Distinction of seropositive NMO spectrum disorder and MS brain lesion distribution

Abstract

Objective: Neuromyelitis optica and its spectrum disorder (NMOSD) can present similarly to relapsingremitting multiple sclerosis (RRMS). Using a quantitative lesion mapping approach, this research aimed to identify differences in MRI brain lesion distribution between aquaporin-4 antibody-positive NMOSD and RRMS, and to test their diagnostic potential.Methods: Clinical brain MRI sequences for 44 patients with aquaporin-4 antibody-positive NMOSD and 50 patients with RRMS were examined for the distribution and morphology of brain lesions. T2 lesion maps were created for each subject allowing the quantitative comparison of the 2 conditions with lesion probability and voxel-wise analysis.Results: Sixty-three percent of patients with NMOSD had brain lesions and of these 27% were diagnostic of multiple sclerosis. Patients with RRMS were significantly more likely to have lesions adjacent to the body of the lateral ventricle than patients with NMOSD. Direct comparison of the probability distributions and the morphologic attributes of the lesions in each group identified criteria of "at least 1 lesion adjacent to the body of the lateral ventricle and in the inferior temporal lobe; or the presence of a subcortical U-fiber lesion; or a Dawson's finger-type lesion," which could distinguish patients with multiple sclerosis from those with NMOSD with 92% sensitivity, 96% specificity, 98% positive predictive value, and 86% negative predictive value. Neuromyelitis optica (NMO) is an inflammatory demyelinating condition of the CNS with a predilection for the optic nerves and spinal cord. NMO spectrum disorder (NMOSD) is a term used to encompass NMO (with both optic neuritis and myelitis) 1 and limited phenotypes such as recurrent optic neuritis or myelitis. It is an autoimmune disorder, mediated in most cases by antibodies to the aquaporin-4 (AQP4) water channel, 2,3 and for the majority of patients serum AQP4 antibodies (AQP4-abs) can be detected with an immunoassay. 4 Making a definitive diagnosis of antibodynegative NMOSD can be challenging because the more prevalent relapsing-remitting multiple sclerosis (RRMS) can present similarly (e.g., with attacks of optic neuritis and myelitis). 1,5,6 It is vitally important to distinguish these 2 conditions: patients with NMOSD require long-term immunosuppression to prevent devastating relapses, and disease-modifying treatments for RRMS such as b-interferon can worsen NMOSD. Conclusion:7,8 Hence, we need other markers to help promptly identify those who should be antibody tested, and to diagnose seronegative disease.MRI is the best noninvasive tool we have for visualizing the pathology of neuroinflammatory diseases in vivo, and has proven particularly useful in identifying patients with longitudinally extensive transverse myelitis (LETM), which is highly suggestive of NMOSD.

MRI characteristics of neuromyelitis optica spectrum disorder

“…12 Although nonspecific small dots and patches of hyperintensity in subcortical and deep white matter on T2-weighted or fluid-attenuated inversion recovery sequences are the most common findings in NMOSD, certain lesions have a location or appearance characteristic for NMOSD. 6,7,[11][12][13][14][15] Before the discovery of anti-AQP4 antibody, brain MRI abnormalities were reported in only 13% to 46% of patients with NMO. 1,8,16 However, when excluding the brain MRI criteria, the incidence of brain MRI abnormalities increased to 50% to 85% using the revised 2006 NMO diagnostic criteria 3,11,13,17,e1-e3 and to 51% to 89% in seropositive patients with NMOSD.…”

“…However, it is now known that MS-like lesions may appear in 10% to 12.5% of cases, 11,e3 and 5% to 42% of patients with NMO fulfill the Barkhof criteria. 6,14,15,47 A recent report showed that 13% and 9% of patients with NMOSD, respectively, met Barkhof and the European Magnetic Imaging in MS diagnostic criteria for MS on brain MRI at onset. 7 Lesion probability maps have not found statistically significant lesion locations in patients positive for anti-AQP4 antibody over those with MS. 6 However, distinguishing features were identified on MS brain MRI that were sensitive and specific, such as the presence of a lateral ventricle and inferior temporal lobe lesion, Dawson fingers, or an S-shaped U-fiber lesion, to classify the patient as MS.…”

“…6,14,15,47 A recent report showed that 13% and 9% of patients with NMOSD, respectively, met Barkhof and the European Magnetic Imaging in MS diagnostic criteria for MS on brain MRI at onset. 7 Lesion probability maps have not found statistically significant lesion locations in patients positive for anti-AQP4 antibody over those with MS. 6 However, distinguishing features were identified on MS brain MRI that were sensitive and specific, such as the presence of a lateral ventricle and inferior temporal lobe lesion, Dawson fingers, or an S-shaped U-fiber lesion, to classify the patient as MS. Imaging sensitive to cortical lesions has revealed their absence in NMO (excluding one Japanese study of NMO pathology 48 ), whereas they are seen in the majority of patients with MS. 49,50 Characteristic MS brain lesions surround central venule in .80% on high-strength MRI.…”

“…Because long-term systematic imaging studies in NMO have not yet been performed, the reported cross-sectional differences compared with MS require further confirmation. Developing algorithms using the brain criteria described by Matthews et al 6 in combination with spinal cord and optic nerve imaging features and possibly nonconventional imaging may further improve the sensitivity and specificity.…”

“…4 In this regard, MRI has an increasingly important role in differentiating NMOSD from other inflammatory disorders of the CNS, particularly from MS. 6,7 Differentiating these conditions is critical because treatments are distinct. Furthermore, recent advanced MRI techniques are detecting additional specific markers and help elucidate the underlying mechanisms of tissue damage in NMOSD.…”