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Background Early neurorehabilitation improves outcomes in patients with disorders of consciousness (DoC) after brain injury, but its applicability in COVID-19 is unknown. We describe our experience implementing an early neurorehabilitation protocol for patients with COVID-19-associated DoC in the intensive care unit (ICU) and evaluate factors associated with recovery. Methods During the initial COVID-19 surge in New York City between March 10 and May 20, 2020, faced with a disproportionately high number of ICU patients with prolonged unresponsiveness, we developed and implemented an early neurorehabilitation protocol, applying standard practices from brain injury rehabilitation care to the ICU setting. Twenty-one patients with delayed recovery of consciousness after severe COVID-19 participated in a pilot early neurorehabilitation program that included serial Coma Recovery Scale-Revised (CRS-R) assessments, multimodal treatment, and access to clinicians specializing in brain injury medicine. We retrospectively compared clinical features of patients who did and did not recover to the minimally conscious state (MCS) or better, defined as a CRS-R total score (TS) ≥ 8, before discharge. We additionally examined factors associated with best CRS-R TS, last CRS-R TS, hospital length of stay, and time on mechanical ventilation. Results Patients underwent CRS-R assessments a median of six (interquartile range [IQR] 3–10) times before discharge, beginning a median of 48 days (IQR 40–55) from admission. Twelve (57%) patients recovered to MCS after a median of 8 days (IQR 2–14) off continuous sedation; they had lower body mass index (p = 0.009), lower peak serum C-reactive protein levels (p = 0.023), higher minimum arterial partial pressure of oxygen (p = 0.028), and earlier fentanyl discontinuation (p = 0.018). CRS-R scores fluctuated over time, and the best CRS-R TS was significantly higher than the last CRS-R TS (median 8 [IQR 5–23] vs. 5 [IQR 3–18], p = 0.002). Earlier fentanyl (p = 0.001) and neuromuscular blockade (p = 0.015) discontinuation correlated with a higher last CRS-R TS. Conclusions More than half of our cohort of patients with prolonged unresponsiveness following severe COVID-19 recovered to MCS or better before hospital discharge, achieving a clinical benchmark known to have relatively favorable long-term prognostic implications in DoC of other etiologies. Hypoxia, systemic inflammation, sedation, and neuromuscular blockade may impact diagnostic assessment and prognosis, and fluctuations in level of consciousness make serial assessments essential. Early neurorehabilitation of these patients in the ICU can be accomplished but is associated with unique challenges. Further research should evaluate factors associated with longer-term neurologic recovery and benefits of early rehabilitation in patients with severe COVID-19.

Background and Purpose We reviewed the literature to evaluate cerebrospinal fluid (CSF) results from patients with coronavirus disease 2019 (COVID‐19) who had neurological symptoms and had an MRI that showed (1) central nervous system (CNS) hyperintense lesions not attributed to ischemia and/or (2) leptomeningeal enhancement. We sought to determine if these findings were associated with a positive CSF severe acute respiratory syndrome associated coronavirus 2 (SARS‐CoV‐2) polymerase chain reaction (PCR). Methods We performed a systematic review of Medline and Embase from December 1, 2019 to November 18, 2020. CSF results were evaluated based on the presence/absence of (1) ≥ 1 CNS hyperintense lesion and (2) leptomeningeal enhancement. Results In 117 publications, we identified 193 patients with COVID‐19 who had an MRI of the CNS and CSF testing. There were 125 (65%) patients with CNS hyperintense lesions. Patients with CNS hyperintense lesions were significantly more likely to have a positive CSF SARS‐CoV‐2 PCR (10% [9/87] vs. 0% [0/43], p = 0.029). Of 75 patients who had a contrast MRI, there were 20 (27%) patients who had leptomeningeal enhancement. Patients with leptomeningeal enhancement were significantly more likely to have a positive CSF SARS‐CoV‐2 PCR (25% [4/16] vs. 5% [2/42], p = 0.024). Conclusion The presence of CNS hyperintense lesions or leptomeningeal enhancement on neuroimaging from patients with COVID‐19 is associated with increased likelihood of a positive CSF SARS‐CoV‐2 PCR. However, a positive CSF SARS‐CoV‐2 PCR is uncommon in patients with these neuroimaging findings, suggesting they are often related to other etiologies, such as inflammation, hypoxia, or ischemia.

STRIVE was a prospective, 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative patients with early relapsing-remitting multiple sclerosis (RRMS).Study objectives examined the effects of natalizumab on cognitive processing speed, confirmed disability improvement (CDI), and patient-reported outcomes (PROs).Clinical and PRO secondary endpoints were assessed annually over 4 years in STRIVE. The Symbol Digit Modalities Test (SDMT) was used as a measure of cognitive processing speed. PROs were assessed using the Multiple Sclerosis Impact Score (MSIS-29) and the Work Productivity and Activity Impairment Questionnaire (WPAI).At all four annual assessments, the proportion of patients in the intent-to-treat (ITT) population (N = 222) who exhibited clinically meaningful improvement in their SDMT score from baseline (i.e., change ≥ 4 points) ranged from 41.9 to 54.0%. The cumulative probability of CDI at 4 years in patients in the ITT population with a baseline Expanded Disability Status Scale score ≥ 2 (N = 133) was 43.9%. Statistically significant reductions in the mean change from screening in the MSIS-29 physical and psychological scores, indicating improved quality of life, were observed over all 4 years (P ≤ 0.0012 for all). A statistically significant decrease from screening in the impact of MS on regular activities, signifying an improvement in this WPAI measure, was also observed over all 4 years of the study.These results further extend our knowledge of the effectiveness, specifically regarding improvements in cognitive processing speed, disability and PROs, of long-term natalizumab treatment in early RRMS patients.GOV: NCT01485003 (5 December 2011).

Limited data exists evaluating predictors of long-term outcomes after hospitalization for COVID-19.We conducted a prospective, longitudinal cohort study of patients hospitalized for COVID-19. The following outcomes were collected at 6 and 12-months post-diagnosis: disability using the modified Rankin Scale (mRS), activities of daily living assessed with the Barthel Index, cognition assessed with the telephone Montreal Cognitive Assessment (t-MoCA), Neuro-QoL batteries for anxiety, depression, fatigue and sleep, and post-acute symptoms of COVID-19. Predictors of these outcomes, including demographics, pre-COVID-19 comorbidities, index COVID-19 hospitalization metrics, and life stressors, were evaluated using multivariable logistic regression.Of 790 COVID-19 patients who survived hospitalization, 451(57%) completed 6-month (N = 383) and/or 12-month (N = 242) follow-up, and 77/451 (17%) died between discharge and 12-month follow-up. Significant life stressors were reported in 121/239 (51%) at 12-months. In multivariable analyses, life stressors including financial insecurity, food insecurity, death of a close contact and new disability were the strongest independent predictors of worse mRS, Barthel Index, depression, fatigue, and sleep scores, and prolonged symptoms, with adjusted odds ratios ranging from 2.5 to 20.8. Other predictors of poor outcome included older age (associated with worse mRS, Barthel, t-MoCA, depression scores), baseline disability (associated with worse mRS, fatigue, Barthel scores), female sex (associated with worse Barthel, anxiety scores) and index COVID-19 severity (associated with worse Barthel index, prolonged symptoms).Life stressors contribute substantially to worse functional, cognitive and neuropsychiatric outcomes 12-months after COVID-19 hospitalization. Other predictors of poor outcome include older age, female sex, baseline disability and severity of index COVID-19.

A woman presented at age 18 years with partial myelitis and diplopia and experienced multiple subsequent relapses. Her MRI demonstrated T2 abnormalities characteristic of multiple sclerosis (MS) (white matter ovoid lesions and Dawson fingers), and CSF demonstrated an elevated IgG index and oligoclonal bands restricted to the CSF. Diagnosed with clinically definite relapsing-remitting MS, she was treated with various MS disease-modifying therapies and eventually began experiencing secondary progression. At age 57 years, she developed an acute longitudinally extensive transverse myelitis and was found to have AQP4 antibodies by cell-based assay. Our analysis of the clinical course, radiographic findings, molecular diagnostic methods, and treatment response characteristics support the hypothesis that our patient most likely had 2 CNS inflammatory disorders: MS, which manifested as a teenager, and neuromyelitis optica spectrum disorder, which evolved in her sixth decade of life. This case emphasizes a key principle in neurology practice, which is to reconsider whether the original working diagnosis remains tenable, especially when confronted with evidence (clinical and/or paraclinical) that raises the possibility of a distinctively different disorder.

A 62-year-old man presented with headache, fever, and malaise. He was diagnosed with Anaplasma phagocytophilum, confirmed by serum polymerase chain reaction, and started on oral doxycycline. After 5 days of treatment, the patient began to experience gait imbalance with frequent falls, as well as myoclonus, and confusion. Examination was notable for opsoclonus-myoclonus-ataxia (OMA) and hypometric saccades. Cerebrospinal fluid (CSF) autoimmune encephalitis panel demonstrated a markedly elevated neuronal intermediate filament (NIF) immunoglobulin G antibody titer of 1:16, with positive neurofilament light- and heavy-chain antibodies. These antibodies were suspected to have been triggered by the Anaplasma infection. Repeat CSF examination 8 days later still showed a positive immunofluorescence assay for NIF antibodies, but the CSF titer was now less than 1:2. Body computed tomography imaging was unrevealing for an underlying cancer. Our patient illustrates a postinfectious mechanism for OMA and saccadic hypometria after Anaplasma infection.

Introduction STRIVE was a 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative (JCV-negative) relapsing-remitting multiple sclerosis (RRMS) patients with disease duration ≤ 3 years. The objective of STRIVE was to examine no evidence of disease activity (NEDA) status and predictors of NEDA in natalizumab-treated patients with early RRMS. Methods Proportions of patients with NEDA were evaluated along with baseline predictors of NEDA, annualized relapse rate, 24-week confirmed disability worsening (CDW), magnetic resonance imaging assessments (T2 and gadolinium-enhancing lesions), and serious adverse events. Results In years 1 and 2, 56.1% (95% confidence interval [CI] 48.7–63.4%) and 73.6% (95% CI 66.2–80.2%) of patients (intent-to-treat population [N = 222]), respectively, achieved NEDA. In years 3 and 4, 84.6% (95% CI 78.0–89.9%) and 91.9% (95% CI 86.4–95.8%) of patients, respectively, achieved Clinical NEDA (no relapses or 24-week CDW). Baseline predictors of NEDA in year 4 were Expanded Disability Status Scale score ≤ 2.0 (odds ratio [OR] = 3.85 [95% CI 1.54–9.63]; p = 0.004) and T2 lesion volume > 4 cc (OR = 0.39 [95% CI 0.15–0.98]; p = 0.046), with the latter also predicting Clinical NEDA in year 4 (OR = 0.21 [95% CI 0.05–0.92]; p = 0.038). The cumulative probability of CDW at year 4 was 19.3%. Serious adverse events were reported in 11.3% of patients. Conclusion These results support the long-term safety and effectiveness of natalizumab. Baseline predictors of NEDA help to inform benefit-risk assessments of natalizumab treatment in JCV-negative patients with early RRMS. Trial Registration ClinicalTrials.gov identifier NCT01485003. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01722-w.

We reviewed the literature on cerebrospinal fluid (CSF) studies in patients who had a seizure in the setting of COVID-19 infection to evaluate for evidence of viral neuroinvasion. We performed a systematic review of Medline and Embase to identify publications that reported one or more patients with COVID-19 who had a seizure and had CSF testing preformed. The search ranged from December 1st 2019 to November 18th 2020. We identified 56 publications which described 69 unique patients who met our inclusion criteria. Of the 54 patients whose past medical history was provided, 2 (4%) had epilepsy and 1 (2%) had a prior seizure in the setting of hyperglycemia, but the remaining 51 (94%) had no history of seizures. Seizure was the initial symptom of COVID-19 for 15 (22%) patients. There were 26 (40%) patients who developed status epilepticus. SARS-CoV-2 PCR testing was performed in the CSF for 45 patients; 6 (13%) had a positive CSF SARS-CoV-2 PCR, only 1 (17%) of whom had status epilepticus. The cycle thresholds were not reported. Evaluation for CSF SARS-CoV-2 antibodies (directly or indirectly, via testing for CSF oligoclonal bands or immunoglobulins) was performed in 26 patients, only 2 (8%) of whom had evidence of intrathecal antibody synthesis. Of the 11 patients who had CSF autoimmune antibody panels tested, 1 had NMDA antibodies and 1 had Caspr-2 antibodies. Detection of SARS-CoV-2 in the CSF of patients with seizures who have COVID-19 is uncommon. Our review suggests that seizures in this patient population are not likely due to direct viral invasion of the brain.

Background Toxic metabolic encephalopathy (TME) has been reported in 7–31% of hospitalized patients with coronavirus disease 2019 (COVID-19); however, some reports include sedation-related delirium and few data exist on the etiology of TME. We aimed to identify the prevalence, etiologies, and mortality rates associated with TME in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients. Methods We conducted a retrospective, multicenter, observational cohort study among patients with reverse transcriptase–polymerase chain reaction-confirmed SARS-CoV-2 infection hospitalized at four New York City hospitals in the same health network between March 1, 2020, and May 20, 2020. TME was diagnosed in patients with altered mental status off sedation or after an adequate sedation washout. Patients with structural brain disease, seizures, or primary neurological diagnoses were excluded. The coprimary outcomes were the prevalence of TME stratified by etiology and in-hospital mortality (excluding comfort care only patients) assessed by using a multivariable time-dependent Cox proportional hazards models with adjustment for age, race, sex, intubation, intensive care unit requirement, Sequential Organ Failure Assessment scores, hospital location, and date of admission. Results Among 4491 patients with COVID-19, 559 (12%) were diagnosed with TME, of whom 435 of 559 (78%) developed encephalopathy immediately prior to hospital admission. The most common etiologies were septic encephalopathy (n = 247 of 559 [62%]), hypoxic-ischemic encephalopathy (HIE) (n = 331 of 559 [59%]), and uremia (n = 156 of 559 [28%]). Multiple etiologies were present in 435 (78%) patients. Compared with those without TME (n = 3932), patients with TME were older (76 vs. 62 years), had dementia (27% vs. 3%) or psychiatric history (20% vs. 10%), were more often intubated (37% vs. 20%), had a longer hospital length of stay (7.9 vs. 6.0 days), and were less often discharged home (25% vs. 66% [all P

ObjectiveTo determine the prevalence and associated mortality of well-defined neurologic diagnoses among patients with coronavirus disease 2019 (COVID-19), we prospectively followed hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–positive patients and recorded new neurologic disorders and hospital outcomes.MethodsWe conducted a prospective, multicenter, observational study of consecutive hospitalized adults in the New York City metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between patients with COVID-19 with and without neurologic disorders.ResultsOf 4,491 patients with COVID-19 hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were reverse transcriptase PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all p < 0.05). After adjusting for age, sex, SOFA scores, intubation, history, medical complications, medications, and comfort care status, patients with COVID-19 with neurologic disorders had increased risk of in-hospital mortality (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.17–1.62, p < 0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63–0.85, p < 0.001).ConclusionsNeurologic disorders were detected in 13.5% of patients with COVID-19 and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.

This paper presents 4 male, adult cases of leukoencephalopathy following COVID-19 infection at New York University Langone Health-associated hospitals between 2 and 29 April 2020 Their clinical data, laboratory values, treatment and outcome are described, and the possible mechanisms that could lead to leukoencephalopathy are discussed

The COVID-19 pandemic is causing world-wide social dislocation, operational and economic dysfunction, and high rates of morbidity and mortality. Medical practices are responding by developing, disseminating, and implementing unprecedented changes in health care delivery. Telemedicine has rapidly moved to the frontline of clinical practice due to the need for prevention and mitigation strategies; these have been encouraged, facilitated, and enabled by changes in government rules and regulations and payer-driven reimbursement policies. We describe our neurology department's situational transformation from in-person outpatient visits to a largely virtual neurology practice in response to the COVID-19 pandemic. Two key factors enabled our rapid deployment of virtual encounters in neurology and its subspecialties. The first was a well-established robust information technology infrastructure supporting virtual urgent care services at our institution; this connected physicians directly to patients using both the physician's and the patient's own mobile devices. The second is the concept of one patient, one chart, facilitated by a suite of interconnected electronic medical record (EMR) applications on several different device types. We present our experience with conducting general teleneurology encounters using secure synchronous audio and video connections integrated with an EMR. This report also details how we perform virtual neurologic examinations that are clinically meaningful and how we document, code, and bill for these virtual services. Many of these processes can be used by other neurology providers, regardless of their specific practice model. We then discuss potential roles for teleneurology after the COVID-19 global pandemic has been contained.

We describe an educational intervention for neurology residents aimed at developing feedback skills. An objective structured clinical examination case was designed to simulate the provision of feedback to a medical student. After the simulated case session, residents received structured, individualized feedback on their performance and then participated in a group discussion about feedback methods. Survey data were collected from the standardized medical student regarding residents' performance and from residents for assessments of their performance and of the Objective Structured Clinical Examination case. This article aims to describe this educational intervention and to demonstrate the feasibility of this approach for feedback skills development.

Background/ObjectivesLittle is known about trajectories of recovery 12-months after hospitalization for severe COVID.MethodsWe conducted a prospective, longitudinal cohort study of patients with and without neurological complications during index hospitalization for COVID-19 from March 10, 2020-May 20, 2020. Phone follow-up batteries were performed at 6- and 12-months post-COVID symptom onset. The primary 12-month outcome was the modified Rankin Scale (mRS) comparing patients with or without neurological complications using multivariable ordinal analysis. Secondary outcomes included: activities of daily living (Barthel Index), telephone Montreal Cognitive Assessment (t-MoCA) and Neuro-QoL batteries for anxiety, depression, fatigue and sleep. Changes in outcome scores from 6 to 12-months were compared using non-parametric paired-samples sign test.ResultsTwelve-month follow-up was completed in N=242 patients (median age 65, 64% male, 34% intubated during hospitalization) and N=174 completed both 6- and 12-month follow-up. At 12-months 197/227 (87%) had ≥1 abnormal metric: mRS>0 (75%), Barthel50% of patients.DiscussionAt 12-months post-hospitalization for severe COVID, 87% of patients had ongoing abnormalities in functional, cognitive or Neuro-QoL metrics and abnormal cognition persisted in 50% of patients without a prior history of dementia/cognitive abnormality. Only fatigue severity differed significantly between patients with or without neurological complications during index hospitalization. However, significant improvements in cognitive (t-MoCA) and anxiety (Neuro-QoL) scores occurred in 56% and 45% of patients, respectively, between 6- to 12-months. These results may not be generalizable to those with mild/moderate COVID.

The primary objective was to determine the effect of the COVID-19 pandemic on volume, demographics, and mechanisms of injury (MOI) for patients seen at an urban multidisciplinary concussion center. During the first phase of the pandemic in the United States, stay-at-home orders led to decreased group activities and required cancellation of outpatient appointments or initiation of telemedicine visits.This study was a retrospective chart review of 3500 patient electronic medical records (EMR). Patients aged 1-99 years were eligible if they had been seen at New York University Langone Health Concussion Center during March 1-December 31, 2019 (control/pre-pandemic period) or during the same period in 2020 (pandemic period). Injury date, appointment date, age, sex, and MOI were captured; statistical analyses were performed using Stata17 (StataCorp, College Station, TX).There were 48% fewer visits during the COVID-19 pandemic period compared to the 2019 control period. There was a decreased proportion of pediatric patients (15% control, 6% pandemic; p = 0.007, chi-square test). Fewer concussions were related to team sports (21% control, 5% pandemic; p 0.001), and a greater proportion were caused by bicycle accidents (4% control, 8% pandemic; p = 0.037) and assault/domestic violence (3% control, 9% pandemic; p 0.001).The relative proportions of concussion MOI, age distributions, and visit volumes were significantly associated with pre-pandemic vs. pandemic periods, suggesting that COVID-19 changed concussion epidemiology during the pandemic period. This study demonstrates how epidemiologic data may inform future resource allocation during public health emergencies.

Optic neuritis is an inflammatory optic neuropathy that is commonly indicative of autoimmune neurological disorders including multiple sclerosis, myelin-oligodendrocyte glycoprotein antibody-associated disease, and neuromyelitis optica spectrum disorder. Early clinical recognition of optic neuritis is important in determining the potential aetiology, which has bearing on prognosis and treatment. Regaining high-contrast visual acuity is common in people with idiopathic optic neuritis and multiple sclerosis-associated optic neuritis; however, residual deficits in contrast sensitivity, binocular vision, and motion perception might impair vision-specific quality-of-life metrics. In contrast, recovery of visual acuity can be poorer and optic nerve atrophy more severe in individuals who are seropositive for antibodies to myelin oligodendrocyte glycoprotein, AQP4, and CRMP5 than in individuals with typical optic neuritis from idiopathic or multiple-sclerosis associated optic neuritis. Key clinical, imaging, and laboratory findings differentiate these disorders, allowing clinicians to focus their diagnostic studies and optimise acute and preventive treatments. Guided by early and accurate diagnosis of optic neuritis subtypes, the timely use of high-dose corticosteroids and, in some instances, plasmapheresis could prevent loss of high-contrast vision, improve contrast sensitivity, and preserve colour vision and visual fields. Advancements in our knowledge, diagnosis, and treatment of optic neuritis will ultimately improve our understanding of autoimmune neurological disorders, improve clinical trial design, and spearhead therapeutic innovation.

Although visual symptoms are common following concussion, quantitative measures of visual function are missing from concussion evaluation protocols on the athletic sideline. For the past half century, rapid automatized naming (RAN) tasks have demonstrated promise as quantitative neuro-visual assessment tools in the setting of head trauma and other disorders but have been previously limited in accessibility and scalability. The Mobile Interactive Cognitive Kit (MICK) App is a digital RAN test that can be downloaded on most mobile devices and can therefore provide a quantitative measure of visual function anywhere, including the athletic sideline. This investigation examined the feasibility of MICK App administration in a cohort of Division 1 college football players. Participants (n = 82) from a National Collegiate Athletic Association (NCAA) Division 1 football team underwent baseline testing on the MICK app. Total completion times of RAN tests on the MICK app were recorded; magnitudes of best time scores and between-trial learning effects were determined by paired t-test. Consistent with most timed performance measures, there were significant learning effects between the two baseline trials for both RAN tasks on the MICK app: Mobile Universal Lexicon Evaluation System (MULES) (p 0.001, paired t-test, mean improvement 13.3 s) and the Staggered Uneven Number (SUN) (p 0.001, mean improvement 3.3 s). This study demonstrated that the MICK App can be feasibly administered in the setting of pre-season baseline testing in a Division I environment. These data provide a foundation for post-injury sideline testing that will include comparison to baseline in the setting of concussion.

Saccadic slowing as a component of supranuclear saccadic gaze palsy is an important diagnostic sign in multiple neurologic conditions, including degenerative, inflammatory, genetic, or ischemic lesions affecting brainstem structures responsible for saccadic generation. Little attention has been given to the accuracy with which clinicians correctly identify saccadic slowing. We compared clinician (n = 19) judgements of horizontal and vertical saccade speed on video recordings of saccades (from 9 patients with slow saccades, 3 healthy controls) to objective saccade peak velocity measurements from infrared oculographic recordings. Clinician groups included neurology residents, general neurologists, and fellowship-trained neuro-ophthalmologists. Saccades with normal peak velocities on infrared recordings were correctly identified as normal in 57% (91/171; 171 = 9 videos × 19 clinicians) of clinician decisions; saccades determined to be slow on infrared recordings were correctly identified as slow in 84% (224/266; 266 = 14 videos × 19 clinicians) of clinician decisions. Vertical saccades were correctly identified as slow more often than horizontal saccades (94% versus 74% of decisions). No significant differences were identified between clinician training levels. Reliable differentiation between normal and slow saccades is clinically challenging; clinical performance is most accurate for detection of vertical saccade slowing. Quantitative analysis of saccade peak velocities enhances accurate detection and is likely to be especially useful for detection of mild saccadic slowing.

Background STRIVE is a multicenter, observational, open-label, single-arm study of natalizumab in anti–JC virus (JCV) seronegative patients with early relapsing-remitting multiple sclerosis (RRMS). The objective of this prespecified 2-year interim analysis was to determine the effectiveness of natalizumab in establishing and maintaining no evidence of disease activity (NEDA) in early RRMS. Methods Patients aged 18–65 years had an RRMS diagnosis

A 55-year-old obese woman with a history of migraine and tension-type headaches presented with headache for 5 days with acute worsening for 1 day. The headache was throbbing, holocephalic, and maximal at the left temple, and worsened with both standing and lying down and with exertion. The headache was initially mild for 4 days before acutely worsening in severity and waking her from sleep with associated nausea and photophobia. Unlike her typical headaches, it did not improve with over-the-counter analgesics and was more prolonged. There were no associated visual complaints, hearing changes or phonophobia, jaw claudication, weakness, numbness, or paresthesias.

Objective To determine the optimal thresholds for intereye differences in retinal nerve fiber and ganglion cell + inner plexiform layer thicknesses for identifying unilateral optic nerve lesions in multiple sclerosis. Current international diagnostic criteria for multiple sclerosis do not include the optic nerve as a lesion site despite frequent involvement. Optical coherence tomography detects retinal thinning associated with optic nerve lesions. Methods In this multicenter international study at 11 sites, optical coherence tomography was measured for patients and healthy controls as part of the International Multiple Sclerosis Visual System Consortium. High- and low-contrast acuity were also collected in a subset of participants. Presence of an optic nerve lesion for this study was defined as history of acute unilateral optic neuritis. Results Among patients (n = 1,530), receiver operating characteristic curve analysis demonstrated an optimal peripapillary retinal nerve fiber layer intereye difference threshold of 5μm and ganglion cell + inner plexiform layer threshold of 4μm for identifying unilateral optic neuritis (n = 477). Greater intereye differences in acuities were associated with greater intereye retinal layer thickness differences (p ≤ 0.001). Interpretation Intereye differences of 5μm for retinal nerve fiber layer and 4μm for macular ganglion cell + inner plexiform layer are robust thresholds for identifying unilateral optic nerve lesions. These thresholds may be useful in establishing the presence of asymptomatic and symptomatic optic nerve lesions in multiple sclerosis and could be useful in a new version of the diagnostic criteria. Our findings lend further validation for utilizing the visual system in a multiple sclerosis clinical trial setting. Ann Neurol 2019;85:618-629.

Purpose of review To review emerging vision-based assessments in the evaluation of concussion. Recent findings Involvement of the visual pathways is common following concussion, the mildest form of traumatic brain injury. The visual system contains widely distributed networks that are prone to neurophysiologic changes after a concussion, resulting in visual symptoms and ocular motor dysfunction. Vision-based testing is increasingly used to improve detection and assess head injury. Several rapid automatized naming (RAN) tasks, such as the King-Devick test and the Mobile Universal Lexicon Evaluation System, show capacity to identify athletes with concussion. Video-oculography (VOG) has gained widespread use in eye-tracking and gaze-tracking studies of head trauma from which objective data have shown increased saccadic latencies, saccadic dysmetria, errors in predictive target tracking, and changes in vergence in concussed individuals. Summary RAN tasks demonstrate promise as rapid screening tools for concussion. Further investigation will involve assessment of the role for age, characterization of learning effects over repeated measurements, and identification of optimal thresholds for clinically significant performance decrements. Various RAN tasks are likely to be functionally distinct, engaging different neural networks according to the demands of each task. Measures of saccades, smooth pursuit eye-movements, the vestibulo-ocular reflex and, more recently, disparity vergence are candidate vision-based markers for concussion. Work to adopt these assessments to the sideline or clinical environments is ongoing.