Faculty Bibliography

OBJECTIVE: To educate physicians about appropriate acute migraine treatment guidelines by determining (1) where headache patients were first prescribed opioids and barbiturates, and (2) the characteristics of the patient population who had been prescribed opioids and barbiturates. BACKGROUND: Several specialty societies issued recommendations that caution against the indiscriminate use of opioids or barbiturate containing medications for the treatment of migraine. These medications are still being prescribed in various medical settings and could put headache specialists in a difficult position when patients request these agents. METHODS: Patients presenting to a headache center comprised of eight physicians were asked to complete a survey that assessed headache types, comorbid conditions, and whether they had ever been prescribed opioids or barbiturates. If they responded affirmatively to the latter question, they were asked about the prescribing doctor, medication effectiveness, and whether they were currently on the medication. Data collection took place over a one month period. RESULTS: Two hundred forty-four patients were given the survey and 218 of these patients completed it. The predominant diagnosis was migraine (83.9%). More than half of the patients reported having been prescribed an opioid (54.8%) or a barbiturate (56.7%). About one fifth were on opioids (19.4%) or barbiturates (20.7%) at the time of completing the survey. Most patients reported being on opioids for more than 2 years (24.6%) or less than one week (32.1%). The reasons most frequently cited for stopping opioids were that the medications did not help (30.9%) or that they saw a new doctor who would not prescribe them (29.4%). Among patients who had previously been on barbiturates, 32.2% had been on these for over 2 years. Most patients (61.8%) stopped barbiturates because they did not find the medication helpful, while 17.6% said they saw a new doctor who would not prescribe them. The physician specialty most frequently cited as being the first prescriber for opioids was emergency medicine (20.2%) with family doctors and general neurologists the next groups at 17.7% each. General neurologists were the most frequent (37.8%) first prescribers of barbiturates. CONCLUSIONS: Approximately 20% of patients presenting to a headache center reported current use of opioids and/or barbiturates. ED physicians were reported to be the most frequent first prescribers of opioids and general neurologists were the most frequent first prescribers of barbiturates. Taken as a whole, these data provide a useful snapshot of the wide variety of physician specialties that might benefit from additional education on the appropriate use of opioids and barbiturate-containing medications in patients with headaches.

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.

Optical coherence tomography (OCT) is a relatively new technology that is now routinely and very widely used by ophthalmologists for structural documentation of the optic nerve and retina. In neuro-ophthalmology and neurology, the value of OCT is ever expanding; its role in an increasing number of conditions is being reported in parallel with the advances of the technology. Currently, as a clinical tool, OCT is particularly useful for the structural measurement of peripapillary retinal nerve fiber layer thickness, optic nerve head volumetric analysis, and macular anatomy. Optic neuropathies of varied etiology (particularly from multiple sclerosis) may be the most common clinical indications for neurologists to obtain OCT imaging. Documentation and follow-up of disc edema of varied etiology (papilledema and idiopathic intracranial hypertension), discriminating true disc swelling from pseudopapilledema, and differentiating optic neuropathy from maculopathy are some other examples from clinical practice.

BACKGROUND:: Sports-related concussion commonly affects the visual pathways. Current sideline protocols test cognition and balance but do not include assessments of visual performance. We investigated how adding a vision-based test of rapid number naming could increase our ability to identify concussed athletes on the sideline at youth and collegiate levels. METHODS:: Participants in this prospective study included members of a youth ice hockey and lacrosse league and collegiate athletes from New York University and Long Island University. Athletes underwent preseason baseline assessments using: 1) the King-Devick (K-D) test, a <2-minute visual performance measure of rapid number naming, 2) the Standardized Assessment of Concussion (SAC), a test of cognition, and 3) a timed tandem gait test of balance. The SAC and timed tandem gait are components of the currently used Sport Concussion Assessment Tool, 3rd Edition (SCAT3 and Child-SCAT3). In the event of a concussion during the athletic season, injured athletes were retested on the sideline/rink-side. Nonconcussed athletes were also assessed as control participants under the same testing conditions. RESULTS:: Among 243 youth (mean age 11 +/- 3 years, range 5-17) and 89 collegiate athletes (age 20 +/- 1 years, range 18-23), baseline time scores for the K-D test were lower (better) with increasing participant age (P < 0.001, linear regression models). Among 12 athletes who sustained concussions during their athletic season, K-D scores worsened from baseline by an average of 5.2 seconds; improvement by 6.4 seconds was noted for the nonconcussed controls (n = 14). The vision-based K-D test showed the greatest capacity to distinguish concussed vs control athletes based on changes from preseason baseline to postinjury (receiver operating characteristic [ROC] curve areas from logistic regression models, accounting for age = 0.92 for K-D, 0.87 for timed tandem gait, and 0.68 for SAC; P = 0.0004 for comparison of ROC curve areas). CONCLUSIONS:: Adding a vision-based performance measure to cognitive and balance testing enhances the detection capabilities of current sideline concussion assessment. This observation in patients with mild traumatic brain injury reflects the common involvement and widespread distribution of brain pathways dedicated to vision.

Idiopathic demyelinating optic neuritis (ON) most commonly presents as acute unilateral vision loss and eye pain and is frequently associated with multiple sclerosis. Although emphasis is often placed on the good recovery of high-contrast visual acuity, persistent deficits are frequently observed in other aspects of vision, including contrast sensitivity, visual field testing, color vision, motion perception, and vision-related quality of life. Persistent and profound structural and functional changes are often revealed by imaging and electrophysiologic techniques, including optical coherence tomography, visual-evoked potentials, and nonconventional MRI. These abnormalities can impair patients' abilities to perform daily activities (e.g., driving, working) so they have important implications for patients' quality of life. In this article, we review the sequelae from ON, including clinical, structural, and functional changes and their interrelationships. The unmet needs in each of these areas are considered and the progress made toward meeting those needs is examined. Finally, we provide an overview of past and present investigational approaches for disease modification in ON.

Clinical case reports and prospective trials have demonstrated a reproducible benefit of hypothalamic-pituitary-adrenal (HPA) axis modulation on the rate of recovery from acute inflammatory central nervous system (CNS) demyelination. As a result, corticosteroid preparations and adrenocorticotrophic hormones are the current mainstays of therapy for the treatment of acute optic neuritis (AON) and acute demyelination in multiple sclerosis. Despite facilitating the pace of recovery, HPA axis modulation and corticosteroids have failed to demonstrate long-term benefit on functional recovery. After AON, patients frequently report visual problems, motion perception difficulties and abnormal depth perception despite 'normal' (20/20) vision. In light of this disparity, the efficacy of these and other therapies for acute demyelination require re-evaluation using modern, high-precision paraclinical tools capable of monitoring tissue injury. In no arena is this more amenable than AON, where a new array of tools in retinal imaging and electrophysiology has advanced our ability to measure the anatomic and functional consequences of optic nerve injury. As a result, AON provides a unique clinical model for evaluating the treatment response of the derivative elements of acute inflammatory CNS injury: demyelination, axonal injury and neuronal degeneration. In this article, we examine current thinking on the mechanisms of immune injury in AON, discuss novel technologies for the assessment of optic nerve structure and function, and assess current and future treatment modalities. The primary aim is to develop a framework for rigorously evaluating interventions in AON and to assess their ability to preserve tissue architecture, re-establish normal physiology and restore optimal neurological function.

OBJECTIVE: To evaluate the efficacy and safety of subcutaneous peginterferon beta-1a over 2 years in patients with relapsing-remitting multiple sclerosis in the ADVANCE study. METHODS: Patients were randomized to placebo or 125 microg peginterferon beta-1a every 2 or 4 weeks. For Year 2 (Y2), patients originally randomized to placebo were re-randomized to peginterferon beta-1a every 2 weeks or every 4 weeks. Patients randomized to peginterferon beta-1a in Year 1 (Y1) remained on the same dosing regimen in Y2. RESULTS: Compared with Y1, annualized relapse rate (ARR) was further reduced in Y2 with every 2 week dosing (Y1: 0.230 [95% CI 0.183-0.291], Y2: 0.178 [0.136-0.233]) and maintained with every 4 week dosing (Y1: 0.286 [0.231-0.355], Y2: 0.291 [0.231-0.368]). Patients starting peginterferon beta-1a from Y1 displayed improved efficacy versus patients initially assigned placebo, with reductions in ARR (every 2 weeks: 37%, p<0.0001; every 4 weeks: 17%, p=0.0906), risk of relapse (every 2 weeks: 39%, p<0.0001; every 4 weeks: 19%, p=0.0465), 12-week disability progression (every 2 weeks: 33%, p=0.0257; every 4 weeks: 25%, p=0.0960), and 24-week disability progression (every 2 weeks: 41%, p=0.0137; every 4 weeks: 9%, p=0.6243). Over 2 years, greater reductions were observed with every 2 week versus every 4 week dosing for all endpoints and peginterferon beta-1a was well tolerated. CONCLUSIONS: Peginterferon beta-1a efficacy is maintained beyond 1 year, with greater effects observed with every 2 week versus every 4 week dosing, and a similar safety profile to Y1. Clinicaltrials.gov Registration Number: NCT00906399.

BACKGROUND: The relation of fatigue in multiple sclerosis (MS) to the visual system, an emerging structural and functional surrogate in MS, has not been well established. OBJECTIVE: We examined how physical and cognitive fatigue could be associated with visual dysfunction and neurologic impairment. METHODS: At a single time-point, we assessed 143 patients with: Low-contrast letter acuity (LCLA) and high-contrast visual acuity (VA) testing, the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and Neuro-Ophthalmic Supplement, the Modified Fatigue Impact Scale (MFIS), the MS Functional Composite (MSFC), and the Expanded Disability Status Scale (EDSS). RESULTS: Worse binocular LCLA scores were associated with increased levels of total and physical fatigue (p