Concordant GRADE-3 Truncal Ataxia and Ocular Laterodeviation in Acute Medullary Stroke.

Background: Severe truncal ataxia associated with an inability to sit up without assistance (STA grade 3) is frequent in patients with central acute vestibular syndrome (AVS) involving the brainstem or cerebellum. When these patients have nystagmus, central HINTS excludes peripheral lesions; however, additional localization and lateralization signs are helpful, not only to resolve the peripheral versus central vestibular lesion dilemma, but to zero in on a precise lesion localization/lateralization to the lateral medulla, the most common ischemic lesion localization associated with an initially false-negative stroke MRI. Methods: This is a study of AVS patients with additional inclusion criteria: grades 2 or 3 ataxia with an eventual diagnosis of medullary stroke (MS), either involving the lateral medulla (LMS) or the medial medulla (MMS), and horizontal (h) gaze paralysis was the main exclusion criteria. All patients sat on the side of the bed or stretcher, with assistance if needed. A general neurologic examination followed in the sitting position, the testing protocol included the head impulse, spontaneous nystagmus, and skew deviation (HINTS) tests, followed by observation of the effect of brief 3-5 sec eyelid closure on ocular position, and saccade and pursuit eye movement tests. If they could sit, the protocol included the ability to stand with a wide base, then a narrow base, the Romberg test, and tandem gait. Radiographic lesion localization and horizontal gaze deviation concluded the protocol. Results: A total of 34 patients met the entry criteria, 34 MS (13 in the lateral medulla, 12 previously described, and 1 new patient), and 1 new MMS. Among them, n = 10/12 had grade 3 ataxia, and 3 (1 new patient) had grade 2 ataxia. In addition, overt ocular laterodeviation (OLD) was present in thirteen of them (35.3%). All OLD patients had gaze deviation and ipsilateral saccade and truncal lateropulsion, 1 medial medulla stroke patient had grade 3 truncal contrapulsion and contralateral hemiparesis without OLD, n = 20/21 patients with LMS without OLD had grade 3 truncal ataxia, and 1 had grade 2 truncal ataxia. Discussion: AVS patients with severe truncal ataxia (inability to sit without assistance) potentially have brainstem, cerebellum, or subcortical lesions. All patients had central HINTS; however, simultaneous direction-concordant STA 3 and OLD provided greater lateral medulla localization specificity, affecting the ipsilateral medulla. Future work to explore a practical posterior circulation stroke scale that includes HINTS, STA, and OLD will potentially select cases for thrombolysis even in the event of initially false-negative imaging.

Impact of Clinician Training Background and Stroke Location on Bedside Diagnostic Test Accuracy in the Acute Vestibular Syndrome - A Meta-Analysis.

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.

Generalized vestibular hyporeflexia and chronic upbeat nystagmus due to thiamine deficiency.

BACKGROUND: Ocular motor and vestibular manifestations of Wernicke's thiamine deficiency (WTD) are frequent and heterogeneous. Previous neuropathological and neuroimaging findings identified brainstem and cerebellar lesions responsible for these findings, however, peripheral vestibular lesions are probably uncommon in human WTD, though noted on an avian thiamine deficient study. MATERIAL: Single case study of a WTD patient post-gastric bypass who developed ataxia, oscillopsia and nystagmus, with low serum thiamine, and increased MRI T2 signal in the thalami, but normal brainstem and cerebellum. Vestibular evaluation showed significant vestibular hyporreflexia affecting all six canals, and a chronic upbeat nystagmus, now for 14 months after WTD onset. METHODS: Serial clinical, video head impulse, nystagmus analysis, cervical and ocular vestibular evoked responses. She is undergoing treatment with Memantine, Clonazepam and vestibular rehabilitation, and feels improvement. CONCLUSION: This report shows a novel combination of central and peripheral vestibular findings, of relevance for diagnosis and treatment, in addition to the development of a coherent hypothesis on the ocular motor and vestibular findings in WTD.

Inflammatory Sixth Nerve Palsy Post-COVID-19 Vaccination: Magnetic Resonance Imaging Findings.

Sixth nerve palsy is the most common post-vaccination oculomotor palsy. It is generally transient with most patients making a complete recovery. We report the case of a 46-year-old healthy male patient who presented with a painless sixth nerve palsy after the second dose of the Pfizer BioNTech COVID-19 vaccine, which recovered over the course of the next month. We confirmed the lesion localisation by demonstrating enhancement of the root exit zone and the cisternal portion of the sixth nerve on sequential magnetic resonance imaging during the symptomatic period. Here, a temporal relationship between vaccine application and diplopia onset suggests an aetiologic relationship. Moreover, the lack of pre-existing medical conditions suggests a post-vaccination inflammatory process.

Role of incubitus truncal ataxia, and equivalent standing grade 3 ataxia in the diagnosis of central acute vestibular syndrome.

INTRODUCTION AND OBJECTIVES: acute vestibular syndrome is a diagnostic challenge, requiring a rapid and precise diagnosis to take therapeutic actions. Truncal ataxia, inability to sit still, and Babinski flexor dysergy were evaluated. Material anf methods: 52 patients with central pathology (stroke in aica and pica territory) and vestibular neuritis were prospectively studied. MRI of the brain was used as the gold standard. RESULTS: A combination of grade 2-3 ataxia to differentiate patients with vestibular neuritis from patients with stroke resulted in a 92% sensitivity (95% CI 79-100%), a 67% specificity (95% CI 47-86%). Flexion asynergy had a 70% sensitivity (95% CI 47-92%), and an 88% specificity (95% CI 69-100%). The inability to sit still correlated well with truncal ataxia. CONCLUSIONS: vestibulospinal signs are useful in the differential diagnosis of acute vestibular syndromes, and the inability to sit is a good substitute for truncal ataxia when it cannot be evaluated.

Case report: Acute vestibular syndrome and cerebellitis in anti-Yo paraneoplastic syndrome.

Background: We define acute vestibular syndrome (AVS) as a sudden onset vertigo, nausea, vomiting, and head motion intolerance, more frequently associated with an acute peripheral and unilateral vestibulopathy. About 10-20% of all cases with central vestibulopathy are secondary to stroke. We report three patients evaluated over the past decade with an acute AVS along with subtle downbeat nystagmus (DBN), followed by dysarthria and progressive truncal and limb ataxia, as well as increasing DBN intensity. Methods: All patients underwent neurologic examination, video-oculography, MRI, serum cancer markers, spinal fluid examination, paraneoplastic panel testing, and oncologic workup. With a consolidated diagnosis of cancer/paraneoplastic syndrome, we treated with plasma exchange (PLEX), high-dose steroids, surgery, and oncologic investigation. We additionally provided oncotherapy in one out of three patients. Results: All three patients had an acute AVS, downbeat nystagmus DBN, and inability to perform tandem gait. Two of three patients had a normal head impulse test (HIT). As acute vertigo, nausea, and vomiting subsided, a progressive cerebellar syndrome ensued characterized by persistent DBN, impaired horizontal and vertical pursuit, impaired VOR suppression, truncal and limb ataxia, and dysarthria. All patients had normal MRI brain studies excluding stroke. CSF studies demonstrated lymphocytic pleocytosis and elevated protein. One patient had confirmed ovarian cancer with high CA-125 serum levels; another had undifferentiated cancer of unknown primary with high CA-125 and one patient with esophageal cancer. All had a positive PCA-1 antibody titer, also known as anti-Yo antibody. In one patient with expeditious immunosuppression, the ataxia progression slowed for 18 months, whereas the other two patients with delayed initiation of treatment had more rapidly progressive ataxia. Discussion: Paraneoplastic encephalitis related to PCA-1 antibody (Anti-Yo) targets Purkinje cells and cells in the granular layer of the cerebellar cortex. Clinically, our patients had a central AVS characterized by DBN and followed with progressive ataxia and unremarkable neuroimaging studies. Rapid initiation of treatment may offer a greater chance to prevent further neurologic decline. Any patient with an AVS as well as DBN and normal MRI should have an expeditious workup to rule out metabolic, toxic, and infectious causes just prior to considering prompt treatment with high-dose steroids and plasma exchange (PLEX) to mitigate the risk of rapidly progressive and irreversible neurologic decline.

Truncal ataxia and the vestibulo spinal reflex. A historical review.

The vestibulospinal pathway was described many years ago. Along with it, the vestibulospinal signs that are used for the diagnosis of vestibular disorders were described. In this work we summarize the history of the vestibulospinal pathway, the classic signs and the new signs that can be used in the diagnosis of vestibular disorders, paying special attention to truncal ataxia as a useful element to differentiate central from peripheral pathology.

Effect of convergence on the horizontal VOR in normal subjects and patients with peripheral and central vestibulopathy.

BACKGROUND: Vestibular compensatory eye movements provide visual fixation stabilization during head movement. The anatomic pathways mediating a normal horizontal vestibulo-ocular reflex (h-VOR), when lesioned, cause spontaneous nystagmus. While previous reports address the effect of convergence on different spontaneous nystagmus types, to our knowledge, a study of acute vestibular nystagmus suppression viewing near targets comparing patients with peripheral or central vestibular lesions has not been previously reported. METHODS: We attempt to clarify potential vestibular and near-reflex interaction by comparing near and far h-VOR gain in 19 healthy controls, six patients with acute/subacute peripheral vestibular lesion (PVL), and one patient with unilateral vestibular nuclear lesion (VNL) in the pontine tegmentum. RESULTS: The horizontal (h)-VOR in normal subjects increased with convergence in both eyes (P = 0.027, P < 0.001). In unilateral PVL patients, gain failed to increase in either direction (P = 0.25, P = 0.47). In contrast, when fixating at 15 cm, the h-aVOR in the VNL lesion, gain did not increase, and a right h-nystagmus developed. Even though we found inability to increase gain in PVL with near target fixation, this did not interfere with h-nystagmus suppression upon converging. Our VNL patient had normal h-nystagmus suppression viewing far distance targets and lacked near target h-nystagmus suppression. CONCLUSION: We hypothesize that normal IO/flocculus pathway suppressed spontaneous nystagmus in PVL. Impaired h-VOR near adaptation in the medial vestibular nucleus was responsible for h-nystagmus direction with fixation block. Additionally, impaired viewing distance estimate contributed to near h-nystagmus suppression failure.

Postinfectious SARS-CoV-2 Opsoclonus-Myoclonus-Ataxia Syndrome.

BACKGROUND: The opsoclonus-myoclonus-ataxia syndrome (OMAS) represents a pathophysiology and diagnostic challenge. Although the diverse etiologies likely share a common mechanism to generate ocular, trunk, and limb movements, the underlying cause may be a paraneoplastic syndrome, as the first sign of cancer, or may be a postinfectious complication, and thus, the outcome depends on identifying the trigger mechanism. A recent hypothesis suggests increased GABAA receptor sensitivity in the olivary-oculomotor vermis-fastigial nucleus-premotor saccade burst neuron circuit in the brainstem. Therefore, OMAS management will focus on immunosuppression and modulation of GABAA hypersensitivity with benzodiazepines. METHODS: We serially video recorded the eye movements at the bedside of 1 patient with SARS-CoV-2-specific Immunoglobulin G (IgG) serum antibodies, but twice-negative nasopharyngeal reverse transcription polymerase chain reaction (RT-PCR). We tested cerebrospinal fluid (CSF), serum, and nasopharyngeal samples. After brain MRI and chest, abdomen, and pelvis CT scans, we treated our patient with clonazepam and high-dose Solu-MEDROL, followed by a rituximab infusion after her formal eye movement analysis 10 days later. RESULTS: The recordings throughout her acute illness demonstrated different eye movement abnormalities. While on high-dose steroids and clonazepam, she initially had macrosaccadic oscillations, followed by brief ocular flutter during convergence the next day; after 10 days, she had bursts of opsoclonus during scotopic conditions with fixation block but otherwise normal eye movements. Concern for a suboptimal response to high-dose Solu-MEDROL motivated an infusion of rituximab, which induced remission. An investigation for a paraneoplastic etiology was negative. CSF testing showed elevated neuron-specific enolase. Serum IgG to Serum SARS-CoV2 IgG was elevated with negative RT-PCR nasopharyngeal testing. CONCLUSION: A recent simulation model of macrosaccadic oscillations and OMAS proposes a combined pathology of brainstem and cerebellar because of increased GABAA receptor sensitivity. In this case report, we report 1 patient with elevated CSF neuronal specific enolase, macrosaccadic oscillations, ocular flutter, and OMAS as a SARS-CoV-2 postinfectious complication. Opsoclonus emerged predominantly with fixation block and suppressed with fixation, providing support to modern theories on the mechanism responsible for these ocular oscillations involving cerebellar-brainstem pathogenesis.

Mild Bilateral Internuclear Ophthalmoplegia: The Diagnostic Role of the Vertical Posterior Canal Vestibulo-Ocular Reflex in Acute Brainstem Demyelination, a Clinical-Radiologic Correlation.

BACKGROUND: The ocular signs of internuclear ophthalmoplegia (INO) with slow, restricted adduction of one eye and abduction nystagmus of the contralateral eye are easily recognized and have a high localizing/lateralizing value. However, subtle INO is difficult to diagnose. Recent reports identified novel vestibular abnormalities in unilateral and bilateral INO. Frequent findings include decreased horizontal and posterior canal gains, and generally relative sparing of both anterior canals. We studied one patient with a subtle bilateral INO, performed serial quantitative saccade (QS) and video head impulse test (vHIT), and correlated clinical-radiological findings caused by acute demyelination. METHODS: Single case study of a 30-year-old man presented with 1 week of painless, binocular, horizontal diplopia in left gaze. We performed 3 serial neurological examination, QS, vHIT, and clinical-MRI correlation (1 pretreatment and 2 post steroid treatment). RESULTS: We found bilateral slow adducting, clinically positive posterior canal HITs, and borderline abducting saccade velocity, without abducting nystagmus. The videonystagmography with fixation block showed bilateral horizontal gaze evoked nystagmus, and vHIT testing confirmed decreased right horizontal and bilateral posterior canal gains. The abnormalities resolved after steroid treatment. MRI showed acute bilateral medial longitudinal fascicle demyelinating lesions. CONCLUSIONS: A bilaterally positive, posterior, canal HIT and slow adduction saccades are localizing findings in bilateral INO, even in the absence of abduction nystagmus. Quantitative confirmation of these findings suggest most frequently an ischemic or demyelinating disorder and are a compelling indication for MRI. This case shows value to testing multiaxial head impulses and performing QS and vHIT in brainstem lesions.

Paraneoplastic Progressive Downbeat Nystagmus, Ataxia and Sensorineural Hearing Loss due to the ANTI-Kelch-11 Protein Antibody.

ABSTRACT: A 45-year-old man with a history of testicular seminoma treated 8 years earlier presented with chronic progressive truncal and limb ataxia, progressive sensorineural hearing loss, and episodic vertigo. Eye movement and neuro-otology examinations showed localizing abnormalities to the bilateral cerebellar flocculus, vermis, and bilateral cerebellar hemispheres. Audiometric testing showed bilateral symmetric sensorineural hearing loss. There was a normal MRI of the brain. Cerebrospinal fluid (CSF) showed modest lymphocytic pleocytosis, and there was an elevated serum choriogonadotrophic hormone. An abdominal CT scan showed a solitary, large retroperitoneal lymph node, and histopathologic examination of the node biopsy showed granulomatous inflammation without microorganisms; eventually, immunohistochemical markers confirmed the diagnosis of metastatic seminoma. Although normal neuroimaging and inflammatory CSF reaction suggested a paraneoplastic etiology, the initial paraneoplastic antibody testing was negative. Subsequent investigation identified a positive kelch-11 protein antibody, thus confirming the paraneoplastic connection between the metastatic seminoma and the subacute neurologic-cochleovestibular syndrome.

Resolved External Ophthalmoplegia and Hearing Loss in Wernicke's Encephalopathy With Thiamine Replacement.

BACKGROUND: Wernicke encephalopathy (WE) is classically described by a clinical triad consisting of confusion, ataxia, and ophthalmoplegia, but recent reports emphasize a history of malnutrition along with 2 elements of the WE triad (Caine's criteria) to enhance diagnostic sensitivity. The ophthalmoplegia, vestibular, and auditory expeditious improvement with intravenous thiamine usually confirms the diagnosis; serum levels generally provide additional diagnostic certainty. METHODS: Here, we discuss the case of a woman with a distant history of gastric sleeve, poor nutrition and protracted vomiting, who developed acute confusion, imbalance, near-total external ophthalmoplegia (EO), and hearing loss. The baseline thiamine level was 28 πmol/L (Normal: 70-180 πmol/L). We performed serial neurological, vestibular, and audiological examination to document over 5 days, the effect of intravenous (IV) thiamine, and again at 3 months with continued oral supplementation. We provide serial documentation with photographs and video recording of oculomotor abnormalities, audiometric testing, and a video of horizontal head impulse testing, and imaging findings. RESULTS: Over the course of 5 days of IV thiamine supplementation, we demonstrate our patient's resolution of near complete EO. We assessed vestibular paresis with horizontal head impulse testing, after complete resolution of the EO. The initially positive bilateral h-HIT showed decreased gain and overt corrective saccades, it clinically resolved by day 5, but video h-HIT testing demonstrated persistent decreased horizontal vestibulo-ocular reflex (VOR) gain and covert horizontal saccades, which persisted at the 3-month examination. By contrast, the vertical VOR gain was normal without corrective saccades. Bedside audiometry completed during the acute phase demonstrated severely restricted auditory speech comprehension, which normalized 3 months later. Severe truncal ataxia improved as well. CONCLUSIONS: This case is an example of how awareness of the variations in the clinical presentation of WE can be crucial in achieving an early diagnosis and obtaining better outcomes. A history of the poor nutritional status can be an important clue to aid in this early diagnosis.

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.

Ocular lateral deviation with brief removal of visual fixation differentiates central from peripheral vestibular syndrome.

OBJECTIVE: Ocular lateral deviation (OLD) is a conjugate, ipsilesional, horizontal ocular deviation associated with brief (3-5 s) closing of the eyes, commonly linked to the lateral medullary syndrome (LMS). There is limited information regarding OLD in patients with the acute vestibular syndrome (AVS). In one case series 40 years ago OLD was suggested to be a central sign. Recently, horizontal ocular deviation on imaging (RadOLD) was frequently associated with anterior circulation stroke and horizontal gaze palsy. Similarly, RadOLD has been associated with posterior circulation stroke, e.g., LMS and cerebellar stroke, but without clinical correlation with OLD. METHODS: This is a prospective, cross-sectional diagnostic study of 151 acute AVS patients. Patients had spontaneous nystagmus. Horizontal gaze paralysis was an exclusion criterion. We noted the effect of brief 3-5 s eyelid closure on eye position, and then used the HINTS algorithm (the head-impulse test, nystagmus characteristics and skew deviation) and RadOLD, to establish a correlation between clinical and radiologic findings RESULTS: Of the 151 AVS patients, 100 had a central lesion and 51 a peripheral lesion; 29 of the central lesions were LMS, and 11 had OLD. Additionally, one lateral pontine syndrome had OLD. On opening the eyes 11 patients with OLD and LMS made multiple, hypometric corrective saccades to bring gaze back to straight ahead. 10/11 patients with LMS showed RadOLD. CONCLUSIONS: OLD with multiple hypometric corrective saccades on opening the eyes was infrequent but highly localizing and lateralizing. We emphasize how simple it is to test for OLD, with the caveat that to be specific, it must be present after just brief (3-5 s) eyelid closure.