Faculty Bibliography

Neurologic complications of bariatric surgery have become increasingly recognized with the rising numbers of procedures and the increasing prevalence of obesity in the US. Deficits are most commonly seen with thiamine, vitamin B(12), folate, vitamin D, vitamin E, and copper deficiencies. The neurological findings observed with these nutritional deficiencies are variable and include encephalopathy, optic neuropathy, myelopathy, polyradiculoneuropathy, and polyneuropathy. We review the neurological complications of bariatric surgery and emphasize that these findings may vary based on the specific type of bariatric surgery and time elapsed from the procedure.

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:: In cases of progressive optic neuropathy, diagnostic uncertainty often persists despite extensive work-up. Optic nerve biopsy (ONB) can be considered, especially when visual decline of the affected or fellow eye ensues despite empiric therapy. We aimed to evaluate both diagnostic and therapeutic utilities of ONB based on the long-term experience at a tertiary care institution. METHODS:: This was a retrospective chart review of biopsies over 20 years at a single institution involving intrinsic or adherent optic nerve masses. Main outcome measures included the impact of tissue sampling on reaching a diagnosis and on guiding treatment. Secondary measures included vision in the eye of the ONB and the fellow eye. RESULTS:: Fifteen patients with a mean age of 51.7 +/- 17.4 years underwent biopsies. At the time of biopsy, visual acuity was no light perception in 8 (53%) eyes, light perception to counting fingers in 5 (33%), and 20/400 or better in 2 (13%). The fellow eye of 7 patients (47%) experienced some degree of sequential vision loss before biopsy. Seven specimens included en bloc biopsy of the nerve, 7 contained the dural sheath (usually with a portion of the optic nerve), and 1 only of the compressive mass. Six patients (40%) had tumors. Six of 8 inflammatory lesions biopsied required further clinical data to arrive at specific diagnoses. In one case, a clinical diagnosis could not be made. No patients experienced further vision loss in the fellow eye at last follow-up (median, 8 months). CONCLUSIONS:: In diverse circumstances of progressive optic neuropathy, ONB can be beneficial in establishing the diagnosis. ONB can help direct specific local or systemic treatment, particularly when infectious or inflammatory etiologies are identified. ONB, if considered early in the disease course, can potentially halt or prevent vision loss when the fellow eye is threatened.

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 <1-minute test that involves rapid number naming. 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.

OBJECTIVE: Low-contrast letter acuity has demonstrated treatment effects for sustained visual loss in trials of natalizumab for relapsing multiple sclerosis (MS). To test new therapies that may involve neuroprotection and repair, it will be essential for outcome measures to detect improvement as well as loss of visual function. We determined the effects of natalizumab on the frequency and cumulative probability of visual improvement using low-contrast letter acuity a prespecified tertiary outcome measure in AFFIRM. METHODS: AFFIRM was a randomized, double-blind, placebo-controlled, phase 3 trial that evaluated efficacy and safety of natalizumab (n=627) vs. placebo (n=315) in relapsing-remitting MS. Binocular acuities were measured at low-contrast (1.25%, 2.5%) and high-contrast visual acuity (VA). Improvement was defined as 12-week sustained increases from baseline. Clinically meaningful change for primary analyses was pre-defined as 7-letter improvement for low-contrast acuity and 5-letter improvement for VA based upon previous studies. RESULTS: Compared to placebo, cumulative probabilities of sustained visual improvement were greater in the natalizumab group by 57% for 2.5% contrast (21.7% vs. 14.0%; HR=1.57; 95% CI: 1.11-2.22; P=0.012) and 39% for 1.25% contrast (32.5% vs. 25.0%; HR=1.39; 95% CI: 1.07-1.82; P=0.014). The 5- and 10-letter low-contrast assessments did not show treatment differences. High-contrast VA was insensitive to changes over time and treatment effects. CONCLUSION: Low-contrast letter acuity detected treatment effects on sustained visual improvement in patients with relapsing MS. The ability to detect visual improvement and loss makes low-contrast acuity an important measure for future trials assessing the impact of therapy on this outcome and the potential of a therapy for neuroprotection and repair.

PURPOSE: We used high-resolution spectral-domain optical coherence tomography (SD-OCT) with retinal segmentation to determine how ganglion cell loss relates to history of acute optic neuritis (ON), retinal nerve fiber layer (RNFL) thinning, visual function, and vision-related quality of life (QOL) in multiple sclerosis (MS). DESIGN: Cross-sectional study. PARTICIPANTS: A convenience sample of patients with MS (n = 122; 239 eyes) and disease-free controls (n = 31; 61 eyes). Among MS eyes, 87 had a history of ON before enrollment. METHODS: The SD-OCT images were captured using Macular Cube (200x200 or 512x128) and ONH Cube 200x200 protocols. Retinal layer segmentation was performed using algorithms established for glaucoma studies. Thicknesses of the ganglion cell layer/inner plexiform layer (GCL+IPL), RNFL, outer plexiform/inner nuclear layers (OPL+INL), and outer nuclear/photoreceptor layers (ONL+PRL) were measured and compared in MS versus control eyes and MS ON versus non-ON eyes. The relation between changes in macular thickness and visual disability was also examined. MAIN OUTCOME MEASURES: The OCT measurements of GCL+IPL and RNFL thickness; high contrast visual acuity (VA); low-contrast letter acuity (LCLA) at 2.5% and 1.25% contrast; on the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement composite score. RESULTS: Macular RNFL and GCL+IPL were significantly decreased in MS versus control eyes (P<0.001 and P = 0.001) and in MS ON versus non-ON eyes (P<0.001 for both measures). Peripapillary RNFL, macular RNFL, GCL+IPL, and the combination of macular RNFL+GCL+IPL were significantly correlated with VA (P