Faculty Bibliography

OBJECTIVE:Measures of rapid automatized naming (RAN) have been used for over 50 years to capture vision-based aspects of cognition. The Mobile Universal Lexicon Evaluation System (MULES) is a test of rapid picture naming under investigation for detection of concussion and other neurological disorders. MULES was designed as a series of 54 grouped color photographs (fruits, random objects, animals) that integrates saccades, color perception and contextual object identification. Recent changes to the MULES test have been made to improve ease of use on the athletic sidelines. Originally an 11 × 17-inch single-sided paper, the test has been reduced to a laminated 8.5 × 11-inch double-sided version. We identified performance changes associated with transition to the new, MULES, now sized for the sidelines, and examined MULES on the sideline for sports-related concussion. METHODS:We administered the new laminated MULES to a group of adult office volunteers as well as youth and collegiate athletes during pre-season baseline testing. Athletes with concussion underwent sideline testing after injury. Time scores for the new laminated MULES were compared to those for the larger version (big MULES). RESULTS:Among 501 athletes and office volunteers (age 16 ± 7 years, range 6-59, 29% female), average test times at baseline were 44.4 ± 14.4 s for the new laminated MULES (n = 196) and 46.5 ± 16.3 s for big MULES (n = 248). Both versions were completed by 57 participants, with excellent agreement (p < 0.001, linear regression, accounting for age). Age was a predictor of test times for both MULES versions, with longer times noted for younger participants (p < 0.001). Among 6 athletes with concussion thus far during the fall sports season (median age 15 years, range 11-21) all showed worsening of MULES scores from pre-season baseline (median 4.0 s, range 2.1-16.4). CONCLUSION/CONCLUSIONS:The MULES test has been converted to an 11 × 8.5-inch laminated version, with excellent agreement between versions across age groups. Feasibly administered at pre-season and in an office setting, the MULES test shows preliminary evidence of capacity to identify athletes with sports-related concussion.

BACKGROUND:The optic nerve is a frequent site for involvement in multiple sclerosis (MS). Optical coherence tomography (OCT) detects thinning of the retinal nerve fiber layer (RNFL) in eyes of patients with MS and in those meeting criteria for clinically or radiologically isolated demyelinating syndromes. Current international diagnostic criteria for MS do not include the optic nerve as an imaging lesion site despite the high prevalence of acute optic neuritis (ON), or occult optic neuropathy, among early MS and clinically isolated syndrome patients; as well as most MS patients over the course of the disease. We sought to determine optimal thresholds for intereye difference in peripapillary RNFL thickness that are most predictive of a unilateral optic nerve lesion. METHODS:We analyzed spectral domain OCT data of 31 healthy volunteers and 124 patients with MS at a single center as part of an ongoing collaborative investigation of visual outcomes. Intereye differences in peripapillary (360°) RNFL thickness were calculated as the absolute value of the difference. First, we determined the 95th percentile value of intereye difference for the healthy volunteers. This value was applied to the convenience sample group of MS patients as a validation cohort determining how well this threshold could distinguish patients with vs without a history of unilateral ON. The relation of intereye differences in peripapillary RNFL thickness to binocular low-contrast letter acuity scores was also examined. RESULTS:Among healthy volunteer participants (n = 31), the 95th percentile value for intereye difference (upper boundary of expected for normal controls) was 6.0 μm. This value was applied to the convenience sample group of MS patients (n = 124, validation cohort). Positive predictive value, negative predictive value, sensitivity, and specificity for identifying MS patients with a history of unilateral ON were calculated for the 6-μm threshold value in a 2 × 2 table analysis with the application of χ tests (P < 0.0001). The 6-μm threshold was predictive of worse binocular low-contrast acuity scores at 2.5% (P = 0.03) and 1.25% (P = 0.002 by linear regression analyses). A receiver operating characteristic curve analysis demonstrated an optimal intereye difference threshold of 5 μm for identifying unilateral ON in the MS cohort. CONCLUSIONS:An intereye difference of 5-6 μm in RNFL thickness is a robust structural threshold for identifying the presence of a unilateral optic nerve lesion in MS.

The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.

OBJECTIVE:To evaluate the performance of the EyeTribe compared to the EyeLink for eye movement recordings during a rapid number naming test in healthy control participants. BACKGROUND:With the increasing accessibility of portable, economical, video-based eye trackers such as the EyeTribe, there is growing interest in these devices for eye movement recordings, particularly in the domain of sports-related concussion. However, prior to implementation there is a primary need to establish the validity of these devices. One current limitation of portable eye trackers is their sampling rate (30-60 samples per second, or Hz), which is typically well below the benchmarks achieved by their research-grade counterparts (e.g., the EyeLink, which samples at 500-2000 Hz). METHODS:We compared video-oculographic measurements made using the EyeTribe with those of the EyeLink during a digitized rapid number naming task (the King-Devick test) in a convenience sample of 30 controls. RESULTS:EyeTribe had loss of signal during recording, and failed to reproduce the typical shape of saccadic main sequence relationships. In addition, EyeTribe data yielded significantly fewer detectable saccades and displayed greater variance of inter-saccadic intervals than the EyeLink system. CONCLUSION/CONCLUSIONS:Caution is advised prior to implementation of low-resolution eye trackers for objective saccade assessment and sideline concussion screening.

BACKGROUND: The King-Devick (K-D) test of rapid number naming is a reliable visual performance measure that is a sensitive sideline indicator of concussion when time scores worsen (lengthen) from preseason baseline. Within cohorts of youth athletes <18 years old, baseline K-D times become faster with increasing age. We determined the relation of rapid number-naming time scores on the K-D test to electronic measurements of saccade performance during preseason baseline assessments in a collegiate ice hockey team cohort. Within this group of young adult athletes, we also sought to examine the potential role for player age in determining baseline scores. METHODS: Athletes from a collegiate ice hockey team received preseason baseline testing as part of an ongoing study of rapid rink-side performance measures for concussion. These included the K-D test (spiral-bound cards and tablet computer versions). Participants also performed a laboratory-based version of the K-D test with simultaneous infrared-based video-oculographic recordings using an EyeLink 1000+. This allowed measurement of the temporal and spatial characteristics of eye movements, including saccadic velocity, duration, and intersaccadic interval (ISI). RESULTS: Among 13 male athletes, aged 18-23 years (mean 20.5 +/- 1.6 years), prolongation of the ISI (a combined measure of saccade latency and fixation duration) was the measure most associated with slower baseline time scores for the EyeLink-paired K-D (mean 38.2 +/- 6.2 seconds, r = 0.88 [95% CI 0.63-0.96], P = 0.0001), the K-D spiral-bound cards (36.6 +/- 5.9 seconds, r = 0.60 [95% CI 0.08-0.87], P = 0.03), and K-D computerized tablet version (39.1 +/- 5.4 seconds, r = 0.79 [95% CI 0.42-0.93], P = 0.001). In this cohort, older age was a predictor of longer (worse) K-D baseline time performance (age vs EyeLink-paired K-D: r = 0.70 [95% CI 0.24-0.90], P = 0.008; age vs K-D spiral-bound cards: r = 0.57 [95% CI 0.03-0.85], P = 0.04; age vs K-D tablet version: r = 0.59 [95% CI 0.06-0.86], P = 0.03) as well as prolonged ISI (r = 0.62 [95% CI 0.11-0.87], P = 0.02). Slower baseline K-D times were not associated with greater numbers of reported prior concussions. CONCLUSIONS: Rapid number-naming performance using the K-D at preseason baseline in this small cohort of collegiate ice hockey players is best correlated with ISI among eye movement-recording measures. Baseline K-D scores notably worsened with increasing age, but not with numbers of prior concussions in this small cohort. While these findings require further investigation by larger studies of contact and noncontact sports athletes, they suggest that duration of contact sports exposure may influence preseason test performance.

Background/UNASSIGNED:Sports concussion has an annual incidence of approximately 3.8 million. Over half go unreported and a substantial number may be asymptomatic. A rapid, cost-effective, and reliable tool that facilitates diagnosis of concussion is needed. The King-Devick (K-D) test is a vision-based tool of rapid number naming for assessment of concussion. In this study, we evaluated the utility of the K-D test in real time for identification of symptomatic concussion in youth athletes and to determine if similar impairment (subclinical concussion) exists in youth athletes without an obvious head injury or symptoms. Methods/UNASSIGNED:Youth hockey players underwent K-D testing preseason, postseason, and immediately after suspected concussion. Additional testing was performed in a subgroup of nonconcussed athletes immediately before and after a game to determine effects of fatigue on K-D scores. Results/UNASSIGNED:< 0.05) and 51 nonconcussed players assessed before and after a game revealed no significant time change as a result of fatigue. Conclusions/UNASSIGNED:Rapid number naming using the K-D test accurately identifies real-time, symptomatic concussion in youth athletes. Scores in concussed players may remain abnormal over time. Athletes should undergo preseason and postseason K-D testing, with additional evaluation real time to inform the assessment of suspected concussion. Classification of Evidence/UNASSIGNED:This study provides Class III evidence that the K-D test accurately identifies real-time concussions in youth athletes.

Introduction: The optic nerve and visual pathway are frequent sites for involvement in multiple sclerosis (MS). Optical coherence tomography (OCT) detects retinal nerve fiber layer (RNFL) thinning in eyes of patients with MS or in the case of clinically-or radiologically-isolated syndromes. Current diagnostic criteria do not include the optic nerve as an imaging lesion site despite a high prevalence of acute optic neuritis (ON) among early MS and clinically isolated syndrome (CIS) patients. We sought to determine optimal thresholds for inter-eye difference in RNFL thickness that are most predictive of an optic nerve lesion. Methods: Spectral-domain (SD-)OCT data from an ongoing collaborative study of visual outcomes in MS were analyzed for a single site. Median values for inter-eye difference in RNFL thickness were also calculated from the RENEW trial cohort at the 6-month endpoint. RENEW was a randomized, placebo-controlled trial of opicinumab in subjects with a first episode of acute unilateral ON, and represents the most well-characterized cohort of CIS patients with ON incorporating modern tests of visual structure and function. RENEW utilized SD-OCT with a centralized reading center. Results: Among healthy volunteer control participants in the collaborative investigation (convenience sample, n=31), the 95th percentile value for inter-eye difference (upper boundary of expected for normals) was 6.0 microns. This value, as well as median intereye differences from the RENEW cohort (8.5 microns for placebo, n=41; 13.0 microns for opicinumab, n=41), were applied to convenience sample group of MS patients (n=136) as a validation cohort. Positive predictive value, sensitivity and specificity for identifying MS patients with a history of unilateral ON were greatest for the 6-micron value compared to the RENEW medians in a 2x2 table analysis (p< 0.0001, chi-square). The 6-micron threshold was also predictive of worse binocular low-contrast acuity at 2.5% (p=0.02) and 1.25% (p=0.002, linear regression). ROC curve analysis demonstrated an optimal inter-eye difference threshold of 5 microns for identifying unilateral ON in the MS cohort. Conclusion: Inter-eye differences of 5-6 microns in RNFL thickness are thus far optimal for predicting a unilateral optic nerve lesion in MS. Larger international collaborative investigations involving 20 or more MS validation cohort sites are underway to maximize precision and generalizability for these OCT-based thresholds