Laura J. Balcer

Due to the recent focus on concussion in sports, a number of tests have been developed to diagnose and manage concussion. While each test measures different brain functions, no single test has been shown to quickly and reliably assess concussion in all cases. In addition, most of the current concussion tests have not been validated by scientific investigation. This review identifies the pros and cons of the most commonly used noninvasive tests for concussion in order to provide a more complete picture of the resources that are available for concussion testing. The potential utility of research tools such as the head impact telemetry system, advanced magnetic resonance imaging protocols, and biomarkers are discussed in the context of the currently employed tools.

Background: Benign multiple sclerosis (MS), traditionally defined as Expanded Disability Status Scale (EDSS) score ≤3 and ≥15-year disease duration, is thought to follow a milder clinical course. We determined the extent of visual pathway axonal loss by optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness in a benign MS cohort and examined the relation to vision and quality of life (QOL). Methods: In this longitudinal study of vision in MS at 3 academic centers, a subset of patients with EDSS, visual function, OCT, and QOL assessments was analyzed. Low- and high-contrast letter acuity was performed to assess visual function. RNFL thickness was determined using time-domain OCT. QOL scales included the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and Short Form-36 Health Survey. Results: Among 68 patients (135 eyes) studied longitudinally, 13 (26 eyes) had benign MS using criteria of EDSS score ≤3 and ≥15-year disease duration. Benign MS eyes had as much RNFL thinning (−3.6 μm, P = 0.0008 vs baseline, paired t test) as typical MS eyes (−3.3 μm, P < 0.0001). Both groups had significant low-contrast acuity loss. History of optic neuritis (ON) was more frequent in benign MS (69% vs 33% of eyes). History of ON distinguished benign vs typical MS (P = 0.002) and correlated with RNFL thickness at baseline (P = 0.002) and disease duration (P = 0.03) but not EDSS (P = 0.32, logistic regression). NEI-VFQ-25 scores were also worse for benign MS, accounting for age (75 ± 21 vs 88 ± 11, P = 0.005). Conclusion: Patients with benign MS have RNFL axonal loss that is as marked as that of typical MS and have reduced vision and QOL. While overall neurologic impairment is mild, visual dysfunction, not well captured by the EDSS, accounts for a substantial degree of disability in benign MS.

Objective: The current study investigates the effect of sleep deprivation on the speed and accuracy of eye movements as measured by the King-Devick (K-D) test, a Methods: In this cohort study, neurology residents and staff from the University of Pennsylvania Health System underwent baseline followed by postcall K-D testing (n = 25); those not taking call (n = 10) also completed baseline and follow-up K-D testing. Differences in the times and errors between baseline and follow-up K-D scores were compared between the 2 groups. Results: Residents taking call had less improvement from baseline K-D times when compared to participants not taking call (p < 0.0001, Wilcoxon rank sum test). For both groups, the change in K-D time from baseline was correlated to amount of sleep obtained (r_s = −0.50, p = 0.002) and subjective evaluation of level of alertness (r_s = 0.33, p = 0.05) but had no correlation to time since last caffeine consumption (r_s = −0.13, p = 0.52). For those residents on their actual call night, the duration of sleep obtained did not correlate with change in K-D scores from baseline (r_s = 0.13, p = 0.54). Conclusions: The K-D test is sensitive to the effects of sleep deprivation on cognitive functioning, including rapid eye movements, concentration, and language function. As with other measures of sleep deprivation, K-D performance demonstrated significant interindividual variability in vulnerability to sleep deprivation. Severe fatigue appears to reduce the degree of improvement typically observed in K-D testing.

Visual dysfunction is one of the most common clinical manifestations of multiple sclerosis (MS). Just over a decade ago, MS clincial trials did not include visual outcomes, but experts recognized the need for more sensitive measures of visual function. Low-contrast letter acuity emerged as the leading candidate to measure visual disability in MS, and subsequent studies found low-contrast acuity testing to correlate well with brain MRI lesion burden, visual-evoked potentials, quality of life (QOL), and retinal nerve fiber layer (RNFL) loss, as measured by optical coherence tomography (OCT). OCT in MS has allowed for assessment of structure-function correlations that make the anterior visual pathway and acute optic neuritis (ON) ideal models for testing novel agents for neuroprotection and repair. New therapies that reduce axonal loss by neuroprotective or myelin repair mechanisms can now be assessed noninvasively by OCT and coupled with visual function data. Based on OCT studies in MS, RNFL thickness is reduced significantly among patients (92 μm) vs controls (105 μm) and is particularly reduced in MS eyes with a history of ON (85 μm). Worsening of visual function by a clinically significant ≥7 letters or approximately 1.5 lines for low-contrast acuity is associated with approximately 4.5 μm reductions in RNFL thickness in MS eyes. Longitudinal studies of OCT have also shown RNFL axonal loss over time that occurs even in the absence of acute ON and that correlates with clinically meaningful worsening of vision and QOL, even in patients with benign MS. The latest OCT investigations involve high-resolution spectral-domain (SD) OCT with segmentation and measurement of specific retinal layers using computerized algorithms. These methods allow quantitation of ganglion cell (neuronal) layer loss and axonal degeneration in MS in vivo. In this review, we examine the data from these studies and ongoing trials that highlight the entity of ON as a model to investigate neuroprotection and neurorepair. In doing so, we also present representative group data from studies that have examined visual function, OCT measures, and QOL scales in patients with MS and ON and disease-free controls. These data, and those from recent meta-analyses, may be used to provide reference values for the development of clinical trial protocols.

Background: Neuronal loss in the retina has been demonstrated pathologically in eyes of patients with multiple sclerosis (MS). In vivo, MS eyes have reduced total macular volumes by optical coherence tomography (OCT). Using a high-resolution spectral-domain OCT, this pilot study used a manual method to measure ganglion cell layer (GCL) volumes and to determine the relation of these volumes to visual function in MS eyes. Methods: Sixteen eyes of 8 patients with MS and 8 eyes of 5 disease-free control participants were studied using fast macular OCT scans performed with Spectralis OCT (Heidelberg Engineering). Visual function tests of low-contrast letter acuity and high-contrast visual acuity were administered. Results: MS patient eyes had significantly lower GCL volumes than the control eyes (P < 0.001 vs controls, generalized estimating equation regression models accounting for age and within-patient intereye correlations). Within the MS group, eyes with a history of optic neuritis (ON, n = 4) had significantly lower GCL volumes than MS eyes with no ON history (P < 0.001). In contrast to measures of high-contrast visual acuity (P = 0.14), decreased GCL volumes were associated with worse performance on low-contrast letter acuity testing (P = 0.003). Conclusions: This pilot study has characterized thinning of the GCL in MS patient eyes, particularly in those with a history of acute ON, which corresponded to a reduced performance on low-contrast letter acuity testing. Studies utilizing computerized segmentation algorithms will continue to facilitate the detection of GCL loss on a larger scale and provide important information in vivo on the role and timing of neuronal vs axonal loss in MS eyes.