Faculty Bibliography

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.

OBJECTIVE: To employ a novel stimulation paradigm in order to elicit multifocal electroretinography (mfERG)-induced optic nerve head component (ONHC) responses, believed to be contingent upon the transformation in electrical transmission properties of retinal ganglion cell axons from membrane to saltatory conduction mechanisms, as they traverse the lamina cribrosa and obtain oligodendrocyte myelin. We further sought to characterize abnormalities in ONHC responses in eyes from patients with multiple sclerosis (MS). METHODS: In 10 normal subjects and 7 patients with MS (including eyes with and without a history of acute optic neuritis), we utilized a novel mfERG stimulation paradigm that included interleaved global flashes in order to elicit the ONHC responses from 103 retinal patches of pattern-reversal stimulation. RESULTS: The number of abnormal or absent ONHC responses was significantly increased in MS patient eyes compared to normal subject eyes (p < 0.001, by general estimating equation modeling, and accounting for age and within-subject, intereye correlations). CONCLUSION: Studying the relationship between ONHC abnormalities and alterations in validated structural and functional measures of the visual system may facilitate the ability to dissect and characterize the pathobiological mechanisms that contribute to tissue damage in MS, and may have utility to detect and monitor neuroprotective or restorative effects of novel therapies.

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.

BACKGROUND: Alemtuzumab is a monoclonal antibody directed against CD52 that depletes T and B lymphocytes. OBJECTIVE: To evaluate the treatment effect of alemtuzumab on low-contrast vision in relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: This was a pre-defined exploratory analysis within a randomized, rater-blinded trial (CAMMS223) that was run at 49 academic medical centers in the US and in Europe. Patients with untreated, early, RRMS (McDonald, n = 334) were randomized 1:1:1 to subcutaneous interferon beta-1a (IFNB-1a), or alemtuzumab 12 mg or 24 mg. Visual contrast sensitivity was measured for each eye at baseline and quarterly, with Pelli-Robson charts. RESULTS: The eyes of patients in the pooled alemtuzumab group (versus IFNB-1a) had a greater than 2-fold higher rate of both 3-month and 6-month sustained visual improvement, of at least 0.3 log units (2 triplets, 6 letters) (At 3 months the hazard ratio (HR) = 2.26; CI = 1.19 to 4.31; P = 0.013; and at 6 months the HR = 2.44; CI =1.16 to 5.15; P = 0.019), and they had a lower risk of 3- and 6-month sustained worsening of at least 0.15 log units (1 triplet, 3 letters) (At 3 months the HR = 0.58; CI = 0.38 to 0.89; P = 0.012; and at 6 months HR = 0.55; CI=0.35 to 0.87; P = 0.010). Over the 36-month study period, the eyes of patients in the pooled alemtuzumab group improved in mean contrast sensitivity to a greater extent than those in the IFNB-1a group (0.080 log units versus 0.038 log units; P = 0.0102). CONCLUSIONS: Alemtuzumab was associated with a greater chance of improved contrast sensitivity in patients with RRMS and may delay the worsening of visual function. Contrast sensitivity testing was sensitive to treatment effects, even within an active comparator study design. These results support the validity of low-contrast vision testing as a clinical outcome in MS trials.

OBJECTIVE: The Sports Concussion Assessment Tool 2 (SCAT2) and King-Devick (K-D) tests have both been proposed as sideline tools to detect sports-related concussion. We performed an exploratory analysis to determine the relation of SCAT2 components, particularly the Standardized Assessment of Concussion (SAC), to K-D test scores in a professional ice hockey team cohort during pre-season baseline testing. We also examined changes in scores for two athletes who developed concussion and had rinkside testing. METHODS: A modified SCAT2 (no balance testing) and the K-D test, a brief measure of rapid number naming, were administered to 27 members of a professional ice hockey team during the 2011-2012 pre-season. Athletes with concussion also underwent rinkside testing. RESULTS: Lower (worse) scores for the SCAT2 SAC Immediate Memory Score and the overall SAC score were associated with greater (worse) times required to complete the K-D test at baseline. On average, for every 1-point reduction in SAC Immediate Memory Score, we found a corresponding increase (worsening) of K-D time score of 7.3s (95% CI 4.9, 9.7, p<0.001, R(2)=0.62, linear regression, accounting for age). For the overall SAC score, 1-point reductions were associated with K-D score worsening of 2.2s (95% CI 0.6, 3.8, p=0.01, R(2)=0.25, linear regression). In two players tested rinkside immediately following concussion, K-D test scores worsened from baseline by 4.2 and 6.4s. These athletes had no differences found for SCAT2 SAC components, but reported symptoms of concussion. CONCLUSION: In this study of professional athletes, scores for the K-D test, a measure for which saccadic (fast) eye movements are required for the task of rapid number naming, were associated with reductions in Immediate Memory at a pre-season baseline. Both working memory and saccadic eye movements share closely related anatomical structures, including the dorsolateral prefrontal cortex (DLPFC). A composite of brief rapid sideline tests, including SAC and K-D (and balance testing for non-ice hockey sports), is likely to provide an effective clinical tool to assess the athlete with suspected concussion.

An 81-year-old man with retinitis pigmentosa had severe, slowly progressive visual loss that began at age 20. Intermittent nystagmus was observed for 1 decade. Examination revealed severe retinal atrophy and periodic alternating nystagmus (PAN) that occurred only in darkness (video on the Neurology(R) Web site at www.neurology.org).