Do monosymptomatic stroke patients with dizziness present a vestibular syndrome without nystagmus? An underestimated entity.

BACKGROUND AND PURPOSE: Vestibular symptoms are common in emergency department (ED) patients and have various causes, including stroke. Accurate identification of stroke in patients with vestibular symptoms is crucial for timely management. We conducted a prospective cross-sectional study from 2015 to 2019 to determine stroke prevalence and associated symptoms in ED patients with vestibular symptoms, aiming to improve diagnosis and outcomes. METHODS: As part of the DETECT project, we screened 1647 ED patients with acute vestibular symptoms. Following a retrospective analysis of 961 head and neck magnetic resonance imaging (MRI) scans, we included 122 confirmed stroke cases and assessed them for vestibular signs and symptoms. RESULTS: Stroke prevalence in dizzy patients was 13% (122/961 MRI scans). Most patients (95%) presented with acute vestibular symptoms with or without nystagmus, whereas 5% had episodic vestibular syndrome (EVS). Nystagmus was present in 50% of stroke patients. Eighty percent had a purely posterior circulation stroke, and nystagmus was absent in 46% of these patients. Seven patients (6%) had lesions in both the anterior and posterior circulation. Vertigo was experienced by 52% regardless of territory. CONCLUSIONS: A stroke was identified in 13% of ED patients presenting with acute vestibular symptoms. In 5%, it was EVS. Most strokes were in the posterior circulation territory; vertigo occurred with similar frequency in anterior and posterior circulation stroke, and absence of nystagmus was common in both.

The acute vestibular syndrome: prevalence of new hearing loss and its diagnostic value.

OBJECTIVES: To assess the prevalence of new hearing losses in patients with acute vestibular syndrome (AVS) and to start to evaluate its diagnostic value for the differentiation between peripheral and central causes. DESIGN: We performed a cross-sectional prospective study in AVS patients presenting to our Emergency Department (ED) from February 2015 to November 2020. All patients received an MRI, Head-impulse test, Nystagmus test and Test of skew ('HINTS'), caloric testing and a pure-tone audiometry. RESULTS: We assessed 71 AVS patients, 17 of whom had a central and 54 a peripheral cause of dizziness. 12.7% had an objective hearing loss. 'HINTS' had an accuracy of 78.9% to diagnose stroke, whereas 'HINTS' plus audiometry 73.2%. 'HINTS' sensitivity was 82.4% and specificity 77.8% compared to 'HINTS' plus audiometry showing a sensitivity of 82.4% and specificity of 70.4%. The four patients with stroke and minor stroke had all central 'HINTS'. 55% of the patients did not perceive their new unilateral hearing loss. CONCLUSIONS: We found that almost one-eighth of the AVS patients had a new onset of hearing loss and only half had self-reported it. 'HINTS' plus audiometry proved to be less accurate to diagnose a central cause than 'HINTS' alone. Audiometry offered little diagnostic accuracy to detect strokes in the ED but might be useful to objectify a new hearing loss that was underestimated in the acute phase. Complete hearing loss should be considered a red flag, as three in four patients suffered from a central cause.

Vestibular syndromes, diagnosis and diagnostic errors in patients with dizziness presenting to the emergency department: a cross-sectional study.

OBJECTIVES: We aimed to determine the frequency of vestibular syndromes, diagnoses, diagnostic errors and resources used in patients with dizziness in the emergency department (ED). DESIGN: Retrospective cross-sectional study. SETTING: Tertiary referral hospital. PARTICIPANTS: Adult patients presenting with dizziness. PRIMARY AND SECONDARY OUTCOME MEASURES: We collected clinical data from the initial ED report from July 2015 to August 2020 and compared them with the follow-up report if available. We calculated the prevalence of vestibular syndromes and stroke prevalence in patients with dizziness. Vestibular syndromes are differentiated in acute (AVS) (eg, stroke, vestibular neuritis), episodic (EVS) (eg, benign paroxysmal positional vertigo, transient ischaemic attack) and chronic (CVS) (eg, persistent postural-perceptual dizziness) vestibular syndrome. We reported the rate of diagnostic errors using the follow-up diagnosis as the reference standard. RESULTS: We included 1535 patients with dizziness. 19.7% (303) of the patients presented with AVS, 34.7% (533) with EVS, 4.6% (71) with CVS and 40.9% (628) with no or unclassifiable vestibular syndrome. The three most frequent diagnoses were stroke/minor stroke (10.1%, 155), benign paroxysmal positional vertigo (9.8%, 150) and vestibular neuritis (9.6%, 148). Among patients with AVS, 25.4% (77) had stroke. The cause of the dizziness remained unknown in 45.0% (692) and 18.0% received a false diagnosis. There was a follow-up in 662 cases (43.1%) and 58.2% with an initially unknown diagnoses received a final diagnosis. Overall, 69.9% of all 1535 patients with dizziness received neuroimaging (MRI 58.2%, CT 11.6%) in the ED. CONCLUSIONS: One-fourth of patients with dizziness in the ED presented with AVS with a high prevalence (10%) of vestibular strokes. EVS was more frequent; however, the rate of undiagnosed patients with dizziness and the number of patients receiving neuroimaging were high. Almost half of them still remained without diagnosis and among those diagnosed were often misclassified. Many unclear cases of vertigo could be diagnostically clarified after a follow-up visit.

Artificial intelligence for early stroke diagnosis in acute vestibular syndrome.

Objective: Measuring the Vestibular-Ocular-Reflex (VOR) gains with the video head impulse test (vHIT) allows for accurate discrimination between peripheral and central causes of acute vestibular syndrome (AVS). In this study, we sought to investigate whether the accuracy of artificial intelligence (AI) based vestibular stroke classification applied in unprocessed vHIT data is comparable to VOR gain classification. Methods: We performed a prospective study from July 2015 until April 2020 on all patients presenting at the emergency department (ED) with signs of an AVS. The patients underwent vHIT followed by a delayed MRI, which served as a gold standard for stroke confirmation. The MRI ground truth labels were then applied to train a recurrent neural network (long short-term memory architecture) that used eye- and head velocity time series extracted from the vHIT examinations. Results: We assessed 57 AVS patients, 39 acute unilateral vestibulopathy patients (AUVP) and 18 stroke patients. The overall sensitivity, specificity and accuracy for detecting stroke with a VOR gain cut-off of 0.57 was 88.8, 92.3, and 91.2%, respectively. The trained neural network was able to classify strokes with a sensitivity of 87.7%, a specificity of 88.4%, and an accuracy of 87.9% based on the unprocessed vHIT data. The accuracy of these two methods was not significantly different (p = 0.09). Conclusion: AI can accurately diagnose a vestibular stroke by using unprocessed vHIT time series. The quantification of eye- and head movements with the use of machine learning and AI can serve in the future for an automated diagnosis in ED patients with acute dizziness. The application of different neural network architectures can potentially further improve performance and enable direct inference from raw video recordings.

Videooculography "HINTS" in Acute Vestibular Syndrome: A Prospective Study.

Objective: A three-step bedside test ("HINTS": Head Impulse-Nystagmus-Test of Skew), is a well-established way to differentiate peripheral from central causes in patients with acute vestibular syndrome (AVS). Nowadays, the use of videooculography gives physicians the possibility to quantify all eye movements. The goal of this study is to compare the accuracy of VOG "HINTS" (vHINTS) to an expert evaluation. Methods: We performed a prospective study from July 2015 to April 2020 on all patients presenting at the emergency department with signs of AVS. All the patients underwent clinical HINTS (cHINTS) and vHINTS followed by delayed MRI, which served as a gold standard for stroke confirmation. Results: We assessed 46 patients with AVS, 35 patients with acute unilateral vestibulopathy, and 11 patients with stroke. The overall accuracy of vHINTS in detecting a central pathology was 94.2% with 100% sensitivity and 88.9% specificity. Experts, however, assessed cHINTS with a lower accuracy of 88.3%, 90.9% sensitivity, and 85.7% specificity. The agreement between clinical and video head impulse tests was good, whereas for nystagmus direction was fair. Conclusions: vHINTS proved to be very accurate in detecting strokes in patients AVS, with 9% points better sensitivity than the expert. The evaluation of nystagmus direction was the most difficult part of HINTS.

Paradigm shift in acute dizziness: is caloric testing obsolete?

OBJECTIVE: Cold and warm water ear irrigation, also known as bithermal caloric testing, has been considered for over 100 years the 'Gold Standard' for the detection of peripheral vestibular hypofunction. Its discovery was awarded a Nobel Prize. We aimed to investigate the diagnostic accuracy of Caloric Testing when compared to the video head impulse test (vHIT) in differentiating between vestibular neuritis and vestibular strokes in acute dizziness. DESIGN: Prospective cross-sectional study (convenience sample). SETTING: All patients presenting with signs of an acute vestibular syndrome at the emergency department of a tertiary referral center. PARTICIPANTS: One thousand, six hundred seventy-seven patients were screened between February 2015 and May 2020 for Acute Vestibular Syndrome (AVS), of which 152 met the inclusion criteria and were enrolled. Inclusion criteria consisted of a state of continuous dizziness, associated with nausea or vomiting, head-motion intolerance, new gait or balance disturbance and nystagmus. Patients were excluded if they were younger than 18 years, if symptoms lasted < 24 h or if the index ED visit was > 72 h after symptom onset. Of the 152 included patients 85 completed testing. We assessed 58 vestibular neuritis and 27 stroke patients. MAIN OUTCOME MEASURES: All patients underwent calorics and vHIT followed by a delayed MRI which served as a gold standard for vestibular stroke confirmation. RESULTS: The overall sensitivity and specificity for detecting stroke with a caloric asymmetry cut-off of 30.9% was 75% and 86.8%, respectively [negative likelihood ratio (NLR) 0.29] compared to 91.7% and 88.7% for vHIT (NLR 0.094). Best VOR gain cut-off was 0.685. Twenty-five percent of vestibular strokes were misclassified by calorics, 8% by vHIT. CONCLUSIONS: Caloric testing proved to be less accurate than vHIT in discriminating stroke from vestibular neuritis in acute dizziness. Contrary to classic teaching, asymmetric caloric responses can also occur with vestibular strokes and might put the patient at risk for misdiagnosis. We, therefore, recommend to abandon caloric testing in current practice and to replace it with vHIT in the acute setting. Caloric testing has still its place as a diagnostic tool in an outpatient setting.

Acute vestibular syndrome: is skew deviation a central sign?

OBJECTIVE: Skew deviation results from a dysfunction of the graviceptive pathways in patients with an acute vestibular syndrome (AVS) leading to vertical diplopia due to vertical ocular misalignment. It is considered as a central sign, however, the prevalence of skew and the accuracy of its test is not well known . METHODS: We performed a prospective study from February 2015 until September 2020 of all patients presenting at our emergency department (ED) with signs of AVS. All patients underwent clinical HINTS and video test of skew (vTS) followed by a delayed MRI, which served as a gold standard for vestibular stroke confirmation. RESULTS: We assessed 58 healthy subjects, 53 acute unilateral vestibulopathy patients (AUVP) and 24 stroke patients. Skew deviation prevalence was 24% in AUVP and 29% in strokes. For a positive clinical test of skew, the cut-off of vertical misalignment was 3 deg with a very low sensitivity of 15% and specificity of 98.2%. The sensitivity of vTS was 29.2% with a specificity of 75.5%. CONCLUSIONS: Contrary to prior knowledge, skew deviation proved to be more prevalent in patients with AVS and occurred in every forth patient with AUVP. Large skew deviations (> 3.3 deg), were pointing toward a central lesion. Clinical and video test of skew offered little additional diagnostic value compared to other diagnostic tests such as the head impulse test and nystagmus test. Video test of skew could aid to quantify skew in the ED setting in which neurotological expertise is not always readily available.

Bruns' nystagmus revisited: A sign of stroke in patients with the acute vestibular syndrome.

OBJECTIVE: Gaze-evoked nystagmus (GEN) is a central sign in patients with the acute vestibular syndrome (AVS); however, discriminating between a pathological and a physiologic GEN is a challenge. Here we evaluate GEN in patients with AVS. METHODS: In this prospective cross-sectional study, we used video-oculography (VOG) to compare GEN in the light (target at 15° eccentric) in 64 healthy subjects with 47 patients seen in the emergency department (ED) who had AVS; 35 with vestibular neuritis and 12 with stroke. All patients with an initial non-diagnostic MRI received a confirmatory, delayed MRI as a reference standard in detecting stroke. RESULTS: Healthy subjects with GEN had a time constant of centripetal drift >18 s. VOG identified pathologic GEN (time constant ≤ 18 s) in 33% of patients with vestibular strokes, specificity was 100%, accuracy was 83%. Results were equivalent to examination by a clinical expert. As expected, since all patients with GEN had a SN in straight-ahead position, they showed the pattern of a Bruns' nystagmus. CONCLUSIONS: One third of patients with AVS due to central vestibular strokes had a spontaneous SN in straight-ahead gaze and a pathological GEN, producing the pattern of a Bruns' nystagmus with a shift of the null position. The localization of the side of the lesion based on the null was not consistent, presumably because the circuits underlying gaze-holding are widespread in the brainstem and cerebellum. Nevertheless, automated quantification of GEN with VOG was specific, and accurately identified patients in the ED with AVS due to strokes.

Stroke Prediction Based on the Spontaneous Nystagmus Suppression Test in Dizzy Patients: A Diagnostic Accuracy Study.

OBJECTIVE: Failure of fixation suppression of spontaneous nystagmus is sometimes seen in patients with vestibular strokes involving the cerebellum or brainstem; however, the accuracy of this test for the discrimination between peripheral and central causes in patients with an acute vestibular syndrome (AVS) is unknown. METHODS: Patients with AVS were screened and recruited (convenience sample) as part of a prospective cross-sectional study in the emergency department between 2015 and 2020. All patients received neuroimaging, which served as a reference standard. We recorded fixation suppression with video-oculography (VOG) for forward, right, and left gaze. The ocular fixation index (OFI) and the spontaneous nystagmus slow velocity reduction was calculated. RESULTS: We screened 1,646 patients reporting dizziness in the emergency department and tested for spontaneous nystagmus in 148 patients with AVS. We analyzed 56 patients with a diagnosed acute unilateral vestibulopathy (vestibular neuritis) and 28 patients with a confirmed stroke. There was a complete nystagmus fixation suppression in 49.5% of patients with AVS, in 40% of patients with vestibular neuritis, and in 62.5% of patients with vestibular strokes. OFI scores had no predictive value for detecting strokes; however, a nystagmus reduction of less than 2 °/s showed a high accuracy of 76.9% (confidence interval 0.59-0.89) with a sensitivity of 62.2% and specificity of 84.8% in detecting strokes. CONCLUSIONS: The presence of fixation suppression does not rule out a central lesion. The magnitude of suppression was lower compared to patients with vestibular neuritis. The nystagmus suppression test predicts vestibular strokes accurately provided that eye movements are recorded with VOG. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with an AVS, decreased fixation suppression recorded with VOG occurred more often in stroke (76.9%) than in vestibular neuritis (37.8%).

Impaired fixation suppression of horizontal vestibular nystagmus during smooth pursuit: pathophysiology and clinical implications.

BACKGROUND AND PURPOSE: A peripheral spontaneous nystagmus (SN) is typically enhanced or revealed by removing fixation. Conversely, failure of fixation suppression of SN is usually a sign of a central disorder. Based on Luebke and Robinson (Vision Res 1988, vol. 28 (8), pp. 941-946), who suggested that the normal fixation mechanism is disengaged during pursuit, it is hypothesized that vertical tracking in the light would bring out or enhance a horizontal SN. METHODS: Eighteen patients with acute vestibular neuritis were studied. Eye movements were recorded using video-oculography at straight-ahead gaze with and without visual fixation, and during smooth pursuit. The slow-phase velocity and the fixation suppression indices of nystagmus (relative to SN in darkness) were compared in each condition. RESULTS: During vertical tracking, the slow-phase velocity of horizontal SN with eyes near straight-ahead gaze was significantly higher (median 2.7°/s) than under static visual fixation (median 1.2°/s). Likewise, the fixation index was significantly higher (worse suppression) during pursuit (median 48%) than during fixation (median 26%). A release of SN was also suggested during horizontal pursuit, if one assumes superposition of SN on a normal and symmetrical pursuit capability.

How Good Are We in Evaluating a Bedside Head Impulse Test?

OBJECTIVES: Clinicians performing a horizontal head impulse test (HIT) are looking for a corrective saccade. The detection of such saccades is a challenge. The aim of this study is to assess an expert's likelihood of detecting corrective saccades in subjects with vestibular hypofunction. DESIGN: In a prospective cohort observational study at a tertiary referral hospital, we assessed 365 horizontal HITs performed clinically by an expert neurootologist from a convenience sample of seven patients with unilateral or bilateral deficient vestibulo-ocular reflex (VOR). All HITs were recorded simultaneously by video-oculography, as a gold standard. We evaluated saccades latency and amplitude, head velocity, and gain. RESULTS: Saccade amplitude was statistically the most significant parameter for saccade detection (p < 0.001).The probability of saccade detection was eight times higher for HIT toward the pathological side (p = 0.029). In addition, an increase in saccade amplitude resulted in an increased probability of detection (odds ratio [OR] 1.77 [1.31 to 2.40] per degree, p < 0.001). The sensitivity to detect a saccade amplitude of 1 degree was 92.9% and specificity 79%. Saccade latency and VOR gain did not significantly influence the probability of the physician identifying a saccade (OR 1.02 [0.94 to 1.11] per 10-msec latency and OR 0.84 [0.60 to 1.17] per 0.1 VOR gain increase). CONCLUSIONS: The saccade amplitude is the most important factor for accurate saccade detection in clinically performed head impulse tests. Contrary to current knowledge, saccade latency and VOR gain play a minor role in saccade detection.

VOR gain calculation methods in video head impulse recordings.

BACKGROUND: International consensus on best practices for calculating and reporting vestibular function is lacking. Quantitative vestibulo-ocular reflex (VOR) gain using a video head impulse test (HIT) device can be calculated by various methods. OBJECTIVE: To compare different gain calculation methods and to analyze interactions between artifacts and calculation methods. METHODS: We analyzed 1300 horizontal HIT traces from 26 patients with acute vestibular syndrome and calculated the ratio between eye and head velocity at specific time points (40 ms, 60 ms) after HIT onset ('velocity gain'), ratio of velocity slopes ('regression gain'), and ratio of area under the curves after de-saccading ('position gain'). RESULTS: There was no mean difference between gain at 60 ms and position gain, both showing a significant correlation (r2 = 0.77, p < 0.001) for artifact-free recordings. All artifacts reduced high, normal-range gains modestly (range -0.06 to -0.11). The impact on abnormal, low gains was variable (depending on the artifact type) compared to artifact-free recordings. CONCLUSIONS: There is no clear superiority of a single gain calculation method for video HIT testing. Artifacts cause small but significant reductions of measured VOR gains in HITs with higher, normal-range gains, regardless of calculation method. Artifacts in abnormal HITs with low gain increased measurement noise. A larger number of HITs should be performed to confirm abnormal results, regardless of calculation method.

New insights into vestibular-saccade interaction based on covert corrective saccades in patients with unilateral vestibular deficits.

In response to passive high-acceleration head impulses, patients with low vestibulo-ocular reflex (VOR) gains often produce covert (executed while the head is still moving) corrective saccades in the direction of deficient slow phases. Here we examined 23 patients using passive, and 9 also active, head impulses with acute (< 10 days from onset) unilateral vestibular neuritis and low VOR gains. We found that when corrective saccades are larger than 10°, the slow-phase component of the VOR is inhibited, even though inhibition increases further the time to reacquire the fixation target. We also found that 1) saccades are faster and more accurate if the residual VOR gain is higher, 2) saccades also compensate for the head displacement that occurs during the saccade, and 3) the amplitude-peak velocity relationship of the larger corrective saccades deviates from that of head-fixed saccades of the same size. We propose a mathematical model to account for these findings hypothesizing that covert saccades are driven by a desired gaze position signal based on a prediction of head displacement using vestibular and extravestibular signals, covert saccades are controlled by a gaze feedback loop, and the VOR command is modulated according to predicted saccade amplitude. A central and novel feature of the model is that the brain develops two separate estimates of head rotation, one for generating saccades while the head is moving and the other for generating slow phases. Furthermore, while the model was developed for gaze-stabilizing behavior during passively induced head impulses, it also simulates both active gaze-stabilizing and active gaze-shifting eye movements.NEW & NOTEWORTHY During active or passive head impulses while fixating stationary targets, low vestibulo-ocular gain subjects produce corrective saccades when the head is still moving. The mechanisms driving these covert saccades are poorly understood. We propose a mathematical model showing that the brain develops two separate estimates of head rotation: a lower level one, presumably in the vestibular nuclei, used to generate the slow-phase component of the response, and a higher level one, within a gaze feedback loop, used to drive corrective saccades.

Determinants for a Successful Sémont Maneuver: An In vitro Study with a Semicircular Canal Model.

OBJECTIVE: To evaluate the effect of time between the movements/steps, angle of body movements as well as the angular velocity of the maneuvers in an in vitro model of a semicircular canal (SCC) to improve the efficacy of the Sémont maneuver (SM) in benign paroxysmal positional vertigo. MATERIALS AND METHODS: Sémont maneuvers were performed on an in vitro SCC model. Otoconia trajectories were captured by a video camera. The effects of time between the movements, angles of motion (0°, 10°, 20°, and 30° below the horizontal line), different angular velocities (90, 135, 180°/s), and otoconia size (36 and 50 µm) on the final position of the otoconia in the SCC were tested. RESULTS: Without extension of the movements beyond the horizontal, the in vitro experiments (with particles corresponding to 50 µm diameter) did not yield successful canalith repositioning. If the movements were extended by 20° beyond the horizontal position, SM were successful with resting times of at least 16 s. For larger extension angles, the required time decreased. However, for smaller particles (36 µm), the required time doubled. The angular maneuver velocity (tested between 90 and 180°/s) did not have a major impact on the final position of the otoconia. INTERPRETATION: The two primary determinants for success of the SM are the time between the movements and the extension of the movements beyond the horizontal. The time between the movements should be at least 45 s. Angles of 20° or more below horizontal line (so-called Sémont+) should increase the success rate of SM.