Cerebrospinal Fluid Oligoclonal Bands Research Articles

Inter-assay diagnostic accuracy of cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis.

Cerebrospinal fluid (CSF) kappa free light chain (κFLC) measures gained increasing interest as diagnostic markers in multiple sclerosis (MS). However, the lack of studies comparing assay-dependent diagnostic cutoff values hinders their use in clinical practice. Additionally, the optimal κFLC parameter for identifying MS remains a subject of ongoing debate. The aim of this study was to compare same-sample diagnostic accuracies of the κFLC index, κIgG index, CSF κFLC/IgG ratio, and isolated CSF κFLC (iCSF-κFLC) between two reference centers using different methods. Paired serum and CSF samples were analyzed for κFLC and albumin concentrations by Freelite®-Optilite (Sint-Jan Bruges hospital) and N Latex®-BNII (Ghent University hospital). Diagnostic performance to differentiate MS from controls was assessed using ROC curve analysis. A total of 263 participants were included (MS, n = 80). Optimal diagnostic cutoff values for the κFLC index (Freelite®-Optilite: 7.7; N Latex®-BNII: 4.71), κIgG index (Freelite®-Optilite: 14.15, N Latex®-BNII: 12.19), and CSF κFLC/IgG ratio (Freelite®-Optilite: 2.27; N Latex®-BNII: 1.44) differed between the two methods. Sensitivities related to optimal cutoff values were 89.9% (Freelite®-Optilite) versus 94.6% (N Latex®-BNII) for the κFLC index, 91% (Freelite®-Optilite) versus 92.2% (N Latex®-BNII) for the κIgG index, and 81.3% (Freelite®-Optilite) versus 91.4% (N Latex®-BNII) for the CSF κFLC/IgG ratio. However, for iCSF-κFLC, optimal diagnostic cutoff values (0.36 mg/L) and related specificities (81.8%) were identical with a related diagnostic sensitivity of 89.9% for Freelite®-Optilite and 90.5% for N Latex®-BNII. The diagnostic performance of the κFLC index [area under the curve (AUC) Freelite®-Optilite: 0.924; N Latex®-BNII: 0.962] and κIgG index (AUC Freelite®-Optilite: 0.929; N Latex®-BNII: 0.961) was superior compared to CSF oligoclonal bands (AUC: 0.898, sensitivity: 83.8%, specificity: 95.9%). The κFLC index and the κIgG index seem to be excellent markers for identifying MS, irrespective of the method used for κFLC quantification. Based on the AUC, they appear to be the measures of choice. For all measures, optimal cutoff values differed between methods except for iCSF-κFLC. iCSF-κFLC might therefore serve as a method-independent, more cost-efficient, initial screening measure for MS. These findings are particularly relevant for clinical practice given the potential future implementation of intrathecal κFLC synthesis in MS diagnostic criteria and for future multicentre studies pooling data on κFLC measures.

Predicting the conversion from clinically isolated syndrome to multiple sclerosis: An explainable machine learning approach

IntroductionPredicting the conversion of clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) is critical to personalizing treatment planning and benefits for patients. The aim of this study is to develop an explainable machine learning (ML) model for predicting this conversion based on demographic, clinical, and imaging data. MethodThe ML model, Extreme Gradient Boosting (XGBoost), was employed on the public dataset of 273 Mexican mestizo CIS patients with 10-year follow-up. The data was divided into a training set for cross-validation and feature selection, and a holdout test set for final testing. Feature importance was determined using the SHapley Additive Explanations library (SHAP). Then, two experiments were conducted to optimize the model's performance by selectively adding variables and selecting the most contributive variables for the final model. ResultsNine variables including age, gender, schooling, motor symptoms, infratentorial and periventricular lesion at imaging, oligoclonal band in cerebrospinal fluid, lesion and symptoms types were significant. The model achieved an accuracy of 83.6 %, AUC of 91.8 %, sensitivity of 83.9 %, and specificity of 83.4 % in cross-validation. In the final testing, the model achieved an accuracy of 78.3 %, AUC of 85.8 %, sensitivity of 75 %, and specificity of 81.1 %. Finally, a web-based demo of the model was created for testing purposes. ConclusionThe model, focusing on feature selection and interpretability, effectively stratifies risk for treatment decisions and disability prevention in MS patients. It provides a numerical risk estimate for CDMS conversion, enhancing transparency in clinical decision-making and aiding in patient care.

Routine CSF parameters as predictors of disease course in multiple sclerosis: an MSBase cohort study

BackgroundIt remains unclear whether routine cerebrospinal fluid (CSF) parameters can serve as predictors of multiple sclerosis (MS) disease course.MethodsThis large-scale cohort study included persons with MS with CSF data documented...

Myelitis associated with COVID-19: clinical, radiological, and laboratory characteristics

Aim: The current study aimed to describe various types of myelitis associated with a novel coronavirus infection [coronavirus disease 2019 (COVID-19)] as well as to analyze cytokine profiles and cerebrospinal fluid (CSF) parameters in affected patients and to compare them to patients with other immune-mediated disorders—multiple sclerosis (MS), in order to identify possible common pathogenetic pathways and consequently treatment targets. Methods: Clinical, radiological, and laboratory characteristics were studied based on patients’ history. CSF from patients with myelitis associated with COVID-19 (11 patients) was compared with CSF of healthy controls (HC) (7 patients) and patients with MS (37 patients) from the non-COVID era. CSF cytological examination, protein levels and oligoclonal bands (OCBs) evaluation, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus detection and cytokine profiling using Bio-Plex Pro Human Inflammation Panel 1, 37-Plex were performed. Results: In total 11 patients with different types of myelitis developed up to 3 months after COVID-19 were enrolled in the study. Radiological findings were diverse: short transverse myelitis (lesion of fewer than 3 segments) (n = 6), longitudinal extensive transverse myelitis (LETM) (n = 2), multifocal spinal cord lesions (n = 1), and myelitis involving dorsal and lateral columns (n = 2). The most pronounced response to treatment was observed in patients with partial transverse myelitis and patients with anti-myelin oligodendrocyte glycoprotein (MOG) antibodies (MOG Abs). Multiple comparisons have demonstrated decreased levels of interleukin-10 (IL-10), interferon-α2 (IFN-α2), IFN-β, and thymic stromal lymphopoietin (TSLP), and increased IL-19 and B cell activating factor (BAFF) in patients with COVID-19 myelitis (CM) compared to the MS group. The highest BAFF and a proliferation-inducing ligand (APRIL) concentrations were found in patients with the most profound neurological disability. Conclusions: Myelitis associated with COVID-19 is clinically and radiologically heterogeneous. Evaluation of cytokine profiles in patients with myelitis associated with COVID-19 revealed their relative similarity with ones of MS patients, except for a few cytokines. BAFF/APRIL system as well as IL-10 is well-known for the role in the development and progression of autoimmune diseases, however, their links with COVID-19 and effects on the development of immune-mediated central nervous system (CNS) disorders after SARS-CoV-2 remain to be further studied.

Characteristics of cerebrospinal fluid oligoclonal band in anti-myelin oligodendrocyte glycoprotein (MOG) antibody associated disease

ObjectiveTo analyze the immune parameters of cerebrospinal fluid (CSF) and oligoclonal band (OCB) type in patients with anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated diseases (MOGAD). MethodsPatients who were seropositive for MOG-IgG and diagnosed with MOGAD according to the diagnosis criteria in the Department of Neurology, Huashan Hospital, Fudan University from December 2020 to June 2022 were retrospectively included in this study. Complete clinical data, blood and cerebrospinal fluid samples were collected from all the participants. Paired serum and CSF MOG-IgG and autoimmune encephalitis antibody were assayed by Cell Based Assay (CBA) based on transfected target antigens. Paired serum and CSF albumin and IgG were detected by turbidimetric scattering method, and OCB was detected by standard operation procedure as described. ResultsA total of 86 patients (44 males and 42 females) with MOGAD were included in this study, with a median age of 30 years (range: 5–82 years). Among all the patients, 73 patients showed OCB type I, 12 patients showed OCB type II, and one patient showed OCB type III. The overall positive rate of CSF-OCB in MOGAD patients was 15.1 %. The 24-h intrathecal synthesis rate of CSF in the OCB-positive group (n = 13) was higher than that in the OCB-negative group [n = 73, 0.62 (0.26) vs 5.11 (13.67), P = 0.003]. Subgroup analysis revealed that the positive rates of CSF-OCB in the single MOG group (n = 61) and the group combined with other antibodies (n = 25) were 14.8 % and 16.0 %, respectively. The incidence of meningoencephalitis (13/61 vs 13/25, P = 0.011) was significantly different between the two groups. The proportion of patients with high (≥1:32) or low (≤1:10) CSF MOG-IgG also showed significant difference in the group combined with other antibodies (P = 0.032). Optic neuritis was more common in the relapse course group (n = 49) than the monophasic course group (n = 37, P < 0.001) No significant diferences of CSF immune parameters were found in the MOG-IgGserum+/CSF− group and the MOG-IgGserum+/CSF + group, and the titer of MOG-IgG in the serum or CSF did not influence CSF immune parameters in different subgroups. ConclusionThe overall positive rate of CSF-OCB in MOGAD patients was 15.1 %. The 24-h intrathecal synthesis rate of cerebrospinal fluid in the OCB-positive group was higher than that in the OCB-negative group. This study illustrated OCB characterization in MOGAD patients, and will shed light on the standardization of OCB test in the study of immune diseases.

Comparing clinical features, severity and prognosis of autoimmune encephalitis and with and without oligoclonal bands.

This study aimed to examine the clinical distinctions among patients diagnosed with autoimmune encephalitis (AE) based on the presence or absence of cerebrospinal fluid (CSF) oligoclonal bands (OCBs). Additionally, it sought to explore the relationship between OCBs and the severity and prognosis of autoimmune encephalitis. A retrospective analysis was conducted on 94 patients diagnosed with AE at the People's Hospital of Zhengzhou University between October 2016 and June 2022. The patients were divided into OCB-positive and OCB-negative groups based on CSF-OCBs. Patient severity at admission was assessed utilizing the Clinical Assessment Scale for Autoimmune Encephalitis (CASE) and the modified Rankin scale (mRS). Additionally, some oligoclonal-positive patients underwent dynamic longitudinal analysis of cerebrospinal fluid test indices. The mRS score was ultimately employed to evaluate patients' short-term prognosis (6 months) and long-term prognosis (at least 12 months) following immunotherapy. Of the 94 patients, 34 (36.2%) belonged to the OCB-positive group, while 60 (63.8%) belonged to the OCB-negative group. The group with anti-n-methyl-d-aspartate receptor (anti-NMDAR) encephalitis exhibited the highest rate of oligoclonal positivity at 27 (49.1%), followed by anti-aminobutyric acid B receptor (GABABR) encephalitis with 4 cases (30.8%), anti-contactin-associated protein-like 2 (CASPR2) encephalitis with 2 cases (20%), and anti-leucine-rich glioma inactivating protein 1 (LGI1) encephalitis with 1 case (6.25%). No statistically significant differences were found between the two groups regarding gender, age, prodromal symptoms, psychiatric disorders, seizures, language disorders, motor dysfunction, cognitive dysfunction, tumor incidence, and magnetic resonance imaging (MRI) abnormalities (p > 0.05). The OCB-positive group exhibited higher rates of autonomic dysfunction, intensive care unit (ICU) admission, CSF leukocytes, and IgG index compared to the OCB-negative group (p < 0.05). Additionally, the OCB-positive group had significantly higher median CASE and mRS scores prior to immunotherapy than the OCB-negative group (p < 0.001 and p < 0.001). Furthermore, in both short-term follow-up and long-term follow-up, the OCB-positive group had a significantly lower proportion of patients with a favorable prognosis compared to the OCB-negative group (50% vs. 71.7, 61.8% vs. 83.3%; p = 0.036, p = 0.002). Autonomic dysfunction, ICU admission, leukocytes in the cerebrospinal fluid, and elevated IgG index are more commonly observed in OCB-positive patients. OCB-positivity has also been linked to the severity and prognosis of AE, making it a potential biomarker. Initial OCB testing aids clinicians in identifying potentially critically ill patients early and monitoring disease progression, thereby optimizing clinical treatment decisions.

Vasculitis in the Central Nervous System: Etiology, Characteristics, and Outcomes in a Large Single-Center Cohort.

For the management of central nervous system (CNS) vasculitis, it is crucial to differentiate between primary and secondary CNS vasculitis and to understand the respective etiologies. We assessed the etiology, characteristics, and outcomes of patients with CNS vasculitis. A single-center retrospective chart review was conducted at the University of Utah, Department of Neurology, between February 2011 and October 2022. The median age of the 44 included patients at diagnosis was 54years; 25.0% were men. Compared to primary CNS vasculitis, secondary CNS vasculitis exhibits higher fever incidence (observed in infectious and connective tissue disorder [CTD]-associated vasculitis), low glucose levels (mostly in infectious vasculitis) and unique cerebrospinal fluid oligoclonal bands (observed in infectious and CTD-associated vasculitis). Patients with inflammatory cerebral amyloid angiopathy (CAA) were older and more commonly had microhemorrhage than primary angiitis of the CNS (PACNS). All patients with CTD-associated vasculitis had a known history of CTD at presentation. Brain biopsies were performed on 10 of 17 PACNS patients and 4 of 8 inflammatory CAA patients, confirming vasculitis in 7 and 4 patients, respectively. Intravenous methylprednisolone was the predominant induction therapy (63.6%), and cyclophosphamide was the most used adjunctive therapy. Cyclophosphamide, rituximab, azathioprine, and mycophenolate mofetil were utilized as maintenance therapy, often with concurrent prednisone. Patients with inflammatory CAA had a higher tendency for relapse rates than PACNS. This study highlights the variations in patients' characteristics, symptoms, and treatment for CNS vasculitis. Understanding these differences can lead to more efficient diagnostic and management strategies.

A multicenter study of radiologically isolated syndrome in children and adolescents: Can we predict the course?

To evaluate clinical characteristics, imaging features and etiological profile of Radiologically Isolated Syndrome (RIS) along with clinical and radiological follow-up. Demographic, clinical and radiological data of patients younger than 18 years fulfilling the criteria for RIS were retrospectively analyzed. RIS was defined by the detection of lesions meeting the revised 2010 McDonald Criteria for dissemination in space on magnetic resonance imaging (MRI) in the absence of any symptoms of demyelinating disease or an alternative cause for the MRI findings. There were total 69 patients (38 girls, 31 boys). The median age at index MRI was 15.7 years, and median follow-up time was 28 months. The most common reason for neuroimaging was headache (60.9%). A first clinical event occurred with median 11 months in 14/69 (20%) of cases. Those with oligoclonal bands (OCB) in cerebrospinal fluid (CSF) and follow-up longer than 3 years were more likely to experience a clinical event (p<0.05): 25% of those with OCB manifested clinical symptoms within the first year and 33.3% within the first two years compared to 6.3% and 9.4%, respectively in those without OCB. Radiological evolution was not associated with any variables: age, sex, reason for neuroimaging, serum 25-hydroxyvitamin D level, elevated IgG index, OCB positivity, total number and localization of lesions, presence of gadolinium enhancement, achievement of 2005 criteria for DIS and duration of follow-up. Children and adolescents with RIS and CSF OCB should be followed-up for at least 3 years in order to detect any clinical symptoms suggestive of a demyelinating event. Because disease-modifying treatments are not approved in RIS and no consensus report justifies their use especially in pediatric RIS, close follow-up of OCB-positive patients is needed for early recognition of any clinical event and timely initiation of specific treatment.

Pathogenic myelin-specific antibodies in multiple sclerosis target conformational proteolipid protein 1-anchored membrane domains.

B cell clonal expansion and cerebrospinal fluid (CSF) oligoclonal IgG bands are established features of the immune response in multiple sclerosis (MS). Clone-specific recombinant monoclonal IgG1 Abs (rAbs) derived from MS patient CSF plasmablasts bound to conformational proteolipid protein 1 (PLP1) membrane complexes and, when injected into mouse brain with human complement, recapitulated histologic features of MS pathology: oligodendrocyte cell loss, complement deposition, and CD68+ phagocyte infiltration. Conformational PLP1 membrane epitopes were complex and governed by the local cholesterol and glycolipid microenvironment. Abs against conformational PLP1 membrane complexes targeted multiple surface epitopes, were enriched within the CSF compartment, and were detected in most MS patients, but not in inflammatory and noninflammatory neurologic controls. CSF PLP1 complex Abs provide a pathogenic autoantibody biomarker specific for MS.

Laboratory evaluation for the differential diagnosis of possible multiple sclerosis in the United States: A physician survey

BackgroundThere is limited evidence and lack of guidelines for diagnostic laboratory evaluation of patients with possible multiple sclerosis (MS). ObjectiveTo survey neurologists on their practice of laboratory testing in patients with possible MS. MethodsAn online survey was developed to query the frequency of serum and cerebrospinal fluid (CSF) studies ordered in the routine evaluation of patients with possible MS, and in three hypothetical clinical cases. Non-MS specialist neurologists who evaluate patients for MS in their practice were invited to participate by MedSurvey (a medical market research company). ResultsThe survey was completed by 190 neurologists. A mean of 17.2 (SD: 17.0) tests in serum and CSF were reported “always” ordered in the evaluation of patients with possible MS. CSF oligoclonal bands was the most frequently selected (“always” among 73.7% of participants). Antinuclear antibody (43.2%), erythrocyte sedimentation rate (34.2%), and thyroid stimulating hormone (31.6%) were also among the most frequently ordered. DiscussionExtensive laboratory evaluations are often completed in the evaluation of possible MS. However, many of these tests have poor specificity and false positive results could yield unnecessary increased costs, diagnostic delay, and potentially misdiagnosis. Further research is needed to identify optimal laboratory approaches for possible MS.

Case 317: Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia.

A 44-year-old previously healthy man with a 9-month history of progressive cognitive decline, depression, urinary incontinence, and inability to perform tasks of daily living presented to the emergency department with worsening cognitive and neuropsychiatric symptoms. He had become more distressed, and his family noticed him departing the house without closing doors, leaving water faucets running, and sending his children to school on Sundays. History taken from the patient's wife revealed that his brother had passed away in his late 30s after a slowly progressing functional and cognitive decline over the course of 5 years. No further detailed family history could be obtained. The review of systems was negative; he had no prior medical, psychiatric, or surgical history; and he denied any history of recent travel, camping, hiking, or vaccination. The patient was not taking any dietary supplements, nor was he taking any over-the-counter or prescription medication. Examination revealed vital signs were within normal limits. Neurocognitive assessment revealed a conscious, coherent, and alert patient with impaired memory and concentration. He showed poor attention, depressed mood, and restricted affect. He was unable to spell the word world forward, nor was he able to understand a request to spell it backward. The rest of the physical and neurologic examination revealed no abnormalities. Extensive laboratory work-up was conducted and included the following: toxicology screening; screening for HIV-1, HIV-2, and syphilis treponemal antibodies; COVID-19 polymerase chain reaction; and measurement of B1 and B12 levels. The results of screening were negative. Cerebrospinal fluid (CSF) assays, including CSF oligoclonal bands and CSF flow cytometry, revealed values within normal limits. CT of the brain without intravenous contrast material was performed in the emergency department to rule out acute intracranial abnormality. Multiplanar multisequence MRI of the brain without and with intravenous contrast material was ordered for further assessment. CT images of chest, abdomen, and pelvis were unremarkable (images not shown).

Defining the natural history of tumefactive demyelination: A retrospective cohort of 257 patients.

To describe demographic, clinical, and radiographic features of tumefactive demyelination (TD) and identify factors associated with severe attacks and poor outcomes. Retrospective review of TD cases seen at Mayo Clinic, 1990-2021. Of 257 patients with TD, 183/257 (71%) fulfilled the 2017 multiple sclerosis (MS) McDonald criteria at the last follow-up, 12/257 (5%) had myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), 0 had aquaporin-4-IgG seropositive neuromyelitis optic spectrum disorders (AQP4+ NMOSD), and 62/257 (24%) were cryptogenic. Onset before age 18 was present in 18/257 (7%). Female to male ratio was 1.3:1. Cerebrospinal fluid oligoclonal (CSF) bands were present in 95/153 (62%). TD was the first demyelinating attack in 176/257 (69%). At presentation, 59/126 (47%) fulfilled Barkhof criteria for dissemination in space, 59/100 (59%) had apparent diffusion coefficient (ADC) restriction, and 57/126 (45%) had mass effect. Despite aggressive clinical presentation at onset, 181/257 (70%) of patients remained fully ambulatory (Expanded Disability Status Scale [EDSS] ≤4) after a 3.0-year median follow-up duration. Severe initial attack-related disability (EDSS ≥4) was more common in patients with motor symptoms (81/143 vs. 35/106, p < 0.0001), encephalopathy (20/143 vs. 2/106, p < 0.0001) and ADC restriction on initial MRI (42/63 vs. 15/33, p = 0.04). Poor long-term outcome (EDSS ≥4) was more common in patients with older onset age (41.9 ± 15 vs. 36.8 ± 15.6, p = 0.02) and motor symptoms at onset (49/76 vs. 66/171, p < 0.0001). Most TD patients should be considered part of the MS spectrum after excluding MOGAD and NMOSD. Motor symptoms and older age at presentation portend a poor outcome.

Oligoclonal Band Status and Features of Radiological and Clinical Findings in Patients with Multiple Sclerosis in Lithuania.

Background and Objectives: Multiple sclerosis (MS) is a widely spread and debilitating disease with 2.8 million people worldwide currently affected. However, the exact pathogenesis of the disease and its progression remains incompletely understood. According to the revised McDonald criteria, cerebrospinal fluid oligoclonal bands (CSF OCBs) magnetic resonance imaging (MRI) results, in conjunction with clinical presentation, remain the gold standard of MS diagnostics. Therefore, this study aims to evaluate the association between CSF OCB status and features of radiological and clinical findings in patients with multiple sclerosis in Lithuania. Materials and Methods: The selection of 200 MS patients was performed in order to find associations between CSF OCB status, MRI data and various disease features. The data were acquired from outpatient records and a retrospective analysis was performed. Results: OCB positive patients were diagnosed with MS earlier and had spinal cord lesions more frequently than OCB negative patients. Patients with lesions in the corpus callosum had a greater increase in the Expanded Disability Status Scale (EDSS) score between their first and last visit. Patients with brainstem lesions had higher EDSS scores during their first and last visit. Even so, the progression of the EDSS score was not greater. The time between the first symptoms and diagnosis was shorter for patients who had juxtacortical lesions than patients who did not. Conclusions: CSF OCBs and MRI data remain irreplaceable tools when diagnosing multiple sclerosis as well as prognosing the development of the disease and disability.

Case 317

A 44-year-old previously healthy man with a 9-month history of progressive cognitive decline, depression, urinary incontinence, and inability to perform tasks of daily living presented to the emergency department with worsening cognitive and neuropsychiatric symptoms. He had become more distressed, and his family noticed him departing the house without closing doors, leaving water faucets running, and sending his children to school on Sundays. History taken from the patient's wife revealed that his brother had passed away in his late 30s after a slowly progressing functional and cognitive decline over the course of 5 years. No further detailed family history could be obtained. The review of systems was negative; he had no prior medical, psychiatric, or surgical history; and he denied any history of recent travel, camping, hiking, or vaccination. The patient was not taking any dietary supplements, nor was he taking any over-the-counter or prescription medication. Examination revealed vital signs were within normal limits. Neurocognitive assessment revealed a conscious, coherent, and alert patient with impaired memory and concentration. He showed poor attention, depressed mood, and restricted affect. He was unable to spell the word world forward, nor was he able to understand a request to spell it backward. The rest of the physical and neurologic examination revealed no abnormalities. Extensive laboratory work-up was conducted and included the following: toxicology screening; screening for HIV-1, HIV-2, and syphilis treponemal antibodies; COVID-19 polymerase chain reaction; and measurement of B1 and B12 levels. The results of screening were negative. Cerebrospinal fluid (CSF) assays, including CSF oligoclonal bands and CSF flow cytometry, revealed values within normal limits. CT of the brain without intravenous contrast material was performed in the emergency department to rule out acute intracranial abnormality (Fig 1). Multiplanar multisequence MRI of the brain without and with intravenous contrast material was ordered for further assessment (Figs 2-4). CT images of chest, abdomen, and pelvis were unremarkable (images not shown).

African-Americans With Multiple Sclerosis Have a Higher Proportion of B-Cell Lineage Cells in Their Cerebrospinal Fluid (CSF) Than White Patients (P9-3.010)

<h3>Objective:</h3> To compare proportions of B-cell lineage CD19+ and CD20+ cells in CSF of African-Americans (AA) and White (W) patients with MS. <h3>Background:</h3> Compared to W patients, AA patients with MS are more likely to have oligoclonal bands in CSF; have higher IgG index in CSF; and have higher circulating plasmablasts in blood. It is unknown whether the proportion of B-cells in CSF differs between AA and white patients in MS. <h3>Design/Methods:</h3> Demographics, disease-related information, and treatment history were retrospectively collected on patients with neurologist-diagnosed MS who self-identified as AA or W, received care at NYU MS Care Center, and underwent flow cytometry of CSF during diagnostic work-up. Lymphocyte subsets (B-lymphocytes, T-lymphocytes, NK cells), monocytes and plasma cells were analyzed with flow cytometry (BD FACSCanto™ and FACSCanto™ II Cell Analyzers). <h3>Results:</h3> 20 AA and 57 W MS patients fulfilled inclusion criteria. The groups had similar age at lumbar puncture, sex ratio, CSF cell counts, protein and glucose CSF concentrations, and oligoclonal band number. IgG index was higher in AA compared to W (<i>1.08 v 0.87, p=0.044</i>). With respect to mononuclear cell counts in CSF, AA had higher proportions of CD19+ (<i>5.45% AA v. 2.27% W, p=0.0061</i>) and CD20+ (<i>5.00% AA v. 1.95% W, p=0.0046</i>) cells, but did not significantly differ in proportion of CD4+, CD8+, CD38+ bright B-cells, NK cells and monocytes. Sensitivity analyses that excluded all patients on disease-modifying therapy at the time of lumbar puncture (n=8) yielded similar conclusions. <h3>Conclusions:</h3> B-cells are overrepresented in the CSF of African American patients with MS relative to Whites. Whether this finding bears on the increased severity of MS disease course in AA patients warrants investigation. <b>Disclosure:</b> Mr. Xue has nothing to disclose. Dr. Arbini has nothing to disclose. Mr. Melton has received personal compensation for serving as an employee of Janssen Pharmaceuticals. Dr. Kister has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech-Roche. The institution of Dr. Kister has received research support from Genentech. Dr. Kister has received publishing royalties from a publication relating to health care.

Variation in processes and reporting of cerebrospinal fluid oligoclonal banding and associated tests and calculated indices across Canadian clinical laboratories

ObjectivesMultiple sclerosis is diagnosed based on clinical and laboratory findings, including cerebrospinal fluid (CSF) oligoclonal banding (OCB) analysis. The lack of updated CSF OCB laboratory guidelines in Canada has likely led to variation in processes and reporting across clinical laboratories. As a first step to developing harmonized laboratory recommendations, we examined current CSF OCB processes, reporting, and interpretation across all Canadian clinical laboratories currently performing this test. Design and methodsA survey of 39 questions was sent to clinical chemists at all 13 Canadian clinical laboratories performing CSF OCB analysis. The survey included questions regarding quality control processes, reporting practices for CSF gel electrophoresis pattern interpretation, and associated tests and calculated indices. ResultsThe survey response rate was 100%. Most (10/13) laboratories use ≥2 CSF-specific bands (2017 McDonald Criteria) as their CSF OCB positivity cut-off and only 2/13 report the number of bands with every report. Most (8/13 and 9/13) laboratories report an inflammatory response pattern and monoclonal gammopathy pattern, respectively. However, the process for reporting and/or confirming a monoclonal gammopathy varies widely. Variation was observed for reference intervals, units, and the panel of reported associated tests and calculated indices. The maximum acceptable time interval between paired CSF and serum collections varied from 24 h to no limit. ConclusionsProfound variation exists in processes, reporting, and interpretation of CSF OCB and associated tests and indices across Canadian clinical laboratories. Harmonization of CSF OCB analysis is required to ensure continuity and quality of patient care. Our detailed assessment of current practice variation highlights the need for clinical stakeholder engagement and further data analysis to support optimal interpretation and reporting practices, which will aid in developing harmonized laboratory recommendations.

Transient headache and neurological deficits with cerebrospinal fluid lymphocytosis syndrome: A comprehensive systematic review of 93 patients from 57 studies.

Headache with neurologic deficits and cerebrospinal fluid lymphocytosis, previously also termed pseudomigraine with temporary neurologic symptoms and lymphocytic pleocytosis, is a self-limiting syndrome characterized by moderate to severe headache associated with focal neurological deficits occurring in the context of lymphocytosis in the cerebrospinal fluid. As a consequence of its rarity, data regarding headache with neurologic deficits and cerebrospinal fluid lymphocytosis is sparse. Therefore, we conducted this review to analyze data related to 93 patients of headache with neurologic deficits and cerebrospinal fluid lymphocytosis, to characterize their demographics, clinical manifestations, investigations and treatment options. We performed a systematic review of cases reported through PubMed and Google scholar database, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Keywords used were 'Headache with Neurologic Deficits and cerebrospinal fluid lymphocytosis', 'Headache with neurologic deficits and cerebrospinal fluid lymphocytosis syndrome'. The quality of the included studies was assessed using the Joanna Briggs Institute Critical Appraisal Tool. We analyzed a total of 93 cases of headache with neurologic deficits and cerebrospinal fluid lymphocytosis with a mean age of 28.8 years at onset. Seventy patients (75.2%) were adults, while 23 (24.7%) belonged to the pediatric age group. Comparing these groups, mean age at onset was 32.5 years and 14.3 years, respectively. The average duration of follow-up was 11.08 months. Thirty percent of patients experienced relapsing episodes of headache with neurologic deficits and cerebrospinal fluid lymphocytosis symptoms. The most common type of headache reported was unilateral severe throbbing episodic headache. Other associated symptoms included sensory deficit (60%) and motor deficits (54.8%). The least common symptoms were nystagmus and agraphia, which were reported in one patient each. Antiviral agents were a common treatment option in the acute phase (n = 23 patients [23.6%]), while Flunarizine was the most commonly used agent in the chronic setting (n = 3 patients [3.2%]). While most of the patients had normal brain magnetic resonance imaging, 20 patients had magnetic resonance imaging abnormalities, including (but not limited to) non-specific white matter lesions (eight patients) and meningeal enhancement (six patients). The most common electroencephalographic findings included diffuse and focal slowing. The mean cerebrospinal fluid opening-pressure was 240.5 mmH2O. Cerebrospinal fluid protein was elevated in 59 (63.4%) patients, with a mean value of 114 mg/dL. Two patients in our cohort were found to have cerebrospinal fluid oligoclonal bands. Headache with neurologic deficits and cerebrospinal fluid lymphocytosis tends to affect young individuals with a slight male predominance. Unilateral severe throbbing episodic headache with associated hemi-paresthesia and hemiparesis were the most common symptoms based on our review. Elevated cerebrospinal fluid opening-pressure can be seen in headache with neurologic deficits and cerebrospinal fluid lymphocytosis syndrome. Early recognition of the syndrome is paramount. Antivirals were found to be among the most widely used treatments in the acute setting. Magnetic resonance imaging of the brain is mostly normal. Diffuse and focal slowing were among the most common electroencephalographic findings. Cerebral flow abnormalities on perfusion scans are not uncommon in headache with neurologic deficits and cerebrospinal fluid lymphocytosis. Prospective studies with a larger sample size are needed to validate our findings and guide the clinical care of these patients.

Selective emergence of antibody-secreting cells in the multiple sclerosis brain.

Although distinct brain-homing B cells have been identified in multiple sclerosis (MS), it is unknown how these further evolve to contribute to local pathology. We explored B-cell maturation in the central nervous system (CNS) of MS patients and determined their association with immunoglobulin (Ig) production, T-cell presence, and lesion formation. Exvivo flow cytometry was performed on post-mortem blood, cerebrospinal fluid (CSF), meninges and white matter from 28 MS and 10 control brain donors to characterize B cells and antibody-secreting cells (ASCs). MS brain tissue sections were analysed with immunostainings and microarrays. IgG index and CSF oligoclonal bands were measured with nephelometry, isoelectric focusing, and immunoblotting. Blood-derived B cells were cocultured under T follicular helper-like conditions to evaluate their ASC-differentiating capacity invitro. ASC versus B-cell ratios were increased in post-mortem CNS compartments of MS but not control donors. Local presence of ASCs associated with a mature CD45low phenotype, focal MS lesional activity, lesional Ig gene expression, and CSF IgG levels as well as clonality. Invitro B-cell maturation into ASCs did not differ between MS and control donors. Notably, lesional CD4+ memory T cells positively correlated with ASC presence, reflected by local interplay with T cells. These findings provide evidence that local B cells at least in late-stage MS preferentially mature into ASCs, which are largely responsible for intrathecal and local Ig production. This is especially seen in active MS white matter lesions and likely depends on the interaction with CD4+ memory T cells. Stichting MS Research (19-1057 MS; 20-490f MS), National MS Fonds (OZ2018-003).

Status of Cerebrospinal Fluid Oligoclonal Bands Among Patients with Multiple Sclerosis MS at King Abdulaziz Medical City

Status of Cerebrospinal Fluid Oligoclonal Bands Among Patients with Multiple Sclerosis MS at King Abdulaziz Medical City

Assessment of oligoclonal bands in cerebrospinal fluid and serum of dogs with meningoencephalitis of unknown origin.

Meningoencephalitis of unknown origin (MUO) is an inflammatory disease of the canine central nervous system (CNS) that shares several features with multiple sclerosis (MS) in humans. In approximately 95% of MS patients, ≥ two immunoglobulin G (IgG) oligoclonal bands (OCBs) are detectable exclusively in the cerebrospinal fluid (CSF). To investigate OCBs in CSF and serum in dogs affected by MUO, intervertebral disc disease (IVDD), idiopathic epilepsy (IE), intracranial neoplasia (IN), steroid-responsive meningitis-arteritis (SRMA), and diseases outside the CNS. We hypothesize that the highest prevalence of CSF-specific OCBs (≥ two OCBs uniquely in the CSF) would be found in dogs affected by MUO. Client-owned dogs (n = 121) presented to the neurology service due to neurological deficits. Prospective study. Measurement of IgG concentration in CSF and serum via a canine IgG ELISA kit. OCB detection via isoelectric focusing (IEF) and immunoblot. Presence of CSF-specific OCBs was significantly higher in dogs with MUO (57%) compared to 22% in IN, 6% in IE, 15% in SRMA, 13% in IVDD, and 0% in the non-CNS group (p < .001). Dogs with MUO were 9.9 times more likely to show CSF-specific OCBs than all other diseases together (95% confidence interval, 3.7-26.4; p < .001). MUO showed the highest prevalence of CSF-specific OCBs, indicating an inflammatory B cell response. Future studies are needed to evaluate the prevalence in the specific MUO subtypes and a possible similarity with human MS.