James Sharpe's Contributions to Neurology and Neuro-ophthalmology: A Posthumous Tribute 10 Years On.

Dr. Sharpe was a leading eye movement researcher who had also been the editor of this journal. We wish to mark the 10th anniversary of his death by providing a sense of what he had achieved through some examples of his research.

Consensus Statement on Visual Rehabilitation in Mild Traumatic Brain Injury.

Optometric visual rehabilitation therapy has been used for a variety of visual disorders. Descriptively named entities such as posttrauma visual syndrome, visual midline shift syndrome, and vertical heterophoria syndrome are frequently diagnosed by neuro-optometrists and/or behavioral optometrists in patients after stroke or head injury or in the setting of dizziness and/or headache. The scientific underpinnings of these diagnoses and treatments are weak, and published clinical studies comprise case reports and case series without comparison to control populations. Neuro-ophthalmologists are frequently questioned by patients about the utility of such treatment strategies. Many ophthalmologists and neurologists also are involved in the care of patients who carry these diagnoses and undergo these visual therapies. Involved physicians may benefit from guidance about the rationale, evidence, and level of evidence for the efficacy of these therapeutic approaches.

Transient Visual Obscurations as the Presenting Symptom of Papilledema from COVID-19-Related Cerebral Venous Sinus Thrombosis.

Coronavirus disease-19 (COVID-19) patients are at an increased risk of cerebral venous sinus thrombosis (CVST). Rapid diagnosis and treatment are vital to ensure a favorable outcome for CVST, so clinicians need to be aware of all its potential presentations. We describe a unique case where transient visual obscurations (TVOs) from papilledema were the presenting symptoms of COVID-19-related CVST. A 43-year-old woman, who had tested positive for severe acute respiratory syndrome coronavirus-2 1 month earlier, developed holocephalic headache, TVOs, and bilateral disc edema. She did not seek medical attention until she developed TVOs. Visual acuity was 20/20 and Humphrey visual field testing showed enlarged blind spots in both eyes. She was diagnosed with papilledema and underwent magnetic resonance imaging and magnetic resonance venography of the brain, which revealed right transverse sinus thrombosis. Lumbar puncture was performed, showing elevated opening pressure and normal cerebrospinal fluid contents. Her optic disc edema resolved and visual function remained normal 6 weeks following warfarin and topiramate therapy. Recanalization of the right transverse sinus occurred after 3 months. Although rare, TVOs are important presenting symptoms of COVID-19-related CVST. Ophthalmologists, who may be the first physicians to assess patients with this presentation, should be aware of TVOs as potential presenting symptoms of CVST, so diagnoses can be made in a timely manner.

Effectiveness of vestibular rehabilitation therapy in patients with idiopathic Cerebellar Ataxia with Bilateral Vestibulopathy (iCABV).

OBJECTIVE: To evaluate the benefit of vestibular rehabilitation therapy (VRT) in the management of patients with idiopathic cerebellar ataxia with bilateral vestibulopathy (iCABV). BACKGROUND: iCABV is a hindbrain degenerative disorder with impairment of both central and peripheral vestibular pathways. There is combined failure of four compensatory eye movement systems including the vestibulo-ocular reflex (VOR), optokinetic reflex, smooth pursuit and the visually enhanced vestibulo-ocular reflex (VVOR). Phenotypic presentation includes postural and gait instability, oscillopsia and dizziness with active head movement. The benefit of VRT in iCABV patients has not been established. METHODS: A retrospective review was performed on a cohort of twelve patients diagnosed with iCABV in a multidisciplinary neuro-otology clinic. All participated in VRT and completed their suggested course of VRT. The following clinical measures were assessed before starting and after finishing VRT: 1) Dizziness Handicap Inventory (DHI), 2) Activities-Specific Balance Confidence (ABC) Scale, 3) Catastrophization scale, 4) Positive Affective Negative Affective Score (PANAS), 5) Dynamic Gait Index (DGI) and 6) Modified Clinical Test of Sensory Interaction in Balance (mCTSIB). The number of falls historically was recorded in addition to gait speed (ft./sec). RESULTS: Following VRT, patients were found to have improved balance on mCTSIB (condition 4 : 7 vs 18 seconds, P = 0.04) and a better postural stability with a reduced number of falls (p = 0.01). No statistically significant improvement was seen in the DHI, ABC, Catastrophization scale, DGI, PANAS and gait speed (p > 0.05). CONCLUSIONS: iCABV patients who underwent VRT were found to have a better postural stability and reduced risk of falls. VRT was not found to significantly improve patients' overall subjective perception of their symptoms or their psychological status.

Receiving Long-Term Disability or Pursuing a Legal Claim May Prevent Recovery From Chronic Dizziness.

OBJECTIVES/HYPOTHESIS: Chronic dizziness (CD) and imbalance have multiple etiologies. CD is strongly linked with psychiatric and psychological comorbidities, thus an interdisciplinary approach, including psychopharmacological interventions, is recommended. Despite the use of this comprehensive treatment approach, the recovery of individuals with CD that pursue long-term disability (LTD) insurance or legal claims (LC) appears hampered. As such, we aimed to compare symptom recovery from CD in an interdisciplinary setting between patients receiving LTD/LC versus those who were not, and to explore the factors that may contribute to changes in symptom severity. STUDY DESIGN: Retrospective cohort study. METHODS: Dizziness-related diagnoses were extracted from the charts of 195 adults in an outpatient interdisciplinary neurotology clinic in Toronto, Canada. Patients with baseline Dizziness Handicap Inventory (DHI) and Dizziness Catastrophizing Scale (DCS) assessments between August 2012 and July 2018 and a mean follow-up visit within approximately 10 months were included. The study participants were categorized as "LTD/LC+" (n = 92) or "LTD/LC-" (n = 103), referring to either receiving or pursuing LTD/LC or not, respectively. RESULTS: There were differences in the mean percentage changes in DHI (t[187] = 3.02, P = .003) and DCS (t[179] = 2.63, P = .009) scores between LTD/LC+ and LTD/LC- patients. LTD/LC+ patients showed 8.0% and 7.6% mean increases in DHI and DCS scores, respectively, whereas LTD/LC- patients showed 21.5% and 25.9% reductions in DHI and DCS scores, respectively, controlling for age, sex, and baseline illness severity. CONCLUSIONS: Patients receiving or pursuing LTD insurance or a legal claim did not improve from CD and dizziness catastrophizing compared to those who were not. Future studies are required to test these findings prospectively and to determine the factors that may contribute to symptom recovery, including the anxiety-aggravating effects of the LTD/LC process and the deleterious consequences of developing a sick-role while afflicted with a chronic illness. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:655-661, 2022.

Vision therapy: Occlusion, prisms, filters, and vestibular exercises for mild traumatic brain injury.

A number of treatment approaches have been advocated for persistent visual complaints following mild traumatic brain injury. These include devices such as binasal occlusion, yoked prisms, vertical prisms, and filters, as well as vestibular training. We discuss the rationale and the evidence for each of these approaches. Binasal occlusion has been advocated for visual motion sensitivity, but it is not clear why this should help, and there is no good evidence for its symptomatic efficacy. Base-in prisms can help manage convergence insufficiency, but there are few data on their efficacy. Midline shift is an unproven concept, and while the yoked prisms advocated for its treatment may have some effect on egocentric neglect, their use in mild traumatic brain injury is more questionable. A wide variety of posttraumatic symptoms have been attributed to vertical heterophoria, but this is an unproven concept and there are no controlled data on the use of vertical prisms for mild traumatic brain injury symptoms. Filters could plausibly ameliorate light intolerance but studies are lacking. Better evidence is emerging for the effects of vestibular therapy, with a few randomized controlled trials that included blinded assessments and appropriate statistical analyses. Without more substantial evidence, the use of many of these techniques cannot be recommended and should be regarded as unproven and in some cases implausible.

Vision Therapy: Ocular Motor Training in Mild Traumatic Brain Injury.

Vision therapy in the form of ocular motor training is increasingly used to treat visual complaints, particularly in the setting of persistent symptoms after mild traumatic brain injury (mTBI). In this review, we discuss the rationale behind this intervention and the evidence for its utility. Although the efficacy of exercises for primary convergence insufficiency is plausible and supported by data, there is not yet strong evidence of benefit for the post-traumatic variant. It is not established that abnormalities in fixation, pursuit, and saccades in mTBI are the cause of post-concussive symptoms, or that these abnormalities arise from ocular motor damage rather than being secondary effects of cognitive problems with attention or executive control. The few studies to date have significant methodological weaknesses. More substantial evidence is required before vision therapy can be accepted as a useful tool in the rehabilitation of patients with brain trauma. ANN NEUROL 2020;88:453-461.

Interdisciplinary integration of nursing and psychiatry (INaP) improves dizziness-related disability.

OBJECTIVES/HYPOTHESIS: The traditional medical care model of "assess and refer" in a sequential fashion fails to recognize the complexities that arise due to overlapping physical and psychiatric comorbidities experienced by patients with chronic dizziness or imbalance, thus resulting in inadequate treatment outcomes. We aimed to evaluate the impact of a novel interdisciplinary approach to care that integrates nursing and psychiatry (INaP) on dizziness-related disability. STUDY DESIGN: Retrospective cohort study. METHODS: We compared the change in clinical assessment scores (i.e., Dizziness Handicap Inventory [DHI], Dizziness Catastrophizing Scale) at approximately 8 months follow-up between those who did (INaP+) and did not receive INaP (INaP-). Data from 229 patients with dizziness or imbalance referred to an interdisciplinary neurotology clinic in Toronto, Ontario, Canada were acquired from August 2012 to December 2016 and January 2011 to December 2013 for the INaP+ and INaP- groups, respectively. RESULTS: A mean group difference in the percentage change in DHI scores was found, with greater reductions in dizziness-related disability in the INaP+ group (n = 121) versus the INaP- group (n = 108). This remained significant after controlling for age, gender, baseline illness severity, and duration between baseline and follow-up visits. CONCLUSIONS: The novel interdisciplinary approach of incorporating INaP appears to be more effective than interdisciplinary care without INaP in reducing dizziness-related disability in patients with chronic dizziness or imbalance. Clinical settings should consider the addition of INaP to achieve better patient outcomes. Future studies are required to test the hypothesis that INaP is more efficient and cost-effective than the traditional model of care. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:1800-1804, 2020.

Interdisciplinary integration of nursing and psychiatry (INaP) for the treatment of dizziness.

OBJECTIVES: The traditional medical care model of "assess and refer" requires revamping to address the multifaceted needs of patients with chronic dizziness and imbalance by adopting an interdisciplinary approach to care that integrates nursing and psychiatry (INaP). We aim to present a novel interdisciplinary approach that incorporates INaP in the care of patients with chronic dizziness and imbalance. METHODS: Presentation of an interdisciplinary model of care that incorporates INaP provided at the Toronto General Hospital in Toronto, Canada. RESULTS: Interdisciplinary care incorporating INaP, which includes the provision of support from an interdisciplinary health care team (ie, neurotologist, neurologist, psychiatrist, physiotherapist, and nurse clinician), psychoeducation about the interaction between chronic dizziness and psychiatric comorbidities, and ongoing access to medical and psychosocial assessment and intervention, addresses the physical and emotional aspects of patients' experience with chronic dizziness. CONCLUSIONS: The novel comprehensive interdisciplinary approach incorporating INaP may be more effective than interdisciplinary care without INaP in improving clinical outcomes in patients with chronic dizziness. In the subsequent study, we present data comparing patients treated for chronic dizziness and imbalance with and without the integration of INaP in an interdisciplinary setting. LEVEL OF EVIDENCE: 5 Laryngoscope, 130:1792-1799, 2020.

An Overview of Central Vertigo Disorders.

Head motion recorded by the vestibular labyrinths is conveyed to specific brainstem and cerebellar structures that relay velocity information to eye muscles to stabilize vision, and to the axial and limb muscles necessary to stabilize balance. Neural networks enhance and extend the primary vestibular signal, and create adaptation to movement when appropriate. Pathological lesions to one or more of these structures may cause central vertigo and imbalance, and may be localized by specific forms of nystagmus and other abnormal neurological signs. Vertigo treatment may be directed to the underlying disease, or it may be lessened by one of several centrally acting pharmacologic agents that have recently shown promise.

Lower ocular pulse amplitude with dynamic contour tonometry is associated with biopsy-proven giant cell arteritis.

OBJECTIVES: To determine the role of the ocular pulse amplitude (OPA) from Pascal dynamic contour tonometry in predicting the temporal artery biopsy (TABx) result in patients with suspected giant cell arteritis (GCA). DESIGN: Prospective validation study. PARTICIPANTS: Adults aged 50 years or older who underwent TABx from March 2015 to April 2017. METHODS: Subjects on high-dose glucocorticoids more than 14 days or without serology before glucocorticoid initiation were excluded. The OPA from both eyes was obtained and averaged just before TABx of the predominantly symptomatic side. The variables chosen for the a priori prediction model were age, average OPA, and C-reactive protein (CRP). Erythrocyte sedimentation rate (ESR), platelets, jaw claudication, and eye findings were also recorded. In this study, subjects with a negative biopsy were considered not to have GCA, and contralateral biopsy was performed if the clinical suspicion for GCA remained high. An external validation set (XVAL) was obtained. RESULTS: Of 109 TABx, 19 were positive and 90 were negative. On univariate logistic regression, the average OPA had 0.60 odds for positive TABx (p = 0.03), with no statistically significant difference in age, sex, CRP, ESR, or jaw claudication. In suspected GCA, an OPA of 1 mm Hg had positive likelihood ratio 4.74 and negative likelihood ratio 0.87 for positive TABx. Multivariate regression of the prediction model using optimal mathematical transforms (inverse OPA, log CRP, age >65 years) had area under the receiver operating characteristic curve (AUROC) = 0.85 and AUROCXVAL = 0.81. CONCLUSIONS: OPA is lower in subjects with biopsy-proven GCA and is a statistically significant predictor of GCA.

The use of real-time image stabilization and augmented reality eyewear in the treatment of oscillopsia.

OBJECTIVES/HYPOTHESIS: The symptom of oscillopsia in patients with bilateral vestibular loss (BVL) can be reduced as dynamic visual acuity (DVA), the reduction in visual acuity during head movement, is improved by using real-time image stabilization, delivered by augmented reality eyewear. SETTING: Tertiary multidisciplinary neurotology clinic. STUDY DESIGN: Prospective experimental study. METHODS: Immersive virtual reality glasses used in combination with a compact digital video camera were used. A software algorithm was developed that used a center-weighted Lucas-Kanade optical flow method to stabilize video in real time. Six patients with BVL were tested for changes in DVA using the eyewear. The ability to read a Snellen chart during a 2-Hz oscillating head rotation DVA test was measured. RESULTS: For combined scores of vertical and horizontal head rotations, the mean number of lines readable at rest was 7.86, which dropped to 2.77 with head movement (a combination of vertical and horizontal perturbations). This increased to a mean of 6.14 lines with the image stabilization software being activated. This difference was statistically significant (P < .001). CONCLUSION: This is the first successful attempt to improve dynamic visual acuity in patients with bilateral vestibular loss. Recent hardware upgrades are promising in improving these results even further.

Double impairment: clinical identification of 33 cases of cerebellar ataxia with bilateral vestibulopathy.

OBJECTIVE: Following recently described small series of patients with the syndrome of cerebellar ataxia with bilateral vestibulopathy (CABV), the authors undertook a careful clinical and laboratory assessment of patients who presented to their unit with characteristics of this syndrome. STUDY DESIGN: Case note review. SETTING: Tertiary, university-based, multidisciplinary neurootology clinic. SUBJECTS: Thirty-three patients whose characteristics fit this syndrome. METHODS: Patients presenting to the Multidisciplinary Neurotology Clinic with characteristics of CABV were entered into a bespoke database. This was analyzed to identify the clinical findings and results of vestibular investigations for this group. RESULTS: Patients presented at a mean age of 54 years (SD, 17.6) with symptoms having been present for a median of 3 years (interquartile ratio, 2.0-9.5). Caloric testing greatly underestimated the disorder, being subnormal in only 18% of patients; the head-thrust test was abnormal and dynamic visual acuity testing was abnormal 88% and 91% of the time, respectively. Of the patients, 76% demonstrated gaze-evoked nystagmus. Impaired smooth pursuit (97% of patients showed low gain with saccadic corrections) and impaired cancellation of the vestibulo-ocular reflex (in 97% of patients) were found. Impaired saccular otolithic function was abnormal in 33%, adding to patient imbalance. CONCLUSION: The unique double-pathway balance impairment in CABV patients causes a high prevalence of subnormal function of both central and peripheral vestibular function. This is an easily missed clinical entity that is often associated with normal caloric investigations. As many patients with this syndrome are poor candidates for vestibular rehabilitation therapy, resources are better devoted to the early implementation of assistance with their safe ambulation and activities of daily living.

The clinical utility of search coil horizontal vestibulo-ocular reflex testing.

CONCLUSION: Testing of the horizontal vestibulo-ocular reflex (VOR) with head rotations (including head impulses) using the magnetic scleral search coil technique (SCT HHI) provides valuable additional diagnostic information in patients with persistent dizziness, oscillopsia or imbalance. It identifies high and low frequency/acceleration vestibular abnormalities that are frequently missed using other methods. OBJECTIVES: To evaluate the diagnostic utility of SCT measurement of the horizontal VOR in the multidisciplinary neurotology clinic of a tertiary referral centre. PATIENTS AND METHODS: The records of 127 consecutive patients referred for persistent dizziness, oscillopsia, imbalance, or with clinical findings suggestive of high frequency/acceleration vestibular dysfunction were reviewed. All had been tested with clinical head impulses, bithermal calorics and vestibular-evoked myogenic potentials. VOR gain (peak eye velocity/peak head velocity) had been measured both in response to sinusoidal oscillations in a rotating chair (0.1-11 Hz) and to manually delivered horizontal head rotations (peak head velocities 50-500 degrees/s) using SCT. RESULTS: Agreement between the different test modalities of horizontal semicircular canal function was moderate. Relative to SCT HHI, clinical HHI showed the highest sensitivity and the lowest specificity (both 70%). SCT HHI appeared to have the greatest diagnostic yield, when compared with calorics and SCT ROT (23% of all abnormalities shown were detected only by SCT HHI) and also allowed detection of significant asymmetries in patients with bilateral vestibular dysfunction.

The high-frequency/acceleration head heave test in detecting otolith diseases.

OBJECTIVE: To investigate whether transient, high-acceleration interaural head heaves (translational vestibulo-ocular reflex [tVOR]) could aid in the diagnosis of otolith diseases. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENTS: Thirteen patients with symptoms suggestive of otolith diseases and 10 age-matched controls. INTERVENTIONS: Patients underwent a clinical otoneurologic examination and standard laboratory audiovestibular evaluation, including audiometry, electronystagmography with bithermal caloric, Halmagyi-Curthoys head thrust test with search coils, and vestibular-evoked myogenic potential. All subjects underwent subjective visual vertical (SVV) and tVOR testings. MAIN OUTCOME MEASURES: Sensitivity (ratio of peak eye to peak head velocities) and velocity gain (ratio of actual to ideal peak eye velocities). RESULTS: Five of 13 patients showed no abnormality in any tests. Of the remaining 8, 3 (38%) had reduced tVOR responses, whereas 1 (13%) had abnormal SVV. Sensitivity and velocity gains were symmetrically reduced in 2 patients, who had symptoms for 8 and 24 months. A third patient, symptomatic for 7 weeks, had asymmetric reduction of tVOR responses and a deviated SVV. CONCLUSION: Both head heave and SVV tests detect acute, asymmetric otolith diseases. Subjective visual vertical test relies on imbalance of utricular tone and may not detect bilateral symmetric diseases or partial diseases with central compensation. Our preliminary data in a small group of patients show that measuring the tVOR in a higher and more physiologic range of frequencies may serve as useful adjunct to detect acute and chronic otolith dysfunction and seems to be superior to the SVV in detecting bilateral symmetric or asymmetric otolith diseases.