The chemokine CXCL13 in acute neuroborreliosis

Objective Recent studies have suggested an important role of the B cell chemoattractant CXCL13 in acute neuroborreliosis (NB). Our aim was to confirm the diagnostic role of CXCL13 and to evaluate its relevance as a therapy response and disease activity marker in NB. Methods CXCL13 was measured in cerebrospinal fluid (CSF) and serum of patients with NB (n = 28), systemic borreliosis (SB, n = 9), Guillaine-Barre syndrome (GBS, n = 11), Bell's palsy (BP, n = 19), other cranial nerve palsies (CNP, n = 5), cephalgia (C, n = 20), bacterial CNS infections (B-CNS-I, n = 16) and viral CNS infections (V-CNS-I, n = 18). For follow-up studies, serial sample pairs were evaluated from 25 patients with NB (n = 56), 11 with B-CNS-I (n = 25) and 14 with V-CNS-I (n = 36). Results CSF-CXCL13 was significantly elevated in NB compared with other neurological diseases (p<0.001). Using receiver operating characteristic analysis, 337 ng/g was determined as a cut-off with a sensitivity of 96.4% and a specificity of 96.9%. Of all the parameters investigated, CSF CXCL13 showed the fastest response to antibiotic therapy, decreasing significantly (p = 0.008) within 1 week. In untreated patients, CSF CXCL13 was elevated in patients with a short duration of disease. Borrelia burgdorferi antibody index showed no significant (p = 0.356) change over follow-up. Conclusions The study confirms the relevance of CXCL13 as a diagnostic biomarker of NB and suggests that CSF CXCL13 in NB is linked to duration of disease and could be a marker of disease activity and response to antibiotic therapy

Associations between multiple sclerosis and incidence of heart diseases : Systematic review and meta-analysis of observational studies

Background: Observational studies have described associations between multiple sclerosis (MS) and heart diseases, but the results were mixed. Methods: Medline, Embase, and Cochrane CENTRAL were searched up to 5 October 2020 according to a protocol (PROSPERO registration number CRD42020184493). We included longitudinal non-randomized studies of exposure comparing the incidence of acquired heart diseases between people with multiple sclerosis (pwMS) and people without multiple sclerosis. We used ROBINS-E and the GRADE approach to assess risk of bias and the certainty of evidence, respectively. Data were pooled using random-effect models. Results: Of 5,159 studies, nine studies met the inclusion criteria. MS was associated with an increased risk for myocardial infarction (HR 1.6, 95% CI 1.2 to 2.0, I2 86%, n = 1,209,079) and heart failure (HR 1.7, 95% CI 1.3 to 2.2, I2 49%, n = 489,814). The associations were more pronounced among women and younger people in subgroup analyses. We found no difference for ischemic heart disease (HR 1.0, 95% CI 0.8 to 1.4, I2 86%, n = 679,378) and bradycardia (HR 1.5, 95% CI 0.4 to 5.0, I2 50%, n = 187,810). The risk of atrial fibrillation was lower in pwMS (HR 0.7, 95% CI 0.6 to 0.8, I2 0%, n = 354,070), but the risk of bias was high, and the certainty of evidence was rated as very low. One study found more cases of infectious endocarditis among pwMS (HR 1.2, 95% CI 1.0 to 1.4, n = 83,712). Conclusions: Myocardial infarction and heart failure should be considered in people with multiple sclerosis during follow-up examinations

CSF Free Light Chains as a Marker of Intrathecal Immunoglobulin Synthesis in Multiple Sclerosis: A Blood-CSF Barrier Related Evaluation in a Large Cohort

Objectives: The importance of immunoglobulin G (IgG) oligoclonal bands (OCB) in the diagnosis of multiple sclerosis (MS) was reaffirmed again in the recently revised MS diagnostic criteria. Since OCB testing is based on non-quantitative techniques and demands considerable methodological experience, measurement of CSF immunoglobulin free light chains (FLC) has been suggested as quantitative alternative to OCB. We aimed to establish reference values for FLC measures and evaluate their diagnostic accuracy with regard to the diagnosis of MS.Methods: Immunoglobulin kappa (KFLC) and lambda (LFLC) free light chains were prospectively measured by nephelometry in CSF and serum sample pairs in 1,224 patients. The analyzed cohort included patients with MS, other autoimmune or infectious inflammatory diseases of the nervous system as well as 989 patients without signs for nervous system inflammation.Results: Regarding diagnosis of MS, the diagnostic sensitivity and specificity of intrathecal KFLC ratio were 93.3 and 93.7% using the CSF-serum albumin ratio-dependent reference values, 92.0 and 95.9% for intrathecal KFLC ratio applying the ROC-curve determined cut-off levels, 62.7 and 98.3% for IgG index, 64.0 and 98.8% for intrathecal IgG synthesis according to Reiber diagrams, and 94.7 and 93.3% for OCB. Diagnostic sensitivity and specificity of intrathecal LFLC were clearly lower than KFLC.Conclusions: Intrathecal KFLC and OCB showed the highest diagnostic sensitivities for MS. However, specificity was slightly lower compared to other quantitative IgG parameters. Consequently, CSF FLC may not replace OCB, but it may support diagnosis in MS as a quantitative parameter

Retrospective cohort study to devise a treatment decision score predicting adverse 24-month radiological activity in early multiple sclerosis

Background: Multiple sclerosis (MS) is a chronic neuroinflammatory disease affecting about 2.8 million people worldwide. Disease course after the most common diagnoses of relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) is highly variable and cannot be reliably predicted. This impairs early personalized treatment decisions. Objectives: The main objective of this study was to algorithmically support clinical decision-making regarding the options of early platform medication or no immediate treatment of patients with early RRMS and CIS. Design: Retrospective monocentric cohort study within the Data Integration for Future Medicine (DIFUTURE) Consortium. Methods: Multiple data sources of routine clinical, imaging and laboratory data derived from a large and deeply characterized cohort of patients with MS were integrated to conduct a retrospective study to create and internally validate a treatment decision score [Multiple Sclerosis Treatment Decision Score (MS-TDS)] through model-based random forests (RFs). The MS-TDS predicts the probability of no new or enlarging lesions in cerebral magnetic resonance images (cMRIs) between 6 and 24 months after the first cMRI. Results: Data from 65 predictors collected for 475 patients between 2008 and 2017 were included. No medication and platform medication were administered to 277 (58.3%) and 198 (41.7%) patients. The MS-TDS predicted individual outcomes with a cross-validated area under the receiver operating characteristics curve (AUROC) of 0.624. The respective RF prediction model provides patient-specific MS-TDS and probabilities of treatment success. The latter may increase by 5–20% for half of the patients if the treatment considered superior by the MS-TDS is used. Conclusion: Routine clinical data from multiple sources can be successfully integrated to build prediction models to support treatment decision-making. In this study, the resulting MS-TDS estimates individualized treatment success probabilities that can identify patients who benefit from early platform medication. External validation of the MS-TDS is required, and a prospective study is currently being conducted. In addition, the clinical relevance of the MS-TDS needs to be established

Varicella zoster virus-induced neurological disease after COVID-19 vaccination: a retrospective monocentric study

The description of every possible adverse effect or event related to vaccines is mandatory during the ongoing worldwide COVID-19 vaccination program. Although cases of cutaneous varicella zoster virus (VZV) reactivation after COVID-19 vaccination have been increasingly reported in literature and database sets, a description of VZV-induced neurological disease (VZV-ND) is still lacking. In the present study, we retrospectively evaluated patients admitted to our clinic and diagnosed with VZV-ND during the COVID-19 vaccination campaign (January-April 2021) and in the same months in the previous two years. We identified three patients with VZV-ND after COVID-19 vaccination and 19 unvaccinated VZV-ND cases as controls. In the case-control analysis, the two groups showed no difference in clinical features, results of diagnostic investigations, and outcome. Thus, VZV reactivation with neurological involvement might be a possible event triggered by COVID-19 vaccination, but the benefit following COVID-19 vaccination overcomes significantly the potential risk associated with a VZV reactivation

Phelan McDermid Syndrome: Multiple Sclerosis as a Rare but Treatable Cause for Regression—A Case Report

Phelan McDermid syndrome (PMcD) is a neurogenetic disease associated with haploinsufficiency of the SHANK3 gene due to a spectrum of anomalies in the terminal region of the long arm of chromosome 22. SHANK3 is the abbreviation for SH3 domain and ankyrin repeat-containing protein, a gene that encodes for proteins of the postsynaptic density (PSD) of excitatory synapses. This PSD is relevant for the induction and plasticity of spine and synapse formation as a basis for learning processes and long-term potentiation. Individuals with PMcD present with intellectual disability, muscular hypotonia, and severely delayed or absent speech. Further neuropsychiatric manifestations cover symptoms of the autism spectrum, epilepsy, bipolar disorders, schizophrenia, and regression. Regression is one of the most feared syndromes by relatives of PMcD patients. Current scientific evidence indicates that the onset of regression is variable and affects language, motor skills, activities of daily living and cognition. In the case of regression, patients normally undergo further diagnostics to exclude treatable reasons such as complex-focal seizures or psychiatric comorbidities. Here, we report, for the first time, the case of a young female who developed progressive symptoms of regression and a dystonic-spastic hemiparesis that could be traced back to a comorbid multiple sclerosis and that improved after treatment with methylprednisolone

Cerebrospinal fluid immunoglobulin kappa light chain in clinically isolated syndrome and multiple sclerosis.

BACKGROUND: Oligoclonal bands (OCB) are the most widely used CSF test to support the diagnosis of MS and to predict conversion of clinically isolated syndrome (CIS) to multiple sclerosis (MS). Since OCB tests are based on non-quantitative and difficult to standardise techniques, measurement of immunoglobulin kappa free light chains (KFLC) may represent an easier to use quantitative test. METHODS: KFLC were measured in CSF and serum of 211 patients using ELISA. These include patients without any inflammatory central nervous system reaction (NIND, n = 77), MS (n = 20), viral CNS infections (V-CNS-I, n = 10), neuroborreliosis (NB, n = 17) and other bacterial CNS infections (B-CNS-I, n = 10). Furthermore a cohort of 77 patients with CIS, including 39 patients that remained CIS over follow-up of two years (CIS-CIS) and 38 patients that developed MS over the same follow-up time (CIS-MS). RESULTS: CSF-serum ratio of KFLC (Q KFLC) was elevated in all patients with MS, 86.8% of patients with CIS-MS and 61.5% of patients with CIS-CIS. It was significantly elevated in CIS with presence of OCB (p<0.001). Q KFLC significantly correlated with other CSF variables such as CSF leukocyte count (p<0.001, R = 0.46), CSF CXCL13 levels (p<0.001, R = 0.64) and also intrathecal IgG synthesis (p<0.001, R = 0.74) as determined by nephelometry and quotient diagram. OCB were detected in 66.7% of CIS-CIS and in 92.1% of CIS-MS. CONCLUSIONS: Although the measurement of CSF KFLC is a rapid and quantitative easy to standardize tool, it is almost equal but not superior to OCB with regard to diagnostic sensitivity and specificity in patients with early MS

Tick-Borne Encephalitis: A Differential Pattern of Intrathecal Humoral Immune Response and Inflammatory Cell Composition Compared with Other Viral CNS Infections

To investigate whether and how cerebrospinal fluid (CSF) findings can contribute to distinguish tick-borne encephalitis (TBE) from herpes simplex virus (HSV) and varicella zoster virus (VZV) induced central nervous system (CNS) infections (HSV-I, VZV-I). Chart review and identification of TBE, HSV- I, and VZV-I was carried out, fulfilling the following criteria: (1) clinical signs of encephalitis and/or meningitis, (2) complete CSF analysis and confirmed viral etiology by either PCR or antibody testing in CSF, (3) hospitalized patients, and (4) available brain magnetic resonance imaging (MRI). Fifty-nine patients with 118 CSF/serum pairs were included. These comprised 21 with TBE (35 CSF/serum pairs), 20 (40 CSF/serum pairs) with HSV-I, and 18 (43 CSF/serum pairs) with VZV-I. In contrast to HSV-I and VZV-I, CSF cell differentiation in TBE showed more often an increased (&gt;20%) proportion of granulocytes (p &lt; 0.01) and a more frequent quantitative intrathecal IgM synthesis (p = 0.001 and p &lt; 0.01, respectively), while the second was even more pronounced when follow-up CSF analyses were included (p &lt; 0.001). CSF findings help to distinguish TBE from other viral infections. In cases with CSF pleocytosis and a positive history for a stay in or near an endemic area, TBE antibodies in CSF and serum should be determined, especially if granulocytes in CSF cell differentiation and/or an intrathecal IgM synthesis is present