Progressive loss of hearing and balance in superficial siderosis due to occult spinal dural defects.

PURPOSE: Superficial siderosis, a progressive, debilitating, neurological disease, often presents with bilateral impairment of auditory and vestibular function. We highlight that superficial siderosis is often due to a repairable spinal dural defect of the type that can also cause spontaneous intracranial hypotension. METHODS: Retrospective chart review of five patients presenting with moderate to severe, progressive bilateral sensorineural hearing loss as well as vestibular loss. All patients had developed superficial siderosis from spinal dural defects: three after trauma, one after spinal surgery and one from a thoracic discogenic microspur. RESULTS: The diagnosis was made late in all five patients; despite surgical repair in four, hearing and vestibular loss failed to improve. CONCLUSIONS: In patients presenting with progressive bilateral sensorineural hearing loss, superficial siderosis should be considered as a possible cause. If these patients also have bilateral vestibular loss, cerebellar impairment and anosmia, then the diagnosis is likely and the inevitable disease progress might be halted by finding and repairing the spinal dural defect.

Bioinformatics-Based Identification of Expanded Repeats: A Non-reference Intronic Pentamer Expansion in RFC1 Causes CANVAS.

Genomic technologies such as next-generation sequencing (NGS) are revolutionizing molecular diagnostics and clinical medicine. However, these approaches have proven inefficient at identifying pathogenic repeat expansions. Here, we apply a collection of bioinformatics tools that can be utilized to identify either known or novel expanded repeat sequences in NGS data. We performed genetic studies of a cohort of 35 individuals from 22 families with a clinical diagnosis of cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS). Analysis of whole-genome sequence (WGS) data with five independent algorithms identified a recessively inherited intronic repeat expansion [(AAGGG)exp] in the gene encoding Replication Factor C1 (RFC1). This motif, not reported in the reference sequence, localized to an Alu element and replaced the reference (AAAAG)11 short tandem repeat. Genetic analyses confirmed the pathogenic expansion in 18 of 22 CANVAS-affected families and identified a core ancestral haplotype, estimated to have arisen in Europe more than twenty-five thousand years ago. WGS of the four RFC1-negative CANVAS-affected families identified plausible variants in three, with genomic re-diagnosis of SCA3, spastic ataxia of the Charlevoix-Saguenay type, and SCA45. This study identified the genetic basis of CANVAS and demonstrated that these improved bioinformatics tools increase the diagnostic utility of WGS to determine the genetic basis of a heterogeneous group of clinically overlapping neurogenetic disorders.

Modeling the interaction among three cerebellar disorders of eye movements: periodic alternating, gaze-evoked and rebound nystagmus.

A woman, age 44, with a positive anti-YO paraneoplastic cerebellar syndrome and normal imaging developed an ocular motor disorder including periodic alternating nystagmus (PAN), gaze-evoked nystagmus (GEN) and rebound nystagmus (RN). During fixation there was typical PAN but changes in gaze position evoked complex, time-varying oscillations of GEN and RN. To unravel the pathophysiology of this unusual pattern of nystagmus, we developed a mathematical model of normal function of the circuits mediating the vestibular-ocular reflex and gaze-holding including their adaptive mechanisms. Simulations showed that all the findings of our patient could be explained by two, small, isolated changes in cerebellar circuits: reducing the time constant of the gaze-holding integrator, producing GEN and RN, and increasing the gain of the vestibular velocity-storage positive feedback loop, producing PAN. We conclude that the gaze- and time-varying pattern of nystagmus in our patient can be accounted for by superposition of one model that produces typical PAN and another model that produces typical GEN and RN, without requiring a new oscillator in the gaze-holding system or a more complex, nonlinear interaction between the two models. This analysis suggest a strategy for uncovering gaze-evoked and rebound nystagmus in the setting of a time-varying nystagmus such as PAN. Our results are also consistent with current ideas of compartmentalization of cerebellar functions for the control of the vestibular velocity-storage mechanism (nodulus and ventral uvula) and for holding horizontal gaze steady (the flocculus and tonsil).

Clinical, oculographic, and vestibular test characteristics of vestibular migraine.

BACKGROUND: We characterise the history, vestibular tests, ictal and interictal nystagmus in vestibular migraine. METHOD: We present our observations on 101 adult-patients presenting to an outpatient facility with recurrent spontaneous and/or positional vertigo whose final diagnosis was vestibular migraine (n = 27) or probable vestibular migraine (n = 74). Ictal and interictal video-oculography, caloric and video head impulse tests, vestibular-evoked myogenic potentials and audiometry were performed. RESULTS: Common presenting symptoms were headache (81.2%), spinning vertigo (72.3%), Mal de Débarquement (58.4%), and motion sensitivity (30.7%). With fixation denied, ictal and interictal spontaneous nystagmus was observed in 71.3 and 14.9%, and purely positional nystagmus in 25.8 and 55.4%. Spontaneous ictal nystagmus was horizontal in 49.5%, and vertical in 21.8%. Ictal spontaneous and positional nystagmus velocities were 5.3 ± 9.0°/s (range 0.0-57.4), and 10.4 ± 5.8°/s (0.0-99.9). Interictal spontaneous and positional nystagmus velocities were <3°/s in 91.8 and 23.3%. Nystagmus velocities were significantly higher when ictal (p < 0.001/confidence interval: 2.908‒6.733, p < 0.001/confidence interval: 5.308‒10.085). Normal lateral video head impulse test gains were found in 97.8% (mean gain 0.95 ± 0.12) and symmetric caloric results in 84.2% (mean canal paresis 7.0 ± 23.3%). Air- and bone-conducted cervical-vestibular-evoked myogenic potential amplitudes were symmetric in 88.4 and 93.4% (mean corrected amplitude 1.6 ± 0.7, 1.6 ± 0.8) with mean asymmetry ratios of 13.0 and 9.0%. Air- and bone-conducted ocular-vestibular-evoked myogenic potentials were symmetric in 67.7 and 97.2% (mean amplitude 9.2 ± 6.4 and 20.3 ± 12.8 µV) with mean asymmetry ratios of 15.7 and 9.9%. Audiometry was age consistent and symmetric in 85.5%. CONCLUSION: Vestibular migraine is characterised by low velocity ictal spontaneous nystagmus, which can be horizontal, vertical, or torsional, and normal audiovestibular test results.

Video Head Impulse Testing: From Bench to Bedside.

Over 30 years ago, the head impulse test (HIT) was measured with search coil recordings and it provided robust evidence for a new test of vestibular function that could detect impairment of a single semicircular canal, that is, the lateral canal. Over the next two decades, the diagnostic spectrum of HIT was expanded to the testing of vertical canals, differentiation of central from peripheral vestibulopathy, and incorporation of visual interaction-the suppressed head impulse. However, HIT measurement was limited to very few specialized laboratories that were able to maintain the time-consuming and expensive operation of the scleral search coil system, which is the gold standard in eye movement recording. The video HIT (vHIT) was validated for the first time over 10 years ago, against the search coils, and its introduction into dizzy clinics worldwide has revolutionized the practice of neuro-otology. Here we review the basic physiology, practical aspects, and clinical application of the vHIT.

Nystagmus goggles: how to use them, what you find and what it means.

A fundamental characteristic of peripheral vestibular nystagmus, in particular horizontal nystagmus, is that it is suppressed by visual fixation. This means that a patient with a vertigo attack of peripheral vestibular origin might have no obvious spontaneous nystagmus on clinical examination. Goggles that reduce or remove visual fixation allow the cliniican to observe nystagmus in this situation. Nystagmus goggles are essential for any clinician dealing with dizzy patients. Here, we discuss why this is so and how easy it is to acquire and use them.

The human vestibulo-ocular reflex and saccades: normal subjects and the effect of age.

Here we characterize in 80 normal subjects (16-84 yr (means ± SD, 47 ± 19 yr) the vestibulo-ocular reflex (VOR) and saccades in response to three-dimensional head impulses with a monocular video head impulse test (vHIT) of the right eye. Impulses toward the right lateral, right anterior, and left posterior canals (means: 0.98, 0.91, 0.79) had slightly higher mean gains compared with their counterparts (0.95, 0.86, 0.76). In the older age group (>60 yr), gains of the left posterior canal dropped 0.09 and left anterior canals rose 0.09 resulting in symmetry. All canal gains reduced with increasing head velocity (0.02-0.13 per 100°/s). Comparison of lateral canal gains calculated using five published algorithms yielded lower values (~0.80) when a narrow detection window was used. Low-amplitude refixation saccades (amplitude: 1.11 ± 0.98°, peak velocity: 63.9 ± 34.0°/s at 262.0 ± 93.9 ms) were observed among all age groups (frequency: 40.2 ± 23.4%), increasing in amplitude, peak velocity, and frequency in older subjects. Impulses toward anterior canals showed the least frequent saccades and lateral and posterior canals were similar, but lateral canal impulses showed the smallest saccades and the posterior canal showed the largest saccades. Saccade peak-velocity approximate amplitude "main sequence" slope was steeper for the horizontal canals compared with the vertical planes (60 vs. <40°/s per 1°). In summary, we found small but significant asymmetries in monocular vHIT gain that changed with age. Healthy subjects commonly have minuscule refixation saccades that are moderately to strongly correlated with vHIT gain. NEW & NOTEWORTHY Gaze fixation is normally stabilized during rapid "head-impulse" movements by the bisynaptic vestibulo-ocular reflex (VOR), but earlier studies of normal subjects also report small amplitude saccades. We found that with increased age of the subject the vertical VOR became more variable, while in all semicircular canal directions the saccade frequency, amplitude, and peak velocity increased. We also found that the VOR gain algorithm significantly influences values.

Immune-mediated conditions affecting the brain, eye and ear (BEE syndromes).

The triad of central nervous system symptoms, visual disturbance and hearing impairment is an oft-encountered clinical scenario. A number of immune-mediated diseases should be considered among the differential diagnoses including: Susac syndrome, Cogan syndrome or Vogt-Koyanagi-Harada disease; demyelinating conditions such as multiple sclerosis or neuromyelitis optica spectrum disorder; systemic diseases such as systemic lupus erythematosus, Sjögren syndrome or Behcet disease and granulomatous diseases such as sarcoidosis. In this article, we coin the term 'BEE syndromes' to draw attention to the various immune-mediated diseases that affect the brain, eye and ear. We present common disease manifestations and identify key clinical and investigation features.

Dizziness demystified.

Four vestibular presentations caused by six different disorders constitute most of the neuro-otology cases seen in clinical practice. 'Acute vestibular syndrome' refers to a first-ever attack of acute, spontaneous, isolated vertigo and there are two common causes: vestibular neuritis / labyrinthitis and cerebellar infarction. Recurrent positional vertigo is most often caused by benign paroxysmal positional vertigo and less commonly is central in origin. Recurrent spontaneous vertigo has two common causes: Ménière's disease and vestibular migraine. Lastly, chronic vestibular insufficiency (imbalance) results from bilateral, or severe unilateral, peripheral vestibular impairment. These six disorders can often be diagnosed on the basis of history, examination, audiometry, and in some cases, basic vestibular function testing. Here we show that most common neuro-otological problems can be readily managed by general neurologists.

Rheumatoid leptomeningitis presenting with an acute neuropsychiatric disorder.

Leptomeningitis is a rare central nervous system manifestation of rheumatoid arthritis, generally in patients with established chronic rheumatoid disease. We report a 41-year-old man without previous rheumatoid arthritis or psychiatric disorder who presented with an acute neuropsychiatric disturbance and polyarthralgia. His MR scan of brain showed asymmetric bifrontal leptomeningitis, confirmed on (18F)-fluoro-D-glucose-positron emission tomography. Other investigations showed highly positive serum and cerebrospinal fluid anti-cyclic citrullinated peptide. A leptomeningeal biopsy showed necrotising leptomeningeal inflammation with ill-defined granulomas and lymphoplasmacytic infiltrate without organisms. Prolonged high-dose corticosteroids and then rituximab resulted in recovery. Chronic leptomeningitis can present with an acute neuropsychiatric disorder. We highlight that early rheumatoid disease can, rarely, cause a chronic leptomeningitis, reversible with immunotherapy.

Neurophysiological evidence for generalized sensory neuronopathy in cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome.

INTRODUCTION: Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) is a recently described multisystem ataxia defined by the presence of cerebellar ataxia, bilateral vestibulopathy, and a somatosensory deficit. The characteristic clinical sign is an abnormal visually enhanced vestibuloocular reflex. The somatosensory deficit contributes to a significant level of disability in CANVAS. METHODS: This study was a neurophysiological investigation of 14 patients with CANVAS. RESULTS: Findings revealed uniformly absent sensory nerve action potentials in all limbs, abnormal blink reflexes in 13 of 14 patients, and abnormal masseter reflexes in 6 of 11 patients. Tibial H-reflexes were absent in 11 of 14 patients. Somatosensory evoked potentials were abnormal in 10 of the 11 patients tested, and brainstem auditory evoked responses were abnormal in 3 of 8. Cutaneous silent period responses were abnormal in 7 of 14 patients. CONCLUSIONS: We suggest that a sensory neuronopathy should be sought in cerebellar and/or vestibular ataxias, particularly where the degree of ataxia is out of proportion to the clinically identified cerebellar and/or vestibular dysfunction.

Diagnosing Stroke in Acute Vertigo: The HINTS Family of Eye Movement Tests and the Future of the "Eye ECG".

Patients who present to the emergency department with symptoms of acute vertigo or dizziness are frequently misdiagnosed. Missed opportunities to promptly treat dangerous strokes can result in poor clinical outcomes. Inappropriate testing and incorrect treatments for those with benign peripheral vestibular disorders leads to patient harm and unnecessary costs. Over the past decade, novel bedside approaches to diagnose patients with the acute vestibular syndrome have been developed and refined. A battery of three bedside tests of ocular motor physiology known as "HINTS" (head impulse, nystagmus, test of skew) has been shown to identify acute strokes more accurately than even magnetic resonance imaging with diffusion-weighted imaging (MRI-DWI) when applied in the early acute period by eye-movement specialists. Recent advances in lightweight, high-speed video-oculography (VOG) technology have made possible a future in which HINTS might be applied by nonspecialists in frontline care settings using portable VOG. Use of technology to measure eye movements (VOG-HINTS) to diagnose stroke in the acute vestibular syndrome is analogous to the use of electrocardiography (ECG) to diagnose myocardial infarction in acute chest pain. This "eye ECG" approach could transform care for patients with acute vertigo and dizziness around the world. In the United States alone, successful implementation would likely result in improved quality of emergency care for hundreds of thousands of peripheral vestibular patients and tens of thousands of stroke patients, as well as an estimated national health care savings of roughly $1 billion per year. In this article, the authors review the origins of the HINTS approach, empiric evidence and pathophysiologic principles supporting its use, and possible uses for the eye ECG in teleconsultation, teaching, and triage.

Machine learning models help differentiate between causes of recurrent spontaneous vertigo.

BACKGROUND: Vestibular migraine (VM) and Menière's disease (MD) are two common causes of recurrent spontaneous vertigo. Using history, video-nystagmography and audiovestibular tests, we developed machine learning models to separate these two disorders. METHODS: We recruited patients with VM or MD from a neurology outpatient facility. One hundred features from six "feature subsets": history, acute video-nystagmography and four laboratory tests (video head impulse test, vestibular-evoked myogenic potentials, caloric testing and audiogram) were used. We applied ten machine learning algorithms to develop classification models. Modelling was performed using three "tiers" of data availability to simulate three clinical settings. "Tier 1" used all available data to simulate the neuro-otology clinic, "Tier 2" used only history, audiogram and caloric test data, representing the general neurology clinic, and "Tier 3" used history alone as occurs in primary care. Model performance was evaluated using tenfold cross-validation. RESULTS: Data from 160 patients with VM and 114 with MD were used for model development. All models effectively separated the two disorders for all three tiers, with accuracies of 85.77-97.81%. The best performing algorithms (AdaBoost and Random Forest) yielded accuracies of 97.81% (95% CI 95.24-99.60), 94.53% (91.09-99.52%) and 92.34% (92.28-96.76%) for tiers 1, 2 and 3. The best feature subset combination was history, acute video-nystagmography, video head impulse test and caloric testing, and the best single feature subset was history. CONCLUSIONS: Machine learning models can accurately differentiate between VM and MD and are promising tools to assist diagnosis by medical practitioners with diverse levels of expertise and resources.

Post Cochlear Implantation Vertigo: Ictal Nystagmus and Audiovestibular Test Characteristics.

OBJECTIVE: To investigate ictal nystagmus and audiovestibular characteristics in episodic spontaneous vertigo after cochlear implantation (CI). STUDY DESIGN: Retrospective and prospective case series. PATIENTS: Twenty-one CI patients with episodic spontaneous vertigo after implantation were recruited. INTERVENTIONS: Patient-initiated home video-oculography recordings were performed during one or more attacks of vertigo, using miniature portable home video-glasses. To assess canal and otolith function, video head-impulse tests (vHITs) and vestibular-evoked myogenic potential tests were conducted. MAIN OUTCOME MEASURES: Nystagmus slow-phase velocities (SPVs), the presence of horizontal direction-changing nystagmus, and post-CI audiovestibular tests. RESULTS: Main final diagnoses were post-CI secondary endolymphatic hydrops (48%) and exacerbation of existing Ménière's disease (29%). Symptomatic patients demonstrated high-velocity horizontal ictal-nystagmus (SPV, 44.2°/s and 68.2°/s in post-CI secondary endolymphatic hydrop and Ménière's disease). Direction-changing nystagmus was observed in 80 and 75%. Two were diagnosed with presumed autoimmune inner ear disease (SPV, 6.6°/s and 172.9°/s). One patient was diagnosed with probable vestibular migraine (15.1°/s).VHIT gains were 0.80 ± 0.20 (lateral), 0.70 ± 0.17 (anterior), and 0.62 ± 0.27 (posterior) in the implanted ear, with abnormal values in 33, 35, and 35% of each canal. Bone-conducted cervical and ocular vestibular-evoked myogenic potentials were asymmetric in 52 and 29% of patients (all lateralized to the implanted ear) with mean asymmetry ratios of 51.2 and 35.7%. Reversible reduction in vHIT gain was recorded in three acutely symptomatic patients. CONCLUSION: High-velocity, direction-changing nystagmus time-locked with vertigo attacks may be observed in post-CI implant vertigo and may indicate endolymphatic hydrops. Fluctuating vHIT gain may be an additional marker of a recurrent peripheral vestibulopathy.

Venous hypertension as the cause of intracranial hypertension in patients with transverse sinus dural arteriovenous fistula.

We describe 2 patients with transverse sinus dural arteriovenous fistulas (DAVFs) who presented with headache and papilledema due to intracranial hypertension. It has been proposed, but never proven, that venous hypertension causes the intracranial hypertension in DAVF. The data from our patients support this hypothesis. An additional factor leading to intracranial hypertension could be stenosis of the fellow transverse sinus.

Spinal leptomeningeal lymphoma presenting as pseudotumor syndrome.

We describe 2 patients with inexorably progressive pseudotumor syndrome (intracranial hypertension without mass lesion or ventriculomegaly) both initially misdiagnosed as having idiopathic intracranial hypertension and who were eventually found to have spinal leptomeningeal lymphoma. Neither had, at any time, any clinical signs of a spinal cord or root lesion. We discuss the possible implications of these observations regarding the diagnosis and mechanism of the pseudotumor syndrome.

Neuro-ophthalmology of invasive fungal sinusitis: 14 consecutive patients and a review of the literature.

BACKGROUND: Invasive fungal sinusitis is a rare condition that usually occurs in immunocompromised patients and often presents as an orbital apex syndrome. It is frequently misdiagnosed on presentation and is almost always lethal without early treatment. DESIGN: Retrospective case series of 14 consecutive patients with biopsy-proven invasive fungal sinusitis from four tertiary hospitals. PARTICIPANTS: Fourteen patients (10 men and 4 women; age range 46-82 years). METHODS: Retrospective chart review of all patients presenting with invasive fungal sinusitis between 1994 and 2010 at each hospital, with a close analysis of the tempo of the disease to identify any potential window of opportunity for treatment. MAIN OUTCOME MEASURES: Demographic data, background medical history (including predisposing factors), symptoms, signs, radiological findings, histopathological findings, treatment approach and subsequent clinical course were recorded and analysed. RESULTS: Only one patient was correctly diagnosed at presentation. Only two patients were not diabetic or immunocompromised. The tempo was acute in two patients, subacute in nine patients and chronic in three patients. In the subacute and chronic cases, there was about 1 week of opportunity for treatment, from the time there was a complete orbital apex syndrome, and still a chance for saving the patient, to the time there was central nervous system invasion, which was invariably fatal. Only two patients survived - both had orbital exenteration, as well as antifungal drug treatment. CONCLUSIONS: Invasive fungal sinusitis can, rarely, occur in healthy individuals and should be suspected as a possible cause of a progressive orbital apex syndrome.