Publications by authors named "Laura J Balcer"

192 Publications

Exploration of Rapid Automatized Naming and Standard Visual Tests in Prodromal Alzheimer Disease Detection.

J Neuroophthalmol 2021 May 17. Epub 2021 May 17.

Departments of Neurology (SZW, RNK, NM, LH, BJ, AC, JCR, SLG, TMW, AVM, and LJB), Population Health (RNK and LJB), and Ophthalmology (SZW, JCR, SLG, and LJB), New York University Grossman School of Medicine, New York, New York.

Background: Visual tests in Alzheimer disease (AD) have been examined over the last several decades to identify a sensitive and noninvasive marker of the disease. Rapid automatized naming (RAN) tasks have shown promise for detecting prodromal AD or mild cognitive impairment (MCI). The purpose of this investigation was to determine the capacity for new rapid image and number naming tests and other measures of visual pathway structure and function to distinguish individuals with MCI due to AD from those with normal aging and cognition. The relation of these tests to vision-specific quality of life scores was also examined in this pilot study.

Methods: Participants with MCI due to AD and controls from well-characterized NYU research and clinical cohorts performed high and low-contrast letter acuity (LCLA) testing, as well as RAN using the Mobile Universal Lexicon Evaluation System (MULES) and Staggered Uneven Number test, and vision-specific quality of life scales, including the 25-Item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement. Individuals also underwent optical coherence tomography scans to assess peripapillary retinal nerve fiber layer and ganglion cell/inner plexiform layer thicknesses. Hippocampal atrophy on brain MRI was also determined from the participants' Alzheimer disease research center or clinical data.

Results: Participants with MCI (n = 14) had worse binocular LCLA at 1.25% contrast compared with controls (P = 0.009) and longer (worse) MULES test times (P = 0.006) with more errors in naming images (P = 0.009) compared with controls (n = 16). These were the only significantly different visual tests between groups. MULES test times (area under the receiver operating characteristic curve [AUC] = 0.79), MULES errors (AUC = 0.78), and binocular 1.25% LCLA (AUC = 0.78) showed good diagnostic accuracy for distinguishing MCI from controls. A combination of the MULES score and 1.25% LCLA demonstrated the greatest capacity to distinguish (AUC = 0.87). These visual measures were better predictors of MCI vs control status than the presence of hippocampal atrophy on brain MRI in this cohort. A greater number of MULES test errors (rs = -0.50, P = 0.005) and worse 1.25% LCLA scores (rs = 0.39, P = 0.03) were associated with lower (worse) NEI-VFQ-25 scores.

Conclusions: Rapid image naming (MULES) and LCLA are able to distinguish MCI due to AD from normal aging and reflect vision-specific quality of life. Larger studies will determine how these easily administered tests may identify patients at risk for AD and serve as measures in disease-modifying therapy clinical trials.
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http://dx.doi.org/10.1097/WNO.0000000000001228DOI Listing
May 2021

The APOSTEL 2.0 Recommendations for Reporting Quantitative Optical Coherence Tomography Studies.

Neurology 2021 Apr 28. Epub 2021 Apr 28.

Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany.

Objective: To update the consensus recommendations for reporting of quantitative optical coherence tomography (OCT) study results, thus revising the previously published Advised Protocol for OCT Study Terminology and Elements (APOSTEL) recommendations.

Methods: To identify studies reporting quantitative OCT results, we performed a PubMed search for the terms "quantitative" and "optical coherence tomography" from 2015 to 2017. Corresponding authors of the identified publications were invited to provide feedback on the initial APOSTEL recommendations via online surveys following the principle of a modified Delphi method. The results were evaluated and discussed by a panel of experts, and changes to the initial recommendations were proposed. A final survey was recirculated among the corresponding authors to obtain a majority vote on the proposed changes.

Results: One hundred sixteen authors participated in the surveys, resulting in 15 suggestions, of which 12 were finally accepted and incorporated into an updated 9-point-checklist. We harmonized the nomenclature of the outer retinal layers, added the exact area of measurement to the description of volume scans; we suggested reporting device-specific features. We advised to address potential bias in manual segmentation or manual correction of segmentation errors. References to specific reporting guidelines and room light conditions were removed. The participants' consensus with the recommendations increased from 80% for the previous APOSTEL version to greater than 90%.

Conclusions: The modified Delphi method resulted in an expert-led guideline (evidence class III, GRADE criteria) concerning study protocol, acquisition device, acquisition settings, scanning protocol, fundoscopic imaging, post-acquisition data selection, post-acquisition analysis, nomenclature and abbreviations, and statistical approach. It will still be essential to update these recommendations to new research and practices regularly.
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http://dx.doi.org/10.1212/WNL.0000000000012125DOI Listing
April 2021

National Institute of Neurological Disorders and Stroke Consensus Diagnostic Criteria for Traumatic Encephalopathy Syndrome.

Neurology 2021 05 15;96(18):848-863. Epub 2021 Mar 15.

From the Boston University CTE Center (D.I.K.), Department of Neurology, Boston University School of Medicine, Boston; Brain Injury Program (D.I.K.), Encompass Health Braintree Rehabilitation Hospital, Braintree, MA; University of Washington Memory & Brain Wellness Clinic (C.B.), Department of Neurology, University of Washington School of Medicine, Seattle; Department of Neurology (D.W.D., C.H.A.), Mayo Clinic, Scottsdale, AZ; Boston University CTE Center (J.M., M.L.A.), Boston University Alzheimer's Disease Center, Department of Neurology, Boston University School of Medicine; Boston University CTE Center (M.L.M.), Boston University School of Medicine, MA; Departments of Neurology (L.J.B.), Ophthalmology, and Population Health, New York University Grossman School of Medicine; Departments of Neurosciences and Psychiatry University of California San Diego (S.J.B.), La Jolla; Departments of Neurology and Psychiatry (W.B.B.), New York University Grossman School of Medicine; Center for Neuroscience and Regenerative Medicine (D.L.B.), Uniformed Services University of the Health Sciences, Department of Neurology, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Boston University CTE Center (R.C.C.), Boston University Alzheimer's Disease Center, Departments of Neurology and Neurosurgery, Boston University School of Medicine, MA; Departments of Rehabilitation Medicine and Neurology (K.D.-O.C.), Icahn School of Medicine, Mount Sinai, New York; Department of Neurology (Y.E.G.), Barrow Neurological Institute, Phoenix, AZ; Rancho Los Amigos National Rehabilitation Center (B.D.J.), Downey, CA; Department of Neurology (B.D.J.), Keck School of Medicine of USC. Los Angeles, CA; Departments of Psychiatry and Neurology (T.W.M.), Indiana University School of Medicine, Indianapolis; Veterans Affairs Northwest Mental Illness (E.R.P.), Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA; Department of Psychiatry and Behavioral Sciences (E.R.P.), University of Washington School of Medicine, Seattle; Mayo Clinic Alzheimer's Disease Research Center (R.C.P.), Mayo Clinic, Rochester, MN; Department of Psychiatry and Psychology (J.V.W.), Mayo Clinic, Scottsdale, AZ; Department of Physical Medicine and Rehabilitation (R.D.Z.), Spaulding Rehabilitation Hospital, Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston; Faculty of Psychology and Neuroscience (É.M.F.), Maastricht University, the Netherlands, Department of Psychiatry, University of Cambridge, United Kingdom; National Institute of Neurological Disorders and Stroke (D.J.B.), National Institutes of Health; National Institute of Neurological Disorders and Stroke (W.J.K.), Bethesda, MD; Boston University CTE Center (Y.T.), Boston University Alzheimer's Disease Center, Boston University School of Medicine, Department of Biostatistics, Boston University School of Public Health; Boston University CTE Center (A.C.M.), Boston University Alzheimer's Disease Center, Departments of Neurology and Pathology & Laboratory Medicine, Boston University School of Medicine; VA Boston Healthcare System (A.C.M.), US Department of Veteran Affairs, MA; Psychiatry Neuroimaging Laboratory (M.E.S.), Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, University of Nevada School of Integrated Health Sciences; Cleveland Clinic Lou Ruvo Center for Brain Health (J.L.C.), Las Vegas, NV; Banner Alzheimer's Institute (E.M.R.), Arizona State University; Department of Psychiatry (E.M.R.), University of Arizona, Phoenix, AZ; and Boston University CTE Center (R.A.S.), Boston University Alzheimer's Disease Center, Departments of Neurology, Neurosurgery, and Anatomy & Neurobiology, Boston University School of Medicine, MA.

Objective: To develop evidence-informed, expert consensus research diagnostic criteria for traumatic encephalopathy syndrome (TES), the clinical disorder associated with neuropathologically diagnosed chronic traumatic encephalopathy (CTE).

Methods: A panel of 20 expert clinician-scientists in neurology, neuropsychology, psychiatry, neurosurgery, and physical medicine and rehabilitation, from 11 academic institutions, participated in a modified Delphi procedure to achieve consensus, initiated at the First National Institute of Neurological Disorders and Stroke Consensus Workshop to Define the Diagnostic Criteria for TES April, 2019. Before consensus, panelists reviewed evidence from all published cases of CTE with neuropathologic confirmation, and they examined the predictive validity data on clinical features in relation to CTE pathology from a large clinicopathologic study (n = 298).

Results: Consensus was achieved in 4 rounds of the Delphi procedure. Diagnosis of TES requires (1) substantial exposure to repetitive head impacts (RHIs) from contact sports, military service, or other causes; (2) core clinical features of cognitive impairment (in episodic memory and/or executive functioning) and/or neurobehavioral dysregulation; (3) a progressive course; and (4) that the clinical features are not fully accounted for by any other neurologic, psychiatric, or medical conditions. For those meeting criteria for TES, functional dependence is graded on 5 levels, ranging from independent to severe dementia. A provisional level of certainty for CTE pathology is determined based on specific RHI exposure thresholds, core clinical features, functional status, and additional supportive features, including delayed onset, motor signs, and psychiatric features.

Conclusions: New consensus diagnostic criteria for TES were developed with a primary goal of facilitating future CTE research. These criteria will be revised as updated clinical and pathologic information and in vivo biomarkers become available.
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http://dx.doi.org/10.1212/WNL.0000000000011850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166432PMC
May 2021

Sleep-deprived residents and rapid picture naming performance using the Mobile Universal Lexicon Evaluation System (MULES) test.

eNeurologicalSci 2021 Mar 2;22:100323. Epub 2021 Feb 2.

Departments of Neurology, New York University Grossman School of Medicine, New York, NY, USA.

Objective: The Mobile Universal Lexicon Evaluation System (MULES) is a rapid picture naming task that captures extensive brain networks involving neurocognitive, afferent/efferent visual, and language pathways. Many of the factors captured by MULES may be abnormal in sleep-deprived residents. This study investigates the effect of sleep deprivation in post-call residents on MULES performance.

Methods: MULES, consisting of 54 color photographs, was administered to a cohort of neurology residents taking 24-hour in-hospital call ( = 18) and a group of similar-aged controls not taking call (n = 18). Differences in times between baseline and follow-up MULES scores were compared between the two groups.

Results: MULES time change in call residents was significantly worse (slower) from baseline (mean 1.2 s slower) compared to non-call controls (mean 11.2 s faster) ( < 0.001, Wilcoxon rank sum test). The change in MULES time from baseline was significantly correlated to the change in subjective level of sleepiness for call residents and to the amount of sleep obtained in the 24 h prior to follow-up testing for the entire cohort. For call residents, the duration of sleep obtained during call did not significantly correlate with change in MULES scores. There was no significant correlation between MULES change and sleep quality questionnaire score for the entire cohort.

Conclusion: The MULES is a novel test for effects of sleep deprivation on neurocognition and vision pathways. Sleep deprivation significantly worsens MULES performance. Subjective sleepiness may also affect MULES performance. MULES may serve as a useful performance assessment tool for sleep deprivation in residents.
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http://dx.doi.org/10.1016/j.ensci.2021.100323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876539PMC
March 2021

Practical Approach to the Tele-Neuro-Ophthalmology and Neuro-Otology Visits: Instructional Videos.

J Neuroophthalmol 2021 03;41(1):10-12

Department of Neurology (RC, SNG, CC, SLG, LJB, JCR), New York University Grossman School of Medicine, New York, New York; Department of Ophthalmology (NR, LS), University of California San Francisco, San Francisco, California; Departments of Ophthalmology (SLG, LJB, JCR) and Population Health (LJB), New York University Grossman School of Medicine, New York, New York.

Abstract: A collection of instructional videos that illustrate a step by step approach to tele-neuro-ophthalmology and neuro-otology visits. These videos provide instruction for patient preparation for their video visit, patient and provider interface with an electronic medical record associated video platform, digital applications to assist with vision testing, and practical advice for detailed remote neuro-ophthalmologic and neuro-otologic examinations.
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http://dx.doi.org/10.1097/WNO.0000000000001195DOI Listing
March 2021

How sandbag-able are concussion sideline assessments? A close look at eye movements to uncover strategies.

Brain Inj 2021 Mar 2;35(4):426-435. Epub 2021 Feb 2.

Department of Neurology, NYU School of Medicine, New York, NY, United States.

Sideline diagnostic tests for concussion are vulnerable to volitional poor performance ("sandbagging") on baseline assessments, motivated by desire to subvert concussion detection and potential removal from play. We investigated eye movements during sandbagging versus best effort on the King-Devick (KD) test, a rapid automatized naming (RAN) task. Participants performed KD testing during oculography following instructions to sandbag or give best effort. Twenty healthy participants without concussion history were included (mean age 27 ± 8 years). Sandbagging resulted in longer test times (89.6 ± 39.2 s vs 48.2 ± 8.5 s, < .001), longer inter-saccadic intervals (459.5 ± 125.4 ms vs 311.2 ± 79.1 ms, < .001) and greater numbers of saccades (171.4 ± 47 vs 138 ± 24.2, < .001) and reverse saccades (wrong direction for reading) (21.2% vs 11.3%, < .001). Sandbagging was detectable using a logistic model with KD times as the only predictor, though more robustly detectable using eye movement metrics. KD sandbagging results in eye movement differences that are detectable by eye movement recordings and suggest an invalid test score. Objective eye movement recording during the KD test shows promise for distinguishing between best effort and post-injury performance, as well as for identifying sandbagging red flags.
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http://dx.doi.org/10.1080/02699052.2021.1878554DOI Listing
March 2021

The complexity of eye-hand coordination: a perspective on cortico-cerebellar cooperation.

Cerebellum Ataxias 2020 Nov 13;7(1):14. Epub 2020 Nov 13.

Department of Rehabilitation Medicine, NYU Grossman School of Medicine, New York, NY, USA.

Background: Eye-hand coordination (EHC) is a sophisticated act that requires interconnected processes governing synchronization of ocular and manual motor systems. Precise, timely and skillful movements such as reaching for and grasping small objects depend on the acquisition of high-quality visual information about the environment and simultaneous eye and hand control. Multiple areas in the brainstem and cerebellum, as well as some frontal and parietal structures, have critical roles in the control of eye movements and their coordination with the head. Although both cortex and cerebellum contribute critical elements to normal eye-hand function, differences in these contributions suggest that there may be separable deficits following injury.

Method: As a preliminary assessment for this perspective, we compared eye and hand-movement control in a patient with cortical stroke relative to a patient with cerebellar stroke.

Result: We found the onset of eye and hand movements to be temporally decoupled, with significant decoupling variance in the patient with cerebellar stroke. In contrast, the patient with cortical stroke displayed increased hand spatial errors and less significant temporal decoupling variance. Increased decoupling variance in the patient with cerebellar stroke was primarily due to unstable timing of rapid eye movements, saccades.

Conclusion: These findings highlight a perspective in which facets of eye-hand dyscoordination are dependent on lesion location and may or may not cooperate to varying degrees. Broadly speaking, the results corroborate the general notion that the cerebellum is instrumental to the process of temporal prediction for eye and hand movements, while the cortex is instrumental to the process of spatial prediction, both of which are critical aspects of functional movement control.
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http://dx.doi.org/10.1186/s40673-020-00123-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666466PMC
November 2020

Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study.

Res Sq 2020 Oct 26. Epub 2020 Oct 26.

Zinc impairs replication of RNA viruses such as SARS-CoV-1, and may be effective against SARS-CoV-2. However, to achieve adequate intracellular zinc levels, administration with an ionophore, which increases intracellular zinc levels, may be necessary. We evaluated the impact of zinc with an ionophore (Zn+ionophore) on COVID-19 in-hospital mortality rates. A multicenter cohort study was conducted of 3,473 adult hospitalized patients with reverse-transcriptase-polymerase-chain-reaction (RT-PCR) positive SARS-CoV-2 infection admitted to four New York City hospitals between March 10 through May 20, 2020. Exclusion criteria were: death or discharge within 24h, comfort-care status, clinical trial enrollment, treatment with an IL-6 inhibitor or remdesivir. Patients who received Zn+ionophore were compared to patients who did not using multivariable time-dependent cox proportional hazards models for time to in-hospital death adjusting for confounders including age, sex, race, BMI, diabetes, week of admission, hospital location, sequential organ failure assessment (SOFA) score, intubation, acute renal failure, neurological events, treatment with corticosteroids, azithromycin or lopinavir/ritonavir and the propensity score of receiving Zn+ionophore. A sensitivity analysis was performed using a propensity score-matched cohort of patients who did or did not receive Zn+ionophore matched by age, sex and ventilator status. Among 3,473 patients (median age 64, 1947 [56%] male, 522 [15%] ventilated, 545[16%] died), 1,006 (29%) received Zn+ionophore. Zn+ionophore was associated with a 24% reduced risk of in-hospital mortality (12% of those who received Zn+ionophore died versus 17% who did not; adjusted Hazard Ratio [aHR] 0.76, 95% CI 0.60-0.96, P=0.023). More patients who received Zn+ionophore were discharged home (72% Zn+ionophore vs 67% no Zn+ionophore, P=0.003) Neither Zn nor the ionophore alone were associated with decreased mortality rates. Propensity score-matched sensitivity analysis (N=1356) validated these results (Zn+ionophore aHR for mortality 0.63, 95%CI 0.44-0.91, P=0.015). There were no significant interactions for Zn+ionophore with other COVID-19 specific medications. Zinc with an ionophore was associated with increased rates of discharge home and a 24% reduced risk of in-hospital mortality among COVID-19 patients, while neither zinc alone nor the ionophore alone reduced mortality. Further randomized trials are warranted.
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http://dx.doi.org/10.21203/rs.3.rs-94509/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605567PMC
October 2020

Afferent and Efferent Visual Markers of Alzheimer's Disease: A Review and Update in Early Stage Disease.

Front Aging Neurosci 2020 11;12:572337. Epub 2020 Sep 11.

Department of Neurology, New York University Grossman School of Medicine, New York, NY, United States.

Vision, which requires extensive neural involvement, is often impaired in Alzheimer's disease (AD). Over the last few decades, accumulating evidence has shown that various visual functions and structures are compromised in Alzheimer's dementia and when measured can detect those with dementia from those with normal aging. These visual changes involve both the afferent and efferent parts of the visual system, which correspond to the sensory and eye movement aspects of vision, respectively. There are fewer, but a growing number of studies, that focus on the detection of predementia stages. Visual biomarkers that detect these stages are paramount in the development of successful disease-modifying therapies by identifying appropriate research participants and in identifying those who would receive future therapies. This review provides a summary and update on common afferent and efferent visual markers of AD with a focus on mild cognitive impairment (MCI) and preclinical disease detection. We further propose future directions in this area. Given the ease of performing visual tests, the accessibility of the eye, and advances in ocular technology, visual measures have the potential to be effective, practical, and non-invasive biomarkers of AD.
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http://dx.doi.org/10.3389/fnagi.2020.572337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518395PMC
September 2020

Role for OCT in detecting hemi-macular ganglion cell layer thinning in patients with multiple sclerosis and related demyelinating diseases.

J Neurol Sci 2020 Dec 28;419:117159. Epub 2020 Sep 28.

Department of Neurology, New York University Grossman School of Medicine, New York, NY, USA; Department of Ophthalmology, New York University Grossman School of Medicine, New York, NY, USA. Electronic address:

Objective: Investigations have found associations of homonymous thinning of the macular ganglion cell/ inner-plexiform layer (GCIPL) with demyelinating lesions in the post-chiasmal visual pathway among patients with multiple sclerosis (MS). Retinal thinning may also occur through retrograde trans-synaptic degeneration, a process by which lesions in post-geniculate visual pathway structures lead to thinning of the GCIPL across thalamic synapses. The purpose of our study was to determine the frequency of homonymous hemimacular thinning that occurs in association with post-chiasmal visual pathway demyelinating lesions in patients with MS and other demyelinating diseases.

Methods: Adult patients with demyelinating diseases (MS, neuromyelitis optica spectrum disorder [NMOSD], myelin oligodendrocyte glycoprotein antibody disease (anti-MOG)) who were participants in an ongoing observational study of visual pathway structure and function were analyzed for the presence of hemimacular GCIPL thinning on OCT scans. Brain MRI scans were examined for the presence of post-geniculate visual pathway demyelinating lesions.

Results: Among 135 participants in the visual pathway study, 5 patients (3.7%) had homonymous hemimacular GCIPL thinning. Eleven patients (8.1%) had a whole+half pattern of GCIPL thinning, characterized by hemimacular thinning in one eye and circumferential macular thinning in the contralateral eye. All but one patient with homonymous hemimacular thinning had demyelinating lesions in the post-geniculate visual pathway; however, these lesions were located in both cerebral hemispheres.

Conclusion: Homonymous hemimacular thinning in the GCIPL by OCT is associated with post-chiasmal visual pathway demyelinating lesions but it appears to be a relatively uncommon contributor to GCIPL loss. Patients with this pattern of GCIPL often fail to complain of hemifield visual loss. Future studies with prospective and detailed MR imaging may be able to more closely associate demyelinating lesions in anatomically appropriate regions of the post-chiasmal visual pathways with homonymous hemimacular thinning.
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http://dx.doi.org/10.1016/j.jns.2020.117159DOI Listing
December 2020

Contrast Acuity and the King-Devick Test in Huntington's Disease.

Neuroophthalmology 2020 25;44(4):219-225. Epub 2019 Nov 25.

Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Saccadic eye movement abnormalities are among the earliest manifestations of Huntington's disease (HD) but are difficult to quantify at the bedside. Similarly, afferent visual pathway involvement in HD is poorly characterised. The objective was to evaluate afferent and efferent visual function in HD. Participants with manifest HD (n = 19) and healthy controls (n = 20) performed the King-Devick test, a timed test of rapid number naming. Binocular high and low-contrast (2.5% and 1.25%) acuities were measured using low-contrast Sloan letter charts, and pupillometric recordings were made using a handheld NeurOptics PLR-3000 pupillometer. The NEI-VFQ-25 questionnaire with 10-item neuro-ophthalmic supplement were also completed. Unified Huntington's Disease Rating Scale (UHDRS) motor score and other clinical and demographic variables were collected. Comparisons between manifest HD and controls were performed using linear regression adjusted for confounders. Mean King-Devick time scores were 102.9 seconds in patients with manifest HD and 48.2 seconds in controls (p < .01, t-test). In unadjusted analyses, binocular high contrast acuity was seven letters (one Snellen line equivalent) lower in manifest HD than controls (p = .043). This effect was similar for low-contrast acuity, but only low-contrast acuity remained statistically significant after adjusting for covariates. Low-contrast acuity also correlated with UHDRS motor score. There were no differences in pupillary reactivity or self-reported vision-related quality of life. In conclusion, HD is associated with reduced low-contrast acuity and abnormal performance on the King-Devick test of rapid number naming. These tests are easy to administer, providing an objective quantitative measure of visual function which could be incorporated into optimised rating scales.
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http://dx.doi.org/10.1080/01658107.2019.1669668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518319PMC
November 2019

Concerning Vision Therapy and Ocular Motor Training in Mild Traumatic Brain Injury.

Ann Neurol 2020 11 16;88(5):1053-1054. Epub 2020 Sep 16.

Department of Neurology, NYU Grossman School of Medicine, New York, NY, USA.

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http://dx.doi.org/10.1002/ana.25875DOI Listing
November 2020

The psychosocial implications of COVID-19 for a neurology program in a pandemic epicenter.

J Neurol Sci 2020 09 14;416:117034. Epub 2020 Jul 14.

New York University Grossman School of Medicine Department of Neurology, New York, NY, USA; New York University Grossman School of Medicine Department of Ophthalmology, New York, NY, USA. Electronic address:

Objective: We discuss the psychosocial implications of the COVID-19 pandemic as self-reported by housestaff and faculty in the NYU Langone Health Department of Neurology, and summarize how our program is responding to these ongoing challenges.

Methods: During the period of May 1-4, 2020, we administered an anonymous electronic survey to all neurology faculty and housestaff to assess the potential psychosocial impacts of COVID-19. The survey also addressed how our institution and department are responding to these challenges. This report outlines the psychosocial concerns of neurology faculty and housestaff and the multifaceted support services that our department and institution are offering in response. Faculty and housestaff cohorts were compared with regard to frequencies of binary responses (yes/ no) using the Fisher's exact test.

Results: Among 130 total survey respondents (91/191 faculty [48%] and 37/62 housestaff [60%]), substantial proportions of both groups self-reported having increased fear (79%), anxiety (83%) and depression (38%) during the COVID-19 pandemic. These proportions were not significantly different between the faculty and housestaff groups. Most respondents reported that the institution had provided adequate counseling and support services (91%) and that the department had rendered adequate emotional support (92%). Participants offered helpful suggestions regarding additional resources that would be helpful during the COVID-19 pandemic.

Conclusion: COVID-19 has affected the lives and minds of faculty and housestaff in our neurology department at the epicenter of the pandemic. Efforts to support these providers during this evolving crisis are imperative for promoting the resilience necessary to care for our patients and colleagues.
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http://dx.doi.org/10.1016/j.jns.2020.117034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358162PMC
September 2020

The SUN test of vision: Investigation in healthy volunteers and comparison to the mobile universal lexicon evaluation system (MULES).

J Neurol Sci 2020 08 30;415:116953. Epub 2020 May 30.

Department of Neurology, New York University Grossman School of Medicine, New York, NY, USA; Department of Population Health, New York University Grossman School of Medicine, New York, NY, USA; Department of Ophthalmology, New York University Grossman School of Medicine, New York, NY, USA. Electronic address:

Objective: Tests of rapid automatized naming (RAN) have been used for decades to evaluate neurological conditions. RAN tests require extensive brain pathways involving visual perception, memory, eye movements and language. To the extent that different naming tasks capture varied visual pathways and related networks, we developed the Staggered Uneven Number (SUN) test of rapid number naming to complement existing RAN tests, such as the Mobile Universal Lexicon Evaluation System (MULES). The purpose of this investigation was to determine values for time scores for SUN, and to compare test characteristics between SUN and MULES.

Methods: We administered the SUN and MULES tests to healthy adult volunteers in a research office setting. MULES consists of 54 color photographs; the SUN includes 145 single- and multi-digit numbers. Participants are asked to name each number or picture aloud.

Results: Among 54 healthy participants, aged 33 ± 13 years (range 20-66), the average SUN time score was 45.2 ± 8.3 s (range 30-66). MULES test times were 37.4 ± 9.9 s (range 20-68). SUN and MULES time scores did not differ by gender, but were greater (worse) among older participants for MULES (r = 0.43, P = .001). Learning effects between first and second trials were greater for the MULES; participants improved (reduced) their time scores between trials by 5% on SUN and 16% for MULES (P < .0001, Wilcoxon signed-rank test).

Conclusion: The SUN is a new vision-based test that complements presently available picture- and number-based RAN tests. These assessments may require different brain pathways and networks for visual processing, visual memory, language and eye movements.
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http://dx.doi.org/10.1016/j.jns.2020.116953DOI Listing
August 2020

Training in neurology: Flexibility and adaptability of a neurology training program at the epicenter of COVID-19.

Neurology 2020 06 8;94(24):e2608-e2614. Epub 2020 May 8.

From the Departments of Neurology (S.A., S.S., N.A.-F., A.K., L.J.B., S.L.G.), Population Health (L.J.B.), and Ophthalmology (L.J.B., S.L.G.), New York University Grossman School of Medicine, New York.

Objective: To outline changes made to a neurology residency program in response to coronavirus disease 2019 (COVID-19).

Methods: In early March 2020, the first cases of COVID-19 were announced in the United States. New York City quickly became the epicenter of a global pandemic, and our training program needed to rapidly adapt to the increasing number of inpatient cases while being mindful of protecting providers and continuing education. Many of these changes unfolded over days, including removing residents from outpatient services, minimizing the number of residents on inpatient services, deploying residents to medicine services and medical intensive care units, converting continuity clinic patient visits to virtual options, transforming didactics to online platforms only, and maintaining connectedness in an era of social distancing. We have been able to accomplish this through daily virtual meetings among leadership, faculty, and residents.

Results: Over time, our program has successfully rolled out initiatives to service the growing number of COVID-related inpatients while maintaining neurologic care for those in need and continuing our neurologic education curriculum.

Conclusion: It has been necessary and feasible for our residency training program to undergo rapid structural changes to adapt to a medical crisis. The key ingredients in doing this successfully have been flexibility and teamwork. We suspect that many of the implemented changes will persist long after the COVID-19 crisis has passed and will change the approach to neurologic and medical training.
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http://dx.doi.org/10.1212/WNL.0000000000009675DOI Listing
June 2020

Rapid implementation of virtual neurology in response to the COVID-19 pandemic.

Neurology 2020 06 1;94(24):1077-1087. Epub 2020 May 1.

From the Department of Neurology (S.N.G., S.C.H., L.J.B., A.K., H.W., S.L.G., N.A.B.), New York University Grossman School of Medicine; Department of Ophthalmology (L.J.B., S.L.G.), New York University Grossman School of Medicine; and Department of Population Health (L.J.B.), New York University Grossman School of Medicine.

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.
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http://dx.doi.org/10.1212/WNL.0000000000009677DOI Listing
June 2020

Correlation of Visual Quality of Life With Clinical and Visual Status in Friedreich Ataxia.

J Neuroophthalmol 2020 06;40(2):213-217

Division of Neurology (PA, AL, DRL), Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; and Departments of Neurology (RN-K, LJB), Population Health and Ophthalmology, NYU School of Medicine, Sackler Institute of Graduate Biomedical Sciences, New York, New York.

Background: The primary objective was to determine the association of patient-reported vision-specific quality of life to disease status and visual function in patients with Friedreich's ataxia (FRDA).

Methods: Patients with FRDA were assessed with the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) along with measures of disease status (ataxia stage) and visual function (low- and high-contrast letter acuity scores). The relations of NEI-VFQ-25 scores to those for disease status and visual function were examined.

Results: Scores for the NEI-VFQ-25 were lower in patients with FRDA (n = 99) compared with published disease-free controls, particularly reduced in a subgroup of FRDA patients with features of early onset, older age, and abnormal visual function.

Conclusions: The NEI-VFQ-25 captures the subjective component of visual function in patients with FRDA.
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http://dx.doi.org/10.1097/WNO.0000000000000878DOI Listing
June 2020

Education Research: Teaching and assessing communication and professionalism in neurology residency with simulation.

Neurology 2020 02 20;94(5):229-232. Epub 2020 Jan 20.

From the Departments of Neurology (A.M.K., A.L., P.P., S.K.R., A.N., C.Z., K.I., L.J.B.), Neurosurgery (A.L.), Medicine (S.Z.), Ophthalmology (L.J.B., S.L.G.), and Population Health (L.J.B.), New York University School of Medicine.

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http://dx.doi.org/10.1212/WNL.0000000000008895DOI Listing
February 2020

Rapid picture naming in Parkinson's disease using the Mobile Universal Lexicon Evaluation System (MULES).

J Neurol Sci 2020 Mar 9;410:116680. Epub 2020 Jan 9.

Departments of Neurology, New York University School of Medicine, New York, NY, USA; Departments of Population Health, New York University School of Medicine, New York, NY, USA; Departments of Ophthalmology, New York University School of Medicine, New York, NY, USA. Electronic address:

Objective: The Mobile Universal Lexicon Evaluation System (MULES) is a test of rapid picture naming that captures extensive brain networks, including cognitive, language and afferent/efferent visual pathways. MULES performance is slower in concussion and multiple sclerosis, conditions in which vision dysfunction is common. Visual aspects captured by the MULES may be impaired in Parkinson's disease (PD) including color discrimination, object recognition, visual processing speed, and convergence. The purpose of this study was to compare MULES time scores for a cohort of PD patients with those for a control group of participants of similar age. We also sought to examine learning effects for the MULES by comparing scores for two consecutive trials within the patient and control groups.

Methods: MULES consists of 54 colored pictures (fruits, animals, random objects). The test was administered in a cohort of PD patients and in a group of similar aged controls. Wilcoxon rank-sum tests were used to determine statistical significance for differences in MULES time scores between PD patients and controls. Spearman rank-correlation coefficients were calculated to examine the relation between MULES time scores and PD motor symptom severity (UPDRS). Learning effects were assessed using Wilcoxon rank-sum tests.

Results: Among 51 patients with PD (median age 70 years, range 52-82) and 20 disease-free control participants (median age 67 years, range 51-90), MULES scores were significantly slower (worse performance) in PD patients (median 63.2 s, range 37.3-296.3) vs. controls (median 53.9 s, range 37.5-128.6, P = .03, Wilcoxon rank-sum test). Slower MULES times were associated with increased motor symptom severity as measured by the Unified Parkinson's Disease Rating Scale, Section III (r = 0.37, P = .02). Learning effects were greater among patients with PD (median improvement of 14.8 s between two MULES trials) compared to controls (median 7.4 s, P = .004).

Conclusion: The MULES is a complex test of rapid picture naming that captures numerous brain pathways including an extensive visual network. MULES performance is slower in patients with PD and our study suggests an association with the degree of motor impairment. Future studies will determine the relation of MULES time scores to other modalities that test visual function and structure in PD.
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http://dx.doi.org/10.1016/j.jns.2020.116680DOI Listing
March 2020

Optical coherence tomography of the retina in schizophrenia: Inter-device agreement and relations with perceptual function.

Schizophr Res 2020 05 11;219:13-18. Epub 2020 Jan 11.

Department of Psychiatry, New York University School of Medicine, New York, NY, USA; Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA. Electronic address:

Background: Optical coherence tomography (OCT) studies have demonstrated differences between people with schizophrenia and controls. Many questions remain including the agreement between scanners. The current study seeks to determine inter-device agreement of OCT data in schizophrenia compared to controls and to explore the relations between OCT and visual function measures.

Methods: Participants in this pilot study were 12 individuals with schizophrenia spectrum disorders and 12 age- and sex-matched controls. Spectralis and Cirrus OCT machines were used to obtain retinal nerve fiber layer (RNFL) thickness and macular volume. Cirrus was used to obtain ganglion cell layer + inner plexiform layer (GCL + IPL) thickness. Visual function was assessed with low-contrast visual acuity and the King-Devick test of rapid number naming.

Results: There was excellent relative agreement in OCT measurements between the two machines, but poor absolute agreement, for both patients and controls. On both machines, people with schizophrenia showed decreased macular volume but no difference in RNFL thickness compared to controls. No between-group difference in GCL + IPL thickness was found on Cirrus. Controls showed significant associations between King-Devick performance and RNFL thickness and macular volume, and between low-contrast visual acuity and GCL + IPL thickness. Patients did not show significant associations between OCT measurements and visual function.

Conclusions: Good relative agreement suggests that the offset between machines remains constant and should not affect comparisons between groups. Decreased macular volume in individuals with schizophrenia on both machines supports findings of prior studies and provides further evidence that similar results may be found irrespective of OCT device.
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http://dx.doi.org/10.1016/j.schres.2019.10.046DOI Listing
May 2020

Evaluation of multiple sclerosis disability outcome measures using pooled clinical trial data.

Neurology 2019 11 22;93(21):e1921-e1931. Epub 2019 Oct 22.

From the University of Virginia (M.D.G.), Charlottesville; National Multiple Sclerosis Society (N.G.L.), New York, NY; Biogen (R.A.R., G.P.), Cambridge, MA; Critical Path Institute (L.D.H.), Tucson, AZ; Genentech (P.S.C.), South San Francisco, CA; Independent Neurology Clinical Development Consultant (G.S.F.); Premier Research (A.J.), Wokingham, UK; UCL Institute of Neurology (R.K.), London, UK; Imperial College London and UK Dementia Research Institute (P.M.M.); Johns Hopkins (E.M.M.), Baltimore, MD; New York University School of Medicine (L.J.B.), NY; Wave Life Sciences (M.P.), Cambridge, MA; VU University Medical Center (B.M.J.U.), Amsterdam, the Netherlands; and Cleveland Clinic (J.A.C.), OH.

Objective: We report analyses of a pooled database by the Multiple Sclerosis Outcome Assessments Consortium to evaluate 4 proposed components of a multidimensional test battery.

Methods: Standardized data on 12,776 participants, comprising demographics, multiple sclerosis disease characteristics, Expanded Disability Status Scale (EDSS) score, performance measures, and Short Form-36 Physical Component Summary (SF-36 PCS), were pooled from control and treatment arms of 14 clinical trials. Analyses of Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), Low Contrast Letter Acuity (LCLA), and Symbol Digit Modalities Test (SDMT) included measurement properties; construct, convergent, and known group validity; and longitudinal performance of the measures individually and when combined into a multidimensional test battery relative to the EDSS and SF-36 to determine sensitivity and clinical meaningfulness.

Results: The performance measures had excellent test-retest reliability and showed expected differences between subgroups based on disease duration and EDSS level. Progression rates in detecting time to 3-month confirmed worsening were lower for T25FW and 9HPT compared to EDSS, while progression rates for LCLA and SDMT were similar to EDSS. When the 4 measures were analyzed as a multidimensional measure rather than as individual measures, progression on any one performance measure was more sensitive than the EDSS. Worsening on the performance measures analyzed individually or as a multidimensional test battery was associated with clinically meaningful SF-36 PCS score worsening, supporting clinical meaningfulness of designated performance test score worsening.

Conclusion: These results support the use of the 4 proposed performance measures, individually or combined into a multidimensional test battery as study outcome measures.
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http://dx.doi.org/10.1212/WNL.0000000000008519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885577PMC
November 2019

Retinal inner nuclear layer volume reflects inflammatory disease activity in multiple sclerosis; a longitudinal OCT study.

Mult Scler J Exp Transl Clin 2019 Jul-Sep;5(3):2055217319871582. Epub 2019 Sep 5.

Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands.

Background: The association of peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness with neurodegeneration in multiple sclerosis (MS) is well established. The relationship of the adjoining inner nuclear layer (INL) with inflammatory disease activity is less well understood.

Objective: The objective of this paper is to investigate the relationship of INL volume changes with inflammatory disease activity in MS. In this longitudinal, multi-centre study, optical coherence tomography (OCT) and clinical data (disability status, relapses and MS optic neuritis (MSON)) were collected in 785 patients with MS (68.3% female) and 92 healthy controls (63.4% female) from 11 MS centres between 2010 and 2017 and pooled retrospectively. Data on pRNFL, GCIPL and INL were obtained at each centre.

Results: There was a significant increase in INL volume in eyes with new MSON during the study ( = 61/1562, β = 0.01 mm,  < .001). Clinical relapses (other than MSON) were significantly associated with increased INL volume (β = 0.005,  = .025). INL volume was independent of disease progression (β = 0.002 mm,  = .474).

Conclusion: Our data demonstrate that an increase in INL volume is associated with MSON and the occurrence of clinical relapses. Therefore, INL volume changes may be useful as an outcome marker for inflammatory disease activity in MSON and MS treatment trials.
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http://dx.doi.org/10.1177/2055217319871582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728683PMC
September 2019

Eye position-dependent opsoclonus in mild traumatic brain injury.

Prog Brain Res 2019 23;249:65-78. Epub 2019 May 23.

Department of Neurology, New York University School of Medicine, New York, NY, United States; Department of Ophthalmology, New York University School of Medicine, New York, NY, United States. Electronic address:

Opsoclonus consists of bursts of involuntary, multidirectional, back-to-back saccades without an intersaccadic interval. We report a 60-year-old man with post-concussive headaches and disequilibrium who had small amplitude opsoclonus in left gaze, along with larger amplitude flutter during convergence. Examination was otherwise normal and brain MRI was unremarkable. Video-oculography demonstrated opsoclonus predominantly in left gaze and during pursuit in the left hemifield, which improved as post-concussive symptoms improved. Existing theories of opsoclonus mechanisms do not account for this eye position-dependence. We discuss theoretical mechanisms of this behavior, including possible dysfunction of frontal eye field and/or cerebellar vermis neurons; review ocular oscillations in traumatic brain injury; and consider the potential relationship between the larger amplitude flutter upon convergence and post-traumatic ocular oscillations.
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http://dx.doi.org/10.1016/bs.pbr.2019.04.016DOI Listing
May 2020

Outcomes of natalizumab treatment within 3 years of relapsing-remitting multiple sclerosis diagnosis: a prespecified 2-year interim analysis of STRIVE.

BMC Neurol 2019 Jun 8;19(1):116. Epub 2019 Jun 8.

Biogen, 225 Binney St, Cambridge, MA, 02142, USA.

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 < 3 years prior to screening, an Expanded Disability Status Scale (EDSS) score ≤ 4.0, and anti-JCV antibody negative status. Magnetic resonance imaging was performed at baseline and yearly thereafter. Cumulative probabilities of 24-week-confirmed EDSS worsening and improvement were evaluated at 2 years. NEDA (no 24-week-confirmed EDSS worsening, no relapses, no gadolinium-enhancing lesions, and no new/newly enlarging T2-hyperintense lesions) was evaluated over 2 years. The Symbol Digit Modalities Test (SDMT) and Multiple Sclerosis Impact Score (MSIS-29) were assessed at baseline and 1 and 2 years. Statistical analysis used summary statistics and frequency distributions.

Results: The study population (N = 222) had early RRMS, with mean (standard deviation [SD]) time since diagnosis of 1.6 (0.77) years and mean (SD) baseline EDSS score of 2.0 (1.13). NEDA was achieved in 105 of 187 patients (56.1%) during year 1 and 120 of 163 (73.6%) during year 2. Over 2 years, 76 of 171 patients (44.4%) attained overall NEDA. Probabilities of 24-week-confirmed EDSS worsening and improvement were 14.1% and 28.4%, respectively. After 2 years, patients exhibited significant improvements from baseline in SDMT (n = 158; mean [SD]: 4.3 [11.8]; p < 0.001) and MSIS-29 physical (n = 153; mean [SD]: - 3.9 [14.7]; p = 0.001), psychological (n = 152; mean [SD]: - 2.0 [7.9]; p < 0.001), and quality-of-life (n = 153; mean [SD]: - 6.0 [21.3]; p < 0.001) scores.

Conclusions: These results support natalizumab's effectiveness over 2 years, during which nearly half of early RRMS patients achieved NEDA. During year 2, nearly 75% of patients exhibited NEDA. Over 2 years, patients continued to experience significant cognitive and quality-of-life benefits. These results are limited by the lack of a comparator group to determine the extent of a placebo effect.

Trial Registration: clinicaltrials.gov, NCT01485003 , registered 5 December 2011.
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http://dx.doi.org/10.1186/s12883-019-1337-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555913PMC
June 2019

MULES on the sidelines: A vision-based assessment tool for sports-related concussion.

J Neurol Sci 2019 Jul 28;402:52-56. Epub 2019 Apr 28.

Department of Neurology, New York University School of Medicine, New York, NY, USA; Department of Population Health, New York University School of Medicine, New York, NY, USA; Department of Ophthalmology, New York University School of Medicine, New York, NY, USA. Electronic address:

Objective: The Mobile Universal Lexicon Evaluation System (MULES) is a test of rapid picture naming under investigation. Measures of rapid automatic naming (RAN) have been used for over 50 years to capture aspects of vision and cognition. MULES was designed as a series of 54 grouped color photographs (fruits, random objects, animals) that integrates saccades, color perception and contextual object identification. We examined MULES performance in youth, collegiate and professional athletes at pre-season baseline and at the sidelines following concussion.

Methods: Our study teams administered the MULES to youth, collegiate and professional athletes during pre-season baseline testing. Sideline post-concussion time scores were compared to pre-season baseline scores among athletes with concussion to determine degrees and directions of change.

Results: Among 681 athletes (age 17 ± 4 years, range 6-37, 38% female), average test times at baseline were 41.2 ± 11.2 s. The group included 280 youth, 357 collegiate and 44 professional athletes; the most common sports were ice hockey (23%), soccer (17%) and football (11%). Age was a predictor of MULES test times, with longer times noted for younger participants (P < .001, linear regression). Consistent with other timed performance measures, significant learning effects were noted for the MULES during baseline testing with trial 1 test times (mean 49.2 ± 13.1 s) exceeding those for trial 2 (mean 41.3 ± 11.2 s, P < .0001, paired t-test). Among 17 athletes with concussion during the sports seasons captured to date (age 18 ± 3 years), all showed increases (worsening) of MULES time scores from pre-season baseline (median increase 11.2 s, range 0.6-164.2, P = .0003, Wilcoxon signed-rank test). The Symptom Severity Score from the SCAT5 Symptom Evaluation likewise worsened from pre-season baseline following injury among participants with concussion (P = .002).

Conclusions: Concussed athletes demonstrate worsening performance on the MULES test compared to their baseline time scores. This test samples a wide network of brain pathways and complements other vision-based measures for sideline concussion assessment. The MULES test demonstrates capacity to identify athletes with sports-related concussion.
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http://dx.doi.org/10.1016/j.jns.2019.04.036DOI Listing
July 2019

Alterations in the retinal vasculature occur in multiple sclerosis and exhibit novel correlations with disability and visual function measures.

Mult Scler 2020 06 16;26(7):815-828. Epub 2019 May 16.

Division of Neuroimmunology and Neurological Infections, Department of Neurology, The Johns Hopkins Hospital, Baltimore, MD, USA.

Background: The retinal vasculature may be altered in multiple sclerosis (MS), potentially acting as a biomarker of disease processes.

Objective: To compare retinal vascular plexus densities in people with MS (PwMS) and healthy controls (HCs), and examine correlations with visual function and global disability.

Methods: In this cross-sectional study, 111 PwMS (201 eyes) and 50 HCs (97 eyes) underwent optical coherence tomography angiography (OCTA). Macular superficial vascular plexus (SVP) and deep vascular plexus (DVP) densities were quantified, and poor quality images were excluded according to an artifact-rating protocol.

Results: Mean SVP density was 24.1% (SD = 5.5) in MS eyes (26.0% (SD = 4.7) in non-optic neuritis (ON) eyes vs. 21.7% (SD = 5.5) in ON eyes,  < 0.001), as compared to 29.2% (SD = 3.3) in HC eyes ( < 0.001 for all MS eyes and multiple sclerosis optic neuritis (MSON) eyes vs. HC eyes,  = 0.03 for MS non-ON eyes vs. HC eyes). DVP density did not differ between groups. In PwMS, lower SVP density was associated with higher levels of disability (expanded disability status scale (EDSS):  = 0.26,  = 0.004; multiple sclerosis functional composite (MSFC):  = 0.27,  = 0.03) and lower letter acuity scores (100% contrast:  = 0.29; 2.5% contrast:  = 0.40; 1.25% contrast:  = 0.31;  < 0.001 for all).

Conclusions: Retinal SVP density measured by OCTA is reduced across MS eyes, and correlates with visual function, EDSS, and MSFC scores.
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http://dx.doi.org/10.1177/1352458519845116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858526PMC
June 2020

Macular Ganglion Cell and Inner Plexiform Layer Thickness Is More Strongly Associated With Visual Function in Multiple Sclerosis Than Bruch Membrane Opening-Minimum Rim Width or Peripapillary Retinal Nerve Fiber Layer Thicknesses.

J Neuroophthalmol 2019 12;39(4):444-450

Department of Neurology (JN, AR, NG, AA, EO, PAC, and SS), Johns Hopkins University School of Medicine, Baltimore, Maryland; Departments of Neurology (LJB and SLG), Population Health (LJB and SLG), and Ophthalmology (LJB and SLG), New York University School of Medicine, New York, New York; Departments of Neurology (EMF and TF) and Ophthalmology (EMF and TF), Dell Medical School, University of Texas at Austin, Austin, Texas; and Department of Biostatistics (CC), Johns Hopkins University, Baltimore, Maryland.

Background: Optical coherence tomography (OCT) measurements of ganglion cell + inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) thicknesses are associated with visual function (VF) and disability in multiple sclerosis (MS). However, the value of measuring Bruch membrane opening-minimum rim width (BMO-MRW) thickness in MS remains unclear.

Methods: Sixty-eight patients with MS and 22 healthy controls (HCs) underwent spectral domain OCT, 100%-contrast visual acuity (VA), 2.5%- and 1.25%-contrast letter acuity (LA), and Expanded Disability Status Scale (EDSS) testing. Mixed-effects linear regression models, accounting for within-subject, intereye correlations, were used to assess relationships.

Results: The MS cohort exhibited significantly lower BMO-MRW (P = 0.01), pRNFL at 3.7-, 4.1-, and 4.7-mm diameters surrounding the optic disc (P < 0.001 for all), and GCIPL (P < 0.001) thicknesses than HCs. BMO-MRW thickness was associated with 100%-VA (P < 0.001, R = 0.08), 2.5%-LA (P < 0.001; R = 0.13), and 1.25%-LA (P = 0.002; R = 0.11). All measured pRNFL thicknesses were associated with high- and low-contrast VF (all: P < 0.001). GCIPL thickness was more strongly associated with 100%-VA (P < 0.001; R = 0.23), 2.5%-LA (P < 0.001; R = 0.27), and 1.25%-LA (P < 0.001; R = 0.21) than the other OCT measures assessed. All OCT measures were significantly, but weakly, associated with EDSS scores.

Conclusions: BMO-MRW and pRNFL thicknesses are reduced and associated with VF and disability in MS, but GCIPL thickness is a stronger marker of visual impairment. Our findings corroborate the utility of OCT in providing valuable information regarding the MS disease process.
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http://dx.doi.org/10.1097/WNO.0000000000000768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763365PMC
December 2019

Optimal intereye difference thresholds by optical coherence tomography in multiple sclerosis: An international study.

Ann Neurol 2019 05 10;85(5):618-629. Epub 2019 Apr 10.

Department of Neurology, New York University School of Medicine, New York, NY.

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.
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http://dx.doi.org/10.1002/ana.25462DOI Listing
May 2019

Retinal measurements predict 10-year disability in multiple sclerosis.

Ann Clin Transl Neurol 2019 02 19;6(2):222-232. Epub 2019 Jan 19.

Department of Neurology Johns Hopkins University Baltimore Maryland.

Objective: Optical coherence tomography (OCT)-derived measures of the retina correlate with disability and cortical gray matter atrophy in multiple sclerosis (MS); however, whether such measures predict long-term disability is unknown. We evaluated whether a single OCT and visual function assessment predict the disability status 10 years later.

Methods: Between 2006 and 2008, 172 people with MS underwent Stratus time domain-OCT imaging [160 with measurement of total macular volume (TMV)] and high and low-contrast letter acuity (LCLA) testing ( = 150; 87%). All participants had Expanded Disability Status Scale (EDSS) assessments at baseline and at 10-year follow-up. We applied generalized linear regression models to assess associations between baseline TMV, peripapillary retinal nerve fiber layer (pRNFL) thickness, and LCLA with 10-year EDSS scores (linear) and with clinically significant EDSS worsening (binary), adjusting for age, sex, optic neuritis history, and baseline disability status.

Results: In multivariable models, lower baseline TMV was associated with higher 10-year EDSS scores (mean increase in EDSS of 0.75 per 1 mm loss in TMV (mean difference = 0.75; 95% CI: 0.11-1.39;  = 0.02). In analyses using tertiles, individuals in the lowest tertile of baseline TMV had an average 0.86 higher EDSS scores at 10 years (mean difference = 0.86; 95% CI: 0.23-1.48) and had over 3.5-fold increased odds of clinically significant EDSS worsening relative to those in the highest tertile of baseline TMV (OR: 3.58; 95% CI: 1.30-9.82; = 0.008). pRNFL and LCLA predicted the 10-year EDSS scores only in univariate models.

Interpretation: Lower baseline TMV measured by OCT significantly predicts higher disability at 10 years, even after accounting for baseline disability status.
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http://dx.doi.org/10.1002/acn3.674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389740PMC
February 2019