The King-Devick test as a concussion screening tool administered by sports parents.

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.

Weight gain and recurrence in idiopathic intracranial hypertension: a case-control study.

OBJECTIVE: To determine whether weight gain is associated with recurrence in idiopathic intracranial hypertension (IIH). METHODS: Medical records of adult patients with IIH seen between 1993 and 2009 at 2 university hospitals were reviewed to identify those with and without recurrence. Patients with documented height and weight at presentation and at subsequent visits were studied. The Wilcoxon rank sum test was used to compare mean body mass index (BMI) and percent weight change between the groups of patients with recurrence and without recurrence. The signed-rank test was used for comparing BMI within groups at the various time points. RESULTS: Fifty women with IIH were included in the analyses: 26 had IIH recurrence and 24 did not. Patients with recurrence had greater BMI at the time of recurrence compared to BMI at diagnosis (p = 0.02, signed-rank test). They also demonstrated a greater degree of weight gain between initial resolution and recurrence (BMI change +2.0 kg/m(2) [-1.5 to 10.8]) compared to patients without recurrence (-0.75 kg/m(2) [-35 to 3.6], p = 0.0009, Wilcoxon rank sum test). Patients without recurrence demonstrated stable weights (0%[95% CI -9.6 to 10.1%]), while patients with recurrence demonstrated a 6% weight gain ([-3.5 to 40.2%], p = 0.005), with an average rate of BMI gain of 1.3 kg/m(2)/year vs -0.96 kg/m(2)/year in those without recurrence. CONCLUSION: Patients with IIH recurrence had significant increases in BMI compared to patients without recurrence in this cohort. Patients with resolved IIH should be advised that weight gain may be a risk factor for IIH recurrence.

The King-Devick test as a determinant of head trauma and concussion in boxers and MMA fighters.

OBJECTIVE: Sports-related concussion has received increasing attention as a cause of short- and long-term neurologic symptoms among athletes. The King-Devick (K-D) test is based on measurement of the speed of rapid number naming (reading aloud single-digit numbers from 3 test cards), and captures impairment of eye movements, attention, language, and other correlates of suboptimal brain function. We investigated the K-D test as a potential rapid sideline screening for concussion in a cohort of boxers and mixed martial arts fighters. METHODS: The K-D test was administered prefight and postfight. The Military Acute Concussion Evaluation (MACE) was administered as a more comprehensive but longer test for concussion. Differences in postfight K-D scores and changes in scores from prefight to postfight were compared for athletes with head trauma during the fight vs those without. RESULTS: Postfight K-D scores (n = 39 participants) were significantly higher (worse) for those with head trauma during the match (59.1 ± 7.4 vs 41.0 ± 6.7 seconds, p < 0.0001, Wilcoxon rank sum test). Those with loss of consciousness showed the greatest worsening from prefight to postfight. Worse postfight K-D scores (r(s) = -0.79, p = 0.0001) and greater worsening of scores (r(s) = 0.90, p < 0.0001) correlated well with postfight MACE scores. Worsening of K-D scores by ≥5 seconds was a distinguishing characteristic noted only among participants with head trauma. High levels of test-retest reliability were observed (intraclass correlation coefficient 0.97 [95% confidence interval 0.90-1.0]). CONCLUSIONS: The K-D test is an accurate and reliable method for identifying athletes with head trauma, and is a strong candidate rapid sideline screening test for concussion.

Cup to disc ratio by optical coherence tomography is abnormal in multiple sclerosis.

OBJECTIVE: To identify and characterize cup to disc ratio (CDR) and related optic nerve head abnormalities in multiple sclerosis (MS) using spectral domain optical coherence tomography (OCT). BACKGROUND: While CDR is routinely assessed by ophthalmologists in the evaluation of glaucoma, CDR and related optic nerve head metrics remain largely unexplored in MS. DESIGN/METHODS: Cirrus-HD (high density) OCT was used to evaluate average CDR, vertical CDR, optic disc area, optic cup volume, and neuro-retinal rim area in 105 MS patients and 88 age-matched healthy individuals. High-contrast (100%) visual acuity, 2.5% low-contrast letter acuity and 1.25% low-contrast letter acuity were assessed in 77 MS patients. Two-sample t-tests were used in the analysis of OCT-derived optic nerve head measures between healthy controls and MS patients. Multivariate regression (accounting for age and gender) was used to assess relationships between optic nerve head measures and visual function. RESULTS: Average CDR (p=0.007) and vertical CDR (p=0.005) were greater in MS patients compared to healthy controls, while neuro-retinal rim area was decreased in MS patients (p=0.001). CDR increased with retinal nerve fiber layer (RNFL) thinning (r=-0.29, p=0.001). 2.5% low-contrast (p=0.005) and 1.25% low-contrast letter acuity (p=0.03) were lower in MS patients with higher vertical CDR. CONCLUSIONS/RELEVANCE: CDR (as determined by spectral domain OCT) is abnormal in MS and correlates with visual function. OCT-derived CDR and related optic nerve head metrics may represent an objective measure by which to monitor disease progression, and potentially neuroprotection, in therapeutic MS trials.

Associations between retinal nerve fiber layer abnormalities and optic nerve examination.

OBJECTIVE: Retinal nerve fiber layer (RNFL) abnormalities detected by optical coherence tomography (OCT) are useful markers for axonal loss and visual dysfunction in multiple sclerosis (MS), but their role in routine clinical management is not well-studied. METHODS: Clinical and OCT examinations were performed on 240 patients attending a neurology clinic. Using OCT 5th percentile to define abnormal RNFL thickness, we compared eyes classified by neurologists as having optic atrophy to RNFL thickness, and afferent pupillary defect (APD) to RNFL thickness ratios of eye pairs. RESULTS: Mean RNFL thickness was less in eyes classified by neurologists as having optic atrophy (79.4 ± 21 µm; n=63) vs those without (97.0 ± 15 µm; n=417; p < 0.001, t test) and in eyes with an APD (84.1 ± 16 µm; n=44) than without an APD (95.8 ± 17 µm; n=436; p < 0.001). Physicians' diagnostic accuracy for detecting pallor in eyes with an abnormal RNFL thickness was 79% (sensitivity=0.56; specificity=0.82). Accuracy for detecting a RAPD in patients with mean RNFL ratio (affected eye to unaffected eye) <0.90 was 73% (sensitivity=0.30; specificity=0.86). Ability to detect visual pathway injury via assessment of atrophy and APD differed between neurologists. CONCLUSIONS: OCT reveals RNFL abnormality in many patients in whom eyes are not classified by neurologic examiners as having optic atrophy. Further study is needed to define the role of OCT measures in the context of examinations for optic atrophy and APD by neuroophthalmologists. OCT-measured RNFL thickness is likely to have an important future role in the clinical setting.

Assessing disability progression with the Multiple Sclerosis Functional Composite.

BACKGROUND: The initial Multiple Sclerosis Functional Composite (MSFC) proposal was a three-part composite of quantitative measures of ambulation, upper extremity function, and cognitive function expressed as a single composite Z-score. However, the clinical meaning of an MSFC Z-score change is not obvious. This study instead used MSFC component data to define a patient-specific disease progression event. OBJECTIVE: Evaluate a new method for analyzing disability progression using the MSFC. METHODS: MSFC progression was defined as worsening from baseline on scores of at least one MSFC component by 20% (MSFC Progression-20) or 15% (MSFC Progression-15), sustained for >or=3 months. Progression rates were determined using data from natalizumab clinical studies (Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis [AFFIRM] and Safety and Efficacy of Natalizumab in Combination With Interferon Beta-1a in Patients With Relapsing Remitting Multiple Sclerosis [SENTINEL]). Correlations between MSFC progression and other clinical measures were determined, as was sensitivity to treatment effects. RESULTS: Substantial numbers of patients met MSFC progression criteria, with MSFC Progression-15 being more sensitive than MSFC Progression-20, at both 1 and 2 years. MSFC Progression-20 and MSFC Progression-15 were related significantly to Expanded Disability Status Scale (EDSS) score change, relapse rate, and the SF-36 Physical Component Summary (PCS) score change. MSFC Progression-20 and MSFC Progression-15 at 1 year were predictive of EDSS progression at 2 years. Both MSFC progression end points demonstrated treatment effects in AFFIRM, and results were replicated in SENTINEL. CONCLUSION: MSFC Progression-20 and MSFC Progression-15 are sensitive measures of disability progression; correlate with EDSS, relapse rates, and SF-36 PCS; and are capable of demonstrating therapeutic effects in randomized, controlled clinical studies.

Optical coherence tomography helps differentiate neuromyelitis optica and MS optic neuropathies.

OBJECTIVE: To evaluate the retinal nerve fiber layer (RNFL) thickness and macular volume in neuromyelitis optica (NMO) spectrum patients using optical coherence tomography (OCT). BACKGROUND: OCT can quantify damage to retinal ganglion cell axons and can identify abnormalities in multiple sclerosis and optic neuritis (ON) eyes. OCT may also be useful in the evaluation of patients with NMO. METHODS: OCT and visual function testing were performed in 26 NMO spectrum patients with a history of ON, 17 patients with isolated longitudinally extensive transverse myelitis (LETM) without ON, 378 patients with relapsing-remitting multiple sclerosis (RRMS), and 77 healthy controls at 2 centers. RESULTS: Substantial RNFL thinning was seen in NMO ON eyes (63.6 microm) relative to both RRMS ON eyes (88.3 microm, p < 0.0001) and control eyes (102.4 microm, p < 0.0001). A first episode of ON was estimated to cause 24 microm more loss of RNFL thickness in NMO than RRMS. Similar results were seen for macular volume. ON also was associated with more severe visual impairment in NMO spectrum patients than in RRMS patients. Eyes in the LETM group and unaffected NMO eyes were not significantly different from controls, though conclusions about these subgroups were limited by small sample sizes. CONCLUSIONS: Optical coherence tomography (OCT) shows more severe retinal damage after optic neuritis (ON) episodes in neuromyelitis optica (NMO) than in relapsing-remitting multiple sclerosis. Identification of substantial retinal nerve fiber layer loss (>15 microm) after ON in a non-multiple sclerosis patient should prompt consideration of an NMO spectrum condition. OCT may be a useful tool for the evaluation of patients with NMO.

Proof of concept studies for tissue-protective agents in multiple sclerosis.

BACKGROUND: There is considerable interest in tissue-protective treatments for multiple sclerosis (MS). METHODS AND OBJECTIVES: We convened a group of MS clinical trialists and related researchers to discuss designs for proof of concept studies utilizing currently available data and assessment methods. RESULTS: Our favored design was a randomized, double-blind, parallel-group study of active treatment versus placebo focusing on changes in brain volume from a post-baseline scan (3-6 months after starting treatment) to the final visit 1 year later. Study designs aimed at reducing residual deficits following acute exacerbations are less straightforward, depending greatly on the anticipated rapidity of treatment effect onset. CONCLUSIONS: The next step would be to perform one or more studies of potential tissue-protective agents with these designs in mind, creating the longitudinal data necessary to refine endpoint selection, eligibility criteria, and sample size estimates for future trials.

Pediatric optic neuritis: brain MRI abnormalities and risk of multiple sclerosis.

BACKGROUND: Optic neuritis is often the initial presentation of multiple sclerosis (MS). As established by the Optic Neuritis Treatment Trial, an abnormal baseline brain MRI is a strong predictor of MS after isolated optic neuritis in adults. However, the rate of conversion to MS after optic neuritis in children based upon brain MRI findings is unknown. METHODS: We reviewed the medical records of children (<18 years) presenting with optic neuritis between 1993 and 2004 at the Children's Hospital of Philadelphia. Children with a history of demyelinating disease or prior optic neuritis were excluded. Symptoms, ophthalmologic findings, MRI findings, and clinical outcomes were recorded. RESULTS: We identified 29 consecutive children with idiopathic optic neuritis. Eleven patients (38%) had white matter T2/FLAIR lesions in the brain (not including the optic nerves). Eighteen patients were followed for more than 24 months, and 3 of the 18 (17%) developed MS. All 3 patients had an abnormal brain MRI scan at their initial presentation of optic neuritis. None of the patients with a normal brain MRI scan at presentation developed MS over an average follow-up of 88.5 months. Patients with one or more white matter lesions on MRI were more likely to develop MS (3/7 vs 0/11, p = 0.04, Fisher exact test). CONCLUSIONS: Children with brain MRI abnormalities at the time of the diagnosis of optic neuritis have an increased risk of multiple sclerosis. Larger collaborative studies are needed to further define the prognosis for childhood optic neuritis.

Vision related quality of life in multiple sclerosis: correlation with new measures of low and high contrast letter acuity.

OBJECTIVE: To examine the relation between low contrast letter acuity, a new visual function test for multiple sclerosis (MS) trials, and vision targeted health related quality of life (HRQOL). METHODS: Patients in this cross sectional study were part of an ongoing investigation of visual function in MS. Patients were tested binocularly using low contrast letter acuity and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) charts. The 25 Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), 10 Item Neuro-Ophthalmic Supplement to the NEI-VFQ-25, Impact of Visual Impairment Scale and Short Form 36 Health Survey (SF-36) were administered. RESULTS: Among 167 patients, mean age was 48 (10) years, with median Expanded Disability Status Scale (EDSS) 2.0 (range 1.0-7.5), and median binocular Snellen acuity equivalent (ETDRS charts) 20/16 (range 20/12.5 to 20/100). Reductions in vision specific HRQOL were associated with lower (worse) scores for low contrast letter acuity and VA (p<0.001, linear regression, accounting for age). Two line differences in visual function were associated, on average, with >4 point (6.7-10.9 point) worsening in the NEI-VFQ-25 composite score, reductions that are considered clinically meaningful. Scores for the 10 Item Neuro-Ophthalmic Supplement to the NEI-VFQ-25 also correlated well with visual function. Associations between reduced low contrast acuity and worse vision targeted HRQOL remained significant in models accounting for high contrast VA, EDSS and history of acute optic neuritis. CONCLUSIONS: Low contrast letter acuity scores correlate well with HRQOL in MS. Two line differences in scores for low contrast acuity and VA reflect clinically meaningful differences in vision targeted HRQOL. Low contrast acuity testing provides information on patient reported aspects of vision, supporting use of these measures in MS clinical trials.

Optical coherence tomography and disease subtype in multiple sclerosis.

OBJECTIVE: To examine retinal nerve fiber layer (RNFL) thickness, macular volumes (MV), and visual acuity in multiple sclerosis (MS) eyes, with and without history of acute optic neuritis (ON). METHODS: RNFL thickness was measured in 326 MS and 94 control eyes using optical coherence tomography (OCT). MV and vision testing were done in a subset of the cohort. MS subtype was classified as relapsing-remitting (RRMS, n = 135), primary progressive (PPMS, n = 12), and secondary progressive (SPMS, n = 16). RESULTS: MS ON eyes had decreased RNFL thickness (84.2 microm) compared to controls (102.7 microm) (p < 0.0001). Unaffected fellow eyes of MS ON eyes (93.9 microm) (p < 0.01) and patients with MS with no history of ON (95.9 microm) (p < 0.05) also had decreased RNFL. RRMS (94.4 microm) (p < 0.001), PPMS (88.9 microm) (p < 0.01), and SPMS (81.8 microm) (p < 0.0001) (adjusted for age and duration of disease) had decreased RNFL compared to controls. There were significant differences in RNFL thickness within quadrants of peripapillary retina comparing relapsing to progressive MS subtypes. MV was decreased in MS ON eyes (6.2 mm(3)) (p < 0.0001) and SPMS subjects (6.2 mm(3)) (p < 0.05) compared to controls (6.8 mm(3)). CONCLUSION: Retinal nerve fiber layer (RNFL) is significantly decreased in multiple sclerosis (MS) optic neuritis (ON) eyes, unaffected fellow eyes of patients with MS ON, and MS eyes not affected by ON in our cohort. Macular volumes (MV) showed a significant decrease in MS ON eyes. Progressive MS cases showed more marked decreases in RNFL and MV than relapsing-remitting MS. OCT is a promising tool to detect subclinical changes in RNFL and MV in patients with MS and should be examined in longitudinal studies as a potential biomarker of retinal pathology in MS.

Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis.

OBJECTIVE: Optical coherence tomography (OCT) noninvasively quantifies retinal nerve fiber layer (RNFL) thickness. Studies show RNFL thinning in multiple sclerosis (MS), and we assessed its association with brain atrophy. METHODS: RNFL thickness was measured in 40 patients with MS and 15 controls. Brain parenchymal fraction (BPF) and partial brain volumes were estimated from cranial MRI scans using SIENA-X. Multiple linear regression modeling assessed the association between OCT and MRI measures of atrophy. RESULTS: Minimum RNFL thickness and subject age together predict 21% (p = 0.005) of the variance in BPF in all patients with MS and 43% (p = 0.003) of the variance in BPF in the subgroup with relapsing remitting MS (RRMS; n = 20). The partial correlation coefficient between BPF and minimum RNFL thickness, controlling for age, is 0.46 (p = 0.003) in all patients with MS and 0.69 (p = 0.001) in patients with RRMS. These associations are driven by CSF volume but not by gray or white matter volume. There is no significant association of these variables among controls. CONCLUSIONS: In multiple sclerosis (MS), retinal nerve fiber layer thickness is associated with brain parenchymal fraction and CSF volume. These data suggest that quantification of axonal thickness in the retina by optical coherence tomography (OCT) provides concurrent information about MRI brain abnormality in MS. OCT should be examined in longitudinal studies to determine if it could be used as an outcome measure in clinical trials of neuroprotective drugs.

Relation of vision to global and regional brain MRI in multiple sclerosis.

OBJECTIVE: To examine the relation between low-contrast letter acuity, an emerging visual outcome for multiple sclerosis (MS) clinical trials, and brain MRI abnormalities in an MS cohort. METHODS: T2 lesion volume and brain parenchymal fraction were determined for whole brain and within visual pathway regions of interest. Magnetization transfer ratio histograms were examined. Vision testing was performed binocularly using low-contrast letter acuity (2.5%, 1.25% contrast) and high-contrast visual acuity (VA). Linear regression, accounting for age and disease duration, was used to assess the relation between vision and MRI measures. RESULTS: Patients (n = 45) were aged 44 +/- 11 years, with disease duration of 5 years (range <1 to 21), Expanded Disability Status Scale score of 2.0 (0 to 6.0), and binocular Snellen acuity of 20/16 (20/12.5 to 20/25). The average T2 lesion volume was 18.5 mm(3). Patients with lower (worse) low-contrast letter acuity and high-contrast VA scores had greater T2 lesion volumes in whole brain (2.5% contrast: p = 0.004; 1.25%: p = 0.002; VA: p = 0.04), Area 17 white matter (2.5%: p < 0.001; 1.25%: p = 0.02; VA: p = 0.01), and optic radiations (2.5%: p = 0.001; 1.25%: p = 0.02; VA: p = 0.007). Within whole brain, a 3-mm(3) increase in lesion volume corresponded, on average, to a 1-line worsening of low-contrast acuity, whereas 1-line worsening of high-contrast acuity corresponded to a 5.5-mm(3) increase. CONCLUSIONS: Low-contrast letter acuity scores correlate well with brain MRI lesion burden in multiple sclerosis (MS), supporting validity for this vision test as a candidate for clinical trials. Disease in the postgeniculate white matter is a likely contributor to visual dysfunction in MS that may be independent of acute optic neuritis history.

Natalizumab reduces visual loss in patients with relapsing multiple sclerosis.

OBJECTIVE: To examine the effects of natalizumab on low-contrast letter acuity as a prespecified tertiary endpoint in two randomized clinical trials and to evaluate the usefulness of low-contrast letter acuity testing as a candidate test of visual function in multiple sclerosis (MS). METHODS: AFFIRM and SENTINEL were randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trials of natalizumab in relapsing MS. Natalizumab was evaluated as monotherapy in AFFIRM and as add-on to interferon beta-1a in SENTINEL. Vision testing was performed at 100% contrast (visual acuity) and low-contrast (2.5% and 1.25%). RESULTS: The risk of clinically significant visual loss (predefined as a two-line worsening of acuity sustained over 12 weeks) at the lowest contrast level (1.25%) was reduced in the natalizumab treatment arms by 35% in AFFIRM (hazard ratio = 0.65; 95% CI: 0.47 to 0.90; p = 0.008) and by 28% in SENTINEL (hazard ratio = 0.72; 95% CI: 0.54 to 0.98; p = 0.038, Cox proportional hazards models). Mean changes in vision scores from baseline were also significantly different, reflecting worsening in non-natalizumab groups. CONCLUSIONS: Natalizumab reduces visual loss in patients with relapsing multiple sclerosis. Low-contrast acuity testing has the capacity to demonstrate treatment effects and is a strong candidate for assessment of visual outcomes in future multiple sclerosis trials.

Measuring Friedreich ataxia: complementary features of examination and performance measures.

OBJECTIVE: To examine the potential validity of performance measures and examination-based scales in Friedreich ataxia (FA) by examining their correlation with disease characteristics. METHODS: The authors assessed the properties of a candidate clinical outcome measure, the Friedreich Ataxia Rating Scale (FARS), and simple performance measures (9-hole peg test, the timed 25-foot walk, PATA test, and low-contrast letter acuity) in 155 patients with FA from six institutions, and correlated the scores with disease duration, functional disability, activity of daily living scores, age, and shorter GAA repeat length to assess whether these measures capture the severity of neurologic dysfunction in FA. RESULTS: Scores for the FARS and performance measures correlated significantly with functional disability, activities of daily living scores, and disease duration, showing that these measures meet essential criteria for construct validity for measuring the progressive nature of FA. In addition, the FARS and transformed performance measures scores were predicted by age and shorter GAA repeat length in linear regression models accounting for sex and testing site. Correlations between performance measures were moderate in magnitude, suggesting that each test captures separate yet related dimensions of neurologic function in FA and that a composite measure might better predict disease status. Composite measures created using cohort means and standard deviations predicted disease status better than or equal to single performance measures or examination-based measures. CONCLUSIONS: The Friedreich Ataxia Rating Scale, performance measures, and performance measure composites provide valid assessments of disease progression in Friedreich ataxia.

Low-contrast letter acuity testing captures visual dysfunction in patients with multiple sclerosis.

OBJECTIVE: To evaluate concurrent and predictive validity for low-contrast letter acuity (L-CLA) testing as a candidate visual component for the Multiple Sclerosis Functional Composite (MSFC). METHODS: L-CLA testing was conducted in two MS patient cohorts. In the MSFC Validation Study, 137 participants from a Phase III trial of inteferon beta-1a (Avonex) for relapsing-remitting MS were followed. A second cohort included 65 patients with secondary progressive MS who participated in a substudy of the International MS Secondary Progressive Avonex Controlled Trial (IMPACT). The total number of letters read correctly at four contrast levels (100, 5, 1.25, and 0.6%) was correlated with Expanded Disability Status Scale (EDSS), MSFC, Sickness Impact Profile, Multiple Sclerosis Quality of Life Inventory, and brain parenchymal fraction (BPF), as determined by MRI. RESULTS: Low- and high-contrast letter acuity scores correlated with BPF at follow-up in the MSFC Validation Study (5%: r = 0.40, p < 0.0001; 100%: r = 0.31, p = 0.0002). L-CLA also correlated with EDSS (5%: r = -0.35, p < 0.0001; 1.25%: r = -0.26, p = 0.0003) and MSFC (5%: r = 0.47, p < 0.0001; 1.25%: r = 0.45, p < 0.0001). In the IMPACT Substudy, change in L-CLA scores from baseline to year 1 predicted subsequent change in the EDSS from year 1 to 2 at the 5% (p = 0.0142) and the 1.25% (p = 0.0038) contrast levels, after adjusting for change in MSFC scores from baseline to year 1. CONCLUSIONS: Low-contrast letter acuity (L-CLA) scores demonstrate concurrent and predictive validity in patients with relapsing-remitting and secondary progressive multiple sclerosis (MS). L-CLA testing provides additional information relevant to the MS disease process that is not entirely captured by the Multiple Sclerosis Functional Composite.

Contrast letter acuity as a visual component for the Multiple Sclerosis Functional Composite.

BACKGROUND: Visual dysfunction is one of the most common causes of disability in multiple sclerosis (MS). The Multiple Sclerosis Functional Composite (MSFC), a new clinical trial outcome measure, does not currently include a test of visual function. OBJECTIVE: To examine contrast letter acuity as a candidate visual function test for the MSFC. METHODS: Binocular contrast letter acuity testing (Sloan charts) was performed in a subgroup of participants from the International Multiple Sclerosis Secondary Progressive Avonex Controlled Trial (IMPACT Substudy) and in MS patients and disease-free control subjects from a cross-sectional study of visual outcome measures (Multiple Sclerosis Vision Prospective cohort [MVP cohort]). High-contrast visual acuity was measured in both studies; MVP cohort participants underwent additional binocular testing for contrast sensitivity (Pelli-Robson chart), color vision (D-15 desaturated test), and visual field (Esterman test, Humphrey Field Analyzer II). RESULTS: Contrast letter acuity (Sloan charts, p < 0.0001, receiver operating characteristic curve analysis) and contrast sensitivity (Pelli-Robson chart, p = 0.003) best distinguished MS patients from disease-free control subjects in the MVP cohort. Correlations of Sloan chart scores with MSFC and Expanded Disability Statue Scale (EDSS) scores in both studies were significant and moderate in magnitude, demonstrating that Sloan chart scores reflect visual and neurologic dysfunction not entirely captured by the EDSS or MSFC. CONCLUSIONS: Among clinical measures, contrast letter acuity (Sloan charts) and contrast sensitivity (Pelli-Robson chart) demonstrate the greatest capacity to identify binocular visual dysfunction in MS. Sloan chart testing also captures unique aspects of neurologic dysfunction not captured by current EDSS or MSFC components, making it a strong candidate visual function test for the MSFC.

Supranuclear gaze palsy and opsoclonus after Diazinon poisoning.

A 52 year old man developed a supranuclear gaze palsy and opsoclonus after Diazinon poisoning. The diagnosis was confirmed by low plasma and red blood cell cholinesterase activity and urine mass spectroscopy. Saccadic control may be mediated in part by acetylcholine. Opsoclonus in the setting of organophosphate intoxication may occur as a result of cholinergic excess which overactivates the fastigial nuclei.

Evidence-based neuro-ophthalmology: advances in treatment.

This review presents highlights and updates from of the most significant clinical trials in neuro-ophthalmology to date, the Optic Neuritis Treatment Trial, the Controlled High-Risk Avonex Multiple Sclerosis Prevention Study, and the Ischemic Optic Neuropathy Decompression Trial. The quality of evidence for treatment efficacy from these trials and other recent investigations of giant cell arteritis and idiopathic intracranial hypertension is classified herein according to published criteria based on sample size and study design.

Current neuro-ophthalmic therapies.

The clinical characteristics, differential diagnosis, and treatment options are presented for five different categories of neuro-ophthalmic disease. Nystagmus, optic neuritis, diplopia, pseudotumor cerebri, and temporal arteritis, are frequently encountered in neuro-ophthalmic practice. This article focuses on current therapies for these neuro-ophthalmic disorders. Potential differences in approach to pediatric versus adult patients are emphasized.