Optic Neuropathy and Stroke Secondary to Invasive Aspergillus in an Immunocompetent Patient.

Angioinvasive aspergillosis is an aggressive fungal infection that is potentially life threatening without prompt treatment. Optic nerve involvement of Aspergillus can mimic optic neuritis commonly seen in demyelinating and other inflammatory conditions. Treatment of Aspergillus infection with steroids may worsen the clinical course. We describe a unique case of disseminated central nervous system aspergillosis, initially presenting as an optic neuropathy, with subsequent stroke in multiple vascular territories.

Efferent manifestations of multiple sclerosis.

PURPOSE OF REVIEW: To review the various efferent visual system disorders associated with multiple sclerosis (MS). RECENT FINDINGS: Studies have supported the use of internuclear ophthalmoplegia, a model to study effects of fatigue and heat in MS patients. SUMMARY: There are a host of efferent ocular manifestations that can present throughout the course of MS. These may manifest as blurred vision, potentially misleading both the patient and clinician to suspect an afferent visual deficit. Other efferent symptoms include diplopia, oscillopsia, and vertigo. The efferent system can be divided into broad categories: supranuclear, internuclear, nuclear, and gaze-holding systems. This review will briefly touch on the anatomy as well as the signs and symptoms associated with MS-related dysfunction involving these systems.

Clinical Reasoning: A 51-Year-Old Woman With Diplopia and Headache.

A 51-year-old woman presented with a pressure-like headache behind her right eye and horizontal diplopia. On examination, she was unable to abduct or adduct the right eye but had intact vertical eye movements. Her deficits could not be overcome using the oculocephalic reflex. Imaging initially was interpreted as optic neuritis, but on careful review with radiology, a diffuse enhancing hyperintense signal within the orbital apex confirmed an orbital infiltrate. The focus of this case study is to review the localization approach for diplopia and build a differential diagnosis for orbital processes. Another key point is the importance of relying on the physical examination as the guide to a patient's management rather than imaging findings, which can often be misleading.

Comparing Echocardiograms of Haitian and non-Haitian Stroke Patients.

INTRODUCTION: Haitian stroke patients had higher diastolic and mean arterial blood pressures, compared with non-Haitian controls. Therefore, we hypothesized that Haitians would have a higher prevalence of left ventricular hypertrophy and decreased ejection fraction. METHODS: Using the Haitian Stroke Database, a cohort study was conducted. The following transthoracic echocardiographic parameters of 52 Haitians and 111 non-Haitians were compared: left ventricular hypertrophy; ejection fraction; right and left ventricular internal dimension at diastole; and left atrial size. RESULTS: Left ventricular hypertrophy and decreased ejection fraction were more prevalent among Haitians (78% vs. 63%; p=.062 and 21% vs. 13%; p=.173, respectively). Neither reached statistical significance. Left atrial enlargement was significantly more prevalent among non-Haitians (36% vs 15%; p=.007). CONCLUSIONS: Left ventricular hypertrophy and decreased ejection fraction were more prevalent in Haitians, but neither finding reached statistical significance. Larger samples are needed for further understanding of stroke comorbidities in Haitians.

Optical coherence tomography: another useful tool in a neuro-ophthalmologist's armamentarium.

PURPOSE OF REVIEW: Optical coherence tomography (OCT) affords clinicians the ability to quantify the thickness of the retinal nerve fiber layer (RNFL), which is useful in managing diseases of the optic nerve. The purpose of this review is to coalesce the current literature on the use of OCT in neuro-ophthalmology to enhance its use in clinical practice. RECENT FINDINGS: OCT's advancement into spectral domain refined its ability to measure the RNFL by increasing scanner speed. Although OCT was shown to be superior to other instruments in measuring the RNFL in certain conditions, it lacks laser polarimetry's ability to detect microtubule changes. Moreover, OCT's measurements cannot be used interchangeably with other instruments' assessments of the RNFL. OCT has been studied in several neuro-ophthalmic conditions, including anterior ischemic optic neuropathy, optic neuritis/multiple sclerosis, neuromyelitis optica, pseudotumor cerebri, migraine, optic nerve head drusen, compressive optic neuropathy, and Leber's hereditary optic neuropathy. SUMMARY: OCT's wide use in evaluating the optic nerve and the visual system has revolutionized our assessment, management, research, and understanding of neuro-ophthalmic diseases.

Differentiating Acute and Subacute Vertical Strabismus Using Different Head Positions During the Upright-Supine Test.

Importance: Accurate clinical differentiation between skew deviation and fourth nerve palsy (4NP) is critical in the acute and subacute settings. Objective: To determine the sensitivity and specificity of the upright-supine test to detect vertical misalignment changes using different head positions for the diagnosis of acute or subacute skew deviation vs 4NP. Design, Setting, and Participants: This multicenter study enrolled consecutive patients from Coimbra University Hospital Centre, Coimbra, Portugal, and Michigan State University, Lansing, within 2 months of presenting with vertical diplopia and diagnosed as having skew deviation or acquired unilateral 4NP. The study used nonmasked screening and diagnostic test results from June 1, 2013, to December 31, 2016. Data were analyzed from January 1, 2017, to June 30, 2017. Main Outcomes and Measures: A 50% or greater change in vertical misalignment between the upright and supine positions, with the head centered and tilted to either side. Measurements included the alternate prism and cover (APC) test, the double Maddox rod test, the APC test change index ([measurement upright - measurement supine] / [measurement upright + measurement supine]), and the APC test sensitivity and specificity. Results: Of the 37 included patients, the mean (SD) age was 58 (14) years, and 26 (70%) were male. We enrolled 19 patients (51%) with skew deviation and 18 (49%) with 4NP. Eighteen patients with skew deviation (95%) showed additional ocular motor and/or neurological signs. When moving to the supine position, only 1 patient with skew deviation (5%) showed more than a 50% decrease of hypertropia with the head centered (APC test: sensitivity, 5%; specificity, 100%). Three patients with 4NP (17%) showed more than a 50% decrease of hypertropia with the head tilted toward the hypertropic eye, and 10 patients with 4NP (56%) showed more than a 50% increase of hypertropia with the head tilted toward the hypotropic eye. Change indexes were different between the skew deviation and 4NP groups for head tilt to the hypotropic eye (difference, -0.33 prism diopters; 95% CI, -0.43 to -0.20; P < .001). Cyclotorsion worsened in the supine position only in patients with skew deviation (hypertropic eye: difference, -7.6 prism diopters; 95% CI, -13.00 to -0.75; P = .01; hypotropic eye: difference, 8.2 prism diopters; 95% CI, 0 to 15.75; P = .03). Conclusions and Relevance: The upright-supine test with the head centered is not a sensitive method to separate acute or subacute skew deviation from 4NP. Conversion of an incomitant vertical deviation in the upright position to a comitant vertical strabismus in the supine position in all head positions, as well as the absence of additional ocular motor and/or neurologic signs, may constitute a more useful clue.

Retinal Architecture and Melanopsin-Mediated Pupillary Response Characteristics: A Putative Pathophysiologic Signature for the Retino-Hypothalamic Tract in Multiple Sclerosis.

Importance: A neurophysiologic signature of the melanopsin-mediated persistent constriction phase of the pupillary light reflex may represent a surrogate biomarker for the integrity of the retinohypothalamic tract, with potential utility for investigating alterations in homeostatic mechanisms associated with brain disorders and implications for identifying new treatments. Objective: To characterize abnormalities of retinal architecture in patients with multiple sclerosis (MS) and corresponding alterations in the melanopsin-mediated sustained pupillary constriction response. Design, Setting, and Participants: The case-control study was an experimental assessment of various stimulus-induced pupillary response characteristics and was conducted at a university clinical center for MS from September 6, 2012, to February 2015. Twenty-four patients with MS (48 eyes) and 15 individuals serving as controls (30 eyes) participated. The melanopsin-mediated, sustained pupillary constriction phase response following cessation of a blue light stimulus was compared with the photoreceptor-mediated pupillary constriction phase response following cessation of a red light stimulus. Optical coherence tomography was used to characterize the association between pupillary response characteristics and alterations in retinal architecture, specifically, the thickness of the retinal ganglion cell layer and inner plexiform layer (GCL + IPL). Main Outcomes and Measures: Association of pupillary response characteristics with alterations in retinal architecture. Results: Of 24 patients with MS included in the analysis, 17 were women (71%); mean (SD) age was 47 (11) years. Compared with eyes from individuals with MS who had normal optical coherence tomography-derived measures of retinal GCL + IPL thickness, eyes of patients who had GCL + IPL thickness reductions to less than the first percentile exhibited a correspondingly significant attenuation of the melanopsin-mediated sustained pupillary response (mean [SD] pupillary diameter ratios at a point in time, 0.18 [0.1] vs 0.33 [0.09]; P < .001, generalized estimating equation models accounting for age and within-patient intereye correlations). Conclusions and Relevance: In this case-control study, attenuation of the melanopsin-mediated sustained pupillary constriction response was significantly associated with thinning of the GCL + IPL sector of the retina in the eyes of patients with MS, particularly those with a history of acute optic neuritis. Melanopsin-containing ganglion cells in the retina represent, at least in part, the composition of the retinohypothalamic tract. As such, our findings may signify the ability to elucidate a putative surrogate neurophysiologic signature that correlates with a constellation of homeostatic mechanisms in both health and illness.

Risk Mitigation Strategies for Adverse Reactions Associated with the Disease-Modifying Drugs in Multiple Sclerosis.

Over the past several years, the number of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has doubled in number. The 13 approved agents have shown a wide range of efficacy and safety in their clinical trials and post-marketing experience. While the availability of the newer agents allows for a wider selection of therapy for clinicians and patients, there is a need for careful understanding of the benefits and risks of each agent. Several factors such as the medication efficacy, side-effect profile, patient's preference, and co-morbidities need to be considered. An individualized treatment approach is thus imperative. In this review, risk stratification and mitigation strategies of the various disease-modifying agents are discussed.

Sphingosine 1-phosphate receptor modulators in multiple sclerosis.

Sphingosine 1-phosphate (S1P) receptor modulators possess a unique mechanism of action as disease-modifying therapy for multiple sclerosis (MS). Subtype 1 S1P receptors are expressed on the surfaces of lymphocytes and are important in regulating egression from lymph nodes. The S1P receptor modulators indirectly antagonize the receptor's function and sequester lymphocytes in lymph nodes. Fingolimod was the first S1P agent approved in the USA in 2010 for relapsing MS after two phase III trials (FREEDOMS and TRANSFORMS) demonstrated potent efficacy, and good safety and tolerability. Post-marketing experience, as well as a third phase III trial (FREEDOMS II), also showed favorable results. More selective S1P receptor agents-ponesimod (ACT128800), siponimod (BAF312), ozanimod (RPC1063), ceralifimod (ONO-4641), GSK2018682, and MT-1303-are still in relatively early stages of development, but phase I and II trials showed promising efficacy and safety. However, these observations have yet to be reproduced in phase III clinical trials.