Since its initial reports in the 19th century, neuromyelitis optica (NMO) had been thought to involve only the optic nerves and spinal cord. However, the discovery of highly specific antiaquaporin-4 antibody diagnostic biomarker for NMO enabled recognition of more diverse clinical spectrum of manifestations. Brain MRI abnormalities in patients seropositive for anti-aquaporin-4 antibody are common and some may be relatively unique by virtue of localization and configuration. Some seropositive patients present with brain involvement during their first attack and/or continue to relapse in the same location without optic nerve and spinal cord involvement. Thus, characteristics of brain abnormalities in such patients have become of increased interest. In this regard, MRI has an increasingly important role in the differential diagnosis of NMO and its spectrum disorder (NMOSD), particularly from multiple sclerosis. Differentiating these conditions is of prime importance because early initiation of effective immunosuppressive therapy is the key to preventing attack-related disability in NMOSD, whereas some disease-modifying drugs for multiple sclerosis may exacerbate the disease. Therefore, identifying the MRI features suggestive of NMOSD has diagnostic and prognostic implications. We herein review the brain, optic nerve, and spinal cord MRI findings of NMOSD. Neuromyelitis optica (NMO) is an inflammatory disease of the CNS that is characterized by severe attacks of optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM). 1The past decade has witnessed dramatic advances in our understanding of NMO. Such advances were initiated by the discovery of the disease-specific autoantibody, NMO-immunoglobulin G (NMO-IgG), and subsequent identification of the main target autoantigen, aquaporin-4 (AQP4), which has distinguished NMO as a distinct disease from multiple sclerosis (MS). 2Current diagnostic criteria, however, still require both ON and myelitis for an NMO diagnosis.3 Nevertheless, the identification of anti-AQP4 antibodies beyond the current diagnostic criteria of NMO indicates a broader clinical phenotype of this disorder, so-called "NMO spectrum disorder" (NMOSD). 4,5 The NMOSD encompasses anti-AQP4 antibody seropositive patients with limited or inaugural forms of NMO and with specific brain abnormalities. It also includes anti-AQP4 antibody seropositive patients with other autoimmune disorders such as systemic

Neuro-axonal injury is a key factor in the development of permanent disability in multiple sclerosis. Neurofilament light chain in peripheral blood has recently emerged as a biofluid marker reflecting neuro-axonal damage in this disease. We aimed at comparing serum neurofilament light chain levels in multiple sclerosis and healthy controls, to determine their association with measures of disease activity and their ability to predict future clinical worsening as well as brain and spinal cord volume loss. Neurofilament light chain was measured by single molecule array assay in 2183 serum samples collected as part of an ongoing cohort study from 259 patients with multiple sclerosis (189 relapsing and 70 progressive) and 259 healthy control subjects. Clinical assessment, serum sampling and MRI were done annually; median follow-up time was 6.5 years. Brain volumes were quantified by structural image evaluation using normalization of atrophy, and structural image evaluation using normalization of atrophy, cross-sectional, cervical spinal cord volumes using spinal cord image analyser (cordial). Results were analysed using ordinary linear regression models and generalized estimating equation modelling. Serum neurofilament light chain was higher in patients with a clinically isolated syndrome or relapsing remitting multiple sclerosis as well as in patients with secondary or primary progressive multiple sclerosis than in healthy controls (age adjusted P < 0.001 for both). Serum neurofilament light chain above the 90th percentile of healthy controls values was an independent predictor of Expanded Disability Status Scale worsening in the subsequent year (P < 0.001). The probability of Expanded Disability Status Scale worsening gradually increased by higher serum neurofilament light chain percentile category. Contrast enhancing and new/enlarging lesions were independently associated with increased serum neurofilament light chain (17.8% and 4.9% increase per lesion respectively; P < 0.001). The higher the serum neurofilament light chain percentile level, the more pronounced was future brain and cervical spinal volume loss: serum neurofilament light chain above the 97.5th percentile was associated with an additional average loss in brain volume of 1.5% (P < 0.001) and spinal cord volume of 2.5% over 5 years (P = 0.009). Serum neurofilament light chain correlated with concurrent and future clinical and MRI measures of disease activity and severity. High serum neurofilament light chain levels were associated with both brain and spinal cord volume loss. Neurofilament light chain levels are a real-time, easy to measure marker of neuro-axonal injury that is conceptually more comprehensive than brain MRI.

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At present, the diagnosis of multiple sclerosis (MS) relies heavily on the use of MRI, which can demonstrate disease dissemination in space and time [1][2][3][4] . The current 2010 McDonald criteria have enabled earlier diagnosis 5,6 and initiation of disease-modifying treatment, with substantial benefits for disease outcome 7,8 , but they still have imperfect sensitivity and specificity 9,10 . The limited accuracy of the criteria results in challenging cases and misdiagnosis, which are prevalent problems in MS 11,12 . Therefore, more-accurate and pathologically specific MRI criteria are still needed to exclude other disorders that can mimic MS 13,14 .The MRI-detectable central vein inside white matter lesions has recently been proposed as a biomarker of inflammatory demyelination and, thus, may aid the diagnosis of MS 15 . The 'central vein sign' (CVS) has been investigated in various neurological conditions by several groups, and evidence has accumulated that the CVS may have the ability to accurately differentiate MS from its mimics [15][16][17][18][19][20][21] . As a consequence, recent guidelines from the Magnetic Resonance Imaging in MS (MAGNIMS) group 1,4 and the Consortium of MS Centers (CMSC) task force 22 have acknowledged the potential of the CVS and its dedicated MRI acquisitions for the differential diagnosis of MS, while calling for further research before considering a possible modification of the diagnostic criteria. However, the lack of standardization for the definition and imaging of the CVS, as well as a dearth of large-scale prospective studies evaluating the CVS for MS diagnosis, are currently preventing the clinical validation of this potential biomarker 1,23 .This Consensus Statement aims to provide recommendations for the definition, standardization and clinical evaluation of the CVS in the diagnosis of MS. These statements are based on a thorough review of the existing literature on the CVS and the consensus opinion of the members of the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative. E X P E RT C O N S E N S U S D O C U M E N T on behalf of the NAIMS CooperativeAbstract | Over the past few years, MRI has become an indispensable tool for diagnosing multiple sclerosis (MS). However, the current MRI criteria for MS diagnosis have imperfect sensitivity and specificity. The central vein sign (CVS) has recently been proposed as a novel MRI biomarker to improve the accuracy and speed of MS diagnosis. Evidence indicates that the presence of the CVS in individual lesions can accurately differentiate MS from other diseases that mimic this condition. However, the predictive value of the CVS for the development of clinical MS in patients with suspected demyelinating disease is still unknown. Moreover, the lack of standardization for the definition and imaging of the CVS currently limits its clinical implementation and validation. On the basis of a thorough review of the existing literature on the CVS and the consensus opinion of the members of the North American Imaging in Mult...

The Virchow-Robin spaces (VRS), perivascular compartments surrounding small blood vessels as they penetrate the brain parenchyma, are increasingly recognized for their role in leucocyte trafficking as well as for their potential to modulate immune responses. In the present study, we investigated VRS numbers and volumes in different brain regions in 45 multiple sclerosis patients and 30 healthy controls of similar age and gender distribution, applying three different MRI sequence modalities (T(2)-weighted, T(1)-weighted and FLAIR). VRS were detected in comparable numbers in both multiple sclerosis patients and healthy individuals, indicating that perivascular compartments present on MRI are not a unique feature of multiple sclerosis. However, multiple sclerosis patients had significantly larger VRS volumes than healthy controls (P = 0.004). This finding was not explained by a significantly lower brain parenchymal fraction (BPF), resulting from a higher degree of atrophy, in the patient cohort. In a multiple linear regression analysis, age had a significant influence on VRS volumes in the control group but not in multiple sclerosis patients (P = 0.023 and P = 0.263, respectively). A subsequent prospective longitudinal substudy with monthly follow-up MRI over a period of up to 12 months in 18 patients revealed a significant increase in VRS volumes and counts accompanying the occurrence of contrast-enhancing lesions (CEL). At time points when blood-brain barrier (BBB) breakdown was indicated by the appearance of CEL, total VRS volumes and counts were significantly higher compared with preceding time points without CEL (P = 0.011 and P = 0.041, respectively), whereas a decrease thereafter was not statistically significant. Thus, our data points to an association of VRS with CEL as a sign for inflammation rather than with factors such as age, observed in healthy controls, and therefore suggests a role of VRS in inflammatory processes of the brain.

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Identifying effective treatment combinations for MS patients failing standard therapy is an important goal. We report the results of a phase II open label baseline-to-treatment trial of a humanized monoclonal antibody against CD25 (daclizumab) in 10 multiple sclerosis patients with incomplete response to IFN-β therapy and high brain inflammatory and clinical disease activity. Daclizumab was very well tolerated and led to a 78% reduction in new contrast-enhancing lesions and to a significant improvement in several clinical outcome measures.

Anti-NMDAR encephalitis is associated with characteristic alterations of functional connectivity and widespread changes of white matter integrity despite normal findings in routine clinical MRI. These results may help to explain the clinicoradiological paradox in anti-NMDAR encephalitis and advance the pathophysiological understanding of the disease. Correlation of imaging abnormalities with disease symptoms and severity suggests that these changes play an important role in the symptomatology of anti-NMDAR encephalitis.