Jorge C. Kattah

HINTS to Diagnose Stroke in the Acute Vestibular Syndrome Three-Step Bedside Oculomotor Examination More Sensitive Than Early MRI Diffusion-Weighted Imaging

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; &khgr;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.

Normal head impulse test differentiates acute cerebellar strokes from vestibular neuritis

Objective: To test the diagnostic accuracy of the horizontal head impulse test (h-HIT) of vestibulo-ocular reflex (VOR) function in distinguishing acute peripheral vestibulopathy (APV) from stroke. Most patients with acute vertigo, nausea/vomiting, and unsteady gait have benign APV (vestibular neuritis or labyrinthitis) as a cause. However, some harbor life-threatening brainstem or cerebellar strokes that mimic APV. A positive h-HIT (abnormal VOR) is said to predict APV. Methods: Cross-sectional study at an urban, academic hospital over 6 years. Consecutive acute vestibular syndrome patients at high risk for stroke underwent structured examination (including h-HIT), neuroimaging, and admission. Stroke was confirmed by neuroimaging (MRI or CT). APV was diagnosed by normal MRI and appropriate clinical evolution in follow-up. Results: Forty-three subjects enrolled. One had an equivocal h-HIT. Patients with APV had a positive h-HIT (n = 8/8, 100%). Most patients with stroke had a negative h-HIT (n = 31/34, 91%). However, contrary to conventional wisdom, three patients with stroke (9%) demonstrated a positive h-HIT (1 vestibulocerebellar, 1 pontocerebellar, 1 pontocerebello-labyrinthine stroke). Conclusions: Patients with lateral pontine and cerebellar strokes can have a positive horizontal head impulse test (h-HIT), so the sign’s presence cannot be solely relied upon to identify a benign pathology. Additional clinical features (e.g., directionality of nystagmus, severity of truncal instability, nature of hearing loss) must be considered in patients with acute vestibular syndrome with a positive h-HIT before a central localization can be confidently excluded. Nonetheless, the h-HIT remains a useful bedside test—in acute vestibular syndrome patients, a negative h-HIT (i.e., normal VOR) strongly suggests a central lesion with a pseudo-labyrinthine presentation.

Quantitative video-oculography to help diagnose stroke in acute vertigo and dizziness: Toward an ECG for the eyes

Background and Purpose— Strokes can be distinguished from benign peripheral causes of acute vestibular syndrome using bedside oculomotor tests (head impulse test, nystagmus, test-of-skew). Using head impulse test, nystagmus, test-of-skew is more sensitive and less costly than early magnetic resonance imaging for stroke diagnosis in acute vestibular syndrome but requires expertise not routinely available in emergency departments. We sought to begin standardizing the head impulse test, nystagmus, test-of-skew diagnostic approach for eventual emergency department use through the novel application of a portable video-oculography device measuring vestibular physiology in real time. This approach is conceptually similar to ECG to diagnose acute cardiac ischemia. Methods— Proof-of-concept study (August 2011 to June 2012). We recruited adult emergency department patients with acute vestibular syndrome defined as new, persistent vertigo/dizziness, nystagmus, and (1) nausea/vomiting, (2) head motion intolerance, or (3) new gait unsteadiness. We recorded eye movements, including quantitative horizontal head impulse testing of vestibulo-ocular-reflex function. Two masked vestibular experts rated vestibular findings, which were compared with final radiographic gold-standard diagnoses. Masked neuroimaging raters determined stroke or no stroke using magnetic resonance imaging of the brain with diffusion-weighted imaging obtained 48 hours to 7 days after symptom onset. Results— We enrolled 12 consecutive patients who underwent confirmatory magnetic resonance imaging. Mean age was 61 years (range 30–73), and 10 were men. Expert-rated video-oculography–based head impulse test, nystagmus, test-of-skew examination was 100% accurate (6 strokes, 6 peripheral vestibular). Conclusions— Device-based physiological diagnosis of vertebrobasilar stroke in acute vestibular syndrome should soon be possible. If confirmed in a larger sample, this bedside eye ECG approach could eventually help fulfill a critical need for timely, accurate, efficient diagnosis in emergency department patients with vertigo or dizziness who are at high risk for stroke.

Small strokes causing severe vertigo Frequency of false-negative MRIs and nonlacunar mechanisms

Objective: Describe characteristics of small strokes causing acute vestibular syndrome (AVS). Methods: Ambispective cross-sectional study of patients with AVS (acute vertigo or dizziness, nystagmus, nausea/vomiting, head-motion intolerance, unsteady gait) with at least one stroke risk factor from 1999 to 2011 at a single stroke referral center. Patients underwent nonquantitative HINTS “plus” examination (head impulse, nystagmus, test-of-skew plus hearing), neuroimaging to confirm diagnoses (97% by MRI), and repeat MRI in those with initially normal imaging but clinical signs of a central lesion. We identified patients with diffusion-weighted imaging (DWI) strokes ≤10 mm in axial diameter. Results: Of 190 high-risk AVS presentations (105 strokes), we found small strokes in 15 patients (median age 64 years, range 41–85). The most common vestibular structure infarcted was the inferior cerebellar peduncle (73%); the most common stroke location was the lateral medulla (60%). Focal neurologic signs were present in only 27%. The HINTS “plus” battery identified small strokes with greater sensitivity than early MRI-DWI (100% vs 47%, p < 0.001). False-negative initial MRIs (6–48 hours) were more common with small strokes than large strokes (53% [n = 8/15] vs 7.8% [n = 7/90], p < 0.001). Nonlacunar stroke mechanisms were responsible in 47%, including 6 vertebral artery occlusions or dissections. Conclusions: Small strokes affecting central vestibular projections can present with isolated AVS. The HINTS “plus” hearing battery identifies these patients with greater accuracy than early MRI-DWI, which is falsely negative in half, up to 48 hours after onset. We found nonlacunar mechanisms in half, suggesting greater risk than might otherwise be assumed for patients with such small infarctions.

VOR gain by head impulse video-oculography differentiates acute vestibular neuritis from stroke

Objective Vestibular neuritis is often mimicked by stroke (pseudoneuritis). Vestibular eye movements help discriminate the two conditions. We report vestibulo-ocular reflex (VOR) gain measures in neuritis and stroke presenting acute vestibular syndrome (AVS). Methods Prospective cross-sectional study of AVS (acute continuous vertigo/dizziness lasting >24 h) at two academic centers. We measured horizontal head impulse test (HIT) VOR gains in 26 AVS patients using a video HIT device (ICS Impulse). All patients were assessed within 1 week of symptom onset. Diagnoses were confirmed by clinical examinations, brain magnetic resonance imaging with diffusion-weighted images, and follow-up. Brainstem and cerebellar strokes were classified by vascular territory—posterior inferior cerebellar artery (PICA) or anterior inferior cerebellar artery (AICA). Results Diagnoses were vestibular neuritis (n = 16) and posterior fossa stroke (PICA, n = 7; AICA, n = 3). Mean HIT VOR gains (ipsilesional [standard error of the mean], contralesional [standard error of the mean]) were as follows: vestibular neuritis (0.52 [0.04], 0.87 [0.04]); PICA stroke (0.94 [0.04], 0.93 [0.04]); AICA stroke (0.84 [0.10], 0.74 [0.10]). VOR gains were asymmetric in neuritis (unilateral vestibulopathy) and symmetric in PICA stroke (bilaterally normal VOR), whereas gains in AICA stroke were heterogeneous (asymmetric, bilaterally low, or normal). In vestibular neuritis, borderline gains ranged from 0.62 to 0.73. Twenty patients (12 neuritis, six PICA strokes, two AICA strokes) had at least five interpretable HIT trials (for both ears), allowing an appropriate classification based on mean VOR gains per ear. Classifying AVS patients with bilateral VOR mean gains of 0.70 or more as suspected strokes yielded a total diagnostic accuracy of 90%, with stroke sensitivity of 88% and specificity of 92%. Conclusion Video HIT VOR gains differ between peripheral and central causes of AVS. PICA strokes were readily separated from neuritis using gain measures, but AICA strokes were at risk of being misclassified based on VOR gain alone.

Quantifying the vestibulo-ocular reflex with video-oculography: Nature and frequency of artifacts

Video-oculography devices are now used to quantify the vestibulo-ocular reflex (VOR) at the bedside using the head impulse test (HIT). Little is known about the impact of disruptive phenomena (e.g. corrective saccades, nystagmus, fixation losses, eye-blink artifacts) on quantitative VOR assessment in acute vertigo. This study systematically characterized the frequency, nature, and impact of artifacts on HIT VOR measures. From a prospective study of 26 patients with acute vestibular syndrome (16 vestibular neuritis, 10 stroke), we classified findings using a structured coding manual. Of 1,358 individual HIT traces, 72% had abnormal disruptive saccades, 44% had at least one artifact, and 42% were uninterpretable. Physicians using quantitative recording devices to measure head impulse VOR responses for clinical diagnosis should be aware of the potential impact of disruptive eye movements and measurement artifacts. i 2014 S. Karger AG, Basel

Vestibular signs of thiamine deficiency during the early phase of suspected Wernicke encephalopathy

SummaryNon-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.

Cryptococcal meningitis in a multiple sclerosis patient taking natalizumab

IMPORTANCE Natalizumab was approved in 2004 by the US Food and Drug Administration (US-FDA) for treatment of multiple sclerosis (MS), however it was temporarily withdrawn after its use was associated with progressive multifocal leukoencephalopathy (PML). Other reported adverse events have included melanoma, primary central nervous system (CNS) lymphoma, and gastrointestinal cryptosporidiosis. An MS exacerbation may occur after discontinuation and immune reconstitution inflammatory syndrome (IRIS), particularly in the setting of PML, is also possible. We present the first case of cryptococcal meningitis in a patient taking natalizumab. Managements of both cryptococcal meningitis and MS after discontinuation of natalizumab are the focus of this report. OBSERVATIONS This is a case report describing a 49-year old Caucasian man with relapsing-remitting MS (RR-MS) on natalizumab. On the twenty-fourth month of natalizumab treatment, he developed cryptococcal meningitis, prompting its discontinuation. Two months later, off natalizumab, while on antifungal treatment, he developed an MS exacerbation. Cerebrospinal fluid (CSF) JC virus polymerase chain reaction (PCR) and human immunodeficiency virus (HIV) serology were repeatedly negative. CONCLUSIONS AND RELEVANCE Although specific recommendations for treating natalizumab-associated cryptococcal meningitis do not exist, our patient discontinued natalizumab and started conventional anti-fungal treatment. Two months later, he was treated with steroids due to worsening neurologic status from a presumed MS attack. Subsequently, he improved with successful treatment of the cryptococcal meningitis, with no new clinical or radiographic exacerbations.

Downbeat nystagmus as a result of lamotrigine toxicity

BACKGROUND Downbeat nystagmus (DBN) has been reported with phenytoin and carbamazepine toxicity. DBN has not been described as a result of lamotrigine toxicity. METHODS Clinical records, neuroimaging and video recordings were obtained in two patients diagnosed with intractable epilepsy who developed oscillopsia and incoordination while being treated with lamotrigine. One patient had a videonystagmographic (VNG) study. DISCUSSION Lamotrigines half-life is extended when used with valproic acid; hence, the increased chance of neurotoxicity associated with DBN. In our cases, DBN and truncal ataxia occurred in conjunction with toxic lamotrigine serum levels. CONCLUSION Anticonvulsant toxicity should be considered as a cause of DBN. Lamotrigine toxicity may be an unusual cause.

HINTS to Diagnose Stroke in the Acute Vestibular Syndrome

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; &khgr;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.