The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.

/pdf/diagnosis-of-multiple-sclerosis-2017-revisions-of-the-55ct02l5o1.pdf

Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Prior NMO diagnostic criteria required optic nerve and spinal cord involvement but more restricted or more extensive CNS involvement may occur. The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus. The new nomenclature defines the unifying term NMO spectrum disorders (NMOSD), which is stratified further by serologic testing (NMOSD with or without AQP4-IgG). The core clinical characteristics required for patients with NMOSD with AQP4-IgG include clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. More stringent clinical criteria, with additional neuroimaging findings, are required for diagnosis of NMOSD without AQP4-IgG or when serologic testing is unavailable. The IPND also proposed validation strategies and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasic NMOSD and opticospinal MS.

https://n.neurology.org/content/neurology/85/2/177.full.pdf

International consensus diagnostic criteria for neuromyelitis optica spectrum disorders

A subset of patients with neuromyelitis optica spectrum disorders (NMOSD) has been shown to be seropositive for myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) To describe the epidemiological, clinical, radiological, cerebrospinal fluid (CSF), and electrophysiological features of a large cohort of MOG-IgG-positive patients with optic neuritis (ON) and/or myelitis (n = 50) as well as attack and long-term treatment outcomes Retrospective multicenter study The sex ratio was 1:28 (m:f) Median age at onset was 31 years (range 6-70) The disease followed a multiphasic course in 80% (median time-to-first-relapse 5 months; annualized relapse rate 092) and resulted in significant disability in 40% (mean follow-up 75 ± 465 months), with severe visual impairment or functional blindness (36%) and markedly impaired ambulation due to paresis or ataxia (25%) as the most common long-term sequelae Functional blindness in one or both eyes was noted during at least one ON attack in around 70% Perioptic enhancement was present in several patients Besides acute tetra-/paraparesis, dysesthesia and pain were common in acute myelitis (70%) Longitudinally extensive spinal cord lesions were frequent, but short lesions occurred at least once in 44% Fourty-one percent had a history of simultaneous ON and myelitis Clinical or radiological involvement of the brain, brainstem, or cerebellum was present in 50%; extra-opticospinal symptoms included intractable nausea and vomiting and respiratory insufficiency (fatal in one) CSF pleocytosis (partly neutrophilic) was present in 70%, oligoclonal bands in only 13%, and blood-CSF-barrier dysfunction in 32% Intravenous methylprednisolone (IVMP) and long-term immunosuppression were often effective; however, treatment failure leading to rapid accumulation of disability was noted in many patients as well as flare-ups after steroid withdrawal Full recovery was achieved by plasma exchange in some cases, including after IVMP failure Breakthrough attacks under azathioprine were linked to the drug-specific latency period and a lack of cotreatment with oral steroids Methotrexate was effective in 5/6 patients Interferon-beta was associated with ongoing or increasing disease activity Rituximab and ofatumumab were effective in some patients However, treatment with rituximab was followed by early relapses in several cases; end-of-dose relapses occurred 9-12 months after the first infusion Coexisting autoimmunity was rare (9%) Wingerchuk’s 2006 and 2015 criteria for NMO(SD) and Barkhof and McDonald criteria for multiple sclerosis (MS) were met by 28%, 32%, 15%, 33%, respectively; MS had been suspected in 36% Disease onset or relapses were preceded by infection, vaccination, or pregnancy/delivery in several cases Our findings from a predominantly Caucasian cohort strongly argue against the concept of MOG-IgG denoting a mild and usually monophasic variant of NMOSD The predominantly relapsing and often severe disease course and the short median time to second attack support the use of prophylactic long-term treatments in patients with MOG-IgG-positive ON and/or myelitis

/pdf/mog-igg-in-nmo-and-related-disorders-a-multicenter-study-of-3lmh0pnmry.pdf

MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome

In patients presenting with a clinically isolated syndrome, MRI can support and substitute clinical information in the diagnosis of multiple sclerosis by showing disease dissemination in space and time and by helping to exclude disorders that can mimic multiple sclerosis. MRI criteria were first included in the diagnostic work-up for multiple sclerosis in 2001, and since then several modifications to the criteria have been proposed in an attempt to simplify lesion-count models for showing disease dissemination in space, change the timing of MRI scanning to show dissemination in time, and increase the value of spinal cord imaging. Since the last update of these criteria, new data on the use of MRI to establish dissemination in space and time have become available, and MRI technology has improved. State-of-the-art MRI findings in these patients were discussed in a MAGNIMS workshop, the goal of which was to provide an evidence-based and expert-opinion consensus on proposed modifications to MRI criteria for the diagnosis of multiple sclerosis.

/pdf/mri-criteria-for-the-diagnosis-of-multiple-sclerosis-magnims-49e6ewajdo.pdf

MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines.

Population incidence of Guillain-Barre syndrome (GBS) is required to assess changes in GBS epidemiology, but published estimates of GBS incidence vary greatly depending on case ascertainment, definiti

/pdf/population-incidence-of-guillain-barre-syndrome-a-systematic-3smew7p11a.pdf

Population incidence of Guillain-Barré syndrome: a systematic review and meta-analysis.

Editors' Note: The international consensus diagnostic criteria for neuromyelitis optica spectrum disorders (NMOSD) article prompted reactions from our readers. Tan is concerned that the new criteria may include patients without true neuromyelitis optica and may affect treatment funding. Recounting their own experience, Mao et al. caution about overinterpretation of MRI results and suggest that aquaporin-4 antibody (AQP4-Ab) testing be considered in late-onset demyelinating disease. In response, Wingerchuk et al., authors of the guidelines, stress that the diagnostic category of NMOSD without AQP4–immunoglobulin G requires exclusion of alternative diagnoses, believe that the new criteria will facilitate—rather than hinder—insurance coverage for appropriate immunosuppressive treatments, and agree with the observations raised by Mao et al. —Chafic Karam, MD, and Robert C. Griggs, MD 

Wingerchuk et al.1 proposed criteria for neuromyelitis optica (NMO) spectrum disorders (NMOSD) that incorporated unifying the terms NMO and NMOSD, including patients with aquaporin-4 (AQP4)–immunoglobulin G (IgG) negative/unknown, thus giving these patients …

International consensus diagnostic criteria for neuromyelitis optica spectrum disordersAuthor Response

Editors' Note: In reference to the article “Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders,” Mao et al. bring up the conflicting data and many challenges associated with this area of study. Authors Sato et al. address their concerns. Commenting on a p value of <0.0000, Lopez Valle and author Gronseth discuss how low a p value can go. —Megan Alcauskas, MD, and Robert C. Griggs, MD 

Sato et al.1 assessed the differences among patients with neuromyelitis optica spectrum disorders who have myelin oligodendrocyte glycoprotein (MOG) antibodies, aquaporin-4 (AQP4) …

https://n.neurology.org/content/neurology/83/5/475.full.pdf

Distinction between MOG antibody–positive and AQP4 antibody–positive NMO spectrum disordersAuthor Response

The course of myasthenia gravis (MG) may get complicated by the development of other autoimmune diseases. Estimates of the frequency of autoimmune diseases will help inform patients and physicians, direct health policy discussion, provide etiologic clues, and optimize the management of MG. However, the frequency of autoimmune diseases in people with MG is still uncertain. A systematic search for English language studies was conducted by MEDLINE and EMBASE from 1960 through 2010. Incidence studies and case series of all MG subtypes with information about autoimmune diseases were included; 25 studies met the inclusion criteria. Although there was considerable heterogeneity, the pooled estimate of the coexisting autoimmune diseases in MG was 13% (95% confidence interval, 12%–14%). Autoimmune thyroid disease seems to occur more frequently than other autoimmune conditions in MG patients. Heterogeneity in study estimates could be explained by ascertainment bias and case mix. Furthermore, autoimmune diseases occurred significantly more often in females and antiacetylcholine receptor seropositive MG patients. Patients with MG have an increased frequency of coexisting autoimmune diseases. Autoimmune diseases seem to occur more often in female and seropositive MG patients. Further research is needed to expand our understanding of these associations.

Frequency of autoimmune diseases in myasthenia gravis: a systematic review

Predictors associated with stroke after coronary artery bypass grafting: a systematic review.

Background and purpose Myasthenia gravis (MG) is usually comorbid with thymoma. More accurate estimates of the incidence thymoma in MG will help inform patients and their physicians, facilitate health policy discussions, provide etiologic clues, and optimize the management of MG. Methods We conducted a systematic review search of relevant English-language studies published between 1960 and 2012 using MEDLINE and Embase. We identified additional studies by reviewing the bibliographies of the retrieved articles and hand searched the main neurology journals. Only incidence studies and case series of unselected MG patients in which information about thymoma were included. Results Out of 2206 potentially relevant studies, 49 met the inclusion criteria. Although there was a considerable degree of heterogeneity, the pooled estimate of the incidence of thymoma in MG was 21% (95% confidence interval, 20-22%). The pooled incidence was significantly higher for surgery-based studies than for population- and hospital-based studies. A large proportion of the reported thymomas were noninvasive. Furthermore, thymoma appears to occur significantly more frequently among male MG patients and those older than 40 years at the onset of MG. Conclusions Thymoma is common in MG patients, but appears to be found more often in male MG patients and those older than 40 years at the onset of MG. Further research is needed to expand our understanding of these association conditions.

/pdf/incidence-of-thymoma-in-myasthenia-gravis-a-systematic-26b28hw6ud.pdf

Zhifeng Mao

Papers

International consensus diagnostic criteria for neuromyelitis optica spectrum disordersAuthor Response

Distinction between MOG antibody–positive and AQP4 antibody–positive NMO spectrum disordersAuthor Response

Frequency of autoimmune diseases in myasthenia gravis: a systematic review

Predictors associated with stroke after coronary artery bypass grafting: a systematic review.

Incidence of thymoma in myasthenia gravis: a systematic review