Optic-spinal Multiple Sclerosis Research Articles

Prevalence of, and Disability Due to, Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder in Japan by the Fifth Nationwide Survey.

All 4 previous nationwide surveys of multiple sclerosis (MS) in Japan were conducted before the discovery of anti-aquaporin-4 (AQP4) antibodies; thus, neuromyelitis optica spectrum disorder (NMOSD) was included in MS, as optic-spinal MS. We aimed to clarify the epidemiologic features and trends of MS and NMOSD in Japan separately using a fifth nationwide survey. The primary survey, in which a questionnaire was sent to 3,799 selected departments (including neurology/internal medicine, pediatrics, and ophthalmology), explored the estimated number and prevalence of patients with MS or NMOSD in 2017, and the secondary survey collected detailed characteristics of the patients using a second questionnaire. The response rates for the primary and secondary surveys were 60.1% and 53.9%, respectively. The estimated total number of patients with MS or NMOSD was 24,800, 2.5-fold higher than that in the fourth survey in 2003. The crude prevalence was 19.6 per 100,000 patients (14.2 for MS and 5.4 for NMOSD), compared with 7.7 per 100,000 patients in the fourth survey. Patients with MS showed milder disability (median Expanded Disability Status Scale [EDSS] score: 2.0 [interquartile range 1.0-4.5] vs 2.5 [1.0-6.0]), decreased secondary progression (8.5% vs 15.2%), and increased usage of disease-modifying drugs (63.7% vs 37.2%) compared with those with conventional MS in the fourth survey. The proportions of oligoclonal bands and Barkhof criteria fulfillment on MRI, which are features of classical MS, increased with advancing year of birth. Patients with NMOSD also showed less disability and shorter disease duration than patients with optic-spinal MS in the fourth survey (EDSS score: 3.5 [2.0-5.5] vs 3.8 [2.0-6.0]; disease duration: 8.0 [3.9-14.8] vs 10.0 [5.0-16.0]). Among patients with NMOSD, disability was exacerbated by a history of longitudinally extensive spinal cord lesions and anti-AQP4 antibody positivity, which both decreased with advancing year of birth. The prevalences of MS (particularly with classical features) and NMOSD have been increasing in Japan, suggesting the contribution of environmental factors. However, disabilities in patients with MS and NMOSD have been mitigated. Extensive usage of various disease-modifying drugs could be a factor contributing to this disability mitigation in MS.

Brain volume data in Brazilian patients with opticspinal and conventional multiple sclerosis

Opticspinal Multiple Sclerosis (OSMS) is a MS phenotype described in Asian population characterized nowdays by recurrent optic neuritis and transverse myelitis small spinal cord lesions and AQP4 – Ab negative. The objective of the study was to analyze and compare Brain MRI by MSmetrix reports in OSMS and Conventional MS patients (CMS) from Rio de Janeiro where the majority of the population is Afro descendent. 58 MS patients were scanned on HDxt GE 1,5 T. For each scanner a 3D T1 and 3D FLAIR were acquired and analysed blinded in icometrix platform. Data on whole brain volume (WBV), gray matter volume (GMV), total load volume 3DT1, 3DFLAIR image and white matter lesions segmentation were analyzed and compared blinded between OSMS and RRMS groups. OSMS and CMS groups had similar demographic and long term disability (Median EDSS <1.5). OSMS had a longer time of disease (19 versus 13 years) . As shown at Table 1, the total load volume 3DFLAIR and periventricular and deep white matter load lesions were significantly higher in CMS than OSMS. Periventricular lesions were identified in 100% of the participants but infratentorial lesions ocurred in 50% of OSMS and 27,9 of CMS and deep WM lesions in 100% of CMS and 30% of OSMS. Cerebral atrophy measured by the WBV and GMV not differed between the groups, however, the 3DT1 volume was significantly higher in CMS. MSmetrix records showed different T2 and T1 patterns of Brain lesions between OSMS and CMS.

Neuromyelitis optica and optic spinal multiple sclerosis are different diseases?

Neuromyelitis optica and optic spinal multiple sclerosis are different diseases?

AQP4 antibody–positive Thai cases

To evaluate the prevalence of aquaporin-4 (AQP4) antibody in Thai patients with idiopathic inflammatory demyelinating CNS diseases (IIDCDs) and to analyze the significance of the autoantibody to distinguish neuromyelitis optica (NMO) and other NMO spectrum disorders (ONMOSDs) from other IIDCDs, especially multiple sclerosis (MS). We retrospectively evaluated 135 consecutive patients with IIDCDs seen at the MS clinic at Siriraj Hospital, Bangkok, Thailand, and classified them into NMO, ONMOSDs, optic-spinal MS (OSMS), classic MS (CMS), and clinically isolated syndrome (CIS) groups in this order with accepted diagnostic criteria. The patients' coded sera were tested separately for AQP4 antibody. Then the relations between the clinical diagnosis and the AQP4 antibody serologic status were analyzed. Among the 135 patients, 53 (39.3%) were AQP4 antibody-positive. Although the AQP4 antibody-positive group had features of NMO, such as female predominance, long cord lesions (>3 vertebral bodies), and CSF pleocytosis, only 18 patients (33% of 54) fully met Wingerchuk 2006 criteria except for AQP4 antibody-seropositive status. We also detected some AQP4 antibody-positive patients in the OSMS (4 of 7), CMS (11 of 46), and CIS (1 of 16) groups. These patients had been misdiagnosed with MS because they often had brain lesions and never underwent spinal cord MRI examination or lacked long cord lesions. AQP4 antibody was highly prevalent (almost 40%) in Thai patients with IIDCDs. Moreover, only one-third of AQP4 antibody-positive patients fully met Wingerchuk 2006 criteria, and many were misdiagnosed with MS. A sensitive AQP4 antibody assay is required in this region because the therapy for NMO is different from that for MS.

Does detection of anti-AQP4 antibodies trump clinical criteria for neuromyelitis optica?

Neuromyelitis optica (NMO) is a common or even predominant form of CNS demyelinating disease in Asian and African countries, but controversy as to how it can be distinguished from multiple sclerosis (MS) in Asian countries persists. In this issue of Neurology ®, Siritho et al.1 report a retrospective analysis of 135 consecutive Thai patients with idiopathic inflammatory CNS demyelinating disease. These patients were categorized sequentially by satisfying the most specific to least specific clinical criteria, as follows: NMO, based on Wingerchuk et al. 2006 criteria2 (excluding anti-aquaporin 4 [AQP4] seropositivity); NMO spectrum disorder (limited forms of myelitis or optic neuritis syndromes, in some cases with brain lesions now regarded as suggestive of NMO); optic-spinal MS (dominant optic neuritis and myelitis but lacking a longitudinally extensive spinal cord lesion [LESCL], precluding a diagnosis of definite NMO); classic MS; and indeterminate clinically isolated syndromes. Serum was tested blind in Japan for AQP4 autoantibodies using a sensitive cell-based immunofluorescence assay; 40% were seropositive. Although the proportion of seropositive cases in each category declined from NMO (78%) to clinically isolated syndrome (6.3%), the proportion of seropositive cases among the total study population was equally distributed among 3 categories: 34% NMO, 36% NMO spectrum disorder, and 30% others, including classic MS. Considering the specificity of AQP4 antibodies as demonstrated worldwide, at first glance …

IFNβ-1b may severely exacerbate Japanese opticspinal MS in neuromyelitis optica spectrum: Japanese optic-spinal MS: Is it MS or neuromyelitis optica and does the answer dictate treatment?

# {#article-title-2} To the Editor: Shimizu et al.1 report increased demyelination and inflammation following interferon-β-1b (IFNβ-1b) therapy in patients with opticospinal multiple sclerosis (OSMS) and neuromyelitis optica (NMO). In the accompanying editorial, Drs. Weinshenker and Wingerchuk2 discuss whether a shift of immune response secondary to treatment with IFNβ-1b may account for the unpredictable response. We contend that the offset of immune response capable of unpredictable demyelinating attacks is unknown and not necessarily confined to B-cell activity or Th2 shift. A 42-year-old Caucasian woman had, over the course of 6 months, 2 episodes of optic neuritis—one in each eye—and 2 attacks to the spinal cord consistent with acute recurrent myelitis. The MRI brain showed no signs of demyelination and, despite negative NMO–immunoglobulin G (IgG), the patient was started on rituximab. Within 2 weeks, she developed a left hemispheric brain lesion similar to the one shown in figure 1A.1 The brain lesion continued to expand and after 6 courses of monthly cyclophosphamide the active process was suppressed. The pathology obtained via brain biopsy revealed reactive hypercellularity with …

Therapeutic Efficacy of Interferon .BETA.-1b in Japanese Patients with Optic-Spinal Multiple Sclerosis

Optic neuritis and myelitis are manifestations in both multiple sclerosis (MS) and neuromyelitis optica (NMO). But unlike MS, NMO is characterized by severe optic neuritis, longitudinally extensive and transverse myelitis, and the presence of aquaporin-4 antibody. Since patients with optic neuritis and myelitis have often been diagnosed with "optic-spinal MS (OSMS)" in Asia, it was obscure whether "OSMS" is synonymous with NMO or includes both NMO and MS. Interferon β (IFNβ)-1a and -1b are used as the first-line disease-modifying therapy for MS. However, some neurologists have been reluctant to use IFNβ to treat patients with optic-spinal symptoms, because IFNβ therapy is not efficacious in NMO. To evaluate the therapeutic effect of IFNβ in patients with "genuine" OSMS, we retrospectively evaluated Japanese MS patients who fulfilled the following six criteria: 1) Relapsing-remitting MS with optic-spinal presentation alone (no brain symptoms), 2) With or without asymptomatic brain MRI lesions, 3) Oligoclonal IgG band-positive, 4) aquaporin-4 antibody seronegativity, 5) No myelitis extending longitudinally over ≥ 3 vertebral segments, and 6) Duration of IFNβ-1b therapy ≥ 2 years. Among 157 patients with MS, six (four women and two men, age 43.8 ± 8.5 years old) met all the criteria. Their Expanded Disability Status Scale scores were lowered (4.1 ± 2.4 → 3.1 ± 2.8) (P = 0.033) and annualized relapse rate was decreased (0.59 ± 0.34 → 0.13 ± 0.15) (P = 0.027) after IFNβ-1b therapy. These results suggest that IFNβ is therapeutically effective in inhibiting functional worsening and reducing relapse rate in "genuine" OSMS.

Insights into the changing perspectives of multiple sclerosis in India.

Multiple Sclerosis (MS) is being diagnosed in increasing numbers in metropolitan cities of India for which the availability of specialist neurologists and magnetic resonance imaging (MRI) facilities are primarily responsible. Epidemiological data are unavailable. Existing data have been obtained from small often retrospective studies from different parts of the country. These earlier studies suggested that optic nerve and spinal cord involvement are considerably high, and that perhaps optic spinal MS was the most prevalent form in India. On this basis it was also speculated that neuromyelitis optica (NMO) may be overrepresented in Indians. However in recent times, prospective studies backed by MRI data have shown no distinct differences between MS seen in the west and India. Sero positivity for NMO IgG is low though NMO phenotype disorders constitute nearly 20% of demyelinating disorders in India. Genetic susceptibility for MS among Indians may be similar to that for white populations. In the major histocompatibility complex (MHC), HLA DR1∗1501 has been strongly associated with MS in Indians. A recent study that evaluated the established non-MHC multiple sclerosis loci in a small data set of Indian patients suggested a strong similarity with white populations. This review highlights some of the background information available on MS from India and so also some recent studies that unveiled the disease characteristics in Indian patients.

IFNβ-1b may severely exacerbate Japanese optic-spinal MS in neuromyelitis optica spectrum

Interferon-β-1b (IFNβ-1b) has been used to prevent exacerbation of relapsing-remitting multiple sclerosis (RRMS) including optic-spinal multiple sclerosis (OSMS) in Japan. We encountered 2 patients with OSMS with unexpectedly severe exacerbation soon after the initiation of IFNβ-1b therapy. The experience urged us to retrospectively review the patients with RRMS who had been treated with IFNβ-1b to identify similar cases. At neurologic departments of 9 hospitals, the medical records of 56 patients with RRMS were reviewed to identify those who showed severe exacerbation soon after the initiation of IFNβ-1b therapy. Of 56 patients with RRMS, we identified 7 who experienced severe exacerbation (exacerbation with increased scores of Expanded Disability Status Scale ≧7.0) within 90 days of the initiation of IFNβ-1b therapy. In all 7 patients, the exacerbations after the initiation of IFNβ-1b therapy were more severe than those experienced by the individual patients before the use of IFNβ-1b, and seemed to have occurred unexpectedly in a short time after the initiation of INFβ-1b therapy. A retrospective analysis revealed that all 7 patients had antibodies toward aquaporin 4, and the clinical features of all 7 patients after the exacerbation were consistent with those of neuromyelitis optica (NMO) spectrum. Our study suggests that IFNβ-1b may trigger severe exacerbation in patients with the NMO spectrum. In INFβ-1b therapy, cases in NMO spectrum should be carefully excluded.

Japanese optic-spinal MS

A major advance over the past decade in the nosology of CNS inflammatory demyelinating diseases has been the distinction between classic MS (CMS) and neuromyelitis optica (NMO). Japanese investigators were first to recognize the optic-spinal form of MS (OSMS) in which, like NMO, clinical attacks of transverse myelitis and optic neuritis predominate. However, despite diagnostic advances that have facilitated the distinction between CMS and NMO, the relationship of Asian OSMS to MS and NMO as diagnosed in Western countries is still controversial. In both OSMS and NMO, the occurrence of aquaporin-4 autoantibodies and longitudinally extensive spinal cord lesions and less common but highly specific symptoms such as intractable vomiting and hiccough in both OSMS and NMO suggest that they are identical.1,–,3 However, some Japanese and Asian investigators argue that no characteristic is specific and that OSMS and classic MS represent a continuum.4,5 Another source of confusion is the changing definition of the NMO clinical phenotype based on a new biomarker, aquaporin-4 autoantibodies. It is now apparent that brain MRI lesions, once a key exclusion for NMO, occur in most cases, sometimes with patterns specific to NMO.6,7 Japanese investigators do not diagnose OSMS in patients with brain lesions. This issue is more than semantic as standard immunomodulatory MS therapies …

Heterogeneity and continuum of multiple sclerosis phenotypes in Japanese according to the results of the fourth nationwide survey

There are two distinct phenotypes of multiple sclerosis (MS) in Asians, optic-spinal MS (OSMS) and conventional MS (CMS). In 2004, we performed the fourth nationwide epidemiological survey of MS. The epidemiological features were reported elsewhere; here we report the characteristic features of patients with each MS phenotype, classified according to the clinically estimated sites of involvement and MRI findings. Among 1493 MS patients collated, 57.7% were classified as having CMS and 16.5% were classified as having OSMS. Based on MRI findings, MS patients were further subdivided into those with OSMS with or without longitudinally extensive spinal cord lesions (LESCLs) and those with CMS with or without LESCLs. Although disease duration did not differ significantly among the four groups, EDSS scores were significantly higher in patients with LESCLs than in those without LESCLs, irrespective of OSMS or CMS phenotype. Similar trends were found for the frequencies of bilateral visual loss, transverse myelitis, and marked CSF pleocytosis and neutrophilia. Increased IgG index, brain lesions fulfilling the Barkhof criteria and secondary progression were more commonly found in CMS patients than in OSMS patients, while negative brain MRIs were more commonly encountered in OSMS patients than CMS patients, irrespective of the presence of LESCLs. These findings suggest that demographic features not only vary based on CMS or OSMS phenotype, but also with the presence or absence of LESCLs, and that nonetheless, these four phenotypes constitute a continuum.

Increasing prevalence and incidence of multiple sclerosis in northern Japan

Background We previously reported that prevalence of multiple sclerosis (MS) in Japan was 8.6/100,000 individuals in 2001. This was much higher than prevalence previously reported from Asian countries. A second epidemiologic survey was conducted to assess changes in MS prevalence and incidence over the last 30 years in Tokachi province of Hokkaido, the northernmost island of Japan. Methods The authors studied the frequency of MS in the community of Tokachi Province, where the population has stabilized between 350,000 and 360,000 over the last 30 years. The survey was conducted at the same institutions using the same methods as the first survey in 2001. Results On March 31, 2006, 47 subjects satisfied Poser’s criteria for MS. The prevalence rate increased from 8.6 to 13.1/100,000 individuals between 2001 and 2006. The prevalence of conventional MS (C-MS) increased in five years although the prevalence of optic-spinal MS (OS-MS) did not increase. The mean annual incidence increased from 0.15 (1975–1989) to 0.68 (1990–2004). Conclusions The results show the highest MS prevalence in Asia; the increase in MS prevalence in Tokachi Province may be due to increased incidence after 1990.

Characterisation of the spectrum of demyelinating disease in Western Australia

Background: The diversity of multiple sclerosis (MS) and the nosology of the conventional form of MS (CMS), optic-spinal MS (OSMS) and neuromyelitis optica (NMO) have been subject to controversy. Aims:...

Complexity and heterogeneity in demyelinating disease

In 1894, Eugene Devic (1858–1930) described a 45-year-old female hatter in whom ‘l’autopsie revela l’existence d’un foyer de myelite aigue diffuse localisee a la region du renflement lombaire et d’une nevrite optique double bien marquee’ … the autopsy showed a focus of acute diffuse myelitis localized to the lumbar enlargement, as well as a distinct bilateral optic neuritis (Devic, 1894). He called the condition ‘neuromyelite optique aigue’. Subsequently, it has not proved easy to establish the relationship between neuromyelitis optica and multiple sclerosis. Epidemiological studies performed during the second half of the 20th century show clearly that the typical form of demyelinating disease in Africa, Asia, the Far East and Aboriginal populations is neuromyelitis optica or optic-spinal multiple sclerosis. The relapsing-remitting phenotype, affecting many sites within the brain and spinal cord, is relatively uncommon by comparison with these features of multiple sclerosis in northern Europeans. Until recently, criteria for the diagnosis of neuromyelitis optica included: bilateral optic neuritis and acute myelitis with no evidence for clinical disease in other parts; a spinal lesion extending over ≥3 segments on MR imaging and without cerebral lesions; abnormal cerebrospinal fluid with >50 wbc or >5 neutrophils; and the course either monophasic or relapsing and remitting (Wingerchuk et al ., 1999). Meanwhile the neuropathology of human demyelinating disease was undergoing re-evaluation. Neuromyelitis optica is characterized by extensive demyelination with partial necrosis of the spinal cord white and grey matter, acute axonal injury, eosinophil and granulocyte inflammatory infiltrates, deposition of IgG and IgM, and perivascular complement activation (Lucchinetti et al ., 2002). These features mimic those seen in some more typical cases of multiple sclerosis—the so-called pattern II that, alongside cases characterized by predominant T cell and macrophage infiltration (pattern I), hypoxia-like changes (pattern III) or primary damage to oligodendrocytes (pattern IV) supports the …

Magnetic Resonance Imaging of Asians with Multiple Sclerosis was Similar to that of the West

Magnetic resonance imaging (MRI) of the brain is the most important paraclinical diagnostic test in multiple sclerosis (MS). The appearance of MRI in Asians with MS is not well defined. We retrospectively surveyed the first brain and spinal cord MRI in patients diagnosed to have MS, according to Poser's criteria in seven regions throughout Asia to define the MRI changes among Asians with MS. There were 101 patients with first brain, and 86 with first spinal cord MRI, 66 of whom had both. The brain MRI showed a mean of 17 lesions per patient in T2 weighted images, mostly asymptomatic. Almost all the lesions were in the white matter, particularly in the juxtacortical, deep and periventricular white matter. A third of the lesions were greater than 5 mm, 14% enhanced with gadolinium. There were more supratentorial than infratentorial lesions at a ratio of 7.5: 1. Ninety five percent of the spinal cord lesions were in cervical and thoracic regions, 34% enhanced with gadolinium. The lesions extended over a mean of 3.6 +/- 3.3 vertebral bodies in length. Fifty (50%) of the brain and 54 (63%) of the spinal MRI patients had the optic-spinal form of MS. The MRI of the optic-spinal and classical groups of patients were similar in appearance and distribution, except that the optic-spinal MS patients have fewer brain but longer and more severe spinal cord lesions. In conclusion, the brain and spinal cord MRI of Asian patients with MS was similar to that of the West, although, in this study, Asian MS patients had larger spinal cord lesions.

Loss of Aquaporin-4 in Active Perivascular Lesions in Neuromyelitis Optica: A Case Report

Neuromyelitis optica (NMO) is clinically characterized by severe optic neuritis and transverse myelitis. In Japan, NMO has been named optic-spinal multiple sclerosis (OSMS) and it has been thought to be a subtype of multiple sclerosis (MS). However, several clinical and laboratory findings suggest NMO or OSMS is distinct from MS. Recently, the disease-specific antibody (NMO-IgG) was found in the serum from NMO patients, and its target antigen was identified as aquaporin-4 (AQP4) water channel protein which is mainly expressed in astroglial foot processes. However, the pathogenetic role of AQP4 in NMO remains unknown. We herein report a typical case of NMO in which immunohistochemical analysis showed a lack of AQP4 in the spinal cord lesions. The loss of AQP4 was evident in the central gray matter, especially in the perivascular lesions where immunoglobulins and complements were deposited, and glial fibrillary acidic protein (GFAP) staining was weak in those lesions. However, GFAP was strongly stained at the reactive astrogliosis surrounding the lesions. Myelin basic protein (MBP)-stained myelinated fibers were relatively preserved in the lesions where AQP4 was lost. In contrast to these NMO lesions, AQP4 was expressed predominantly in the gray matter in control spinal cords, and AQP4 was preserved in demyelinating MS lesions. Our findings suggest that astrocytic impairment associated with humoral immunity against AQP4 may be primarily involved in the lesion formation of NMO, and that the pathomechanisms of NMO are different from those of MS in which demyelination is the primary pathology.

Interferon beta-1b is effective in Japanese RRMS patients

To assess the efficacy of interferon beta-1b (IFNB-1b) in Japanese patients with relapsing-remitting multiple sclerosis (RRMS). The effects of IFNB in RRMS have been assessed in study populations comprised predominantly of white patients. MS in Japanese patients is different from that in white patients in that there are two different presentations--classic MS (C-MS) and optic-spinal MS (OS-MS)--and chronic progressive forms are infrequent. A total of 205 Japanese patients with RRMS were randomized to receive 50 microg or 250 microg (1.6 or 8.0 MIU) IFNB-1b administered SC every other day for up to 2 years. The primary endpoint was annual relapse rate. Secondary endpoints included further relapse-related and MRI outcome measures, as well as changes in Expanded Disability Status Scale and Neurologic Rating Scale. Efficacy was assessed in 188 patients, and safety was assessed in 192 patients. Supplemental ad hoc subgroup analyses were also performed for patients with OS-MS and those with C-MS. Annual relapse rates were 0.763 in the 250 microg group and 1.069 in the 50 microg group, a relative reduction of 28.6% (p = 0.047). Results for all secondary endpoints favored 250 microg IFNB-1b. Subgroup analyses suggested that the magnitude and direction of treatment effect in patients with OS-MS and C-MS was similar, albeit not significant due to small sample size. Interferon beta-1b (IFNB-1b) 250 microg significantly reduced relapse rates and change in MRI lesion area in Japanese patients with relapsing-remitting multiple sclerosis, and seemed to be comparably effective in optic-spinal multiple sclerosis (MS) and classic MS. The response to treatment with IFNB-1b in Japanese patients with MS suggests that a common pathogenesis and underlying genetic characteristics are shared with white patients.

Western vs optic-spinal MS

In the current issue of Neurology , Saida et al.1 report the results of a randomized, controlled study of two doses of interferon beta-1b in Japanese patients with multiple sclerosis (MS). The study demonstrated superiority of the higher dose, consistent with the results seen in the North American study.2 Unlike the North American study, the study was not placebo-controlled. However, it was conducted between 1995 and 1999, well after the positive results of the North American interferon beta-1b study were announced, and the investigators believed that it would be unethical to conduct a placebo-controlled study. The efficacy of interferon beta in relapsing remitting patients with MS is well established. What does the current study add? This is the first study of interferon beta treatment from Asia. Ethnic differences are often associated with genetic variations; pharmacogenetic studies addressing responsiveness to interferon beta therapy are in their infancy, but …

A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis

Neuromyelitis optica is an inflammatory demyelinating disease with generally poor prognosis that selectively targets optic nerves and spinal cord. It is commonly misdiagnosed as multiple sclerosis. Neither disease has a distinguishing biomarker, but optimum treatments differ. The relation of neuromyelitis optica to optic-spinal multiple sclerosis in Asia is uncertain. We assessed the capacity of a putative marker for neuromyelitis optica (NMO-IgG) to distinguish neuromyelitis optica and related disorders from multiple sclerosis. Indirect immunofluorescence with a composite substrate of mouse tissues identified a distinctive NMO-IgG staining pattern, which we characterised further by dual immunostaining. We tested masked serum samples from 102 North American patients with neuromyelitis optica or with syndromes that suggest high risk of the disorder, and 12 Japanese patients with optic-spinal multiple sclerosis. Control patients had multiple sclerosis, other myelopathies, optic neuropathies, and miscellaneous disorders. We also established clinical diagnoses for 14 patients incidentally shown to have NMO-IgG among 85000 tested for suspected paraneoplastic autoimmunity. NMO-IgG outlines CNS microvessels, pia, subpia, and Virchow-Robin space. It partly colocalises with laminin. Sensitivity and specificity were 73% (95% CI 60-86) and 91% (79-100) for neuromyelitis optica and 58% (30-86) and 100% (66-100) for optic-spinal multiple sclerosis. NMO-IgG was detected in half of patients with high-risk syndromes. Of 14 seropositive cases identified incidentally, 12 had neuromyelitis optica or a high-risk syndrome for the disease. NMO-IgG is a specific marker autoantibody of neuromyelitis optica and binds at or near the blood-brain barrier. It distinguishes neuromyelitis optica from multiple sclerosis. Asian optic-spinal multiple sclerosis seems to be the same as neuromyelitis optica.