Faculty Bibliography

OBJECTIVE: Concussion is a major public health problem and considerable efforts are focused on sideline-based diagnostic testing to guide return-to-play decision-making and clinical care. The King-Devick (K-D) test, a sensitive sideline performance measure for concussion detection, reveals slowed reading times in acutely concussed subjects, as compared to healthy controls; however, the normal behavior of eye movements during the task and deficits underlying the slowing have not been defined. METHODS: Twelve healthy control subjects underwent quantitative eye tracking during digitized K-D testing. RESULTS: The total K-D reading time was 51.24 (+/-9.7) seconds. A total of 145 saccades (+/-15) per subject were generated, with average peak velocity 299.5 degrees /s and average amplitude 8.2 degrees . The average inter-saccadic interval was 248.4ms. Task-specific horizontal and oblique saccades per subject numbered, respectively, 102 (+/-10) and 17 (+/-4). Subjects with the fewest saccades tended to blink more, resulting in a larger amount of missing data; whereas, subjects with the most saccades tended to make extra saccades during line transitions. CONCLUSIONS: Establishment of normal and objective ocular motor behavior during the K-D test is a critical first step towards defining the range of deficits underlying abnormal testing in concussion. Further, it sets the groundwork for exploration of K-D correlations with cognitive dysfunction and saccadic paradigms that may reflect specific neuroanatomic deficits in the concussed brain.

Background/UNASSIGNED:Vision encompasses a large component of the brain's pathways, yet is not represented in current sideline testing. Objectives/UNASSIGNED:We performed a meta-analysis of published data for a vision-based test of rapid number naming (King-Devick [K-D] test). Studies & methods/UNASSIGNED:Pooled and meta-analysis of 15 studies estimated preseason baseline K-D scores and sensitivity/specificity for identifying concussed versus nonconcussed control athletes. Result/UNASSIGNED:= 0.0%; p=0.85 - indicating very little heterogeneity). Sensitivity was 86% (96/112 concussed athletes had K-D worsening; 95% CI: 78%, 92%); specificity was 90% (181/202 controls had no worsening; 95% CI: 85%, 93%). Conclusion/UNASSIGNED:Rapid number naming adds to sideline assessment and contributes a critical dimension of vision to sports-related concussion testing.

Mild head injury such as concussions and subconcussive repetitive impact may lead to subtle changes in brain function and it is imperative to find sensitive and reliable tests to detect such changes. Tests involving the visual system, in particular eye movements, can incorporate higher cortical functioning and involve diffuse pathways in the brain, including many areas susceptible to head impact. With concussions, the clinical neuro-ophthalmic exam is important for detecting abnormalities in vergence, saccades, pursuit, and visual fixation. On the sidelines, the King-Devick test has been used as a visual performance measure that incorporates eye movements and increases the sensitivity in detecting possible concussions in conjunction with standard sideline tests of cognition, symptom checklists, and balance. Much promise lies in the eye movement laboratory to quantitate changes in saccades and pursuit with concussions using video-oculography. A combination of eye movement tasks coupled with neuroimaging techniques and other objective biomarkers may lead to a better understanding of the anatomical and physiological consequences of concussion and to better understand the natural history of this condition.

BACKGROUND: Ipilimumab, a humanized CLTA-4 antibody is a standard therapy in the treatment of advanced melanoma. While ipilimumab provides an overall survival benefit to patients, it can be associated with immune related adverse events (IrAEs). CASE PRESENTATION: Here we describe a patient treated with ipilimumab who experienced known IrAEs, including hypophysitis, as well as a profound vision loss due to optic neuritis. There are rare reports of optic neuritis occurring as an adverse event associated with ipilimumab treatment. Furthermore, the patient experienced multiple complications from high dose steroids used to manage his IrAEs. CONCLUSIONS: This case highlights the need for recognition of atypical immune mediated processes associated with newer checkpoint inhibitor therapies including ipilimumab.

Optical coherence tomography (OCT) is a relatively new technology that is now routinely and very widely used by ophthalmologists for structural documentation of the optic nerve and retina. In neuro-ophthalmology and neurology, the value of OCT is ever expanding; its role in an increasing number of conditions is being reported in parallel with the advances of the technology. Currently, as a clinical tool, OCT is particularly useful for the structural measurement of peripapillary retinal nerve fiber layer thickness, optic nerve head volumetric analysis, and macular anatomy. Optic neuropathies of varied etiology (particularly from multiple sclerosis) may be the most common clinical indications for neurologists to obtain OCT imaging. Documentation and follow-up of disc edema of varied etiology (papilledema and idiopathic intracranial hypertension), discriminating true disc swelling from pseudopapilledema, and differentiating optic neuropathy from maculopathy are some other examples from clinical practice.

Concussion may lead to subtle changes in brain function, and tests involving the visual system probe higher cortical functioning and increase our sensitivity in detecting these changes. Concussions are acutely and sometimes more persistently associated with abnormalities in balance, cognition, and vision. The visual system involves roughly half of the brain's circuits, including many regions susceptible to head impacts. After a concussion, the neuro-ophthalmologic exam commonly detects abnormalities in convergence, accommodation, the vestibulo-ocular reflex, ocular muscle balance, saccades, and pursuit. The King-Devick (K-D) test is a visual performance measure that may increase the sensitivity of detecting concussions on the sideline when used in combination with tests of cognition and balance that are part of the Sports Concussion Assessment Tool (3rd ed.; SCAT3). Portable eye movement trackers and pupillometry may in the future improve our neuro-ophthalmic assessment after concussions. Combining visual tasks with neuroimaging and neurophysiology has allowed subtle changes to be detected, may refine our ability to make appropriate return-to-play decisions, and could potentially determine susceptibility to long-term sequelae of concussion.

A comprehensive analysis of the effect of lesion in-painting on the estimation of cortical thickness using magnetic resonance imaging was performed on a large cohort of 918 relapsing-remitting multiple sclerosis patients who participated in a phase III multicenter clinical trial. An automatic lesion in-painting algorithm was developed and implemented. Cortical thickness was measured using the FreeSurfer pipeline with and without in-painting. The effect of in-painting was evaluated using FreeSurfer's paired analysis pipeline. Multivariate regression analysis was also performed with field strength and lesion load as additional factors. Overall, the estimated cortical thickness was different with in-painting than without. The effect of in-painting was observed to be region dependent, more significant in the left hemisphere compared to the right, was more prominent at 1.5 T relative to 3 T, and was greater at higher lesion volumes. Our results show that even for data acquired at 1.5 T in patients with high lesion load, the mean cortical thickness difference with and without in-painting is ∼2%. Based on these results, it appears that in-painting has only a small effect on the estimated regional and global cortical thickness. Hum Brain Mapp 36:3749-3760, 2015. © 2015 Wiley Periodicals, Inc.

BACKGROUND:: Sports-related concussion commonly affects the visual pathways. Current sideline protocols test cognition and balance but do not include assessments of visual performance. We investigated how adding a vision-based test of rapid number naming could increase our ability to identify concussed athletes on the sideline at youth and collegiate levels. METHODS:: Participants in this prospective study included members of a youth ice hockey and lacrosse league and collegiate athletes from New York University and Long Island University. Athletes underwent preseason baseline assessments using: 1) the King-Devick (K-D) test, a <2-minute visual performance measure of rapid number naming, 2) the Standardized Assessment of Concussion (SAC), a test of cognition, and 3) a timed tandem gait test of balance. The SAC and timed tandem gait are components of the currently used Sport Concussion Assessment Tool, 3rd Edition (SCAT3 and Child-SCAT3). In the event of a concussion during the athletic season, injured athletes were retested on the sideline/rink-side. Nonconcussed athletes were also assessed as control participants under the same testing conditions. RESULTS:: Among 243 youth (mean age 11 +/- 3 years, range 5-17) and 89 collegiate athletes (age 20 +/- 1 years, range 18-23), baseline time scores for the K-D test were lower (better) with increasing participant age (P < 0.001, linear regression models). Among 12 athletes who sustained concussions during their athletic season, K-D scores worsened from baseline by an average of 5.2 seconds; improvement by 6.4 seconds was noted for the nonconcussed controls (n = 14). The vision-based K-D test showed the greatest capacity to distinguish concussed vs control athletes based on changes from preseason baseline to postinjury (receiver operating characteristic [ROC] curve areas from logistic regression models, accounting for age = 0.92 for K-D, 0.87 for timed tandem gait, and 0.68 for SAC; P = 0.0004 for comparison of ROC curve areas). CONCLUSIONS:: Adding a vision-based performance measure to cognitive and balance testing enhances the detection capabilities of current sideline concussion assessment. This observation in patients with mild traumatic brain injury reflects the common involvement and widespread distribution of brain pathways dedicated to vision.