Faculty Bibliography

Although the intestinal microbiome has been increasingly implicated in autoimmune diseases, much is unknown about its roles in Multiple Sclerosis (MS). Our aim was to compare the microbiome between treatment-naïve MS subjects early in their disease course and controls, and between Caucasian (CA), Hispanic (HA), and African American (AA) MS subjects. From fecal samples, we performed 16S rRNA V4 sequencing and analysis from 45 MS subjects (15 CA, 16 HA, 14 AA) and 44 matched healthy controls, and whole metagenomic shotgun sequencing from 24 MS subjects (all newly diagnosed, treatment-naïve, and steroid-free) and 24 controls. In all three ethnic groups, there was an increased relative abundance of the same single genus, Clostridium, compared to ethnicity-matched controls. Analysis of microbiota networks showed significant changes in the network characteristics between combined MS cohorts and controls, suggesting global differences not restricted to individual taxa. Metagenomic analysis revealed significant enrichment of individual species within Clostridia as well as particular functional pathways in the MS subjects. The increased relative abundance of Clostridia in all three early MS cohorts compared to controls provides candidate taxa for further study as biomarkers or as etiologic agents in MS.

Visual symptoms, such as photophobia and blurred vision, are common in patients with concussion. Such symptoms may be accompanied by abnormalities of specific eye movements, such as saccades and convergence, or accommodation deficits. The high frequency of visual involvement in concussion is not surprising, since more than half of the brain's pathways are dedicated to vision and eye movement control. These areas include many that are most vulnerable to head trauma, including the frontal and temporal lobes. Vision and eye movement testing is important at the bedside and on the sidelines of athletic events, where brief performance measures that require eye movements, such as rapid number naming, are reliable and sensitive measures for concussion detection. Tests of vision and eye movements are also being explored clinically to identify and monitor patients with symptoms of both sport- and nonsport-related concussion. Evaluation of vision and eye movements can assist in making important decisions after concussion, including the prognosis for symptom recovery, and to direct further visual rehabilitation as necessary.

Whether disease course in Hispanic Americans (HA) with multiple sclerosis (MS) is different from Caucasian Americans (CA) or African Americans (AA) is unknown. We compared MS severity in the three main ethnic populations in our tertiary MS clinics using disease duration-adjusted rank score of disability: Patient-Derived Multiple Sclerosis Severity Score (P-MSSS). The age- and gender-adjusted P-MSSS was significantly higher in HA (3.9 +/- 2.6) and AA (4.5 +/- 3.0) compared to CA (3.4 +/- 2.6; p < 0.0001 for both). Adjusting for insurance did not change these results. These findings suggest that HA, as AA, have more rapid disability accumulation than CA.

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.

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.

BACKGROUND: Concussion, particularly in relation to sports and combat activities, is increasingly recognized as a potential cause of both short- and long-term neurologic sequelae. This review will focus on the neuro-ophthalmologic findings associated with concussion, the current tests for concussion, and the potential for visual performance measures to improve our detection and assessment of concussions. EVIDENCE ACQUISITION: A PubMed search using the specific key words "concussion," "mild traumatic brain injury," "neuro-ophthalmological findings," and "diagnostic and management tests" was performed. An emphasis was placed on articles published during the past 5 years, but additional articles referenced within recent publications were obtained. RESULTS: Concussion is frequently associated with abnormalities of saccades, pursuit eye movements, convergence, accommodation, and the vestibular-ocular reflex. Current sideline testing for athletes includes the Sports Concussion Assessment Tool, Third Edition (SCAT3) incorporates cognitive and balance testing. The King-Devick (K-D) test is a rapid visual performance measures that can be used on sidelines by nonmedical personnel, including parents of youth athletes. The K-D test complements components of the SCAT3 and improves the detection of concussions. Other vision-based tools for diagnosing and for managing concussion include eye movement tracking devices, pupillary assessment, computerized testing, imaging modalities, and eletrophysiologic testing. Many of the imaging modalities and electrophysiological studies have been combined with vision-based tests. CONCLUSIONS: Concusssion is associated with many neuro-ophthalmologic signs and symptoms. Visual performance measures enhance the detection and management of concussion, and future studies are under way to further incorporate vision-based testing into sideline diagnosis and long-term clinical assessments.