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A 49-year-old woman, status post temporal lobe resection, reported a hemianopia. Examination revealed a right afferent pupillary defect, horizontal bow-tie atrophy OD (temporal and nasal), and temporal atrophy OS. Optical coherence tomography showed a bow-tie pattern OD and predominant superior and inferior nerve fiber layer loss OS (figure 1; figure e-1 at [Neurology.org][1]). The pattern OD is due to the combination of papillomacular bundle and nasal RNFL loss. The pattern OS is due to nerve fiber layer loss temporal to the fovea and, coupled with papillomacular bundle loss, produces temporal pallor.1 MRI confirmed left optic tract atrophy (figure 2). Optical coherence tomography may be sensitive for detecting localizing atrophic patterns.2 [1]: http://neurology.org/lookup/doi/10.1212/WNL.0000000000003310

The incidence of neurologic complications from bariatric surgery is rising with the prevalence of obesity and the increasing number of bariatric surgeries. We report a 25-year-old woman who developed subacute progressive weakness and areflexia followed by confusion, ophthalmoplegia, and nystagmus following bariatric surgery. While the differential of generalized weakness with altered mental status is broad, vitamin deficiency should be routinely suspected after bariatric surgery to prevent permanent neurological injury. Multifocal neurological dysfunction in our patient represented beriberi and Wernicke's encephalopathy related to vitamin B1 deficiency.

The diagnosis of idiopathic intracranial hypertension (IIH) can be challenging and relies heavily on the proper interpretation of ophthalmoscopy. For many patients, the diagnosis can be straightforward when the typical demographic features, fundus findings of papilledema, neuroimaging signs, and CSF findings are present. In other situations, the diagnosis of IIH may be difficult, particularly when fundus findings are normal, subtle, or complicated by pseudopapilledema (as can occur with optic nerve head drusen). Occasionally, true papilledema may coexist with pseudopapilledema. We must also recognize that a small percentage of patients with IIH will not develop papilledema.1,2

BACKGROUND Despite the plenitude of reports concerning partial or complete third nerve palsies, especially as presenting symptoms with posterior communicating artery (PCoA) aneurysms, we present a patient with an unusual variation. CASE DESCRIPTION A 66-year-old woman presented with progressive right-sided headaches and diplopia and was found to have a partial, pupil-sparing third nerve palsy. A small right-sided PCoA aneurysm, nearly indistinguishable from an infundibulum, was identified on magnetic resonance angiography and subsequent digital subtraction angiography. The third nerve palsy improved before surgical repair of the aneurysm. RESULTS Microsurgical exploration revealed a small PCoA aneurysm, which was tethered to the third nerve by arachnoid adhesions. Adhesions were lysed and the aneurysm was repaired sparing the PCoA and its branches. The patient's third nerve function recovered completely postoperatively. CONCLUSIONS Even a very small PCoA aneurysm may present with an improving, pupil-sparing partial third nerve palsy. Selection of patients for imaging studies should take this unusual variant into consideration. We describe the anatomy and potential mechanisms of this pupil-sparing third nerve palsy.

In the setting of head trauma, progressive bradycardia may raise suspicion for intracranial hypertension, especially when accompanied by pupillary abnormalities or systemic hypertension. We describe the case of a patient with concomitant cerebral and ocular trauma who presented with a fixed and dilated pupil and progressive bradycardia due to an oculocardiac reflex. The oculocardiac reflex is an unusual cause of bradycardia due to stimulation of the ophthalmic division of the trigeminal nerve and has been described in a variety of clinical settings. Clinicians should be aware that the oculocardiac reflex might mimic signs of intracranial hypertension in patients with combined facial and cerebral trauma.

Background: Low-contrast vision is thought to be reduced in Parkinson’s disease (PD). This may have a direct impact on quality of life such as driving, using tools, finding objects, and mobility in low-light condition. Low-contrast letter acuity testing has been successful in assessing low-contrast vision in multiple sclerosis. We report the use of a new iPad application to measure low-contrast acuity in patients with PD. Objective: To evaluate low- and high-contrast letter acuity in PD patients and controls using a variable contrast acuity eye chart developed for the Apple iPad. Methods: Thirty-two PD and 71 control subjects were studied. Subjects viewed the Variable Contrast Acuity Chart on an iPad with both eyes open at two distances (40 cm and 2 m) and at high contrast (black and white visual acuity) and 2.5% low contrast. Acuity scores for the two groups were compared. Results: PD patients had significantly lower scores (indicating worse vision) for 2.5% low contrast at both distances and for high contrast at 2 m (p < 0.003) compared to controls. No significant difference was found between the two groups for high contrast at 40 cm (p = 0.12). Conclusions: Parkinson’s disease patients have reduced low and high contrast acuity compared to controls. An iPad app, as used in this study, could serve as a quick screening tool to complement more formal testing of patients with PD and other neurologic disorders.

Summary Traumatic brain injury (TBI) is a major cause of morbidity and mortality. Concussion, a form of mild TBI, might be associated with long-term neurological symptoms. The effects of TBI and concussion are not restricted to cognition and balance. TBI can also affect multiple aspects of vision; mild TBI frequently leads to disruptions in visual functioning, while moderate or severe TBI often causes structural lesions. In patients with mild TBI, there might be abnormalities in saccades, pursuit, convergence, accommodation, and vestibulo-ocular reflex. Moderate and severe TBI might additionally lead to ocular motor palsies, optic neuropathies, and orbital pathologies. Vision-based testing is vital in the management of all forms of TBI and provides a sensitive approach for sideline or post-injury concussion screening. One sideline test, the King-Devick test, uses rapid number naming and has been tested in multiple athlete cohorts.

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.We examined how physical and cognitive fatigue could be associated with visual dysfunction and neurologic impairment.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).Worse binocular LCLA scores were associated with increased levels of total and physical fatigue (p≤0.026). Greater levels of fatigue were also associated with reduced vision-specific QOL (p0.001). Patients with more physical, but not cognitive, fatigue had greater levels of impairment by the Timed 25-Foot Walk (T25W, r=0.39, p0.001), 9-Hole Peg Test (9HP r=0.22, p=0.011) and EDSS (r=0.45, p0.001).Reduced vision in MS is highly associated with physical fatigue and could be used to capture more global, difficult to describe, symptoms. The potential differences in physical vs. cognitive fatigue and their correlates may begin to provide insight into their underlying mechanisms.

Purpose: Sports-related concussion has received increasing attention as a result of neurologic sequelae seen among athletes, highlighting the need for a validated, rapid screening tool. The King---Devick (K---D) test requires vision, eye movements, language function and attention in order to perform and has been proposed as a promising tool for assessment of concussion. We investigated the K---D test as a sideline screening tool in a collegiate cohort to determine the effect of concussion. Methods: Athletes (n = 127, mean age 19.6 ± 1.2 years) from the Wheaton College football and men’s and women’s basketball teams underwent baseline K---D testing at pre-season physicals for the 2012---2013 season. K---D testing was administered immediately on the sidelines for football players with suspected head injury during regular games and changes compared to baseline were determined. Post-season testing was also performed to compare non-concussed athletes’ test performance. Results: Concussed athletes (n = 11) displayed sideline K---D scores that were significantly higher (worse) than baseline (36.5 ± 5.6 s vs. 31.3 ± 4.5 s, p < 0.005, Wilcoxon signed-rank test). Postseason testing demonstrated improvement of scores and was consistent with known learning effects (35.1 ± 5.2 s vs. 34.4 ± 5.0 s, p < 0.05, Wilcoxon signed-rank test). Test-retest reliability was analyzed between baseline and post-season administrations of the K---D test resulting in high levels of test-retest reliability (intraclass correlation coefficient (ICC) = 0.95 [95% Confidence Interval 0.85---1.05]). Conclusions: The data show worsening of K---D test scores following concussion further supporting utility of the K---D test as an objective, reliable and effective sideline visual screening tool to help identify athletes with concussion.

ObjectiveTo describe a novel neurophysiologic signature of the retinal ganglion cell and to elucidate its relationship to abnormalities in validated structural and functional measures of the visual system.MethodsWe used multifocal electroretinogram-generated optic nerve head component (ONHC) responses from normal subjects (n = 18), patients with multiple sclerosis (MS) (n = 18), and those with glaucoma (n = 3). We then characterized the relationship between ONHC response abnormalities and performance on low-contrast visual acuity, multifocal visual-evoked potential-induced cortical responses, and average and quadrant retinal nerve fiber layer (RNFL) thicknesses, as measured by spectral-domain optical coherence tomography.ResultsCompared with the eyes of normal subjects, the eyes of patients with MS exhibited an increased number of abnormal or absent ONHC responses (p < 0.0001). For every 7-letter reduction in low-contrast letter acuity, there were corresponding 4.6 abnormal ONHC responses at 2.5% contrast (p < 0.0001) and 6.6 abnormalities at the 1.25% contrast level (p < 0.0001). Regarding average RNFL thickness, for each 10-μm thickness reduction, we correspondingly observed 6.8 abnormal ONHC responses (p = 0.0002). The most robust association was between RNFL thinning in the temporal quadrant and ONHC response abnormalities (p < 0.0001).ConclusionFurther characterization of ONHC abnormalities (those that are reversible and irreversible) may contribute to the development of novel neurotherapeutic strategies aimed at achieving neuroprotective, and perhaps even neurorestorative, effects in disorders that target the CNS in general, and MS in particular.

PURPOSE: To examine the potential for visual acuity loss, and its relation to extent and location of optic pathway gliomas in a cohort of children with neurofibromatosis type 1 studied with magnetic resonance imaging. METHODS: We reviewed the neuro-ophthalmologic records and brain/orbital magnetic resonance imaging scans for 43 consecutive pediatric patients with neurofibromatosis type 1 and optic pathway gliomas who were followed at the Children's Hospital of Philadelphia. The presence of visual loss, defined as abnormal visual acuity for age in one or both eyes, was determined. Optic pathway gliomas were classified by tumor extent and location according to involvement of the optic nerves, chiasm, and postchiasmal structures by magnetic resonance imaging. RESULTS: Involvement of the optic tracts and other postchiasmal structures at tumor diagnosis was associated with a significantly higher probability of visual acuity loss ( P = .048, chi-square test). Visual loss was noted in 20 of 43 patients (47%) at a median age of 4 years; however, three patients developed visual acuity loss for the first time during adolescence. CONCLUSIONS: In pediatric patients with neurofibromatosis type 1 and optic pathway gliomas, the likelihood of visual loss is dependent on the extent and location of the tumor by magnetic resonance imaging and is particularly associated with involvement of postchiasmal structures. Furthermore, older age during childhood (adolescence) does not preclude the occurrence of visual loss. Close follow-up beyond the early childhood years, particularly for those with postchiasmal tumor, is recommended.

Extracorporeal photopheresis is a safe therapy for cutaneous T-cell lymphoma and may have efficacy in certain autoimmune disorders. We performed a randomized, double-blinded, placebo-controlled trial of monthly photopheresis therapy in 16 patients with clinically definite multiple sclerosis (MS). All patients had progressed during the preceding year with entry Expanded Disability Status Scale (EDSS) scores between 3.0 and 7.0. Patients received photopheresis or sham therapy for 1 year and were followed for an additional 6 to 12 months. Patients were clinically evaluated by three disability scales: (1) EDSS; (2) Ambulation index and (3) Scripp's quantitative neurologic assessment. No serious side effects occurred in either group. There were no differences between the photopheresis and sham therapy groups by the disability measures. Additionally, there were no differences in progression of MRI plaque burden or evoked potential latencies. In this limited study, photopheresis was found to be safe but did not significantly alter the course of chronic progressive MS.

Purpose To report the ophthalmic findings and response to treatment in a patient with glutamic-acid decarboxylase antibodies. Design Case report. Methods A 55-year-old woman developed progressive, painful, low back muscle spasms, vertical diplopia, downbeating nystagmus, and asymmetric appendicular ataxia. Results Downbeating nystagmus was present in primary gaze with an alternating skew deviation in lateral gaze. Serum and cerebrospinal fluid GAD antibodies were detected. Treatment with diazepam led to resolution of spasticity, whereas repeated courses of intravenous immunoglobulin improved cerebellar function, including appendicular ataxia and downbeating nystagmus. Conclusions Patients with GAD antibodies may have elements of both Stiff-person syndrome (muscle rigidity and spasms) and prominent cerebellar dysfunction. Treatment with diazepam rapidly improved Stiff-person symptoms, whereas IVIg was partially effective at the early stage of cerebellar dysfunction.

We investigated the King-Devick (K-D) test of rapid number naming as a visual performance measure in a cohort of patients with multiple sclerosis (MS).In this cross-sectional study, 81 patients with MS and 20 disease-free controls from an ongoing study of visual outcomes underwent K-D testing. A test of rapid number naming, K-D requires saccadic eye movements as well as intact vision, attention and concentration. To perform the K-D test, participants are asked to read numbers aloud as quickly as possible from three test cards; the sum of the three test card times in seconds constitutes the summary score. High-contrast visual acuity (VA), low-contrast letter acuity (1.25% and 2.5% levels), retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT), MS Functional Composite (MSFC) and vision-specific quality of life (QOL) measures (25-Item NEI Visual Functioning Questionnaire [NEI-VFQ-25] and 10-Item Neuro-Ophthalmic Supplement) were also assessed.K-D time scores in the MS cohort (total time to read the three test cards) were significantly higher (worse) compared to those for disease-free controls (P=0.003, linear regression, accounting for age). Within the MS cohort, higher K-D scores were associated with worse scores for the NEI-VFQ-25 composite (P0.001), 10-Item Neuro-Ophthalmic Supplement (P0.001), binocular low-contrast acuity (2.5%, 1.25%, P0.001, and high-contrast VA (P=0.003). Monocular low-contrast vision scores (P=0.001-0.009) and RNFL thickness (P=0.001) were also reduced in eyes of patients with worse K-D scores (GEE models accounting for age and within-patient, inter-eye correlations). Patients with a history of optic neuritis (ON) had increased (worse) K-D scores. Patients who classified their work disability status as disabled (receiving disability pension) did worse on K-D testing compared to those working full-time (P=0.001, accounting for age).The K-D test, a2 minute bedside test of rapid number naming, is associated with visual dysfunction, neurologic impairment, and reduced vision-specific QOL in patients with MS. Scores reflect work disability as well as structural changes as measured by OCT imaging. History of ON and abnormal binocular acuities were associated with worse K-D scores, suggesting that abnormalities detected by K-D may go along with afferent dysfunction in MS patients. A brief test that requires saccadic eye movements, K-D should be considered for future MS trials as a rapid visual performance measure.

ObjectiveTo 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).MethodsIn 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.ResultsThe 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).ConclusionStudying 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.

This article reviews the diagnostic testing used in the evaluation of several common neuro-ophthalmologic entities including optic nerve disease, pseudotumor cerebri, anisocoria, ptosis, and ocular motor palsies. Emphasis is placed on these bedside tests that help to establish the diagnosis of these common clinical problems. The utility of the cocaine and Tensilon (edrophonium chloride) tests as well as the role of neuroimaging in these conditions are reviewed.

Objective. Lyme disease (LD) is a tickborne spirochetal infection with a wide range of neurologic and non-neurologic manifestations. The clinical diversity of LD and limitations in serologic diagnosis often make it difficult to document the diagnosis of neurobor-reliosis with certainty. Methods. We reviewed clinical manifestations in 97 seropositive children with particular attention to neurologic manifestafions. Diagnostic criteria used in other case surveys were applied to determine how often a definitive diagnosis of neuroborreliosis could be made in children. Results. Of 69 children who met criteria for LD, 32% (22) had new neurologic signs, 73% (16) of which were accounted for by facial palsy and aseptic meningitis. Five of those with neurologic findings also had erythema migrans (EM), and one had both EM and arthritis. Among those with neurologic involvement, boys outnumbered girls two to one. Neurologic abnormalities resolved spontaneously in five children before their serologic results were known. Conclusion. In our series, only 27% of children with neurologic abnormalities due to LD had a history of EM or arthritis. Seropositivity commonly constituted the primary basis for diagnosis of LD. Despite its nonspecificity, seropositivity for LD in children with neurologic symptoms usually signifies active neuroborreliosis.

To estimate the proportion of patients presenting with isolated third, fourth, or sixth cranial nerve palsy of presumed microvascular origin versus other causes.Prospective, multicenter, observational case series.A total of 109 patients aged 50 years or older with acute isolated ocular motor nerve palsy.Magnetic resonance imaging (MRI) of the brain.Causes of acute isolated ocular motor nerve palsy (presumed microvascular or other) as determined with early MRI and clinical assessment.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).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.

Crohn disease (CD) is primarily considered an inflammatory condition of the small and large intestine although associated extraintestinal inflammation is relatively common. Ocular manifestations are generally localized to the anterior chamber and ocular surface but rarely can involve the posterior pole, orbit, and optic nerve. We report a case of an otherwise healthy 42-year-old man who was diagnosed with CD after presenting with acute vision loss from optic perineuritis.

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.

We present four patients with sarcoidosis of the anterior visual pathways. The first patient presented with unilateral visual loss, a mass lesion at the optic nerve head, and an enlarged orbital optic nerve. The second patient presented with bilateral progressive painless visual loss, associated with optic nerve pallor and visual field loss. In these two patients, optic nerve biopsy was diagnostic of sarcoidosis. The third patient developed optic nerve and chiasmal involvement after sarcoidosis was established by lacrimal gland biopsy. The fourth pateint had optic nerve, pulmonary, and lymph node involvement with sarcoidosis. A conjunctival and lung biopsy were diagnostic. Computed tomography and magnetic resonance imaging have greatly facilitated diagnosis of sarcoidosis of the anterior visual pathways. Sarcoidosis of the anterior visual pathways may occur alone or in association with other ocular or systemic manifestations. A conjunctival or lacrimal gland biopsy may be preferable as the initial diagnostic approach. Treatment of patients with this condition may require systemic immunosuppression, in addition to corticosteroids, to prevent permanent visual loss.

Visual dysfunction is one of the most common clinical manifestations of multiple sclerosis (MS). Just over a decade ago, MS clincial trials did not include visual outcomes but experts recognized the need for more senstive measures of visual function. Low-contrast letter acuity emerged as the leading candidate to measure visual disability in MS and subsequent studies found low-contrast acuity testing to correlate well with brain MRI lesion burden, visual-evoked potentials (VEPs), quality of life (QOL), and retinal nerve fiber layer (RNFL) loss as measured by optical coherence tomography (OCT). OCT in MS has allowed for assessment of structure-funciton correlations that make the anterior visual pathway and acute optic neuritis (ON) ideal models for testing novel agents for neuroprotection and repair. New therapies that reduce axonal loss by neuroprotective or myelin repair mechanisms can now be assessed non-invasively by OCT and coupled with visual function data. Based on OCT studies in MS, RNFL thickness is reduced significantly among patients (92 µm) versus controls (105 µm), and is particularly reduced in MS eyes with a history of ON (85 µm). Worsening of visual function by a clinically significant ≥7 letters or ~1.5 lines for low-contrast acuity is associated with approximately 4.5 µm reductions in RNFL thickness in MS eyes. Longitudinal studies of OCT have also shown RNFL axonal loss over time that occurs even in the absence of acute ON, and that correlates with clincially meaningful worsening of vision and QOL, even in patients with benign MS. The latest OCT investigations involve high-resolution spectral-domain (SD) OCT with segmentation and measurement of specific retinal layers using computerized algorithms. These methods allow quantitation of ganglion cell (neuronal) layer loss as well as axonal degeneration in MS in vivo. In this review, we examine the data from these studies and ongoing trials that highlight the entity of ON as a model to investigate neuroprotection and neurorepair. In doing so, we also present representative group data from studies that have examined visual function, OCT measures, and QOL scales in patients with MS, ON, and disease-free controls. These data, as well as those from recent meta-analyses, may be used to provide reference values for the development of clinical trial protocols.

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).Cross-sectional study.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.The SD-OCT images were captured using Macular Cube (200×200 or 512×128) and ONH Cube 200×200 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.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.Macular RNFL and GCL+IPL were significantly decreased in MS versus control eyes (P0.001 and P = 0.001) and in MS ON versus non-ON eyes (P0.001 for both measures). Peripapillary RNFL, macular RNFL, GCL+IPL, and the combination of macular RNFL+GCL+IPL were significantly correlated with VA (P≤0.001), 2.5% LCLA (P0.001), and 1.25% LCLA (P≤0.001). Among OCT measurements, reductions in GCL+IPL (P0.001), macular RNFL (P = 0.006), and the combination (macular RNFL+GCL+IPL; P0.001) were most strongly associated with lower (worse) NEI-VFQ-25 and 10-Item Supplement QOL scores; GCL+IPL thinning was significant even accounting for macular RNFL thickness (P = 0.03 for GCL+IPL, P = 0.39 for macular RNFL).We demonstrated that GCL+IPL thinning is most significantly correlated with both visual function and vision-specific QOL in MS, and may serve as a useful structural marker of disease. Our findings parallel those of magnetic resonance imaging studies that show gray matter disease is a marker of neurologic disability in MS.Proprietary or commercial disclosure may be found after the references.

The efficient organization of the human afferent visual system meets enormous computational challenges. Once visual information is received by the eye, the signal is relayed by the retina, optic nerve, chiasm, tracts, lateral geniculate nucleus, and optic radiations to the striate cortex and extrastriate association cortices for final visual processing. At each stage, the functional organization of these circuits is derived from their anatomical and structural relationships. In the retina, photoreceptors convert photons of light to an electrochemical signal that is relayed to retinal ganglion cells. Ganglion cell axons course through the optic nerve, and their partial decussation in the chiasm brings together corresponding inputs from each eye. Some inputs follow pathways to mediate pupil light reflexes and circadian rhythms. However, the majority of inputs arrive at the lateral geniculate nucleus, which relays visual information via second-order neurons that course through the optic radiations to arrive in striate cortex. Feedback mechanisms from higher cortical areas shape the neuronal responses in early visual areas, supporting coherent visual perception. Detailed knowledge of the anatomy of the afferent visual system, in combination with skilled examination, allows precise localization of neuropathological processes and guides effective diagnosis and management of neuro-ophthalmic disorders.

The efficient organization of the human afferent visual system meets enormous computational challenges. Once visual information is received by the eye, the signal is relayed by the retina, optic nerve, chiasm, tracts, lateral geniculate nucleus, and optic radiations to the striate cortex and extrastriate association cortices for final visual processing. At each stage, the functional organization of these circuits is derived from their anatomical and structural relationships. In the retina, photoreceptors convert photons of light to an electrochemical signal that is relayed to retinal ganglion cells. Ganglion cell axons course through the optic nerve, and their partial decussation in the chiasm brings together corresponding inputs from each eye. Some inputs follow pathways to mediate pupil light reflexes and circadian rhythms. However, the majority of inputs arrive at the lateral geniculate nucleus, which relays visual information via second-order neurons that course through the optic radiations to arrive in striate cortex. Feedback mechanisms from higher cortical areas shape the neuronal responses in early visual areas, supporting coherent visual perception. Detailed knowledge of the anatomy of the afferent visual system, in combination with skilled examination, allows precise localization of neuropathological processes and guides effective diagnosis and management of neuro-ophthalmic disorders.

To determine the magnitudes of binocular summation for low- and high-contrast letter acuity in a multiple sclerosis (MS) cohort, and to characterize the roles that MS disease, age, interocular difference in acuity, and a history of optic neuritis have on binocular summation. The relation between binocular summation and monocular acuities and vision-specific quality of life (QoL) was also examined.Cross-sectional observational study.Low-contrast acuity (2.5% and 1.25% contrast) and high-contrast visual acuity (VA) were assessed binocularly and monocularly in patients and disease-free controls at 3 academic centers. Binocular summation was calculated as the difference between the binocular and better eye scores. QoL was measured using the 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) and the 10-item neuro-ophthalmic supplement. The relation of the degree of binocular summation to monocular acuity, clinical history of acute optic neuritis, age, interocular acuity difference, and QoL was determined.Binocular summation was demonstrated at all contrast levels, and was greatest at the lowest level (1.25%). Increasing age (P.0001), greater interocular differences in acuity (P.0001), and prior history of optic neuritis (P = .015) were associated with lower magnitudes of binocular summation; binocular inhibition was seen in some of these patients. Higher magnitudes of summation for 2.5% low-contrast acuity were associated with better scores for the NEI VFQ-25 (P = .02) and neuro-ophthalmic supplement (P = .03).Binocular summation of acuity occurs in MS but is reduced by optic neuritis, which may lead to binocular inhibition. Binocular summation and inhibition are important factors in the QoL and visual experience of MS patients, and may explain why some prefer to patch or close 1 eye in the absence of diplopia or ocular misalignment.

Patients with multiple sclerosis commonly describe visual symptoms that result from several eye movement abnormalities that occur from disruption of critical pathways in the brainstem, cerebellum, and cerebral hemispheres. These abnormalities include internuclear ophthalmoplegia, ocular motor palsy, ocular misalignment, pathologic nystagmus, impaired saccades, saccadic intrusions, and impaired pursuit. Detailed knowledge of these problems and their neuroanatomic localization will aid the physician by guiding diagnosis and therapeutic decision making.

The typical presentation of Heidenhain variant Creutzfeldt-Jakob disease (CJD) is a rapidly progressive visual loss in the setting of a relatively normal ophthalmologic examination. At presentation, patients with this uniformly fatal illness frequently demonstrate only minor cortical abnormalities on MRI. Here, we document the clinical presentation and imaging results of a patient with Heidenhain variant CJD in whom abnormalities on positron emission tomographic imaging were more evident than changes on MRI. These changes were present in striate cortex and visual association areas, providing clinical-anatomical correlation with our patient's visual deficits. Nuclear imaging provides a considerably more sensitive measure of neural dysfunction early in the course of this disease.

Objective To report the first histopathologic description of optic nerve demyelination from tacrolimus (FK 506) toxicity in the absence of toxic levels of tacrolimus in a patient presenting with asymmetric bilateral visual loss after 5 years of tacrolimus therapy. Patients We report a patient status post cardiac and renal transplantation who developed severe, progressive and asynchronous bilateral visual loss after prolonged treatment with tacrolimus. Orbital MRI showed an enlarged left optic nerve that enhanced with gadolinium. Conclusion After extensive negative work up, biopsy of one optic nerve was performed. Microscopic analysis showed extensive demyelination in the absence of vasculitis, neoplastic or infectious etiologies. Our patient illustrates that demyelination of the optic nerve causing asynchronous vision loss can be associated with tacrolimus toxicity in the absence of toxic drug levels.

The SENTINEL study showed that the addition of natalizumab improved outcomes for patients with relapsing multiple sclerosis (MS) who had experienced disease activity while receiving interferon beta-1a (IFNbeta-1a) alone. Previously unreported secondary and tertiary magnetic resonance imaging (MRI) measures are presented here. Patients received natalizumab 300 mg (n=589) or placebo (n=582) intravenously every 4 weeks plus IFNbeta-1a 30 microg intramuscularly once weekly. Annual MRI scans allowed comparison of a range of MRI end points versus baseline. Over 2 years, 67% of patients receiving natalizumab plus IFNbeta-1a remained free of new or enlarging T2-lesions compared with 30% of patients receiving IFNbeta-1a alone. The mean change from baseline in T2 lesion volume over 2 years decreased in patients receiving natalizumab plus IFNbeta-1a and increased in those receiving IFNbeta-1a alone (-277.5mm(3) versus 525.6mm(3); p0.001). Compared with IFNbeta-1a alone, add-on natalizumab therapy resulted in a smaller increase in mean T1-hypointense lesion volume after 2 years (1821.3mm(3) versus 2210.5mm(3); p0.001), a smaller mean number of new T1-hypointense lesions over 2 years (2.3 versus 4.1; p0.001), and a slower rate of brain atrophy during the second year of therapy (-0.31% versus -0.40%; p=0.020). Natalizumab add-on therapy reduced gadolinium-enhancing, T1-hypointense, and T2 MRI lesion activity and slowed brain atrophy progression in patients with relapsing MS who experienced disease activity despite treatment with IFNbeta-1a alone.

Objective Cross-sectional studies of optical coherence tomography (OCT) show that retinal nerve fiber layer (RNFL) thickness is reduced in multiple sclerosis (MS) and correlates with visual function. We determined how longitudinal changes in RNFL thickness relate to visual loss. We also examined patterns of RNFL thinning over time in MS eyes with and without a prior history of acute optic neuritis (ON).

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).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.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 (p0.001, linear regression, accounting for age). Two line differences in visual function were associated, on average, with4 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.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.

In April 2005, a 42-year-old African American man developed insidious, painless visual loss in the left eye which quickly progressed over several weeks. There was no significant medical history. Family history revealed hypertension and diabetes, but no autoimmune disorders, brain tumors, or vision loss. He was a restaurant manager, smoked ½ pack of cigarettes daily, consumed alcohol rarely, and did not use illicit drugs. He presented to another institution, where he was found to have 20/100 acuity, dyschromatopsia, and a relative afferent pupillary defect in the left eye. The left optic nerve head was mildly swollen, without hemorrhage or exudate. Humphrey visual fields of the left eye revealed a dense superior altitudinal defect with a less prominent inferior arcuate defect. The right eye field was full. He was thought to have idiopathic optic neuritis. He was treated briefly with oral corticosteroids, but his vision in the left eye never improved. ### Questions for consideration: 1. What are the diagnostic considerations for subacute monocular visual loss in an adult? 2. What diagnostic workup would you perform? The differential diagnosis for subacute monocular visual loss is broad. Although idiopathic demyelinating optic neuritis is a common cause, the differential also includes inflammatory and infectious conditions, compression, infiltrative or neoplastic processes, hereditary optic neuropathies, glaucoma, retinal disorders, and ischemic optic neuropathy (table 1). View this table: Table 1 Differential diagnosis for subacute monocular visual loss ### Optic neuritis. Optic neuritis most often occurs between the ages of 20 to 50 and is three times more frequent in women.1 Visual loss reaches its nadir within 7 to 10 days and begins to recover within 1 month. Retro-orbital pain, particularly with eye movements, occurs in almost all cases; it may precede the visual loss and typically persists for 1 to 2 weeks.2 Characteristic findings on examination support the diagnosis of typical optic neuritis. Visual field …

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.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.Patients (n = 45) were aged 44 +/- 11 years, with disease duration of 5 years (range1 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%: p0.001; 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.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.

Multiple sclerosis is a common demyelinating disorder of the central nervous system, and neuro-ophthalmologic manifestations occur in the majority of patients. This article provides a review of the pathogenesis, epidemiology, and classification of multiple sclerosis. Neuro-ophthalmologic abnormalities associated with multiple sclerosis, including acute demyelinating optic neuritis and internuclear ophthalmoplegia, are described in detail. Current and emerging technologies designed to assess visual function in multiple sclerosis are discussed. A summary presents the appropriate evaluation and management of patients with optic neuritis and other first demyelinating events (also referred to as clinically isolated syndromes).

PurposeTo determine whether a 10-Item Neuro-Ophthalmic Supplement increases the capacity of the 25-Item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) to capture self-reported visual dysfunction in patients with neuro-ophthalmologic disorders.DesignA cross-sectional survey to examine the characteristics of a 10-Item Neuro-Ophthalmic Supplement to the 25-Item NEI-VFQ-25 in a cohort of patients with neuro-ophthalmologic disorders.MethodsThe 10-Item Neuro-Ophthalmic Supplement was designed previously by our research group by survey and focus-group methods. In the present study, the NEI-VFQ-25 and 10-Item Supplement were administered concurrently to patients and disease-free control subjects. High-contrast visual acuities with patient usual distance correction were measured with the use of Early Treatment Diabetic Retinopathy Study (ETDRS) charts.ResultsDiagnoses for patients (n = 215) included optic neuritis, multiple sclerosis, idiopathic intracranial hypertension, ischemic optic neuropathy, stroke, ocular myasthenia gravis, ocular motor palsies, and thyroid eye disease. Scores for the 10-Item Supplement had a significant capacity to distinguish patients vs disease-free control subjects that was independent of the NEI-VFQ-25 composite score (odds ratio in favor of patient vs control status for 10-point worsening in Supplement scores: 2.7 [95% confidence interval [CI], 1.6, 4.6]; P < .001, logistic regression models that account for NEI-VFQ-25 composite score, age, and gender). Patients with visual dysfunction (binocular Snellen equivalents worse than 20/20) had significantly lower mean scores (9-21 points lower); these differences remained significant after accounting for age and gender (P >or= .001, linear regression). Supplement items and composite scores demonstrated appropriate degrees of internal consistency reliability.ConclusionThe 10-Item Neuro-Ophthalmic Supplement demonstrates a capacity to capture self-reported visual dysfunction beyond that of the NEI-VFQ-25 alone, which supports validity for this new scale. The use of the 10-Item Supplement in clinical trials and epidemiologic studies will examine its capacity to demonstrate treatment effects in longitudinal cohorts.

Supranuclear gaze palsies are an uncommon feature of Creutzfeldt-Jakob disease (CJD). Most reported cases of CJD with features of supranuclear gaze palsy are familial. We report 2 patients with supranuclear vertical gaze abnormalities associated with spongiform changes in the midbrain. Both patients were found to have sporadic CJD after genetic testing. Distinguishing familial from sporadic CJD in this setting has important genetic and epidemiological implications.

We report a patient with anti-Yo associated paraneoplastic cerebellar degeneration (PCD) whose tumor was demonstrated 5 years after developing PCD and had strong expression of Yo (cdr2) antigen. Review of this case along with clinical series and studies of tumor growth rates question the effectiveness of the anti-tumor immune response. These studies and similar cases suggest that the tumor may trigger the anti-Yo immune response at microscopic stages of development. An overwhelming majority of anti-Yo positive patients eventually develop a detectable malignancy, which argues in favor of a poorly effective or non-sustained anti-tumor immune response.

Background Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an α 4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies. Methods We randomly assigned 1171 patients who, despite interferon beta-1a therapy, had had at least one relapse during the 12-month period before randomization to receive continued interferon beta-1a in combination with 300 mg of natalizumab (589 patients) or placebo (582 patients) intravenously every 4 weeks for up to 116 weeks. The primary end points were the rate of clinical relapse at 1 year and the cumulative probability of disability progression sustained for 12 weeks, as measured by the Expanded Disability Status Scale, at 2 years. Results Combination therapy resulted in a 24 percent reduction in the relative risk of sustained disability progression (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Kaplan–Meier estimates of the cumulative probability of progression at two years were 23 percent with combination therapy and 29 percent with interferon beta-1a alone. Combination therapy was associated with a lower annualized rate of relapse over a two-year period than was interferon beta-1a alone (0.34 vs. 0.75, P

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.