonspecific terms. 7 Roughly 250,000 to 500,000 US yearly attendances involve a high-risk-for-stroke clinically presented as an acute vestibular syndrome. 7 Acute vestibular syndrome is a syndrome of severe continuous vertigo or dizziness, nausea or vomiting, gait instability, head motion intolerance, and nystagmus lasting for days to weeks. [7][8] Although classical teaching suggests a focus on long-track or frank cerebellar signs, Acute vestibular syndrome has limb ataxia, dysarthria, or other associated neurological findings. 7,[10][11] Rapid, accurate diagnosis of stroke is important because a large cerebellar infarction later causes brain stem compression and increased intracranial pressure. 12 A small cerebellar stroke is usually caused by a cardiogenic embolism, the early detection and treatment can prevent life-threatening brainstem or cerebellar stroke. 12 Our current practice to rule out posterior circulation stroke in suspected patients is based on neuroimaging (CT scan and/or MRI scanning). CT scan is the initial imaging for stroke evaluation and about 16% to 42% of early ischemic strokes [13][14] detection. Brain MRI is expensive and after posterior fossa, stroke may be falsely negative in up to 20% 7 in the first 24 hours. According to US statistics about one-third of vestibular strokes are missed despite spending hundreds of millions of dollars on brain imaging trying to 'rule out' dangerous central vestibular causes such as stroke. [1][2]15 Therefore, the need for a simple clinical bedside test with high sensitivity and specificity is imperative, which can not only reduce the misdiagnosis of posterior stroke, but also the cost of unnecessary neuroimaging. The HINTS (stands for Head Impulse, Nystagmus, and Test of Skew) oculomotor test has been suggested to be a test of high diagnostic accuracy. It is a three-part oculomotor test, that should only be performed on patients with "acute continuous vertigo". If any portion of the test indicates a central etiology, the test is considered positive and further evaluation for stroke is warranted. The three components of the exam are as follows: Head impulse 16,17,31 Peripheral vertigo has an abnormal (positive) head impulse test, whereas central vertigo has a normal (negative) head impulse test. Horizontal head impulse involves rapid head rotation with the subject's vision fixed on a nearby object. The VOR is impaired in peripheral vertigo; 'rapid rotation of the head toward the affected side will result in loss of fixation and movement of the eyes away from the target', followed by a corrective saccade looks back toward the target. The presence of corrective saccade is abnormal showing a positive test for peripheral vertigo. Patients with posterior stroke in the VOR remain intact and showed no corrective saccade. Patients have an abnormal head impulse test in combined stroke and inner ear infarction cases. The central nature of the lesion will be revealed by any one of three signs direction-changing nystagmus, skew deviation, or unilateral hearing loss. Nystagmas 18 Peripheral vertigo has unidirectional horizontal nystagmus, whereas central vertigo has a rotatory/vertical or direction-changing horizontal nystagmus. The change in direction of the fast phase of horizontal nystagmus indicates a central cause. Test of SKEW 19 Alternate eye cover testing may reveal skew deviation in patients with central vertigo and would be absent in peripheral vertigo. Patients with central vertigo will have a 'vertical misalignment' on the cover uncover test.

Materials and Methods
An extensive search of PUB MED, EMBASE, CINAHL, and Cochrane databases were done with keywords ( Table 1). The Cochrane, the Google advance scholar, and Best BETs databases, including a hand search of the bibliography of the relevant papers, did not reveal any further articles ( Figure 1). The last access date to the databases was 11 th June 2015. All the systematic reviews, meta-analyses, prospective studies, retrospective studies, and case series on the application of the HINTS test were included. Excluded papers consisted of studies focusing only on one component of the HINTS or purely device-based articles, reviews on peripheral causes of vertigo, case reports, and paediatric studies. The articles published in other languages apart from English were also excluded in this practical review.

Results
Overall 173 articles were identified. 64 in MEDLINE, 97 in EMBASE, and 12 from CINAHL. No articles were found from Cochrane, best bets, or google scholar ( Figure 1). A hand search of the bibliography of articles did not yield any further studies. Based on title and abstract, after filtering for duplicates and applying limits 11 articles were found to be relevant. 10 articles were included in this review after reading the full text. One relevant article could not be accessed despite contacting the author as it was not published at the time. 6 out of 10 relevant studies were prospective and two sets of these studies were the continuation of each other. The individual studies have been appraised in  The results of individual studies were calculated by Medcalc 28 online to demonstrate the 95% confidence interval of sensitivity, specificity, positive negative predictive values, and stroke prevalence values (Table  3, 4). The overall sensitivity and specificity of the HINTS exam were calculated by combining the results of all the prospective studies (      Figure 2). Interestingly, some of the studies indicated that the HINTS exam when done by specialists, was more accurate than early MRI up to 48 hours to diagnose stroke in AVS patients.
Despite all these above-discussed limitations, the HINTS exam shows a promise in the assessment of patients with the acute vestibular syndrome. Though more studies are needed to accurately define how much training is required for the Emergency physicians' to be able to perform the exam well. At present, careful use of the HINTS exam should be encouraged among Emergency doctors due to its properties of being a non-invasive and practical bedside tool, especially in the current clinical scenario where there is no fixed or standard exam in ED to assess AVS patients. A pathway is suggested to differentiate posterior stroke from peripheral vertigo in which the HINTS exam can be utilized for the assessment of AVS patients in ED (Figure 3).

Conclusion
Our current practice of suspecting or ruling out posterior circulation stroke in AVS patients without focal neurology relies solely on medical gestalt and thus misdiagnosis is frequent. The pooled analysis of the studies shows that the HINTS examination has a sensitivity of 96.86% with a 95% CI(92.81%-99.0%), a negative likelihood ratio of 0.03, and a specificity of 96.09 with 95% CI(92-98.4). Though the confidence intervals are relatively wide and the utility of the HINTS exam has not been widely tested by Emergency physicians in the ED, given appropriate training to perform the HINTS exam, we have a noninvasive clinical bedside test that can be a useful addition to our standard clinical assessment in patients with AVS. A positive HINTS exam in low-risk patients would suggest the need for further workup, whereas a negative HINTS exam in moderate-risk patients would reduce the need for unnecessary neuroimaging.