Idiopathic Inflammatory Demyelinating Diseases Research Articles

Progress in clinical application of humoral biomarkers for central nervous system inflammatory demyelinating diseases

Central nervous system idiopathic inflammatory demyelinating diseases (CNS-IIDD) is an autoimmune disorder characterized by inflammatory demyelination. The disease follows a course of recurrent attacks and remission, with some cases displaying continuous progression, often resulting in disability. The incidence of CNS-IIDD has been increasing, imposing a substantial burden on both patients' families and society in recent years. A promising strategy for disease management involves the identification of humoral biomarkers to diagnose CNS-IIDD and predict disease attack and progression. Such biomarkers could aid in identifying individuals at high risk of disability, enabling targeted preventive interventions. This study summarizes advancements in the identification of humoral biomarkers and their potential for predicting disease activity and progression to offer novel insights into the management of CNS-IIDD.

Epidemiological Characteristics of Inflammatory Demyelinating Diseases of the Central Nervous System Including Multiple Sclerosis

Relevance. Demyelinating diseases of the central nervous system and multiple sclerosis, in particular, make their debut at a young age and can lead to profound disability and death within a few years. In the last decade, there has been an increase in the number of cases of demyelinating diseases in Russia and in the world, which necessitates an in-depth study of these pathologies. Goal. To study the dynamics and features of the formation of morbidity, prevalence and mortality from demyelinating diseases of the central nervous system, including multiple sclerosis in various population groups in the Russian Federation. Materials and methods. The study design is a descriptive retrospective epidemiological study (continuous). The data was sampled from the forms of the federal state statistical observation on the distribution of the deceased by gender, age groups and causes of death of Rosstat (FSN S-51), as well as from the statistical collections of the Federal State Budgetary Institution "Central Research Institute of the Ministry of Health of the Russian Federation "Morbidity of the population" from 2009 to 2021. Results. The analysis of the data showed that in 2009-2021 in Russia there was an increase in idiopathic inflammatory demyelinating diseases (IDD) and multiple sclerosis (MS) among the adult population and adolescents aged 15 to 17 years. There is no tendency to increase or decrease the incidence among children under 14 years of age. The highest average long–term incidence rates of IDD and MS among adults are observed in the Ufa region (7.13 ± 0.27 and 5.31 ± 0.23 per 100 thousand adults, respectively), among children under 14 - IDD in the Central Federal District (1.88 ± 0.18 per 100 thousand contingent) and MS in the Central Federal District and Volga Federal District (0.22 ± 0.07 per 100 thousand contingent). Among children from 15 to 17 years of age, the highest incidence of IDD is noted in the Northwestern Federal District (4.41 ± 1.10 per 100 thousand contingent) and the Ural Federal District (4.40 ± 1.09 per 100 thousand contingent), RS – in the Central Federal District (2.67 ± 0.51 per 100 thousand contingent). IDD and MS are the least common among all age groups in the Far Eastern Federal District. Over the period from 2000 to 2020, there has been a decrease in MS mortality in the Russian Federation by 34%, from 0.72 to 0.48 per 100,000 population. The average annual mortality rate from MS among men was 0.4 ± 0.021 cases per 100 thousand of the contingent, among women 0.5 ± 0.023 cases per 100 thousand of the contingent. Conclusion. The increase in the incidence of demyelinating diseases and MS, in particular, is an important medical and social problem. These pathologies significantly reduce the quality of life and shorten the duration of work, due to the development of persistent disability in the young population. The study showed the uneven distribution of the disease across the territories of the Russian Federation, which in the future will improve the logistics of drug delivery and the provision of medical personnel, which confirms the relevance of constant and in-depth study of the epidemiology of idiopathic inflammatory demyelinating diseases in Russia.

Use of Complementary and Alternative Medicine in Patients With Idiopathic Inflammatory Demyelinating Diseases of the Central Nervous System: A Cross-Sectional Study in Thailand

BackgroundComplementary and alternative medications (CAM) are common among patients with multiple sclerosis (MS) for physical and psychological support. However, there is insufficient data regarding the application of CAM in the different cultures and beliefs of each community as well as patient's status. ObjectiveTo evaluate the prevalence and modalities of the use of CAM among patients with central nervous system idiopathic inflammatory demyelinating diseases (CNS-IIDD) in a tertiary care hospital MethodsA cross-sectional study was conducted at Siriraj Hospital from June to December 2021 involving patients with MS, neuromyelitis optic spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), idiopathic transverse myelitis (iTM), and optic neuritis (ON) to examine the prevalence and mode of CAM use and its correlation with patient characteristics. ResultsThere were 107 patients. The diagnoses were MS (38), NMOSD (55), MOGAD (5), iTM (7), and ON (2). Most of the patients were female (89.7%), and 61.7% were diagnosed over 5 years. The mean Expanded Disability Status Scale was 2.63 (S.D., 2.38), and the median ambulation index was 0 (range 0–8.5). There were 68 patients (63.6%) with a history of CAM use for at least 3 months, while those with current use decreased to 62 (58.5%). Vitamins and minerals were the most commonly used, particularly vitamin D (97.1%) and calcium (47.7%). Both treatments were primarily prescribed (95.3%) rather than self-administered (24.3%). The main reasons for the use of CAM were to strengthen their health (48.6%) and relieve existing symptoms (28.0%). ConclusionsThe use of CAM is common among patients with Thai CNS-IIDD. Further exploration of patient perspectives and preferences regarding CAM usage may contribute to a more comprehensive management approach for patients with CNS-IIDD.

Diagnostic Value of Multiparameter MRI-Based Radiomics in Pediatric Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorders.

Myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) have a higher prevalence among children. For children undergoing the initial manifestation of MOGAD, prompt diagnosis has paramount importance. This study assessed the performance of multiparameter MRI-based radiomics in distinguishing patients with and without MOGAD with idiopathic inflammatory demyelinating diseases. We enrolled a cohort of 121 patients diagnosed with idiopathic inflammatory demyelinating diseases, including 68 children with MOGAD and 53 children without MOGAD. Radiomics models (T1WI, T2WI, FLAIR, and compound model) using features extracted from demyelinating lesions within the brain parenchyma were developed in the training set. The performance of these models underwent validation within the internal testing set. Additionally, we gathered clinical factors and MRI features of brain parenchymal lesions at their initial presentation. Subsequently, these variables were used in the construction of a clinical prediction model through multivariate logistic regression analysis. The areas under the curve for the radiomics models (T1WI, T2WI, FLAIR, and the compound model) in the training set were 0.781 (95% CI, 0.689-0.864), 0.959 (95% CI, 0.924-0.987), 0.939 (95% CI, 0.898-0.979), and 0.989 (95% CI, 0.976-0.999), respectively. The areas under the curve for the radiomics models (T1WI, T2WI, FLAIR, and the compound model) in the testing set were 0.500 (95% CI, 0.304-0.652), 0.833 (95% CI, 0.697-0.944), 0.804 (95% CI, 0.664-0.918), and 0.905 (95% CI, 0.803-0.979), respectively. The areas under the curve of the clinical prediction model in the training set and testing set were 0.700 and 0.289, respectively. Multiparameter MRI-based radiomics helps distinguish MOGAD from non-MOGAD in patients with idiopathic inflammatory demyelinating diseases.

An Observational Study of Multi-Faceted Demyelinating Disorders.

Idiopathic inflammatory demyelinating diseases of the central nervous system (IIDCDs) are wide-ranging disorders due to their similarities and differences. In order to address these conditions, studying their characteristics is essential. The endpoints of our study were to assess the incidence, presenting features, MRI findings, and predictors of disease progression of prevalent demyelinating disorders. This prospective, observational study was conducted at Srirama Chandra Bhanja (SCB) Medical College and Hospital, India, from August 2018 to November 2021. Individuals of 18-65 years of age with common demyelinating disorders were assessed at baseline, six, 12, and 24 months. Univariate and multivariate analyses were performed for the assessment of predictors. We used R software (version 4.2.1; R Foundation for Statistical Computing, Vienna, Austria) for data analysis. Two hundred twenty (79%) of 278 enrolled participants completed this study. The mean age of the study population was 52.3±11.4 years. One hundred thirty-eight (63%) of them were males. The most common IIDCD in our study was neuromyelitis optica spectrum disorder (NMOSD: 87, 39.5%), followed by multiple sclerosis (MS: 72, 32.7%), acute transverse myelitis (ATM: 35, 15.9%), and acute disseminated encephalomyelitis (ADEM: 26, 11.8%). The univariate analysis revealed that male gender, diabetes mellitus, and history of smoking or alcoholism were significant predictors of the disease progression. The IIDCDs were polysymptomatic at the initial presentation. Male diabetics are more prone to progressive disorders. However, multivariate analysis did not provide statistically significant results.

Evolution in anti-myelin oligodendrocyte glycoprotein antibody detection and its clinical significance: a narrative review.

Myelin oligodendrocyte glycoprotein (MOG) is a protein exclusively expressing on the surface of myelin sheaths and oligodendrocyte plasma membrane in the central nervous system of mammals, and it has a highly conserved nucleotide and amino acid structure between species. Evidence from animal research support that anti-MOG antibodies (MOG-Abs) are pathogenic antibodies rather than a bystander secondary to myelin destruction. Similarly, immunoglobulin-G against myelin oligodendrocyte glycoprotein (MOG-IgG) is considered a demyelinating disease-associated autoantibody in human beings. In clinical studies, several detection methods, including ELISA, immunoblot, radio immunoprecipitation assays and Cell-based assays (CBAs), have been applied in identifying MOG-Abs in idiopathic inflammatory demyelinating diseases (IIDDs) of human beings. CBAs method is recommended by many proposed diagnostic criterions for MOG-Abs-associated disorders (MOGAD). This method involves transfection of mammalian cells with MOG antigen, binding of MOG-Abs to MOG antigen, binding of secondary antibodies to MOG-Abs and quantification method. However, the reliability for CBAs systems of MOG-Abs detection can be influenced by numerous factors, such as length of MOG antigen, expression vectors, cell lines, secondary antibodies, and read-out systems. In addition, there are controversial results on the studies of IIDDs with MOG-IgG positive. Nowadays, more and more evidence suggests that patients positive for MOG-IgG share common features, but further clinical and laboratory researches are needed to clarify if MOGAD is an independent disease entity. In this review, we intend to summarize the detection methods of MOG-Abs and their sensitivity and specificity to MOGAD in human.

Clinical risk factors and prognostic model for idiopathic inflammatory demyelinating diseases after haploidentical hematopoietic stem cell transplantation in patients with hematological malignancies.

Idiopathic inflammatory demyelinating diseases (IIDDs) of the central nervous system (CNS) are rare but serious neurological complications of haploidentical hematopoietic stem cell transplantation (haplo-HSCT). However, the risk factors and a method to predict the prognosis of post-transplantation CNS IIDDs are not available. This retrospective study first reviewed data from 4532 patients who received haplo-HSCT during 2008-2019 in our center, and 184 patients (4.1%) with IIDDs after haplo-HSCT were identified. Grades II to IV acute graft-versus-host disease (aGVHD) (p < 0.001) and chronic GVHD (cGVHD) (p=0.009) were identified as risk factors for developing IIDDs after haplo-HSCT. We then divided the 184 IIDD patients into a derivation cohort and validation cohort due to transplantation time to develop and validate a model for predicting the prognosis of IIDDs. In the multivariate analysis of the derivation cohort, four candidate predictors were entered into the final prognostic model: cytomegalovirus (CMV) infection, Epstein-Barr virus (EBV) infection, IgG synthesis (IgG-syn) and spinal cord lesions. The prognostic model had an area under the receiver operating characteristic curve of 0.864 (95% CI: 0.803-0.925) in the internal validation cohort and 0.871 (95% CI: 0.806-0.931) in the external validation cohort. The calibration plots showed a high agreement between the predicted and observed outcomes. Decision curve analysis indicated that IIDD patients could benefit from the clinical application of the prognostic model. The identification of IIDD patients after allo-HSCT who have a poor prognosis might allow timely treatment and improve patient survival and outcomes.

Idiopathic inflammatory demyelining diseases: optimization of early diagnosis, predictors of the course

Objective: to describe the clinical and epidemiological features of idiopathic inflammatory demyelinating diseases and to determine the factors influencing their course. Materials and methods: the study included 803 patients with idiopathic inflammatory demyelinating diseases using patient questionnaires and scales, laboratory and instrumental research methods. Statistical processing of the results was carried out using a point biserial coefficient and programs for analyzing large data arrays and machine learning. Results: a dynamic increase in the prevalence of some forms of idiopathic inflammatory demyelinating diseases was revealed, the difficulties of differential diagnosis of rare forms of demyelination and the need to create a unified version of their classification are reflected. In the studied population, the effectiveness of liquorological examination in the diagnosis of multiple sclerosis in the early stages of the disease was shown. It has been shown that the likelihood of developing highly active multiple sclerosis is influenced by both a genetic factor and concomitant inflammatory, allergic and autoimmune diseases, surgical interventions, dietary habits, childhood infections, and a history of pregnancy. Conclusions: given the complexity of the differential diagnosis of idiopathic inflammatory demyelinating diseases and the appointment of modifying therapy in multiple sclerosis in the early stages, it is necessary to create a combined classification and maintain a common register.

Tumefactive Demyelination Appearing as Multiple Cystic Brain Lesions

Tumefactive demyelinating lesions (TDLs) are a rare sequelae of idiopathic inflammatory demyelinating diseases of the central nervous system. Their propensity to mimic tumor and abscess poses a diagnostic challenge for the clinician. Our case depicts TDLs causing right-hand focal sensory seizures in an otherwise healthy 35-year-old female. The differential diagnosis of metastatic disease and infection were excluded on histology. Ensuing magnetic resonance imaging of the cord, in addition to cerebral spinal fluid analysis, supported the diagnosis of idiopathic inflammatory demyelinating diseases. This case highlights the need to consider the rare diagnosis of TDL when imaging shows cystic brain lesions in an otherwise healthy young adult.

Neuromyelitis optica is an HLA associated disease different from Multiple Sclerosis: a systematic review with meta-analysis

Neuromyelitis Optica and Multiple Sclerosis are idiopathic inflammatory demyelinating diseases of the central nervous system that currently are considered distinct autoimmune diseases, so differences in genetic susceptibility would be expected. This study aimed to investigate the HLA association with Neuromyelitis Optica by a systematic review with meta-analysis. The STROBE instrument guided research paper assessments. Thirteen papers published between 2009 and 2020 were eligible. 568 Neuromyelitis Optica patients, 41.4% Asians, 32.4% Latin Americans and 26.2% Europeans were analyzed. Only alleles of the DRB1 locus were genotyped in all studies. Neuromyelitis Optica patients have 2.46 more chances of having the DRB1*03 allelic group than controls. Ethnicity can influence genetic susceptibility. The main HLA association with Neuromyelitis Optica was the DRB1*03:01 allele in Western populations and with the DPB1*05:01 allele in Asia. Differences in the Multiple Sclerosis and Neuromyelitis Optica genetic susceptibility was confirmed in Afro descendants. The DRB1*03 allelic group associated with Neuromyelitis Optica has also been described in other systemic autoimmune diseases.

Spectrum of spinal cord demyelination: A retrospective study in a tertiary care hospital of eastern India

Background: The Idiopathic inflammatory demyelinating diseases of Central nervous system (IIDD) are common neurological disorders in neurology indoor. CNS demyelinations which affect brain, spinal cord and optic nerve are important neurological disorder in view of multi axial involvement and frequent relapse and causing significant morbidity. Materials and Methods : It is a retrospective study done in a tertiary care hospital in eastern India from Aug2018-jul2019 (one year). Patients presenting with paraplegia or paraparesis, quadriplegia or quadriparesis with MRI showing features of demyelination were included in the study. Different criteria was taken for diagnosis to know the etiology of disease (mentioned in the introduction). Statistical Analysis Done Using SPSS Software Version-21. Result: Among all spinal cord demyelination longitudinally extended transverse myelitis (LETM) was more common than short segment demyelination. In our study >40yrs group is most commonly affected with more female preponderance. Serum AQP4-Ab was positive in 28% of LETM patients. EDSS was higher in LETM patients than non LETM patients. Conclusion: Among all spinal cord demyelination LETM is more common than short segment demyelination. Optic neuritis and multiphasic course was more associated in LETM with AQP4 positive NMOSD. Tuberculosis is a cause of LETM. Therefore, patients presenting with LETM require a thorough investigative workup to exclude treatable causes like infectious, inflammatory or metabolic. Key message: Spinal cord demyelination possess a wide range with multiple etiologies. Disease course, treatment and prognosis varies in different conditions. All spinal cord demyelination should be evaluated in detail to prevent frequent relapse and morbidity As spinal cord biopsy is an invasive procedure with significant morbidity MRI lesion location, length and enhancement pattern will help to narrow the possibilities. Keywords: LETM, NMOSD, AQ4A

Is Asian type MS an MS phenotype, an NMO spectrum disorder, or a MOG-IgG related disease?

BackgroundA specific particularity of neurological diseases in Asia is the relative commonality of neuromyelitis optica (NMO) and Asian type MS (OSMS). Both conditions also occur in South American patients. The Brazilian population differs from the European and the Asian populations due to the mixture of ancestralities between European colonizers and African slaves. To better know the clinical characteristics of Brazilian patients with Asian type MS this study aimed to analyze the clinical, radiological and serological data that would help to distinguish between OSMS and NMO and clarify, in a Non-Asian population, if OSMS is an MS phenotype, an NMO spectrum disorder by 2015 classification, or a complement activating antibody to myelin oligodendrocyte glycoprotein (MOG-IgG) antibody-related disease. MethodsWe selected cases retrospectively with NMO and OSMS in the medical registry of patients with idiopathic inflammatory demyelinating diseases under follow-up since 1997 in Federal Hospital da Lagoa, the principal reference center for MS treatment in Rio de Janeiro, Brazil. OSMS has selective involvement of the optic nerve and spinal cord with no cerebral or cerebellar symptoms associated with small spinal cord lesions and negativity for the aquaporin-4 antibody (AQP4-IgG). NMO full-filled the revised criteria (2006) associated with longitudinally extensive transverse myelitis (LETM). We recorded the following data: ethnicity/skin color, neurologic impairment “at nadir” and “at recovery” of the index events (optic neuritis and transverse myelitis), long term disability, mortality, health quality of life scores by the SF-36 questionnaire, CSF IgG oligoclonal bands and serological AQP4-IgG and MOG-IgG antibodies tested by Cell-based assay. The last brain MRIs were classified as either satisfying or not satisfying MAGNIMS radiologic criteria for MS or typical or not typical for NMOSD. The new classification of NMO spectrum disorders (2015) was applied. ResultsForty-one OSMS and 122 NMO cases were analyzed. OSMS affected mainly young white women, causing unilateral optic neuritis and partial myelitis with excellent recovery. After a mean disease duration of 20 years, 90% of the patients had free ambulation, and 70% had a mild disability or no disability. Only 7.2% presented a secondary progressive course, and no deaths occurred. All cases had negativity to AQP4-IgG and MOG-IgG biomarkers. 95% had resonance criteria for MS. OSMS differed from NMO by ethnicity, morbidity, and mortality: most were African descendants, with severe motor and visual dysfunction, and one third died. Only NMO cases full-filled the new NMOSD classification (52 AQP4-IgG positive, 29 AQP4-IgG negative, and 41 AQP4-IgG unknown). ConclusionIn Brazilian patients, OSMS and NMO are different immune-mediated diseases. OSMS is a milder MS phenotype.

Frequency of Pseudotumoral Central Nervous System Lesions in an Oncology Center

Brain tumors are frequent in clinical practice and associated with high morbidity and mortality. However, many diseases can present as tumefactive lesions and mimic neoplastic lesions. We aimed to determine the frequency of pseudotumoral central nervous system lesions referred to an oncology center and the frequency of the tumor mimickers. This was a retrospective study at the National Institute of Cancer, Rio de Janeiro, Brazil. Medical charts of patients admitted to the Neurosurgery and Pediatrics services from 2007 to 2011 were reviewed. Clinical and radiologic features of cases initially diagnosed with primary central nervous system tumors but received a final diagnosis of pseudotumoral disease were recorded. Among 891 patients referred as primary brain tumors, 38 cases had pseudotumoral lesions (4.3%). Most were adults (63%), with mean age of 29.4 years, and women (60.5%). Most frequent symptoms were headache (28.9%), motor signs (23.7%), and seizures (15.8%). Mean time from initial symptoms to diagnosis was 12.2 months. Lesions were single in 84.2% of patients, had contrast enhancement in 45.6%, and surrounding edema in 17.4%. Twenty patients (52,6%) underwent biopsy. Systemic autoimmune diseases were the most frequent etiologies (28.9%), followed by idiopathic inflammatory demyelinating diseases, infections, and vascular abnormalities (15.8% each). Good outcome with no major deficits was observed in 60.5%cases. The frequency of pseudotumoral lesions in an oncology reference center was low. Young women were most affected, and lesions were associated more frequently with systemic autoimmune diseases. Prompt recognition is important to avoid unnecessary treatment, because most patients had a good outcome.

Seizure and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Encephalomyelitis in a Retrospective Cohort of Chinese Patients.

Background: Myelin oligodendrocyte glycoprotein (MOG) antibody associated encephalomyelitis is increasingly being considered a distinct disease entity, with seizures and encephalopathy commonly reported. We investigated the clinical features of MOG-IgG positive patients presenting with seizures and/or encephalopathy in a single cohort.Methods: Consecutive patients with suspected idiopathic inflammatory demyelinating diseases were recruited from a tertiary University hospital in Guangdong province, China. Subjects with MOG-IgG seropositivity were analyzed according to whether they presented with or without seizure and/or encephalopathy.Results: Overall, 58 subjects seropositive for MOG-IgG were analyzed, including 23 (40%) subjects presenting with seizures and/or encephalopathy. Meningeal irritation (P = 0.030), fever (P = 0.001), headache (P = 0.001), nausea, and vomiting (P = 0.004) were more commonly found in subjects who had seizures and/or encephalopathy, either at presentation or during the disease course. Nonetheless, there was less optic nerve (4/23, 17.4%, P = 0.003) and spinal cord (6/16, 37.5%, P = 0.037) involvement as compared to subjects without seizures or encephalopathy. Most MOG encephalomyelitis subjects had cortical/subcortical lesions: 65.2% (15/23) in the seizures and/or encephalopathy group and 50.0% (13/26) in the without seizures or encephalopathy group. Cerebrospinal fluid (CSF) leukocytes were elevated in both groups. Subgroup analysis showed that 30% (7/23) MOG-IgG positive subjects with seizures and/or encephalopathy had been misdiagnosed for central nervous system infection on the basis of meningoencephalitis symptoms and elevated CSF leukocytes (P = 0.002).Conclusions: Seizures and encephalopathy are not rare in MOG encephalomyelitis, and are commonly associated with cortical and subcortical brain lesions. MOG-encephalomyelitis often presents with clinical meningoencephalitis symptoms and abnormal CSF findings mimicking central nervous system infection in pediatric and young adult patients.

Идиопатические воспалительные демиелинизирущие заболевания центральной нервной системы: современный взгляд на классификацию, опыт создания регистра

Идиопатические воспалительные демиелинизирущие заболевания центральной нервной системы: современный взгляд на классификацию, опыт создания регистра

Experimental Models of Autoimmune Demyelinating Diseases in Nonhuman Primates.

Human idiopathic inflammatory demyelinating diseases (IIDD) are a heterogeneous group of autoimmune inflammatory and demyelinating disorders of the central nervous system (CNS). These include multiple sclerosis (MS), the most common chronic IIDD, but also rarer disorders such as acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica (NMO). Great efforts have been made to understand the pathophysiology of MS, leading to the development of a few effective treatments. Nonetheless, IIDD still require a better understanding of the causes and underlying mechanisms to implement more effective therapies and diagnostic methods. Experimental autoimmune encephalomyelitis (EAE) is a commonly used animal model to study the pathophysiology of IIDD. EAE is principally induced through immunization with myelin antigens combined with immune-activating adjuvants. Nonhuman primates (NHP), the phylogenetically closest relatives of humans, challenged by similar microorganisms as other primates may recapitulate comparable immune responses to that of humans. In this review, the authors describe EAE models in 3 NHP species: rhesus macaques ( Macaca mulatta), cynomolgus macaques ( Macaca fascicularis), and common marmosets ( Callithrix jacchus), evaluating their respective contribution to the understanding of human IIDD. EAE in NHP is a heterogeneous disease, including acute monophasic and chronic polyphasic forms. This diversity makes it a versatile model to use in translational research. This clinical variability also creates an opportunity to explore multiple facets of immune-mediated mechanisms of neuro-inflammation and demyelination as well as intrinsic protective mechanisms. Here, the authors review current insights into the pathogenesis and immunopathological mechanisms implicated in the development of EAE in NHP.

Cognitive impairment in Chinese IIDDs revealed by MoCA and P300

To investigate the value of MoCA and auditory P300 as a cognitive assessment tool in chinese idiopathic inflammatory-demyelinating diseases (IIDDs), eighty three consecutive patients with IIDDs and thirteen sex- and age-matched healthy controls were recruited in the study. MMSE, MoCA and auditory P300 potential were administrated to each participant. The percentage of cognitive impairment in IIDDs patients was 24.1% by using MMSE, while the percentage was 81.9% by using MoCA. The majority of IIDDs participants had MMSE scores in the normal range. In contrast, few IIDDs participants scored in the normal range on the MoCA. Age, EDSS and depression correlated negatively with the total score of MoCA and MMSE. Years of education correlated positively with MoCA and MMSE. ADEM patients scored lower on all MoCA subtests. Prolonged latency P300 which negatively correlated with MoCA and reduced P300 amplitude which positively correlated with MoCA were detected in IIDDs patients. Thus MoCA is superior to the MMSE as a cognitive impairment scan tool and P300 is useful for detecting cogntive deficiency in chinese IIDDs.

The Prevalence of Anti-Aquaporin 4 Antibody in Patients with Idiopathic Inflammatory Demyelinating Diseases Presented to a Tertiary Hospital in Malaysia: Presentation and Prognosis.

Background. There have been inconsistent reports on the prevalence and pathogenicity of anti-Aquaporin 4 (AQP4) in patients presented with idiopathic inflammatory demyelinating diseases (IIDDs). Objective. To estimate the prevalence of anti-AQP4 antibody in patients with IIDDs presented to University Malaya Medical Centre in terms of patients' clinical and radiological presentations and prognoses. Methods. Retrospective data review of IIDDs patients presented from 2005 to 2015. Patients were classified into classical multiple sclerosis (CMS), opticospinal (OS) presentation, optic neuritis (ON), transverse myelitis (TM), brainstem syndrome (BS), and tumefactive MS. Anti-Aquaporin 4 antibody was tested using the Indirect Immunofluorescence Test (IIFT) cell-based assay. Statistical analysis was done using the SPSS version 20. Results. Anti-AQP4 antibody was detected in 53% of patients presented with IIDDs. CMS was more common in the seronegative group, 27/47 (57.45%; p < 0.001). Conversely, OS involvement was more common in the seropositive group, 26/53 (49.06%; p < 0.001). Longitudinally extensive spinal cord lesions (LESCLs) on MRI were also more common in the seropositive group, 29/40 (72.50%; p = 0.004). Only 2/40 (5.00%) had MRI evidence of patchy or multiple short-segment spinal cord lesions in the AQP4-positive group (p = 0.003). The relapse rate and Expanded Disability Status Scale (EDSS) were also higher in the seropositive group (5.43 versus 3.17, p = 0.005; 4.07 versus 2.51, p = 0.006, resp.). Typical clinical presentations that defined NMO were also seen in the seronegative patients, but in a lower frequency. Conclusion. Our cohort of patients had a higher prevalence of seropositivity of anti-AQP4 antibody as compared to those in Western countries. This was also associated with a more typical presentation of opticospinal involvement with LESCLs on MRI, a higher rate of relapse, and EDSS.

Advances on the diagnosis of idiopathic inflammatory demyelinating diseases of the central nervous system

Advances on the diagnosis of idiopathic inflammatory demyelinating diseases of the central nervous system

Accuracy of the Fluorescence-Activated Cell Sorting Assay for the Aquaporin-4 Antibody (AQP4-Ab): Comparison with the Commercial AQP4-Ab Assay Kit.

BackgroundThe aquaporin-4 antibody (AQP4-Ab) is a disease-specific autoantibody to neuromyelitis optica (NMO). We aimed to evaluate the accuracy of the FACS assay in detecting the AQP4-Ab compared with the commercial cell-based assay (C-CBA) kit.MethodsHuman embryonic kidney-293 cells were transfected with human aquaporin-4 (M23) cDNA. The optimal cut off values of FACS assay was tested using 1123 serum samples from patients with clinically definite NMO, those at high risk for NMO, patients with multiple sclerosis, patients with other idiopathic inflammatory demyelinating diseases, and negative controls. The accuracy of FACS assay and C-CBA were compared in consecutive 225 samples that were collected between January 2014 and June 2014.ResultsWith a cut-off value of MFIi of 3.5 and MFIr of 2.0, the receiver operating characteristic curve for the FACS assay showed an area under the curve of 0.876. Among 225 consecutive sera, the FACS assay and C-CBA had a sensitivity of 77.3% and 69.7%, respectively, in differentiating the sera of definite NMO patients from sera of controls without IDD or of MS. Both assay had a good specificity of 100% in it. The overall positivity of the C-CBA among FACS-positive sera was 81.5%; moreover, its positivity was low as 50% among FACS-positive sera with relatively low MFIis.ConclusionsBoth the FACS assay and C-CBA are sensitive and highly specific assays in detecting AQP4-Ab. However, in some sera with relatively low antibody titer, FACS-assay can be a more sensitive assay option. In real practice, complementary use of FACS assay and C-CBA will benefit the diagnosis of NMO patients, because the former can be more sensitive among low titer sera and the latter are easier to use therefore can be widely used.