Aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies in immune-mediated optic neuritis at long-term follow-up

OBJECTIVES: To re-evaluate serum samples from our 2007 cohort of patients with single-episode isolated ON (SION), recurrent isolated ON (RION), chronic relapsing inflammatory optic neuropathy (CRION), multiple sclerosis-associated ON (MSON) and neuromyelitis optica (NMO). METHODS: We re-screened 103/114 patients with available serum on live cell-based assays (CBA) for aquaporin-4 (AQP4)-M23-IgG and myelin-oligodendrocyte glycoprotein (MOG)-α1-IgG. Further testing included oligoclonal bands, serum levels of glial fibrillar acidic and neurofilament proteins and S100B. We show the impact of updated serology on these patients. RESULTS: Reanalysis of our original cohort revealed that AQP4-IgG seropositivity increased from 56% to 75% for NMO, 5% to 22% for CRION, 6% to 7% for RION, 0% to 7% for MSON and 5% to 6% for SION. MOG-IgG1 was identified in 25% of RION, 25% of CRION, 10% of SION, 0% of MSON and 0% of NMO. As a result, patients have been reclassified incorporating their autoantibody status. Presenting visual acuity was significantly worse in patients who were AQP4-IgG seropositive (p=0.034), but there was no relationship between antibody seropositivity and either ON relapse rate or visual acuity outcome. CONCLUSIONS: The number of patients with seronegative CRION and RION has decreased due to improved detection of autoantibodies over the past decade. It remains essential that the clinical phenotype guides both antibody testing and clinical management. Careful monitoring of the disease course is key when considering whether to treat with prophylactic immune suppression

Prognosis of the individual course of disease - steps in developing a decision support tool for Multiple Sclerosis

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis is a chronic disease of uncertain aetiology. Variations in its disease course make it difficult to impossible to accurately determine the prognosis of individual patients. The Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) developed an "online analytical processing (OLAP)" tool that takes advantage of extant clinical trials data and allows one to model the near term future course of this chronic disease for an individual patient.</p> <p>Results</p> <p>For a given patient the most similar patients of the SLCMSR database are intelligently selected by a model-based matching algorithm integrated into an OLAP-tool to enable real time, web-based statistical analyses. The underlying database (last update April 2005) contains 1,059 patients derived from 30 placebo arms of controlled clinical trials. Demographic information on the entire database and the portion selected for comparison are displayed. The result of the statistical comparison is provided as a display of the course of Expanded Disability Status Scale (EDSS) for individuals in the database with regions of probable progression over time, along with their mean relapse rate. Kaplan-Meier curves for time to sustained progression in the EDSS and time to requirement of constant assistance to walk (EDSS 6) are also displayed. The software-application OLAP anticipates the input MS patient's course on the basis of baseline values and the known course of disease for similar patients who have been followed in clinical trials.</p> <p>Conclusion</p> <p>This simulation could be useful for physicians, researchers and other professionals who counsel patients on therapeutic options. The application can be modified for studying the natural history of other chronic diseases, if and when similar datasets on which the OLAP operates exist.</p

Patient with neuromyelitis optica and inflammatory demyelinating lesions comprising whole spinal cord from C2 level till conus: case report

BACKGROUND: Neuromyelitis optica (NMO) is an idiopathic, severe, inflammatory demyelinating disease of the central nervous system, that causes severe optic neuritis and myelitis attacks. Early discrimination between multiple sclerosis (MS) and NMO is important, as optimum treatment for both diseases may differ considerably. ----- CASE PRESENTATION: We report a case of a patient who initially presented as longitudinally extensive transverse myelitis (LETM), having spastic upper extremities diparesis and spastic paraplegia, C2/C3 sensory level and urinary incontinence, as well as extensive inflammatory spinal cord lesions from C2 level to conus. After 5 months the patient had another attack of transverse myelitis, had electrophysiological findings consistent with optic neuritis, was seropositive for NMO-IgG (aquaporin-4 IgG) and thus fulfilled NMO diagnostic criteria. Following treatment of disease attacks with pulse corticosteroid therapy and intravenous immunoglobulins, we included oral azathioprine in a combination with oral prednisone in the therapy. Since there was no significant clinical improvement, we decided to use cyclophosphamide therapy, which resulted in good clinical improvement and gradual decrease of cord swelling. ----- CONCLUSION: In this NMO case report we wanted to emphasize the extensiveness of inflammatory spinal cord changes in our patient, from C2 level to conus. In the conclusion it is important to say that accurate, early diagnosis and distinction from MS is critical to facilitate initiation of immunosuppressive therapy for attack prevention

Differential diagnosis of suspected multiple sclerosis: a consensus approach

BACKGROUND AND OBJECTIVES: Diagnosis of multiple sclerosis (MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis. METHODS: Using available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases. RESULTS: We present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of "clinically isolated syndromes" (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system. CONCLUSIONS: Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision

Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients

BACKGROUND: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. OBJECTIVE: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. METHODS: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). RESULTS: Seropositive patients were found to be predominantly female (p 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. CONCLUSION: This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients