Diagnostic and Prognostic Value of the Cerebrospinal Fluid Concentration of Immunoglobulin Free Light Chains in Clinically Isolated Syndrome with Conversion to Multiple Sclerosis.

Background and objectiveIn this study, we evaluated the diagnostic and prognostic significance of cerebrospinal fluid free light chains (CSF FLC) at the time of clinically isolated syndrome (CIS).MethodsWe compared FLC-parameters at the moment of CIS in patients with conversion to multiple sclerosis (MS) after 2 years (CIS-MS), patients who remained stable both clinically and radiologically after 2 years (CIS-nonMS), patients with non-inflammatory neurologic diseases (NIND) as a comparison group and patients with other inflammatory neurologic diseases (IND) with intrathecal oligoclonal bands (OCB) synthesis. ROC-analysis was conducted to define FLC-assay characteristics and cut-off values. We also compared FLC-concentrations in CIS patients to determine their OCB-status. A correlation analysis was performed between FLC-concentrations and the expanded disability scale score (EDSS), annualized relapse rate (ARR) and MRI-activity (i.e., number of new and gadolinium-enhancing (Gd+) lesions) in patients.ResultsThe levels of kappa-FLC (k-FLCCSF) and lambda-FLC (λ-FLCCSF) as well as kappa- and lambda-quotients (Q-k and Q-λ) were elevated in CIS-MS compared to the CIS-nonMS and NIND groups. These levels did not differ significantly when compared with the IND group. We identified several patients with high k-FLCCSF and λ-FLCCSF in OCB-negative CIS and IND groups. The level of k-FLCCSF production was significantly higher in OCB-positive patients in the CIS-MS group compared to the CIS-nonMS group. The concentrations of k-FLCCSF and Q-k in the CIS-MS group showed significant correlation with the level of EDSS after 2 years (k-FLC: r = 0.4477,p = 0.0016; Q-k: r = 0.4621, p = 0.0016). λ-FLCCSF and Q-λ inversely correlated with the number of Gd+ lesions (CSF λ-FLC: r = -0.3698, p = 0.0223; Q-λ: r = -0.4527, p = 0.0056).ConclusionThe concentration of CSF FLC predicts conversion to MS within 2 years following CIS. OCB-positive patients with an early conversion have a higher concentration of CSF-FLC. We have also shown a prognostic significance of k-FLCCSF for future EDSS-progression

Systematic evaluation of the guidelines for rehabilitation in multiple sclerosis patients: an overview according to ICF functioning domains

High-quality clinical practice guidelines (CPGs) can provide evidence-based recommendations for optimizing care on managing multiple sclerosis (MS). There is currently no review that compiles recommendations of high-quality CPGs to guide decision-making for MS rehabilitation. The aim was to identify evidence-based recommendations in high-quality multidisciplinary English CPGs for rehabilitation in MS. CPGs published in the last 10 years (2009-2019) that described recommendations on rehabilitation were searched in PubMed, Turning Research into Practice database, International Guideline databases, National Guideline databases and websites of MS organizations. Quality assessment of CPGs was conducted by two evaluators using the Appraisal of Guidelines for Research and Evaluation II instrument. Recommendations were classified according to the International Classification of Functioning, Disability and Health (ICF) and the International Classification of Health Intervention (ICHI) and documented in terms of strength of recommendation and level of evidence. Five CPGs satisfied the inclusion criteria. Of 120 recommendations, 38 had a strong level with moderate to low level of evidence, 61 were of weak strength and 18 were formulated by the consensus of experts. Recommendations were categorized into 12 domains and 1 chapter on the body function level, 1 chapter on activity level and 2 domains on external factors. The existing CPGs demonstrated more than 100 evidence level recommendations to be followed at the clinical practice, most in body functions of the ICF. Developing up-to-date CPGs with more focus on activity and participation domains for countries with various healthcare backgrounds may be useful for a best clinical practice

Data from: Diagnostic and prognostic value of the cerebrospinal fluid concentration of immunoglobulin free light chains in clinically isolated syndrome with conversion to multiple sclerosis

Background and objective: In this study, we evaluated the diagnostic and prognostic significance of cerebrospinal fluid free light chains (CSF FLC) at the time of clinically isolated syndrome (CIS). Methods: We compared FLC-parameters at the moment of CIS in patients with conversion to multiple sclerosis (MS) after 2 years (CIS-MS), patients who remained stable both clinically and radiologically after 2 years (CIS-nonMS), patients with non-inflammatory neurologic diseases (NIND) as a comparison group and patients with other inflammatory neurologic diseases (IND) with intrathecal oligoclonal bands (OCB) synthesis. ROC-analysis was conducted to define FLC-assay characteristics and cut-off values. We also compared FLC-concentrations in CIS patients to determine their OCB-status. A correlation analysis was performed between FLC-concentrations and the expanded disability scale score (EDSS), annualized relapse rate (ARR) and MRI-activity (i.e., number of new and gadolinium-enhancing (Gd+) lesions) in patients. Results: The levels of kappa-FLC (k-FLCCSF) and lambda-FLC (λ-FLCCSF) as well as kappa- and lambda-quotients (Q-k and Q-λ) were elevated in CIS-MS compared to the CIS-nonMS and NIND groups. These levels did not differ significantly when compared with the IND group. We identified several patients with high k-FLCCSF and λ-FLCCSF in OCB-negative CIS and IND groups. The level of k-FLCCSF production was significantly higher in OCB-positive patients in the CIS-MS group compared to the CIS-nonMS group. The concentrations of k-FLCCSF and Q-k in the CIS-MS group showed significant correlation with the level of EDSS after 2 years (k-FLC: r = 0.4477,p = 0.0016; Q-k: r = 0.4621, p = 0.0016). λ-FLCCSF and Q-λ inversely correlated with the number of Gd+ lesions (CSF λ-FLC: r = -0.3698, p = 0.0223; Q-λ: r = -0.4527, p = 0.0056). Conclusion: The concentration of CSF FLC predicts conversion to MS within 2 years following CIS. OCB-positive patients with an early conversion have a higher concentration of CSF-FLC. We have also shown a prognostic significance of k-FLCCSF for future EDSS-progression

COVID-19 Immunopathology and the Central Nervous System: Implication for Multiple Sclerosis and Other Autoimmune Diseases with Associated Demyelination

In the frame of the coronavirus disease 2019 (COVID-19) pandemic, recent reports on SARS-CoV-2 potential neuroinvasion placed neurologists on increased alertness in order to assess early neurological manifestations and their potentially prognostic value for the COVID-19 disease. Moreover, the management of chronic neurological diseases, such as Multiple Sclerosis (MS), underwent guided modifications, such as an Extended Interval Dose (EID) of Disease-Modifying Treatment (DMT) administration, in order to minimize patients’ exposure to the health system, thus reducing the risk of SARS-CoV-2 infection. In this review, we summarize existing evidence of key immune pathways that the SARS-CoV-2 modifies during COVID-19 and the relevant implication for MS and other autoimmune diseases with associated demyelination (such as Systemic lupus erythematosus and Antiphospholipid syndrome), including the context of potential neuroinvasion by SARS-Cov-2 and the alterations that DMT induces to the immune system. Moreover we hereby aim to provide an overview of the possible consequences that COVID-19 may carry for the Central Nervous System (CNS) in People with MS (PwMS) and other demyelinating diseases, which are likely to pose challenges for treating Neurologists with respect to the long-term disease management of these diseases

Immunoglobulin free light chains in clinically isolated syndrome with conversion to multuiple sclerosis

This data file represents the concentrations of immunoglobulin free light chains in 4 groups of patients: 1) CIS-MS (clinically isolated syndrome with conversion to multiple sclerosis during 2 years) 2) CIS-nonMS (clinically isolated syndrome without conversion to multiple sclerosis during 2 years) 3) NIND - non-inflammatory neurologic disorders 4) IND - inflammatory neurologic disorders. This data was collected from clinical database and laboratory tests database for every patient. The data file was created with Microsoft Excel. Abbreviations: FLC - free light chains, CSF - cerebrospinal fluid, Q - quotient of concentration (th ratio of concentrations in CSF/serum), OCB - oligoclonal bands, abs - absent

Concentrations of free light chains in CSF and serum and t-test results (data shown as median and IQR).

<p>CSF-k: concentration of k-FLC in CSF; CSF-λ: concentration of λ-FLC in CSF; Q-k: the ratio of concentrations of kappa FLC in CSF/kappa FLC in serum; Q-λ: the ratio of concentrations of lambda FLC in CSF/lambda FLC in serum; NIND: non-inflammatory neurologic disorders; IND: other inflammatory neurologic diseases.</p><p>Concentrations of free light chains in CSF and serum and t-test results (data shown as median and IQR).</p

Concentration of k-FLC_<i>CSF</i> and λ-FLC_<i>CSF</i> in OCB-positive and OCB-negative patients in both CIS-MS and CIS-nonMS groups (data coupled).

<p>CIS-MS: patients with clinically isolated syndrome who converted to multiple sclerosis after 2 years; CIS-nonMS: patients with clinically isolated syndrome who did not convert to multiple sclerosis after 2 years; OCB: oligoclonal bands.</p

General characteristics of CIS-MS, CIS-nonMS, NIND and IND groups.

<p>CIS-MS, patients who converted to multiple sclerosis within 2 years under observation; CIS-nonMS, patients who did not convert to multiple sclerosis within 2 years under observation; NIND, non-inflammatory neurologic diseases; IND, inflammatory neurologic diseases; AIDS, acquired immunodeficiency syndrome; PML, progressive multifocal leucoencephalopathy; OCB, oligoclonal bands.</p><p>^<b>†</b> for NIND and IND groups the age is counted at the moment of lumbar puncture.</p><p>**** p-value <0.0001 for comparison of age between CIS-MS and NIND groups;</p><p>* p-value <0.05 for comparison of age between the CIS-nonMS and NIND group.</p><p>General characteristics of CIS-MS, CIS-nonMS, NIND and IND groups.</p

Receiver operator curve (ROC) characteristic analysis between CIS-MS and control group.

<p>AUC: area under curve; CSF k-FLC: concentration of kappa free light chains in cerebrospinal fluid (CSF); CSF λ-FLC: concentration of lambda free light chains in CSF; Q-k: CSF/serum quotient of concentrations of kappa free light chains; Q-λ: CSF/serum quotient of concentrations of lambda free light chains.</p