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AimsThe laboratory diagnosis of demyelinating inflammatory disorders (DIDs) relies on both intrathecal oligoclonal band (OCB) positivity and IgG index. Although OCB typing remains the gold-standard test for DIDs, it can be laborious and ambiguous, complicating diagnostics, and unduly increasing diagnostic time. We examined whether serum or cerebrospinal fluid (CSF) parameters can classify OCB types and, thus, be used as a replacement test to standard OCB typing.MethodsWe retrospectively analysed >1000 prospectively collected samples of patients with DIDs and quantified albumin and IgG levels in the CSF and serum. We determined OCB types by isoelectric focusing combined with immunofixation and evaluated the diagnostic accuracies of IgG and albumin indices in discriminating OCB types by receiver operating characteristic curves and multinomial regression.ResultsAn IgG index cut-off of 0.589 differentiated types 2/3 from types 1/4 (area under the curve 0.780, 95% CI 0.761 to 0.812, pConclusionsOur study reveals that IgG and albumin index can differentiate OCB types with adequate accuracy, especially if refined by age and gender.

To investigate whether cerebrospinal fluid (CSF) markers differ between pediatric-onset multiple sclerosis (PoMS, onset

Objectives Oligoclonal band (OCB) determination in cerebrospinal fluid (CSF) is the gold standard to detect intrathecal inflammation. However, there is uncertainty about the significance of one isolated band in CSF. Free light chains kappa (FLC-k) are gaining interest as a complementary method to detect intrathecal inflammation. The aim of this study was to investigate the performance of an additive measurement of FLC-k in patients with one isolated band in CSF. Materials & Methods FLC-k were analyzed using the nephelometric Siemens FLC-k kit in paired samples of CSF and sera (n = 56) in patients with one isolated band in isoelectric focusing. According to medical diagnosis, samples were subdivided in inflammatory neurological disease, non-inflammatory neurological disease controls and symptomatic controls. Intrathecal fraction of FLC-k was plotted in a FLC-k quotient diagram. OCB interpretation was done blinded by three experienced raters. Results Of 6695 OCB analyses, 91 (1.4%) had one isolated band in CSF. After exclusion of patient samples due to unclear OCB pattern after reevaluation and sample availability, 56 patient samples were included in the study. All patients with an inflammatory origin of disease (n = 13) had FLC-k values above the upper discrimination line (Qlim) in the FLC-k quotient diagram, resulting in a sensitivity of 100% with a positive predictive value of 52% and a negative predictive value of 100%. Fourteen patients (36%) with a non-inflammatory origin of disease (n = 39) had FLC-k values above Qlim. Conclusions In patients with one isolated band in CSF, a lack of intrathecal fraction of FLC-k strongly favors a non-inflammatory orgin of disease. Implementation of FLC-k measurement can help the clinician in the diagnostic process of neurological diseases.

Introduction. Immunoglobulins are molecules composed of two heavy and two light chains. Light chains are produced by B lymphocytes during the synthesis of immunoglobulins, and physiologically light chains are generally produced in excess compared to heavy chains. Light chains that are not combined to heavy chains in a whole immunoglobulin are called free light chains (FLCs). B-cell abnormalities are associated with disorders leading to an abnormal concentration of free light chains. In this study, we focus on the described changes of serum and cerebrospinal fluid concentration of free light chains in inflammatory disorders: multiple sclerosis, HIV infection, and HIV-associated lymphomas. Methods. We performed broad research of the literature pertaining to our investigation via the MEDLINE/PubMed database. Results. It has been proven that FLC determination can provide rapid information about intrathecal inflammation in patients with multiple sclerosis. Moreover, literature data suggest that free light chain determination is the most interesting alternative for oligoclonal band analysis. In the present review, we also described that HIV-related immune system dysfunction is associated with an elevated concentration of serum-free light chains. Additionally, FLCs are potentially a strong and sensitive predictor of the risk of developing HIV-associated lymphomas. Conclusion. Based on these published findings, we suggest that free light chains have high diagnostic sensitivity, which probably enables application in laboratory diagnostics.

Peer reviewed: True, BACKGROUND: Inclusion of cerebrospinal fluid (CSF) oligoclonal IgG bands (OCGB) in the revised McDonald criteria increases the sensitivity of diagnosis when dissemination in time (DIT) cannot be proven. While OCGB negative patients are unlikely to develop clinically definite (CD) MS, OCGB positivity may lead to an erroneous diagnosis in conditions that present similarly, such as neuromyelitis optica spectrum disorders (NMOSD) or neurosarcoidosis. OBJECTIVE: To identify specific, OCGB-complementary, biomarkers to improve diagnostic accuracy in OCGB positive patients. METHODS: We analysed the CSF metabolome and proteome of CDMS (n=41) and confirmed non-MS patients (n=64) comprising a range of CNS conditions routinely encountered in neurology clinics. RESULTS: OCGB discriminated between CDMS and non-MS with high sensitivity (85%), but low specificity (67%), as previously described. Machine learning methods revealed CCN5 levels provide greater accuracy, sensitivity, and specificity than OCGB (79%, +5%; 90%, +5%; and 72%, +5% respectively) while glial fibrillary acidic protein (GFAP) identified CDMS with 100% specificity (+33%). A multiomics approach improved accuracy further to 90% (+16%). CONCLUSION: The measurement of a few additional CSF biomarkers could be used to complement OCGB and improve the specificity of MS diagnosis when clinical and radiological evidence of DIT is absent.

Increased immunoglobulin G (IgG) antibodies and oligoclonal bands (OCB) are the most characteristic features of multiple sclerosis (MS), a neuroinflammatory demyelinating disease with neurodegeneration at chronic stages. OCB are shown to be associated with disease activity and brain atrophy. Despite intensive research over the last several decades, the antigen specificities of the IgG in MS have remained elusive. We present evidence which supports that intrathecal IgG is not driven by antigen-stimulation, therefore provide reasoning for failed MS antigen identification. Further, the presence of co-deposition of IgG and activated complement products in MS lesions suggest that the IgG effector functions may play a critical role in disease pathogenesis.

Background Restless legs syndrome/Willis-Ekbom disease (RLS/WED) was shown to have a high prevalence among adults with multiple sclerosis (MS). Objective We aimed to investigate the prevalence of RLS/WED and to define the disease characteristics in young patients with pediatric onset multiple sclerosis (POMS) Method 50 patients with POMS were questioned for the presence of RLS/WED. The demographic, clinical and laboratory data were compared between POMS patients with and without RLS/WED, including the total number of clinical and/or radiological MS attacks, interval between first two attacks, EDSS, number of the hyperintense and/or contrast-enhancing lesions, localization of demyelinating lesions, IgG index in cerebrospinal fluid, oligoclonal band, serum ferritin, C-reactive protein, ratio of neutrophil to lymphocyte count, and 25‑hydroxy vitaminD. Results Eleven patients (22%) had RLS/WED - mostly of moderate in severity (54.5%). Mean EDSS score was significantly higher in POMS patients with RLS/WED than those without (p = 0.003). The Ig G index was almost two times higher in POMS patients with RLS/WED, but it failed to reach to the statistically significant level (p = 0.073). Conclusion Our study demonstrated high prevalence of RLS/WED in young patients with POMS. Higher EDSS scores in patients with POMS and RLS/WED indicates disease-related factors in the emergence of RLS/WED.

Introduction Hirayama disease is a rare clinical entity that presents typically as a unilateral, slowly progressive arms weakness, mostly occurring in young men. Case report We report a case of Hirayama disease in a 20-year-old man presenting with a 4-year history of progressive paresthesia starting in his left arm, progressing to the right arm 1 year later. Four months before the presentation, he experienced bilateral foot paresthesias. Examination revealed weakness of the abductor digiti minimi, hallux extension weakness, and postural tremor bilaterally. He had hypersensitivity to pinprick in both hands with ulnar and median distribution. Sensory examination in the legs was normal. He had a postural tremor in both hands, which worsened on neck flexion. Spinal fluid analysis, including oligoclonal band testing, was normal. Electromyography demonstrated bilateral chronic C7 and C8 radiculopathies. Laboratory tests were normal. Flexion-extension magnetic resonance imaging demonstrated laxity of the dura and ligamentum flavum, with compression of cervical cord, maximal at C5-C6 in neck flexion. Conclusions Laxity of the posterior dura during neck flexion has been postulated to lead to asymmetric lower cervical cord atrophy. Involvement of all 4 limbs is rare, and the condition can be mistaken for progressive multiple sclerosis.

OBJECTIVE To improve the clinical understanding of anti-gamma-aminobutyric-acid B receptor encephalitis (anti-GABABR encephalitis) by analyzing 13 cases. METHODS We retrospectively studied demographic and clinical features including clinical symptoms, serum/cerebrospinal fluid (CSF) laboratory findings (including antibody test), brain magnetic resonance imaging (MRI), electroencephalogram (EEG), treatment plan, and treatment effect for 13 patients with a definitive diagnosis of anti-GABABR encephalitis. RESULTS Seven patients (53.8%, 7/13) were complicated with lung cancer. Epileptic seizures were the most common symptoms at onset in 11 patients (84.6%, 11/13). All patients had seizures in the course of the disease. Abnormalities in craniocerebral MRI examination, including hippocampus, occipital lobe, insular lobe, were found in six of nine tested patients, and EEG abnormalities were found in seven out of nine tested patients. Elevated pro-gastrin releasing peptide (ProGRP) levels were found in 70% of patients with a median value of 490.10 pg/ml; and CSF oligoclonal bands were positive for 4 of 10 tested cases. However, there were no significant differences in modified Rankin Scale (mRS) between the ProGRP or CSF oligoclonal band positive and negative groups at admission and follow-up (p > .05). The value between SCLC and non-SCLC subgroup was significantly different (p

Background and purpose For the diagnosis of relapsing-remitting multiple sclerosis (RRMS), the revised 2017 McDonald criteria include cerebrospinal fluid specific oligoclonal bands as a new criterion for dissemination in time. Amongst other things, one expectation of the new criteria is to marginalize the diagnosis of clinically isolated syndrome (CIS), thus allowing for a faster and at the same time still reliable diagnosis of RRMS. Methods In this study, data from an unselected patient cohort with a typical CIS and dissemination in space at a large German Multiple Sclerosis Center from 2013 to 2016 were re-analysed to compare differences in diagnosing RRMS with the 2017 versus 2010 McDonald criteria in everyday practice. Results Out of a cohort of 290 patients presenting with a typical first demyelinating event, 52% (152 patients) with the diagnosis of RRMS and 48% (138 patients) with the diagnosis of CIS according to the 2010 McDonald criteria were identified. The application of the 2017 McDonald criteria in the same patients increased the number of definite RRMS to 94% (273), thus leaving only 6% of patients with the diagnosis of CIS. The reason for this shift was the presence of cerebrospinal fluid specific oligoclonal bands which was found in 92.7% of the total population and in all patients with 2017 McDonald RRMS. Over a mean follow-up of 1.5 years, 50% of patients formerly diagnosed with CIS who are now RRMS also fulfilled the 2010 McDonald criteria. Conclusions Our data support the use of the 2017 McDonald criteria for a more sensitive, but not that specific, diagnosis of RRMS in everyday practice.

ObjectiveTo determine whether B-cell presence in brainstem and white matter (WM) lesions is associated with poorer pathological and clinical characteristics in advanced MS autopsy cases.MethodsAutopsy tissue of 140 MS and 24 control cases and biopsy tissue of 24 patients with MS were examined for CD20+ B cells and CD138+ plasma cells. The presence of these cells was compared with pathological and clinical characteristics. In corresponding CSF and plasma, immunoglobulin (Ig) G ratio and oligoclonal band (OCB) patterns were determined. In a clinical cohort of 73 patients, the presence of OCBs was determined during follow-up and compared to status at diagnosis.ResultsIn 34% of active and 71% of mixed active/inactive lesions, B cells were absent, which correlated with less pronounced meningeal B-cell infiltration (p < 0.0001). The absence of B cells and plasma cells in brainstem and WM lesions was associated with a longer disease duration (p = 0.001), less frequent secondary progressive MS compared with relapsing and primary progressive MS (p < 0.0001 and p = 0.046, respectively), a lower proportion of mixed active/inactive lesions (p = 0.01), and less often perivascular T-cell clustering (p < 0.0001). Moreover, a lower CSF IgG ratio (p = 0.006) and more frequent absence of OCBs (p < 0.0001) were noted. In a clinical cohort, numbers of patients without OCBs in CSF were increased at follow-up (27.4%).ConclusionsThe absence of B cells is associated with a favorable clinical and pathological profile. This finding may reflect extremes of a continuum of genetic or environmental constitution, but also a regression of WM humoral immunopathology in the natural course of advanced MS.

It remains important to be able to distinguish between multiple sclerosis (MS) and cerebral autosomal dominant arteriopathy and subcortical ischemic leukoencephalopathy (CADASIL), although it has yet to be reported that MS and CADASIL can be seen together. We encountered a 63-year-old female patient compatible with MS in terms of clinical features but compatible with CADASIL in terms of brain magnetic resonance imaging (MRI) findings. Migraine, vascular dementia, and subcortical stroke events, which are among the classic clinical features of CADASIL, were not present. In the cerebrospinal fluid (CSF) examination, the oligoclonal band (OCB) was positive and the NOTCH 3 mutation was negative in the serum. The patient, whose initial symptom was optic neuritis, recovered with IV corticosteroids and azathioprine therapy. The patient's daughter and aunt had previously been diagnosed with MS. We present a case of MS mimicking CADASIL in terms of atypical demyelinating lesions.

Background and purpose: Tumefactive multiple sclerosis (TuMS) (i.e., MS onset presenting with tumefactive demyelinating lesions [TDLs]) is a diagnostic and therapeutic challenge. We performed a multicentre retrospective study to describe the clinical characteristics and the prognostic factors of TuMS. Methods: One hundred two TuMS patients were included in this retrospective study. Demographic, clinical, magnetic resonance imaging (MRI), laboratory data and treatment choices were collected. Results: TuMS was found to affect women more than men (female:male: 2.4), with a young adulthood onset (median age: 29.5years, range: 11–68 years, interquartile range [IQR]: 38 years). At onset, 52% of TuMS patients presented with the involvement of more than one functional system and 24.5% of them with multiple TDLs. TDLs most frequently presented with an infiltrative MRI pattern (38.7%). Cerebrospinal fluid immunoglobulin G oligoclonal bands were often demonstrated (76.6%). In 25.3% of the cases, more than one acute-phase treatment was administered, and almost one-half of the patients (46.6%) were treated with high-efficacy treatments. After a median follow-up of 2.3years (range: 0.1–10.7 years, IQR: 3.4 years), the median Expanded Disability Status Scale (EDSS) score was 1.5 (range: 0–7, IQR: 2). Independent risk factors for reaching an EDSS score ≥3 were a higher age at onset (odds ratio [OR]: 1.08, 95% confidence interval [CI]: 1.03–1.14, p&nbsp

Highlights • Patients with COVID-19 and neurological manifestations have diverse CSF profiles. • Detection of SARS-CoV-2 RNA in the cerebrospinal fluid is infrequent. • Oligoclonal bands are found in CSF of COVID-19 patients with neurological diseases. • CNS inflammation promotes neuronal injury in patients with COVID-19. • CSF levels of NfL is elevated in inflammatory neurological diseases in COVID-19. • SARS-CoV-2 replication in CNS may trigger the infiltration by immune cells., Objectives To analyze the cerebrospinal fluid (CSF) of patients with SARS-CoV-2 infection and neurological manifestations to provide evidence for the understanding of mechanisms associated with central nervous system (CNS) involvement in COVID-19. Methods Patients (n = 58) were grouped according to their main neurological presentation: headache (n = 14); encephalopathy (n = 24); inflammatory neurological diseases, including meningoencephalitis (n = 4), acute myelitis (n = 3), meningitis (n = 2), acute disseminated encephalomyelitis (ADEM) (n = 2), encephalitis (n = 2), and neuromyelitis optica (n = 1); and Guillain-Barré syndrome (n = 6). Data about age, sex, cerebrovascular disease, and intracranial pressure were evaluated in combination with CSF profiles defined by cell counts, total protein and glucose levels, concentration of total Tau and neurofilament light chain (NfL) proteins, oligoclonal band patterns, and detection of SARS-CoV-2 RNA. Results CSF of patients with inflammatory neurological diseases was characterized by pleocytosis and elevated total protein and NfL levels. Patients with encephalopathy were mostly older men (mean age of 61.0 ± 17.6 years) with evidence of cerebrovascular disease. SARS-CoV-2 RNA in CSF was detected in 2 of 58 cases: a patient with refractory headache, and another who developed ADEM four days after COVID-19 symptoms onset. Three patients presented intrathecal IgG synthesis, and four had identical oligoclonal bands in CSF and serum, indicating systemic inflammation. Conclusion Patients with neurological manifestations associated with COVID-19 had diverse CSF profiles, even within the same clinical condition. Our findings indicate a possible contribution of viral replication on triggering CNS infiltration by immune cells and the inflammation promoting neuronal injury.

[This corrects the article DOI: 10.3389/fimmu.2021.811351.]., (Copyright © 2022 Probert, Yeo, Zhou, Sealey, Arora, Palace, Claridge, Hillenbrand, Oechtering, Kuhle, Leppert and Anthony.)

Background Multiple sclerosis (MS) commonly affects young adults at the ages 20 to 40 years old, but it can onset at each age. Late-onset multiple sclerosis (LOMS) is defined as symptoms initiating after the age of 50. Misdiagnosis and a remarkable gap in diagnosis of LOMS is a challenge of the elderly population so in this article we described the proportion of LOMS and the clinical features and phenotype of the disease in this age group. Methods After registration of the study protocol, an electronic search was performed in 3 databases and for full coverage of the published studies, we also checked the references of each related article. Two independent researchers screened the records in title/abstract and full-text stages and extracted the data using a data extraction table. The risk of bias was assessed using Joanna Briggs Institute checklist and meta-analysis was conducted by CMA 2. Only the studies with 50 years old cut-off and using McDonald or Poser diagnostic criteria were included in the meta-analysis. Results After removing duplicated studies, out of 733 results of electronic and hand searching, 31 studies met our inclusion criteria for the systematic review, and 11 of them were included in the quantitative synthesis. With different cut-offs and diagnostic methods 1.1% to 21.3% proportion of LOMS, has been reported in the studies. Meta-analysis reached a 5.01% (95% CI: 3.78% to 6.57%), proportion of LOMS in total MS cases. The female cases were more than males (range between 57.7% to 70.2%) and 64.46% (95% CI: 61.94% to 66.91%) proportion of females has been found in this study. 65.00% (95% CI: 44.71% to 81.02%) proportion of spinal cord involvements and 49.80% (95% CI: 39.28% to 60.24%) proportion of relapsing-remitting multiple sclerosis (RRMS) was also observed in LOMS cases. In 4 of included studies, the progressive form was the predominant phenotype. The most prevalent first disease presentation of LOMS was motor dysfunction (ranges between 100% to 35.4%) followed by sensory problems (ranges between 94% to 5%), visual symptoms (ranges between 22.9% to 5%), and brainstem dysfunction (ranges between 25% to 12.3%). The proportion of positive oligoclonal band (OCB), was varied from 46% to 98% in different studies and positive immunoglobulin G (IgG) index also was seen in 45.04% and 66% of the patients. 2.2% - 12.5% of the LOMS cases had a positive family history. Conclusion In about 5% of cases, MS can be diagnosed at ages above 50 years old. There is an increasing concern of a more progressive form of MS in LOMS cases. Unlike the adult-onset MS, the first presentation of LOMS is usually motor dysfunction. Understanding the proportion and clinical features of LOMS will help clinicians with the diagnosis of MS in this age group and prevention of wrong management plans and complications in these patients. Although the proportion of females is still more than males in LOMS cases; but there is a trend to increase in male cases with aging.

Objective: Early and accurate diagnosis of multiple sclerosis (MS) remains a clinical challenge. The main objective is to evaluate the diagnostic and prognostic value of the routinely performed immunoglobulin G (IgG) index for MS patients in the Asian population.Methods: A retrospective study was conducted among a cohort of clinically isolated syndrome (CIS) patients in China with known oligoclonal band (OCB) status and IgG index at baseline. We first evaluated the predictive value of IgG index for OCB status. Secondly, the diagnostic utility and prognostic value of IgG index alone were tested. Lastly, we incorporated IgG index into the 2017 McDonald criteria by replacing OCB with either “IgG index or OCB” (modified criteria 1), “IgG index and OCB” (modified criteria 2), or “IgG index” (modified criteria 3). The diagnostic utility of different criteria was calculated and compared.Results: In a CIS cohort in China (n = 105), IgG index > 0.7 forecasted OCB positivity (X2 = 22.90, P < 0.001). An elevated IgG index was highly prognostic of more clinical relapses [1-year adjusted odds ratio [OR] = 1.32, P = 0.015; 2-years adjusted OR = 1.69, P = 0.013] and Expanded Disability Status Scale worsening (1-year adjusted OR = 1.76, P = 0.040; 2-years adjusted OR = 1.85, P = 0.032). Under the 2017 McDonald criteria (Positive Likelihood Ratio = 1.54, Negative Likelihood Ratio = 0.56), an IgG index > 0.7 in CIS patients increased the likelihood of developing MS within 2 years, either when OCB status was unknown (Positive Likelihood Ratio = 2.11) or with OCB positivity (Positive Likelihood Ratio = 2.11) at baseline; An IgG index ≤ 0.7, along with a negative OCB, helped rule out the MS diagnosis (Negative Likelihood Ratio = 0.53).Conclusions: IgG index > 0.7 predicts OCB positivity at the initial attack of MS and is prognostic of early disease activity. IgG index serves as an easily-obtainable and accurate OCB surrogate for MS diagnosis in the Asian population.

The latest revision of multiple sclerosis diagnosis guidelines emphasizes the role of oligoclonal band detection in isoelectric focusing images of cerebrospinal fluid. Recent studies suggest tears as a promising noninvasive alternative to cerebrospinal fluid. We are developing the first automatic method for isoelectric focusing image analysis and oligoclonal band detection in cerebrospinal fluid and tear samples. The automatic analysis would provide an accurate, fast analysis and would reduce the expert-dependent variability and errors of the current visual analysis. In this paper, we describe a new effective model for the fully automated segmentation of highly distorted lanes in isoelectric focusing images. This approach is a new formulation of the classic parametric active contour problem, in which an open active contour is constrained to move from the top to the bottom of the image, and the x-axis coordinate is expressed as a function of the y-axis coordinate. The left and right edges of the lane evolved together in a ribbon-like shape so that the full width of the lane was captured reliably. The segmentation algorithm was implemented using a multiresolution approach in which the scale factor and the active contour control points were progressively increased. The lane segmentation algorithm was tested on a database of 51 isoelectric focusing images containing 419 analyzable lanes. The new model gave robust results for highly curved lanes, weak edges, and low-contrast lanes. A total of 98.8% of the lanes were perfectly segmented, and the remaining 1.2% had only minor errors. The computation time (1 s per membrane) is negligible. This method precisely defines the region of interest in each lane and thus is a major step toward the first fully automatic tool for oligoclonal band detection in isoelectric focusing images. Graphical abstract.

Background. The diagnostic sensitivity of CSF specific oligoclonal bands (OCBs) in multiple sclerosis (MS), using state of the art methods, has been clearly established to be over 95% in patients with a predominantly Caucasian background. This is not the case for other geographical regions, where reports of OCB prevalence can be much lower, and a relationship between OCB frequency and latitude has been suggested. Objective. The aim of the present study was to assess the frequency of OCBs in a cohort of MS patients evaluated at the Institute of Neurology and Neurosurgery (Havana, Cuba), and to review the scientific literature in order to investigate the possible relationship between OCB status and latitude in the region of Latin America. Methods. Fifty-three patients (47 with definite MS and 6 with clinically isolated syndrome – CIS) were included. Isoelectric focusing (IEF) with IgG immunoblotting for OCB analyses, was performed placing paired CSF and serum samples in the same analytical run. PubMed, Scielo and Google Scholar were searched for papers containing information concerning CSF OCB status (employing isoelectric focusing with IgG immunoblotting) in patients with definite MS in Latin America and the Caribbean. Results. In Cuban patients with definite MS, an OCB prevalence of 87% was observed, while the frequency in CIS patients was lower (67%). The prevailing pattern was that of OCBs restricted to the CSF (type 2), which was observed in 71% of definite MS patients and in all CIS patients with intrathecal IgG synthesis. OCB prevalence was slightly lower, but very close to that reported in Caucasian populations. Comparison with other Latin American countries revealed a significant correlation between OCB prevalence and latitude. Conclusions. A prevalence of CSF restricted OCBs of 87% was observed in definite MS patients, a frequency which was slightly lower, but similar to that reported in Caucasian populations. The analysis of OCB frequency in Latin American countries revealed a possible relationship between OCB prevalence and latitude, but this must be further investigated in more countries and larger samples of patients.

Optic neuritis (ON) is an inflammatory disease of the optic nerve characterized by pain and visual lossand often associated with multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMOSD).Autoantibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been reported in patientswith inflammatory central nervous system disorders including isolated optic neuritis (ON).Objective: To investigate the differences of clinical features, cerebrospinal fluid (CSF), MRI findings andresponse to steroid therapies between patients with optic neuritis (ON) who have myelin oligodendrocyteglycoprotein (MOG) antibodies and seronegative group. This study was done in a period between June2015 and July 2018, 65 patients were included in this study with ON who ophthalmologists had diagnosedas having or suspected to have ON with acute visual impairment and declined critical flicker frequency,abnormal findings of brain MRI, optical coherence tomography and fluorescein fundus angiography at theironset or recurrence. After exclusion of all patients who fulfilled the diagnostic criteria of neuromyelitisoptica (NMO)/NMO spectrum disorders (NMOSD), MS McDonald’s criteria, we defined 40 patients withidiopathic ON (12 males, 28 females, age range 15-60 years). Sera from patients were tested for antibodiesto MOG and aquaporin-4 (AQP4) with a cell-based assay.Results: 37.5% (15/40) were positive for MOG antibodies, 2.5% (1/40) were positive for AQP4 and 25(62.5%) were seronegative. Among the 15 patients with MOG antibodies, four had optic pain (p=0.007) andfive had prodromal infection (p=0.05). Two of the 15 MOG-positive patients showed significantly high CSFlevels of myelin basic protein (p=0.05) and none were positive for oligoclonal band in CSF. On MRIs, fiveMOG-positive patients showed high signal intensity on optic nerve, four had a cerebral lesion and two had aspinal cord lesion. Six of the eight MOG-positive patients had a good response to steroid therapy.Conclusions: The present results indicate that Patients with NMOSD and MOG positive antibodies havedistinct clinical features, fewer attacks and better recovery than seronegative patients.

Overview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression. Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from, This study was supported by grants PI15/00513, PI18/00572, and RD17/0015 (Red Espanola de Esclerosis Multiple) from Instituto de Salud Carlos III, Ministerio de Economia y Empresa, Spain.

BACKGROUND AND PURPOSE Cerebrospinal fluid (CSF) kappa free light chains (FLCs) may be a more sensitive marker of intrathecal immunoglobulin (Ig)G synthesis compared with oligoclonal bands (OCBs). Our aim was to retrospectively determine the additional value of the kappa and lambda index (CSF FLC/serum FLC)/(CSF albumin/serum albumin) in predicting a multiple sclerosis (MS) diagnosis in a group of OCB-negative patients with suspected MS. METHODS The CSF and serum kappa and lambda FLCs were tested using the Freelite kit (serum) and Freelite Mx (CSF) assay (The Binding Site Group, Bimingham, UK) in 391 OCB-negative patients with suspected/possible MS and in 54 OCB-positive patients with MS. RESULTS The CSF kappa FLC levels were below the detection limit (0.27 mg/L) in 61% of patients. Using quantitative data, we found the best kappa index cut-off value for the prediction of MS to be 5.8. A kappa index ≥5.8 was present in 25% of OCB-negative MS (23/92) and in 98% of OCB-positive patients with MS. Using a qualitative approach and a kappa index cut-off of 5.9, based on literature data, we likewise found that 24% of OCB-negative patients with MS had a kappa index ≥5.9, compared with 5.4% of OCB-negative patients without MS (P

In 208 children with opsoclonus-myoclonus syndrome (OMS), CSF IgG oligoclonal bands (OCB) and 22 immunomarkers in CSF and 21 in serum/blood were measured. In 36 untreated OMS, 58% were OCB(+), whereas 55% of treated OMS were OCB(−). OCB positivity or negativity did not alter concentrations or frequencies of immunomarkers. The phenotypes of OCB(+) and OCB(−) patients were not distinctive. CSF B cells were expanded in untreated OMS regardless of OCB positivity. These data reveal a much higher frequency of OCB positivity in untreated OMS than previously realized and a disconnect between intrathecal OCB and inflammatory mediator production.