Background and Purpose— Acute vestibular syndrome (AVS) is often due to vestibular neuritis but can result from vertebrobasilar strokes. Misdiagnosis of posterior fossa infarcts in emergency care settings is frequent. Bedside oculomotor findings may reliably identify stroke in AVS, but prospective studies have been lacking. Methods— The authors conducted a prospective, cross-sectional study at an academic hospital. Consecutive patients with AVS (vertigo, nystagmus, nausea/vomiting, head-motion intolerance, unsteady gait) with ≥1 stroke risk factor underwent structured examination, including horizontal head impulse test of vestibulo-ocular reflex function, observation of nystagmus in different gaze positions, and prism cross-cover test of ocular alignment. All underwent neuroimaging and admission (generally <72 hours after symptom onset). Strokes were diagnosed by MRI or CT. Peripheral lesions were diagnosed by normal MRI and clinical follow-up. Results— One hundred one high-risk patients with AVS included 25 peripheral and 76 central lesions (69 ischemic strokes, 4 hemorrhages, 3 other). The presence of normal horizontal head impulse test, direction-changing nystagmus in eccentric gaze, or skew deviation (vertical ocular misalignment) was 100% sensitive and 96% specific for stroke. Skew was present in 17% and associated with brainstem lesions (4% peripheral, 4% pure cerebellar, 30% brainstem involvement; χ ² , P =0.003). Skew correctly predicted lateral pontine stroke in 2 of 3 cases in which an abnormal horizontal head impulse test erroneously suggested peripheral localization. Initial MRI diffusion-weighted imaging was falsely negative in 12% (all <48 hours after symptom onset). Conclusions— Skew predicts brainstem involvement in AVS and can identify stroke when an abnormal horizontal head impulse test falsely suggests a peripheral lesion. A 3-step bedside oculomotor examination (HINTS: Head-Impulse—Nystagmus—Test-of-Skew) appears more sensitive for stroke than early MRI in AVS.

Following the initial description of HINTS to diagnose acute vestibular syndrome (AVS) in 2009, there has been significant interest in the systematic evaluation of HINTs to diagnose stroke and other less common central causes of AVS. This trend increased with availability of the video head impulse test (video-HIT). This article reviews the original papers and discusses the main publications from 2009 to 2017. Many authors use video-HIT in the diagnosis of patients with AVS; this paper focuses on the major publications on the topic featuring nystagmus, manual and video-HIT, and skew deviation. Twenty-five papers provide a summary of the last 8 years’ application of HINTS, the video-HIT added quantitative information to the early clinical observations. Further research will undoubtedly provide specific combination of abnormalities with high degree of lesion localisation and aetiology. In a short time following the original description, neurotologist and neurologists in the evaluation of AVS use the HINTS triad. The introduction of the video-HIT added greater understanding of the complex interaction between the primary vestibular afferents, brainstem and cerebellum. In addition, it permits evaluation of the angular vestibulo-ocular reflex in the plane of all six semicircular canals, with accurate peripheral versus central lesion localisation often corroborated by brain imaging.

Objective: Acute dizziness/vertigo is usually due to benign inner‐ear causes but is occasionally due to dangerous neurologic ones, particularly stroke. Because symptoms and signs overlap, misdiagnosis is frequent and overuse of neuroimaging is common. We assessed the accuracy of bedside findings to differentiate peripheral vestibular from central neurologic causes.Methods: We performed a systematic search (MEDLINE and Embase) to identify studies reporting on diagnostic accuracy of physical examination in adults with acute, prolonged dizziness/vertigo (“acute vestibular syndrome” [AVS]). Diagnostic test properties were calculated for findings. Results were stratified by examiner type and stroke location.Results: We identified 6,089 citations and included 14 articles representing 10 study cohorts (n = 800). The Head Impulse, Nystagmus, Test of Skew (HINTS) eye movement battery had high sensitivity 95.3% (95% confidence interval [CI] = 92.5–98.1) and specificity 92.6% (95% CI = 88.6–96.5). Sensitivity was similar by examiner type (subspecialists 94.3% [95% CI = 88.2–100.0] vs non‐subspecialists 95.0% [95% CI = 91.2–98.9],p = 0.55), but specificity was higher among subspecialists (97.6% [95% CI = 94.9–100.0] vs 89.1% [95% CI = 83.0–95.2],p = 0.007). HINTS sensitivity was lower in anterior cerebellar artery (AICA) than posterior inferior cerebellar artery (PICA) strokes (84.0% [95% CI = 65.3–93.6] vs 97.7% [95% CI = 93.3–99.2],p = 0.014) but was “rescued” by the addition of bedside hearing tests (HINTS+). Severe (grade 3) gait/truncal instability had high specificity 99.2% (95% CI = 97.8–100.0) but low sensitivity 35.8% (95% CI = 5.2–66.5). Early magnetic resonance imaging (MRI)‐diffusion‐weighted imaging (DWI; within 24–48 hours) was falsely negative in 15% of strokes (sensitivity 85.1% [95% CI = 79.2–91.0]).Interpretation: In AVS, HINTS examination by appropriately trained clinicians can differentiate peripheral from central causes and has higher diagnostic accuracy for stroke than MRI‐DWI in the first 24–48 hours. These techniques should be disseminated to all clinicians evaluating dizziness/vertigo. ANN NEUROL 2023;94:295–308

Summary Non-encephalopathic presentations of CNS thiamine deficiency may be difficult to diagnose. We describe neuro-otologic findings of Wernicke syndrome in 5 patients with vestibular manifestations. Diagnosis was confirmed by low serum levels, response to replacement, and brain MRI to exclude other causes. All had bilaterally abnormal horizontal head impulse vestibulo-ocular reflex (VOR) responses and pathologic gaze-evoked nystagmus, without encephalopathy. After thiamine replacement, 4 had total resolution of vestibular and oculomotor findings. Novel findings included 2 patients whose VOR function improved within minutes of IV repletion and 1 whose recovery was documented by serial quantitative recordings. Early diagnosis of Wernicke by examining vestibular reflexes and prompt IV treatment might prevent encephalopathy and other neurologic or systemic complications of thiamine depletion.

Objective To explain (1) why an initial upbeat nystagmus (UBN) converts to a permanent downbeat nystagmus (DBN) in Wernicke encephalopathy (WE) and (2) why convergence and certain vestibular provocative maneuvers may transiently switch UBN to DBN. Methods Following a literature review and study of our 2 patients, we develop hypotheses for the unusual patterns of vertical nystagmus in WE. Results Our overarching hypothesis is that there is a selective vulnerability and a selective recovery from thiamine deficiency of neurons within brainstem gaze-holding networks. Furthermore, since the circuits affected in WE are commonly paraventricular, especially medially, just under the floor of the fourth ventricle where lie structures important for control of vertical gaze, we suggest the patterns of involvement in WE also reflect a breakdown in vulnerable areas of the blood–brain barrier. Many of the initial deficits of our patients improved over time, but their DBN did not. Irreversible changes in paramedian tract neurons, which project to the cerebellar flocculus, may be the cause. Here we suggest that conversion of UBN to permanent DBN points to thiamine deficiency and may argue for a chronic, nonprogressive DBN/truncal ataxia syndrome. Finally, we posit that the transient switch of UBN to DBN reflects abnormal processing of otolith information about linear acceleration, and often points to a diagnosis of WE. Conclusion Recognizing the unusual patterns of transient switching and then permanent conversion of UBN to DBN in WE is vital since long-term disability from WE may be prevented by timely, parenteral high-dose thiamine.