Opticospinal Multiple Sclerosis Research Articles

Optic neuritis in Asian type opticospinal multiple sclerosis (OSMS-ON) in a non-Asian population: A functional-structural paradox

BackgroundBiomarkers have improved the classification of autoimmune inflammatory disorders, including optic neuritis (ON) as a frequent presentation of multiple sclerosis, neuromyelitis spectrum disorders, MOG antibody-related disease (MOGAD), and opticospinal multiple sclerosis (OSMS). The phenotype of OSMS in non-Asian populations is less well known. ObjectiveWe investigated the clinical features and prognosis of OSMS–ON in a Brazilian cohort. MethodsThis was a single-center cohort study of patients from Rio de Janeiro (Brazil) with OSMS. All individuals were MOG- and AQP4-seronegative, clinically diagnosed with ON, and had magnetic resonance imaging-confirmed transverse myelitis (TM). Subjects and healthy controls (HCs) were assessed for visual acuity (logMAR VA), automated perimetry mean deviation (MD), intraocular pressure, and spectral-domain optical coherence tomography (OCT), followed by automated retinal layer segmentation of the peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell and inner plexiform layer (mGCIPL). Receiver operator characteristic curves were plotted and the area under the curve (AUC) was calculated for group comparisons of retinal asymmetry of the pRNFL and mGCIPL. ResultsThe 30 patients with OSMS were predominantly female and white. The mean age was 48 years (range 20–70 years). Unilateral ON was the index event in 83.3% of patients. Over the average 18-year follow-up period, there were 89 relapses of ON. In individuals with OSMS, the average VA was 0.07±0.14 in the right eye (RE) and 0.13±0.30 in the left eye (LE). The MD was −5.37±5.88 dB and −5.23±3.34 dB for the RE and LE, respectively. There was a significant cumulative loss of VA (p = 0.0003) and MD (p = 0.0001) with a higher number of recurrent episodes. Atrophy of the pRNFL thickness was significant in OSMS (RE, 78.62 ± 16.01 µm; LE, 79.86 ± 13.79 µm) relative to the HC group (RE, 98.87 ± 10.68 µm; LE, 97.87 ± 10.85 µm, p = 0.0001). Likewise, there was significant mGCIPL atrophy in patients with OSMS (RE, 74.96 ± 14.46 µm; LE, 73.88 ± 13.79 µm) relative to the HC group (RE, 90.50 ± 6.74 µm; LE, 90.41± 6.89 µm; p = 0.0001). Retinal asymmetry, inter-eye percentage, and absolute differences accurately separated patients with unilateral ON from HCs (AUC=0.89 and AUC=0.85, respectively). ConclusionA structural-functional paradox was found in OSMS with a high diagnostic value for a novel metric based on retinal asymmetry. The functional visual outcome are excellent despite significant structural damage to the inner retinal layers in patients with a high ON relapse rate and long-term bilateral sequential involvement.

Neuromyelitis optica spectrum disorder in Asia: Epidemiology and risk factors

AbstractIn Asia, prior to the discovery of aquaporin 4 (AQP4) antibody, many cases of neuromyelitis optica spectrum disorder (NMOSD) were misdiagnosed as multiple sclerosis (MS) or the so‐called opticospinal multiple sclerosis (OSMS). The AQP4 antibody discovery was an important milestone in the field of NMOSD, leading to correct diagnosis and reclassification of NMOSD cases, and the subsequent appropriate therapy. This is especially pertinent in Asia where the prevalence of MS is generally much lower than the Caucasian populations. East Asians have a higher NMOSD prevalence rate (~4/100 000) than Caucasians (~1‐1.5/100 000) and other Asian racial groups (Austronesians: 1.2‐1.5/100 000; South Asians: ~1/100 000; Arabs: ~1‐1.5/100 000). Myelin oligodendrocyte glycoprotein (MOG) antibody‐associated disease (MOGAD) comprises cases of AQP4‐antibody‐negative NMOSD, optic neuritis, myelitis, and certain unique phenotypes such as cases with acute disseminated encephalomyelitis (ADEM)‐like presentation, and cerebral cortical encephalitis. MOGAD appears not too uncommon among Japanese, Chinese, Sri Lankans and Indians, but data in different Asian populations and geographical locations are needed. There exist some differences in clinical features of NMOSD and MOGAD between Asians and other populations. As for risk factors, genetic studies have identified certain HLA associations with NMOSD among Asians that were different from other populations. North‐South latitudinal gradient as seen in MS was not observed in NMOSD in Japan and China. Seasonal variation and preceding infection are among some risk factors worth further investigations. Population‐based MOGAD study in Asia, and further genetic and environmental studies are useful to further inform the epidemiology and potential pathogenetic mechanism of this unique neuroinflammatory disease.

Cytokine–chemokine and cognitive profile of multiple sclerosis patients with predominant optic nerve and spinal cord involvement

Context/Objective: Clinical disease activity in multiple sclerosis (MS) may manifest as predominant involvement of optic nerves and spinal cord, as exemplified by opticospinal multiple sclerosis (OSMS) often encountered in Asian countries. Our aim was to compare the clinical features, neuropsychological profile and cytokine/chemokine levels of patients with conventional MS (CMS) and MS presenting predominantly with spinal cord and optic nerve attacks (MS-SCON). Design: Cross-sectional study. Setting: MS Outpatient Clinic. Participants: Fourteen MS-SCON patients, 20 CMS patients without myelitis and optic neuritis attacks and 21 healthy individuals. Outcome measures: IL-8, IL-10, IFN-γ, IL-17 and TNF-α levels were measured by multiplex assay and CXCL2 and CXCL5 levels were measured by ELISA. A panel of neuropsychological tests, Beck depression inventory, 9-hole peg and timed 25-foot walk tests were employed. Results: CMS and MS-SCON patients showed similar clinical features. Both CMS and MS-SCON patients displayed reduced IL-8 and CXCL2 and increased TNF-α levels, while IL-10 and CXCL5 levels were identical among all groups. Conclusion: Neuropsychological and motor function test performances of CMS and MS-SCON patients were highly comparable. CMS and MS-SCON present with similar clinical, neuropsychological and immunological features. Therefore, optic nerve and spinal cord-dominant form of MS does not necessarily establish a distinct entity in our region. Cognitive networks of the central nervous system may be damaged during the disease course of MS, despite the absence of cerebral or cerebellar clinical attacks.

Do Myelin Oligodendrocyte Glycoprotein Antibodies Represent a Distinct Syndrome?

Do Myelin Oligodendrocyte Glycoprotein Antibodies Represent a Distinct Syndrome?

Clinical Features of the Patients with Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory, demyelinating syndrome of the central nervous system (CNS) that predominantly affects the spinal cord and optic nerves. Since it was first described, new information about the pathophysiology gained momentum with the discovery of an antibody against Aquaporin-4, a water channel protein that is predominantly found in the astrocytes. In our study, we evaluated the clinical features of NMOSD and clinically related CNS disorders. In our study, we recruited patients that were followed by Clinic for Multiple Sclerosis and Myelin Disorders at Istanbul University between 1979 and 2016. Thirty-five NMOSD, fifteen relapsing inflammatory optic neuropathy (RION) and ten opticospinal multiple sclerosis (OSMS) patients were recruited in our study. Forty-eight patients (%80) were female and twelve (%20) were male. Age, sex, follow-up period, annualized relapse rate, relapses in the first two years and progression index were similar between the groups. Cerebrospinal fluid (CSF) protein levels were higher in the NMOSD group. Concomitant autoimmune disorders were observed in six NMOSD patients and two OSMS patients. One patient with RION had nonspecific white matter lesions without gadolinium enhancement in the brain MRI. Laboratory and imaging findings suggests that NMOSD is a distinct disorder than RION and OSMS. Further studies are needed to say specific comments about the existence of OSMS.

Opticospinal Multiple Sclerosis Clinical Course and Immunological Parameters

<strong>Objectives</strong>: The clinical course of opticospinal multiple sclerosis (OSMS) is different from that of classical multiple sclerosis (MS) and exhibits a remarkable similarity with that of neuromyelitis optica (NMO). This study aimed to define the immunological parameters of OSMS to distinguish OSMS from classic MS and NMO and to highlight the pathology of OSMS and treatment choice. <br> <strong>Material and Method</strong>: In total, 20 patients with MS, 14 with OSMS, 18 with NMO, and 21 healthy controls were enrolled in the study. Serum cytokine levels were measured using the multiple bead method, and the results were compared with those obtained using the post hoc analysis of variance and Tukey’s test. <br> <strong>Results</strong>: Interleukin (IL)-8 levels were significantly lower in the MS and OSMS groups than in the NMO and control groups (p&lt;0.0001). IL-6 levels were found to be significantly lower in the NMO and control groups than in the MS and OSMS groups (p=0.042). Tumor necrosis factor alpha ( TNF-α) levels were significantly lower in the NMO and control groups than in the MS and OSMS groups (p&lt;0.0001). <br> <strong>Conclusion</strong>: The findings of our study suggest that people with OSMS and NMO exhibit different levels of cytokines and that Aqp-4-negative OSMS, which is not a spinal longitudinal disease, is not a variant of NMO.

The Low Frequency of Antibodies to Myelin Oligodendrocyte Glycoprotein in Japanese Opticospinal Multiple Sclerosis (P1.384)

The Low Frequency of Antibodies to Myelin Oligodendrocyte Glycoprotein in Japanese Opticospinal Multiple Sclerosis (P1.384)

Increased occurrence of anti-AQP4 seropositivity and unique HLA Class II associations with neuromyelitis optica (NMO), among Muslim Arabs in Israel

BackgroundPrevious studies have revealed different human leukocyte antigen (HLA) associations in multiple sclerosis (MS) and neuromyelitis optica (NMO), further discriminating these two demyelinating pathological conditions. In worldwide analyses, NMO and opticospinal MS are represented at higher proportions among demyelinating conditions in African, East-Asian and Latin American populations. There are currently no data regarding the prevalence of NMO in Middle East Muslims. The population in Israel is diverse in many ways, and includes subpopulations, based on religion and ethnicity; some exhibit genetic homogeneity. In Israel, the incidence of MS is lower in the Muslim population than the Jewish population and Muslims carry different allele frequency distribution of HLA haplotypes. ObjectiveTo evaluate the occurrence of anti-AQP4 seropositivity in the Israeli Muslim population among patients with central nervous system (CNS) demyelinating conditions; and to identify the HLA DR and DQ profiles of Muslim Arab Israeli patients with NMO spectrum of diseases (NMOSD). MethodsThe prevalence of anti-AQP4 seropositivity was analyzed in 342 samples, obtained from patients with various CNS demyelinating conditions and in a validation set of 310 samples. HLA class II alleles (HLA-DRB1 and DQB1) were examined in DNA samples from 35 Israeli Muslim Arabs NMO patients and compared to available data from 74 Israeli Muslim controls. ResultsOur data reveal a significantly increased prevalence of anti-AQP4 seropositivity, indicative of NMOSD, in Muslim Arab Israeli patients with initial diagnosis of a CNS demyelinating syndrome. In this population, there was a positive association with the HLA-DRB1*04:04 and HLA-DRB1*10:01 alleles (p=0.03), and a strong negative association with the HLA-DRB1*07 and HLA-DQB1*02:02 alleles (p=0.003, p=0.002). ConclusionsOur findings indicate a possibly increased prevalence of NMOSD in Muslim Arabs in Israel with distinct (positive and negative) HLA associations. Further studies in patients with similar genetic backgrounds worldwide could help to confirm our findings and identify more genetic susceptibility factors for NMO, contributing to our general understanding of the pathogenesis of NMOSD.

Does MOG Ig-positive AQP4-seronegative opticospinal inflammatory disease justify a diagnosis of NMO spectrum disorder?

While neuromyelitis optica (NMO) immunoglobulin (Ig) G is considered the hallmark serologic marker of NMO, its association is not absolute, as NMO IgG is not detected in approximately one-fourth of the patients diagnosed with NMO spectrum disorder (NMOSD). Thus, the recent discovery that antibodies to myelin oligodendrocyte glycoprotein (MOG) are detected in some NMO IgG-seronegative patients manifesting clinical and neuroimaging signs of NMO or NMOSD has created tremendous excitement. However, it may be premature to classify this subgroup as NMOSD. NMO is considered an autoimmune astrocytopathy, and aquaporin-4 (AQP4), expressed on astrocytes, is recognized as the target autoantigen of NMO IgG. As its name denotes, MOG is produced by oligodendrocytes, CNS myelin-producing cells, and MOG is well-recognized as one of the candidate autoantigens in multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). Thus, is it possible that the clinical NMOSD-like phenotype associated with MOG-specific antibodies represents a variant of opticospinal MS or ADEM but not AQP4 autoimmunity or NMOSD? Whether this MOG-Ig positive AQP4-seronegative phenotype should be classified as NMOSD, opticospinal MS, or a unique entity is not simply a theoretical question but rather has practical implications for patients, their physicians, insurance carriers, and clinical investigators conducting NMO treatment trials.

Multiple sclerosis in India: An overview.

Multiple sclerosis (MS) is being increasingly diagnosed in India mainly due to increase in the number of practicing neurologists and easy and affordable availability of magnetic resonance imaging (MRI). The clinical features and course are largely similar to those seen in the West. The term optico-spinal MS (Asian MS) was coined in the pre-MRI days. Many such patients turn out to be cases of neuromyelitis optica — a distinct disorder and not a variant of MS. Others have shown the classical features of MS on MRI scan. Several of the disease-modifying agents, not all, are now available in India. Their use, however, has been limited in view of the high cost.

The developmental history of study on neuromyelitis optica

In 19th century, neuromyelitis optica (NMO) indicated optic neuritis and myelitis with simultaneous onset of both sides. Later studies proposed that the onset of right or left side optic neuritis could be separated by weeks, months even years. The revolutionary discovery of aquaporin 4 (AQP4) antibody in 2004 by Vanda A Lennon challenged and changed the old concept of NMO. The concept of neuromyelitis optica spectrum disorders (NMOSDs) was proposed in 2007. Since then, a series of different terms have been proposed, including opticospinal multiple sclerosis (OSMS), NMOSDs, spectrum of NMO, expanded spectrum of NMO, etc. Through a summary of different concepts of NMO, this paper will make a comprehensive review on the evolution history of NMO study from 19th to 21st century, and the prospective targets of study will also be proposed. doi: 10.3969/j.issn.1672-6731.2014.09.002

Leptin hormone level in serum of opticospinal, neuromyelitisoptica and multiple sclerosis patients

AbstractObjectivesA growing body of evidence shows that leptin acts as a pro‐inflammatory cytokine in autoimmune disorders and is related to multiple sclerosis (MS) pathogenesis. The present study was an analysis of serum leptin levels among healthy volunteers and patients with different subtypes of MS, opticospinal MS (OSMS) and neuromyelitis optica (NMO).MethodsLeptin concentrations in the sera of 121 healthy volunteers and 201 patients with different subtypes of MS, as well as in 27 NMO and 27 OSMS, were measured.ResultsSignificant differences in leptin serum levels were observed between healthy volunteers, and MS, OSMS and NMO patients (P &lt; 0.001). Furthermore, leptin serum concentration was in correlation with expanded disability status scale (EDSS) in primary progressive MS and secondary progressive MS groups. Interestingly, while the female‐to‐male ratio of leptin was approximately 2 in each group, the NMO female patients showed sevenfold higher levels of leptin than males.ConclusionThe present results show that leptin concentration is important in the pathogenesis of different neuroinflammatory diseases of the central nervous system, in particular NMO.

Autologous Hematopoietic Stem Cell Transplantation In Neuromyelitis Optica: A Retrospective Study Of The EBMT Autoimmune Diseases Working Party In Collaboration With The University Of Sao Paulo, Ribeirao Preto, Brazil

BackgroundNeuromyelitis optica (NMO) is an inflammatory and demyelinating disorder of the central nervous system. Recently NMO has been recognized as an autoimmune astrocytopathy, distinct from multiple sclerosis and hallmarked by pathogenic anti-aquaporin 4 (AQP4) antibodies (Kim et al, Mult Scler, 2013). Currently NMO carries a poorer prognosis than multiple sclerosis (MS) and its response to various immunosuppressive treatments remains largely unsatisfactory. Use of Autologous stem cell transplantation (ASCT) has been reported worldwide as a tool for inducing prolonged restoration of self-tolerance in MS and other severe autoimmune diseases (AD), refractory to conventional treatments. In this context, NMO treatment resistant cases were considered for ASCT on a ‘Clinical Option' basis, according to EBMT guidelines (Snowden et al, Bone Marrow Transplant, 2012). Only 2 isolated NMO cases with contradictory results (Matiello et al, Arch Neurol, 2011; Peng et al, Neurologist, 2010) and a Chinese report of 21 opticospinal multiple sclerosis patients treated by ASCT (Xu et al, Ann Hematol, 2011) are reported in the literature. Therefore, the EBMT Autoimmune Diseases Working Party (ADWP) conducted a survey to address NMO disease response following ASCT. MethodsThis retrospective study followed the EBMT study guidelines. All centers were invited to participate. Sixteen patients with aggressive forms of NMO refractory to standard treatments treated by ASCT between 2001 and 2011 had been reported to the EBMT registry. For each case, a specific questionnaire was sent to complete information by referring haematologist and neurologist about NMO, ASCT and outcome including disease response, relapse and progression. Results are reported as median. ResultsPatients (13 females and 3 males) had a median age of 37 years at transplant. Previous treatments had included high-dose steroids (12/16), immunoglobulins (5/16), iv cyclophosphamide (Cy, in 8/16), rituximab (5/16), mitoxantrone (2/16), plasma exchanges (8/16), azathioprine (5/16) and methotrexate (1/16). Median time between NMO diagnosis and transplant was 24 months. Before ASCT, the median EDSS (the Kurtzke Expanded Disability Status Scale) was of 6.5, 10/16 patients were positive for AQP4 antibodies and 11/16 had active lesions on magnetic resonance imaging (MRI). Peripheral blood stem cells mobilization, high-dose alkylating agent such as Cy (14/16) or monoclonal antibodies as Rituximab (2/16), followed by granulocyte colony stimulating factor (G-CSF), was successfully achieved in all cases (16/16). The conditioning regimen consisted of BEAM plus anti-thymocyte globulin (9/16) or Thiotepa-Cy (3/16) or Cy and anti-thymocyte globulin (4/16). Hematopoietic recovery was documented in all patients within 10 days (range 3-25) after ASCT, both for neutrophils and platelets, with a median number of 4 red blood cells and 5 platelet units transfusions. Infectious complications required specific treatment in 9 patients (6 febrile neutropenia, 5 CMV and 2 VZV reactivations, 1 aspergillosis). All patients responded initially. Relapse, necessitating further treatments, occurred in 13/16 at a median of 7 months after ASCT, presenting a median EDSS of 7 (range 3-8.5) and a worsening of MRI (11 cases). NMO progression was observed in 9/16 patients at a median of 10 months after ASCT. In the eight patients evaluable for AQP4 antibodies in the follow-up phase, the pathogenic autoantibodies remained positive after ASCT. Disease-free survival at 3 and 5 years were 31% and 10%, respectively, while progression-free survival at 3 and 5 years were 48%. No secondary malignancy was documented. All patients, but one patient who died from disease progression, are alive at a median follow up of 47 months after ASCT. ConclusionsThis EBMT retrospective study further demonstrates the potential of ASCT to reduce the highly inflammatory picture typical of NMO, at least in the short term, together with a low incidence of toxicities. Despite transient response after ASCT in the majority of cases, NMO relapsed at later time points underlying the need to investigate maintenance strategies to improve disease outcome in the long term after ASCT. Disclosures:No relevant conflicts of interest to declare.

Genetic and environmental factors underlying the rapid changes in epidemiological and clinical features of multiple sclerosis and neuromyelitis optica in Japanese

AbstractThe discovery of a specific biomarker for neuromyelitis optica (NMO), NMO‐immunoglobulin G (IgG)/anti‐aquaporin‐4 (AQP4) antibody, requires us to take it into account when interpreting epidemiological findings on multiple sclerosis (MS). Recent genetic studies showed that HLA‐DRB1*0405 is the most common susceptibility allele for non‐NMO MS in Japanese, and that DRB1*0405 carriers comprise &gt;40% of all Japanese MS patients. Thus, idiopathic central nervous system demyelinating disease in Japanese can be subclassified into DRB1*0405‐positive and ‐negative MS, and anti‐AQP4 antibody‐positive and ‐negative NMO. HLA‐DRB1*0405‐positive MS patients show younger age at onset, fewer brain lesions and a slower progression. The recent increase in the numbers of MS patients in this subgroup could explain the decrease in age at onset, as shown by the fourth nationwide survey in Japanese MS patients. Among HLA‐DRB1*0405‐negative MS patients, DRB1*1501 is a risk factor for MS, and DRB1*1501 carriers have high frequencies of brain lesions fulfilling the Barkhof criteria and cerebrospinal fluid IgG abnormalities. HLA‐DRB1*0405‐negative MS patients have higher frequencies of Epstein–Barr virus infection, but a lower frequency of Helicobacter pylori infection, which reflects improved sanitation in childhood. Anti‐AQP4 antibody‐positive NMO is associated with H. pylori and Chlamydia pneumoniae infections. The effects of improved sanitation on this subgroup might explain the decrease in incidence of opticospinal MS with longitudinally extensive spinal cord lesions, regarded as the same disease as NMO, as suggested by the fourth nationwide survey. Therefore, changes in environmental factors could have differentially influenced susceptibility to each disease subtype in Japanese.

Spinal cord lesions and disability in Hispanics with multiple sclerosis

Longitudinally extensive spinal cord lesions (LESCLs) are believed to occur predominantly with opticospinal multiple sclerosis (OSMS) and are associated with disability. The purpose of this study is to describe the prevalence and patterns of spinal cord lesions in Hispanics with multiple sclerosis (MS) and OSMS and their association with disability. A cross-sectional study of 164 patients with complete MRIs was used. In each case the spinal cord was classified: LESCLs, scattered spinal cord lesions (sSCLs) or no spinal cord lesions (noSCLs). Clinical course was defined as classical MS or OSMS. Risk of disability (Expanded Disability Status Scale≥4.0) was adjusted for age, disease duration and sex using logistic regression.A total of 125/164 (73%) MS patients had spinal cord lesions (sSCLs, 57%; LESCLs, 19%), but only 11 (7%) had OSMS. LESCLs were associated with disability (p<0.0001), longer disease duration (p<0.0001) and MS (n=21 vs. n=10 OSMS; p<0.0001). LESCLs were also associated with the greatest risk to disability (OR 7.3, 95% CIs 1.9-26.5; p=0.003; sSCLs OR 2.5, 95% CIs 0.9-7.1; p=0.09) compared with noSCLs. LESCLs are more common than OSMS and are associated with worse disability even in patients with MS. These results suggest that LESCLs are a more important marker of disability in MS than OSMS and may be an early indicator of more aggressive disease in this population.

Central nervous system inflammatory demyelinating disorders among Hong Kong Chinese

Classical multiple sclerosis (CMS) and neuromyelitis optica spectrum disorders (NMOSD) are distinct central nervous system inflammatory demyelinating disorders (CNS IDD). Early diagnosis of CNS IDD is important as appropriate immunotherapies to optimize prognosis. We studied the diagnoses of CNS IDD among Hong Kong Chinese in a hospital-based setting. Consecutive Chinese patients who presented to our hospital with clinically isolated syndrome and subsequently diagnosed to have CNS IDD from 1980 to 2010 were reviewed. Patients with known diagnosis of CNS IDD referred for further care were excluded. Serial sera were assayed for aquaporin-4 autoantibodies (AQP4 Ab), at least 3 assays within 2–5years. A total of 210 patients diagnosed to have CNS IDD with disease duration of at least 2years were studied. Among 198 patients with serial sera available, 40 (20.2%, 20 had NMO and 20 other NMOSD) were AQP4 Ab-positive. Four patients who were AQP4 Ab-negative on the initial assay converted to AQP4 Ab-positive on repeated assays. The diagnoses of 210 patients were CMS in 88 (41.9%), NMOSD 47 (22.4%, 27 NMO, 20 other NMOSD), single attack of myelitis 23 (11.0%), single attack of optic neuritis 21 (10.0%), relapsing myelitis 10 (4.8%), acute disseminated encephalomyelitis (ADEM) 9 (4.3%), relapsing optic neuritis in 6 (2.9%), opticospinal multiple sclerosis 3 (1.4%) and single attack of brainstem encephalitis 3 (1.4%). Compared to CMS, NMOSD patients had older onset age, lower frequencies of brain MRI abnormalities and CSF OCB, higher frequency of LETM, higher CNS inflammation attack frequency in the first 2years, worse clinical outcome with higher EDSS score and mortality rate. This hospital-based study suggests that CMS (41.9%) and NMOSD (22.4%) are the most common CNS IDD among Hong Kong Chinese. NMOSD has worse clinical outcome than CMS. Detection of AQP4 Ab facilitates early diagnosis and prompts immunotherapies of NMOSD.

Relation of Helicobacter pylori infection and multiple sclerosis in Iranian patients

Multiple sclerosis (MS) is the most prevalent central nervous system demyelinating disease. There are known risk factors for MS. However, there is uncertainty in its protective factors. Few studies have demonstrated that some chronic infections may have protective effects on this disease. We carried this study to investigate the relation between Helicobacter pylori (HP) infection and the prevalence and severity of MS. In this case-control study, 163 MS patients and 150 sex- and age- matched controls were included. Blood samples for IgG and IgM anti HP antibodies were collected from all individuals. Also, the Expanded Disability Status Scale (EDSS) was used to evaluate the MS patients. Suitable statistical analysis was applied. A Significant difference was observed in seropositivity between these two groups (P<0.001) but no significant difference was seen in seropositivity between conventional and opticospinal MS (P=0.522). No significant difference was observed in seropositivity among ages (P=0.075) and between genders (P=0.204). A significant difference was seen in EDSS value between seropositive and seronegative patients (P=0.017). We concluded that patients with HP infection had lower incidence of multiple sclerosis and MS patients with HP infection showed lower neurologic complications, which can demonstrate that HP infection may have a protective influence on MS pathogenesis.

The role of aquaporin-4 antibodies in Chinese patients with neuromyelitis optica

We determined the presence of aquaporin-4 (AQP4) antibodies by indirect immunofluorescence in human AQP4-transfected cells, and evaluated the diagnostic and prognostic relevance of AQP4 antibodies in 210 Chinese patients with neuromyelitis optica (NMO), high-risk NMO (HR-NMO), classic multiple sclerosis (MS), and other neurologic diseases. Patients were enrolled from The General Hospital of the Chinese People’s Liberation Army and followed-up for a median of 2years. The patients with HR-NMO had optico-spinal MS (OSMS; n=3), longitudinally extensive transverse myelitis (TM) (n=35), recurrent optic neuritis (ON) (n=2), ON with Sjögren’s syndrome (n=1) and TM positive for Sjögren-A(SSA) antibody (n=1). The sensitivity and specificity of AQP4 antibodies in NMO were 70.9% and 91%, respectively. The median AQP4 antibody titer was significantly higher in patients with NMO (1:320) than in those with HR-NMO (1:100) and MS (1:50). Relapse of ON or TM was more likely in patients with AQP4 seropositive, than AQP4 seronegative, HR-NMO. Among AQP4 seropositive patients, 66.7% (36/55) had severe ON, 75.9% (41/55) had TM, and 55.6% (30/55) had spinal cord lesions longer than three segments, and there were relapses in eight of 55 patients with ON (14.8%) and 19 of 55 patients with TM (35.2%) during the 2-year follow-up. In conclusion, our study reveals that AQP4 antibody is a sensitive and specific biomarker for discrimination of NMO, classic MS, and other neurological diseases, and is particularly useful for the diagnosis of HR-NMO. AQP4 antibody-positive patients showed higher frequencies of relapse of ON or TM compared with AQP4 antibody-negative patients.

Interferon-β1b Increases Th2 Response in Neuromyelitis Optica

A Japanese randomized controlled study showed that Interferon â (IFN-â1b) therapy is clinically effective in decreasing the frequency of attacks in multiple sclerosis (MS), even in optico-spinal MS (OSMS). However, recent studies have shown that IFN-â (IFN-â1a/IFN-â1b) treatment was not effective in neuromyelitis optica (NMO) patients and that the diminished benefit of IFN-â treatment in NMO may be due to different immune responses to IFN-â. We determined longitudinally the expression of CCR5, CXCR3 and CCR4 on CD4+ T and CD8+ T cells in the blood from patients with NMO and MS treated with IFN-â1b. During a 12-month period of IFN-â1b therapy, the annualized relapse rate decreased in MS patients but not in NMO patients. There was no significant difference in the expression of the chemokine receptors between NMO and MS at baseline. The percentages of CD4+CCR5+ and CD4+CXCR3+ T cells, representative of the Th1 response, were decreased in both NMO and MS after treatment. The percentage of CD4+CCR4+ T cells, representative of the Th2 response, was decreased in MS, but those for NMO was significantly increased compared with the pretreatment levels. Our results indicate that IFN-â1b-induced up-modulation of the Th2 response in NMO patients may be the source of differences in the therapeutic response to IFN-â1b therapy. In the present study, Th2 predominance is involved in the pathogenesis of NMO.

The Brown Norway opticospinal model of demyelination: Does it mimic multiple sclerosis or neuromyelitis optica?

Opticospinal demyelinating diseases in humans are mostly characterized by the opticospinal form of multiple sclerosis (MS) and neuromyelitis optica (NMO). Increasing attention has recently focused on astrocyte markers, aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) in these diseases. We induced opticospinal demyelination in Brown Norway rats with soluble recombinant rat myelin oligodendrocyte glycoprotein (1–116) and incomplete Freund's adjuvant. Clinical, MRI, neuropathological and immunological evaluations were performed, with a focus on AQP4 and GFAP. We confirmed the opticospinal phenotype, including extensive myelitis, but also showed the MRI-characterized involvement of the periventricular area. Expression levels of myelin, AQP4 and GFAP showed the early involvement of astrocytes before demyelination in the optic nerve. The overexpression of AQP4 was particularly pronounced in the spinal cord and was concomitant with demyelination and astrocyte apoptosis. The disability scores were correlated with demyelination and inflammation but not with AQP4/GFAP expression. No antibodies against the linear and conformational epitopes of AQP4 were detected. Whereas a NMO-like phenotype was observed in this model, the AQP4/GFAP expression during the disease process was more closely related to opticospinal MS than NMO. However, this model raises the question of a continuum between opticospinal MS and the seronegative NMO subtype.