Faculty Bibliography

PURPOSE/OBJECTIVE:To determine relationships between visual function and GCIP thickness, and neuropsychological measures in MS. METHODS:Ninety-five relapsing-remitting (RRMS) and thirty-six progressive MS patients underwent 100%-contrast visual acuity (VA), 2.5%- and 1.25%-contrast letter acuity (LA) testing, Cirrus-HD OCT, and neuropsychological assessments. Mixed effects regression models were used to assess relationships. RESULTS:Across the cohort, 1.25%-contrast LA was associated with Symbol Digit Modalities Test (SDMT; β = 2.17, p = 0.005), and Brief Visuospatial Memory Test Revised (BVMT-R) Total Recall (TR) and Delayed Recall (DR) scores (β = 0.31, p < 0.001; β = 0.15, p = 0.039, respectively). 2.5%-contrast LA was associated with BVMT-R TR scores (β = 0.27, p = 0.006). In the RRMS cohort, 1.25%-contrast LA was generally more significantly associated with cognitive measures; SDMT (β = 2.97, p = 0.001), BVMT-R TR (β = 0.32, p < 0.001) and DR (β = 0.22, p = 0.012). CONCLUSION/CONCLUSIONS:This study suggests that visual pathway measures, particularly visual function measures, reflect aspects of cognitive function in MS, further supporting their roles as complementary outcomes in MS neuroprotection trials.

: BACKGROUND:: The visual pathways are increasingly recognized as an ideal model to study neurodegeneration in multiple sclerosis (MS). Low-contrast letter acuity (LCLA) and optical coherence tomography (OCT) are validated measures of function and structure in MS. In fact, LCLA was the topic of a recent review by the Multiple Sclerosis Outcome Assessments Consortium (MSOAC) to qualify this visual measure as a primary or secondary clinical trial endpoint with the Food and Drug Administration (FDA) and other regulatory agencies. This review focuses on the use of LCLA and OCT measures as outcomes in clinical trials to date of MS disease-modifying therapies.

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 Pulfrich phenomenon (PF) is the illusory perception that an object moving linearly along a 2-D plane appears to instead follow an elliptical 3-D trajectory, a consequence of inter-eye asymmetry in the timing of visual object identification in the visual cortex; with optic neuritis as a common etiology. OBJECTIVE:We have designed an objective method to identify the presence and magnitude of the PF, in conjunction with a cooresponding strategy by which to abolish the effect; with monocular application of neutral density filters to the less affected fellow eye, in patients with MS and a history of optic neuropathy (e.g. related to acute optic neuritis or subclinical optic neuropathy). METHODS:Twenty-three MS patients with a history of acute unilateral or bilateral optic neuritis, and ten healthy control subjects (HC) were recruited to participate in a pilot study to assess our strategy. Subjects were asked to indicate whether a linearly moving pendulum ball followed a linear 2-D path versus an illusory 3-D elliptical object-motion trajectory, by reporting the ball's approximation to one of nine horizontally-oriented colored wires that were positioned parallel to one another and horizontal to the linear pendulum path. Perceived motion of the bob that moved along wires behind or in front (along the 'Z' plane) of the middle reference wire indicated an illusory elliptical trajectory of ball motion consistent with the PF. RESULTS:When the neutral density filter titration was applied to the fellow eye the severity of the PF decreased, eventually being fully abolished in all but one patient. The magnitude of neutral density filtering required correlated to the severity of the patient's initial PF magnitude (p < 0.001). CONCLUSIONS:We ascertained the magnitude of the visual illusion associated with the PF, and the corresponding magnitude of neutral density filtering necessary to abolish it.