Faculty Bibliography

IMPORTANCE Retrospective studies have demonstrated disparate outcomes following acute optic neuritis in individuals of African descent compared with individuals of white race/ethnicity. However, published analyses of the prospectively collected Optic Neuritis Treatment Trial (ONTT) data identified no association between worse visual outcomes and black race/ethnicity. OBJECTIVES To investigate the associations of age, sex, and race/ethnicity with visual outcomes following acute optic neuritis through application of longitudinal data analysis techniques to the ONTT data set. DESIGN Secondary analysis of the ONTT (a prospective randomized controlled trial) data set. Our models included effects of treatment (placebo, oral prednisone, or intravenous methylprednisolone), time, and treatment x time interaction, as well as demographic covariates of age, sex, and race/ethnicity. SETTING AND PARTICIPANTS The ONTT data were collected at multiple centers in the United States. Patients of black (n = 58) and white (n = 388) race/ethnicity with acute optic neuritis who enrolled in the ONTT within 8 days of symptom onset were included in analyses. MAIN OUTCOMES AND MEASURES The contrast sensitivity and visual acuity (logMAR) in the affected eye were modeled using 2-stage mixed-effects regression techniques. All available follow-up data from baseline to 15 to 18 years were included. RESULTS The data identified no relationship of age, sex, or treatment with contrast sensitivity or visual acuity outcomes. Race/ethnicity was significantly related to contrast sensitivity (P < .001) and visual acuity (P < .001) during a 15-year period following acute optic neuritis, with black race/ethnicity being associated with worse scores for both. CONCLUSIONS AND RELEVANCE Race/ethnicity seems to be associated with contrast sensitivity and visual acuity outcomes in affected eyes following acute optic neuritis. To our knowledge, this is the largest cohort of black race/ethnicity with acute optic neuritis to be studied and represents the first evidence from a prospectively collected data set to support a hypothesis of race/ethnicity-dependent visual outcomes of acute optic neuritis.

BACKGROUND: The King-Devick (KD) test measures the speed of rapid number naming, and is postulated to require fast eye movements, attention, language, and possibly other aspects of cognitive functions. While used in multiple sports concussion studies, it has not been applied to the field of movement disorders. METHODS: Forty-five Parkinson's disease (PD), 23 essential tremor (ET), and 65 control subjects were studied. Subjects performed two trials of reading out loud single-digit numbers separated by varying spacing on three test cards that were of different formats. The sum time of the faster trial was designated the KD score and compared across the three groups. RESULTS: PD patients had higher (worse) KD scores, with longer reading times compared to ET and control subjects (66 s vs. 49 s vs. 52 s, p < 0.001, adjusting for age and gender). No significant difference was found between ET and control (Delta = -3 s, 95% CI: -10 to 4). CONCLUSIONS: This is the first study of the King-Devick Test in Parkinson's disease. PD patients were found to have a slower rapid number naming speed compared to controls. This test may be a simple and rapid bedside tool for quantifying correlates of visual and cognitive function in Parkinson's disease.

BACKGROUND: Sports-related concussion has received increasing awareness due to short- and long-term neurologic sequelae seen among athletes. The King-Devick (K-D) test captures impairment of eye movements and other correlates of suboptimal brain function. We investigated the K-D test as a screening for concussion when administered by layperson sports parents in a cohort of amateur boxers. METHODS: The K-D test was administered pre-fight and post-fight by laypersons masked to the head trauma status of each athlete. Matches were watched over by a ringside physician and boxing trainer. Athletes with suspected head trauma received testing with the Military Acute Concussion Evaluation (MACE) by the ringside physician to determine concussion status. Athletes sustaining concussion were compared to the athletes screened using the K-D test. RESULTS: Post-fight K-D scores were lower (better) than the best baseline score (41 vs. 39.3 s, P=0.34, Wilcoxon signed-rank test), in the absence of concussion. One boxer sustained a concussion as determined by the ringside physician. This boxer was accurately identified by the layperson K-D testers due to a worsening in K-D test compared to baseline (3.2 seconds) and an increased number of errors. High levels of test-retest reliability were observed (intraclass correlation coefficient 0.90 [95% CI 0.84-0.97]). Additionally, 6 boxers who participated in multiple bouts showed no worsening of their K-D times further supporting that scores are not affected by the fatigue associated with sparring. CONCLUSION: The K-D test is a rapid sideline screening tool for concussion that can be effectively administered by non-medically trained laypersons.

BACKGROUND:: Patients with multiple sclerosis (MS) demonstrate thinning of peripapillary retinal nerve fiber layer (RNFL) and decreased macular volume as measured by optical coherence tomography (OCT). To our knowledge, there are no previous reports from a large MS OCT database with strict quality control measures that quantitate RNFL and macula in patients with relapsing-remitting multiple sclerosis. METHODS:: The University of California Davis OCT Reading Center gathered OCT data at baseline as part of the North American phase 3 trial of fingolimod (Gilenya). Average RNFL thickness (RNFLT) and macular volume (TMV) were measured using time domain OCT (TD-OCT). RNFL quadrants, clock hours, and macular subfields were included. With strict quality control and accounting for signal strength differences, scans were categorized as "reduced" or "not reduced" for each field, based on being less than 5th percentile for age-matched controls derived from the normative database in the scanner software. Patients were deemed "abnormal" if at least 1 eye had reduced values for a given parameter. Patients with abnormalities in corresponding RNFL and macular subfields were compared by cross-tabulation. RESULTS:: The TD-OCT data were prospectively collected from 939 of the 1,083 trial patients, 712 of whom met all final quality and data inclusion criteria. Of the final cohort, 242 (34.0%) demonstrated reduced (less than 5th percentile) average RNFLT in at least 1 eye. One hundred seventy-eight (25.0%) patients had reduced TMV. One hundred twenty-eight (18.0%) demonstrated both reduced TMV and RNFLT in the same eye, whereas 42 (5.8%) had reduced TMV and RNFLT in both eyes. Of the 242 patients with reduced average RNFL thickness, 128 (52.9%) also had reduced TMV. Fifty patients had reduced TMV in the absence of reduced RNFLT in at least 1 eye, a cohort prevalence of 7.0%. Quadrant and subfield analysis showed a predominance of temporal and inferior RNFL thinning, with inferior macular thinning corresponding best to RNFL thinning. CONCLUSION:: RNFL and macular thinning/volume loss is common at baseline in relapsing-remitting multiple sclerosis, as measured by TD-OCT. When the RNFL is thin, the macular volume is reduced in more than half of the patients. There is a population of reduced TMV without any reduction in RNFLT. Documenting the prevalence and distribution of these structural abnormalities supports recent reports and suggests new retinal areas to probe for functional vision changes in MS.

PURPOSE: To estimate the proportion of patients presenting with isolated third, fourth, or sixth cranial nerve palsy of presumed microvascular origin versus other causes. DESIGN: Prospective, multicenter, observational case series. PARTICIPANTS: A total of 109 patients aged 50 years or older with acute isolated ocular motor nerve palsy. TESTING: Magnetic resonance imaging (MRI) of the brain. MAIN OUTCOME MEASURES: Causes of acute isolated ocular motor nerve palsy (presumed microvascular or other) as determined with early MRI and clinical assessment. RESULTS: Among 109 patients enrolled in the study, 22 had cranial nerve III palsy, 25 had cranial nerve IV palsy, and 62 had cranial nerve VI palsy. A cause other than presumed microvascular ischemia was identified in 18 patients (16.5%; 95% confidence interval, 10.7-24.6). The presence of 1 or more vasculopathic risk factors (diabetes, hypertension, hypercholesterolemia, coronary artery disease, myocardial infarction, stroke, and smoking) was significantly associated with a presumed microvascular cause (P = 0.003, Fisher exact test). Vasculopathic risk factors were also present in 61% of patients (11/18) with other causes. In the group of patients who had vasculopathic risk factors only, with no other significant medical condition, 10% of patients (8/80) were found to have other causes, including midbrain infarction, neoplasms, inflammation, pituitary apoplexy, and giant cell arteritis (GCA). By excluding patients with third cranial nerve palsies and those with GCA, the incidence of other causes for isolated fourth and sixth cranial nerve palsies was 4.7% (3/64). CONCLUSIONS: In our series of patients with acute isolated ocular motor nerve palsies, a substantial proportion of patients had other causes, including neoplasm, GCA, and brain stem infarction. Brain MRI and laboratory workup have a role in the initial evaluation of older patients with isolated acute ocular motor nerve palsies regardless of whether vascular risk factors are present. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The diagnosis of pseudotumor cerebri, or idiopathic intracranial hypertension (IIH), is most confidently established in the typical patient with evidence of papilledema, imaging that does not suggest a structural lesion, and a CSF examination that shows both normal composition and elevated intracranial pressure (ICP). Prompted by an increasing number of reports over the past decade, Friedman et al.1 propose a revised set of diagnostic criteria for IIH, taking into account the most recent observations from neuroimaging studies. Although the patient with IIH is often a young woman who is above ideal body weight or obese, it is well-recognized that the disorder may also occur in obese men and in children, who are less likely to be obese than their adult counterparts. Several advances in the field prompted the expert authors to provide new guidance. First, a large study of children has redefined normal CSF opening pressure for children.2 In the obese or sedated child, an opening pressure of 280 mm H2O has been suggested as the requirement to claim confidently that the ICP is increased. Otherwise, the diagnostic criteria for children and adults continue to rely on a CSF lumbar opening pressure of 250 mm H2O or greater.