Updates in neuro-otology.

PURPOSE OF REVIEW: Recent updates with clinical implications in the field of neuro-otology are reviewed. RECENT FINDINGS: Important updates relating to several neuro-otologic disorders have been reported in recent years. For benign positional paroxysmal vertigo (BPPV), we provide updates on the characteristics and features of the short arm variant of posterior canal BPPV. For the acute vestibular syndrome, we report important updates on the use of video-oculography in clinical diagnosis. For autoimmune causes of neuro-otologic symptoms, we describe the clinical and paraclinical features of kelch-like protein 11 encephalitis, a newly-identified antibody associated disorder. For cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we report recent genetic insights into this condition. SUMMARY: This review summarizes important recent updates relating to four hot topics in neuro-otology.

Centripetal Nystagmus, Slow Saccades, Cerebellar Ataxia, and Parkinsonism in a Patient With Anti-GAD65-Associated Stiff Person Syndrome Spectrum Disorder.

ABSTRACT: A 68-year-old woman with positional dizziness and progressive imbalance presented for vestibular evaluation. Examination was notable for spontaneous downbeat nystagmus (DBN), horizontal and vertical gaze-evoked nystagmus (GEN) with centripetal and rebound nystagmus, and positional apogeotropic nystagmus. There was also mild-moderate slowing of saccades horizontally and vertically and poor fast phases with an optokinetic stimulus. Further consultation by a movement disorder specialist uncovered asymmetric decrementing bradykinesia and rigidity, masked facies, and a wide-based stance without camptocormia. Screening serum laboratory results for metabolic, rheumatologic, infectious, heavy metal, endocrine, or vitamin abnormalities was normal. Surveillance imaging for neoplasms was unremarkable, and cerebrospinal fluid (CSF) analysis was negative for 14-3-3 and real-time quaking-induced conversion (RT-QuIC). However, her anti-glutamic acid decarboxylase-65 (GAD65) immunoglobulin G (IgG) level was markedly elevated in serum to 426,202 IU/mL (reference range 0-5 IU/mL) and in CSF to 18.1 nmol/L (reference range <0.03 nmol/L). No other autoantibodies were identified on the expanded paraneoplastic panel. The patient was referred to neuroimmunology, where torso rigidity, spasticity, and significant paravertebral muscle spasms were noted. Overall, the clinical presentation, examination findings, and extensive workup were consistent with a diagnosis of anti-GAD65-associated stiff person syndrome-plus (musculoskeletal plus cerebellar and/or brainstem involvement). She was subsequently treated with intravenous immunoglobulin (IVIg) and has been stable since commencing this therapy. In patients with centripetal nystagmus, especially in association with other cerebellar findings, an autoimmune cerebellar workup should be considered.

Current concepts in acute vestibular syndrome and video-oculography.

PURPOSE OF REVIEW: We present here neuro-otological tests using portable video-oculography (VOG) and strategies assisting physicians in the process of decision making beyond the classical 'HINTS' testing battery at the bedside. RECENT FINDINGS: Patients with acute vestibular syndrome (AVS) experience dizziness, gait unsteadiness and nausea/vomiting. A variety of causes can lead to this condition, including strokes. These patients cannot be adequately identified with the conventional approach by stratifying based on risk factors and symptom type. In addition to bedside methods such as HINTS and HINTS plus, quantitative methods for recording eye movements using VOG can augment the ability to diagnose and localize the lesion. In particular, the ability to identify and quantify the head impulse test (VOR gain, saccade metrics), nystagmus characteristics (waveform, beating direction and intensity), skew deviation, audiometry and lateropulsion expands our diagnostic capabilities. In addition to telemedicine, algorithms and artificial intelligence can be used to support emergency physicians and nonexperts in the future. SUMMARY: VOG, telemedicine and artificial intelligence may assist physicians in the diagnostic process of AVS patients.

Neuro-Visual and Vestibular Manifestations of Concussion and Mild TBI.

PURPOSE OF REVIEW: Mild traumatic brain injury, or concussion, is a major cause of disability. Vestibular and visual dysfunction following concussion is common and can negatively affect patients' well-being and prolong recovery. Etiologies of visual and vestibular symptoms are numerous, including ocular, neuro-ophthalmic, otologic, and neuro-vestibular conditions. Some etiologies are benign and may be treatable, while others are potentially vision or life-threatening, making a focused history and examination essential. This review offers an approach to the evaluation and treatment of the most common neuro-visual and vestibular impairments that may result from concussion. RECENT FINDINGS: Treatment of concussion including exercise, computerized programs, transcranial magnetic stimulation, gene therapy, stem cell therapy, and nanoparticles has shown promise. Many novel therapies are in the pipework for visual and vestibular recovery after concussion; however, the treatment mainstay remains therapy and evaluation for co-existing diseases.

Pendular Oscillation and Ocular Bobbing After Pontine Hemorrhage.

The pathophysiology of acute, vertical spontaneous eye movements following pontine hemorrhage is not well understood. Here, we present and discuss the video-oculography findings of a patient with acute pontine hemorrhage who developed vertical pendular oscillation and ocular bobbing while comatose. The amplitudes, peak velocities, frequency distribution, and phase planes (velocity versus position) of the eye movements were analyzed. The vertical pendular oscillation was rhythmic with a peak frequency of 1.7 Hz, but amplitudes (mean 1.9°, range 0.2-8.2°) and peak velocities (mean 20.6°/s; range 5.9-60.6°/sec) fluctuated. Overall, their peak velocities were asymmetric, faster with downward than upward. Higher peak velocities were seen with larger amplitudes (downward phase r = 0.95, p < 0.001; upward phase r = 0.91, p < 0.001) and with movements beginning at eye positions lower in the orbit (downward phase r = - 0.64, p < 0.001; upward phase r = - 0.86, p < 0.001). Interspersed were typical ocular bobbing waveforms with a fast (peak velocity 128.8°/s), large-amplitude (17.5°) downward movement, sometimes followed by a flat interphase interval (0.5 s) when the eye was nearly stationary, and then a slow return to mid-position with a decaying velocity waveform. To account for the presence and co-existence of pendular oscillations and bobbing, we present and discuss three hypothetical models, not necessarily mutually exclusive: (1) oscillations originating in the inferior olives due to disruption of the central tegmental tract(s); (2) unstable neural integrator function due to pontine cell group damage involving neurons involved in gaze-holding; (3) low-frequency saccadic intrusions following omnipause neuron damage.

The fixation suppression test can uncover vertical nystagmus of central origin in some patients with dizziness.

BACKGROUND: Identifying dangerous causes of dizziness is a challenging task for neurologists, as it requires interpretation of subtle bedside exam findings, which become even more subtle with time. Nystagmus can be instrumental in differentiating peripheral from central vestibular disorders. Conventional teaching is that peripheral vestibular nystagmus is accentuated by removal of visual fixation. We sought to systematically test the hypothesis that, in some cases, vertical nystagmus due to central vestibular disorders may also be easier to identify when fixation is removed. METHODS: To identify patients with vertical nystagmus, we retrospectively reviewed clinical, MRI, and VNG data of consecutive patients undergoing VNG in our vestibular clinic over a 9-month period. We analyzed clinical features, bedside neuro-otological examination, MRI results, and VNG findings in fixation as well as those with fixation removed. RESULTS: Two hundred and fourteen charts were reviewed. Twenty-six patients had vertical nystagmus with fixation removed on VNG. Only three (11.5%) of these patients had vertical nystagmus apparent with fixation (and only two had nystagmus observed clearly at the bedside with the unaided eye). Thirteen (50%) of the patients had posterior fossa lesions on MRI and eight of the rest (30.8%) were diagnosed with central vestibular disorders. Of the 13 patients with MRI-confirmed lesions, 3 patients (23.1%) had no neurological signs or conventional bedside oculomotor signs; in these cases, vertical nystagmus without fixation was the only sign of a central lesion. CONCLUSIONS: Our findings go against conventional teaching and show that removing fixation can uncover subtle vertical nystagmus due to central vestibular disease, particularly from focal or chronic lesions.

HINTS Examination in Acute Vestibular Neuritis: Do Not Look Too Hard for the Skew.

BACKGROUND: An ocular tilt reaction (OTR) is a triad of a skew deviation, head tilt, and ocular counter-roll that can be partial or complete. An OTR can occur anywhere along the utriculo-ocular motor pathways from the labyrinth to the interstitial nucleus of Cajal but is almost always central in origin. In acute vestibular neuritis (AVN), case reports have described patients with an OTR due to AVN, although it is unclear whether this examination finding is common or rare. METHODS: The vestibular and ocular motor features of 7 patients presenting with AVN are described. RESULTS: Each of the 7 patients presented with typical features of AVN, including contralesional unidirectional spontaneous nystagmus and an ipsilesional abnormal head impulse test, although each patient also had a complete OTR. None of the patients had vertical diplopia or a skew deviation that was measurable with alternate cover testing (i.e., abnormal "test of skew" according to the Head Impulse, Nystagmus, Test of Skew examination); however, all had a subtle 1 prism diopter hyperphoria that was only measurable with a Maddox rod test. CONCLUSION: Seven cases of typical AVN with an OTR are presented, and in the authors' experience, the presence of a subtle OTR is a common feature of AVN in these patients.

Ocular Motor and Vestibular Characteristics of Antiglutamic Acid Decarboxylase-Associated Neurologic Disorders.

BACKGROUND: Antiglutamic acid decarboxylase (GAD)-associated neurologic disorders are rare, with varied presentations, including stiff-person syndrome (SPS) and cerebellar ataxia (CA). Vestibular and ocular motor (VOM) dysfunction can be the main presentation in a subset of patients. METHODS: Retrospective review of the Johns Hopkins Hospital medical records from 1997 to 2018 identified a total of 22 patients with a diagnosis of anti-GAD-associated SPS or CA who had detailed VOM assessments. Eight had prominent VOM dysfunction at the initial symptom onset and were referred to neurology from ophthalmology or otolaryngology ("early dominant"). Fourteen patients had VOM dysfunction that was not their dominant presentation and were referred later in their disease course from neurology to neuro-ophthalmology ("nondominant"). We reviewed clinical history, immunological profiles, and VOM findings, including available video-oculography. RESULTS: In the 8 patients with early dominant VOM dysfunction, the average age of symptom onset was 53 years, and 5 were men. The most common symptom was dizziness, followed by diplopia. Seven had features of CA, and 4 had additional features of SPS. None had a structural lesion on brain MRI accounting for their symptoms. The most common VOM abnormalities were downbeating and gaze-evoked nystagmus and saccadic pursuit. All received immune therapy and most received symptomatic therapy. Most experienced improvement in clinical outcome measures (modified Rankin scale and/or timed 25-foot walk test) or VOM function. By contrast, in the 14 patients in whom VOM dysfunction was nondominant, most had an SPS phenotype and were women. VOM abnormalities, when present, were more subtle, although mostly still consistent with cerebellar and/or brainstem dysfunction. CONCLUSIONS: Individuals with anti-GAD-associated neurologic disorders may present with prominent VOM abnormalities at the initial symptom onset that localize to the cerebellum and/or brainstem. In our cohort, immune and symptomatic therapies improved clinical outcomes and symptomatology.

Dizziness and Vertigo: The Skillful Examination.

BACKGROUND: The visual, ocular motor and vestibular systems have intimate neural and close anatomical relationship that dictates their assessment in a patient with dizziness and vertigo. RESULTS: Recognition of the pearls and pitfalls of a targeted clinical examination HINTS/HINTS "Plus" allows the clinician to probe at the bedside the most crucial hypothesis in a patient with acute isolated vestibular syndrome, "Is this a stroke?" CONCLUSION: By applying a methodical approach to examination of patients with dizziness and vertigo, localization of the offending lesion, management, and even elucidation of the underlying diagnosis is feasible.

Vestibular Disorders: Pearls and Pitfalls.

Dizziness and vertigo are symptoms that commonly lead patients to seek neurologic or emergency care. Because symptoms are often vague and imprecise, a systematic approach is essential. By categorizing vestibular disorders based on the timing, triggers, and duration of symptoms, as well as emphasizing focused ocular motor and vestibular examinations, the majority of vestibular diagnoses can be made at the bedside. This paper will discuss the pearls and pitfalls in the history and examination of the most common acute, episodic, and chronic vestibular disorders.

Acute Visual Disorders-What Should the Neurologist Know?

Normal vision requires coordination of precisely controlled and coordinated eye movements and normal function of a large cortical and subcortical sensory network. Given the required precision of the system and wide anatomic distribution of the motor and sensory visual systems, vision can be disrupted by a variety of central and peripheral nervous system disorders. While many of these may be relatively benign or have no proven therapy, several may be isolated presentations or harbingers of more serious neurologic conditions. Both monocular and binocular vision losses may be isolated presentations of stroke or its equivalent. Other etiologies of monocular vision loss may represent the initial presentation of potentially disabling conditions. Binocular diplopia, caused by impaired movement of one or both eyes, may represent a condition with no acute therapy and a benign natural history, or a progressive potentially life-threatening syndrome. Most people are heavily reliant upon vision, so that even a subtle change in vision due to disturbed afferent or efferent pathways is invariably noticed, and presentation to the emergency department for eye symptoms is common. The accurate evaluation of these patients in the acute setting is essential to identify the patients requiring immediate testing or treatment.

Ocular Misalignment in Dizzy Patients-Something's A-Skew.

BACKGROUND AND PURPOSE: Both central (eg, brain stem, cerebellum) and peripheral (eg, vestibular, fourth cranial nerve palsy) etiologies can cause a vertical misalignment between the eyes with a resultant vertical diplopia. A vertical binocular misalignment may be due to a skew deviation, which is a nonparalytic vertical ocular misalignment due to roll plane imbalance in the graviceptive pathways. A skew deviation may be 1 component of the ocular tilt reaction. The purposes of this article are (1) to understand the pathophysiology of a skew deviation/ocular tilt reaction and (2) to be familiar with the examination techniques used to diagnose a skew and to differentiate it from mimics such as a fourth cranial nerve palsy. SUMMARY OF KEY POINTS: The presence of a skew deviation usually indicates a brain stem or cerebellar localization. Vertical ocular misalignment is easily missed when observing the resting eye position alone. RECOMMENDATIONS FOR CLINICAL PRACTICE: Physical therapists treating patients with vestibular pathology from central or peripheral causes should screen for vertical binocular disorders.

HINTS in the Acute Vestibular Syndrome: Pearls and Pitfalls.

The acute vestibular syndrome (AVS) is characterized by the rapid onset of vertigo, nausea/vomiting, nystagmus, unsteady gait, and head motion intolerance lasting more than 24 hours. We present 4 patients with AVS to illustrate the pearls and pitfalls of the Head Impulse, Nystagmus, Test of Skew (HINTS) examination.

Dizziness.

Dizziness and vertigo are among the most common symptoms to bring a patient to a neurologist. Because symptoms are often vague and imprecise, a systematic approach is essential. By categorizing vestibular disorders based on timing, triggers, and duration, as well as through focused oculomotor and vestibular examinations, the vast majority of neuro-otologic diagnoses can be made at the bedside. Here the authors discuss historical and examination pearls for the most common neuro-otologic disorders.

Advances in diagnosis and treatment of vestibular migraine and the vestibular disorders it mimics.

Dizziness is one of the most common chief complaints in both the ambulatory care setting and the emergency department. These symptoms may be representative of a broad range of entities. Therefore, any attempt at treatment must first start with determining the etiology. In this current perspective, we focus specifically on the diagnosis of and treatment of vestibular migraine, which is common and overlaps clinically with a variety of other diagnoses. We discuss the traditional treatments for vestibular migraine in addition to the recent explosion of novel migraine therapeutics. Because vestibular migraine can mimic, or co-exist with, a variety of other vestibular diseases, we discuss several of these disorders including persistent postural-perceptual dizziness, benign paroxysmal positional vertigo, post-concussive syndrome, Ménière's disease, and cerebrovascular etiologies. We discuss the diagnosis of each, as well as overlapping and distinguishing clinical features of which the reader should be aware. Finally, we conclude with evidence based as well as expert commentary on management, with a particular emphasis on vestibular migraine.

Treatment of homonymous visual field defects.

OPINION STATEMENT: A clinical presentation of a retrochiasmal or homonymous visual field defect (HVFD) usually represents a permanent visual impairment. The visual and functional ramifications of HVFD will vary by patient. Comprehensive care-the clinical evaluation and consideration for treatment of HVFD-includes vision rehabilitation provided by optometrists, occupational therapists, or ophthalmologists. On the basis of individual patient needs, the eye care practitioner typically uses one or both of the following approaches to treat the HVFD: (1) field enhancement (also referred to in the literature as "field expansion"), in which optical systems incorporating prism are prescribed to optimize the use of the remaining vision, and (2) rehabilitative techniques including saccadic training ("compensation training") or vision restorative therapy ("restitution training"). Although lacking in strength, the evidence does support benefits from field enhancement and saccadic training for patients with HVFD, but vision restorative therapy has not been shown to be an effective option.

Diagnosing and localizing the acute vestibular syndrome - Beyond the HINTS exam.

When assessing the acutely dizzy patient, the HINTS 'Plus' (Head Impulse, Nystagmus, Test of Skew, 'Plus' a bedside assessment of auditory function) exam is a crucial component of the bedside exam. However, there are additional ocular motor findings that can help the clinician distinguish peripheral from central etiologies and enable accurate localization, especially when the patient has acute dizziness, vertigo and/or imbalance but without spontaneous nystagmus. We will review the literature on these findings which are 'beyond HINTS' and include saccades/ocular lateropulsion, smooth pursuit, and provocative maneuvers including head-shaking and positional testing (not part of the HINTS exam). Additionally, we will expound on the localizing value of nystagmus, ocular alignment and the ocular tilt reaction (parts of the HINTS exam). The paper has been organized neuroanatomically, based on brainstem and cerebellar structures that have been reported to cause the acute vestibular syndrome.