Impact of the McDonald Criteria 2017 on Early Diagnosis of Relapsing-Remitting Multiple Sclerosis

Multiple sclerosis is a chronic immune mediated demyelinating disease leading to neurological disabilities that need to be diagnosed and treated early. Guidelines on multiple sclerosis diagnosis and monitoring experienced comprehensive changes over the last decades. The first McDonald criteria published in 2001 emphasized the importance of MR imaging but also recognized the role of cerebrospinal fluid diagnostics. The demonstration of an intrathecal immunoglobulin G synthesis is a well-established additional component and has a long tradition in the diagnosis of relapsing-remitting multiple sclerosis. However, the role of cerebrospinal fluid for diagnostic purposes was rather diminished in each revision of the McDonald criteria. In the latest revision of the McDonald criteria of 2017, the detection of an intrathecal immunoglobulin G synthesis as oligoclonal bands experienced a revival. Patients with the first clinical event suggesting multiple sclerosis who fulfill the criteria for dissemination in space can be diagnosed with relapsing-remitting multiple sclerosis when oligoclonal bands in cerebrospinal fluid are detected. The diagnostic sensitivity of these novel criteria with a focus on dissemination in time and oligoclonal bands as a substitute for dissemination in time was published in different cohorts in the last year and is of special interest in this review. Recently published data show that by applying the 2017 McDonald criteria, multiple sclerosis can be diagnosed more frequently at the time of first clinical event as compared to the 2010 McDonald criteria. The main effect was due to the implementation of oligoclonal bands as a substitute for dissemination in time. However, careful differential diagnosis is essential in patients with atypical clinical manifestations to avoid misdiagnoses

Investigation of Oligoclonal IgG Bands in Tear Fluid of Multiple Sclerosis Patients

Background: Oligoclonal IgG bands (OCB) in the cerebrospinal fluid (CSF) represent a typical marker for inflammation in multiple sclerosis (MS) patients and have a predictive and diagnostic value in patients with a first suspected demyelinating event. The detection in tears remains controversial but some reports suggested a replacement of CSF analysis by OCB detection in tears. We aimed to investigate the value of OCB detection in tears systematically in patients with MS.Methods: Tears of 59 patients with suspected or diagnosed MS were collected with Schirmer filter paper strips. Tear IgG was purified by affinity chromatography with protein G. After isoelectric focusing in polyacrylamide gels OCB detection was performed with direct silver staining. Paired triplets of CSF, serum, and tears were analyzed. For comparison purposes we additionally used other tear collection methods (flush procedure and plastic capillary tubes) or detection techniques (Immunoblotting). Clinical and paraclinical parameters are provided.Results: IgG collection in tears was most reliable by using Schirmer strips. Thirteen patients had to be excluded due to insufficient sample material. Tear specific proteins that interfered with OCB detection were successfully eliminated by IgG purification. The concordance of OCB in tears and CSF of all investigated MS patients was 39% with a high rate of only marginal pattern in tears. Five patients demonstrated restricted bands in tears, neither detectable in CSF nor serum. Occurrence of OCB in tears was significantly associated with pathological visual evoked potentials (P = 0.0094) and a history of optic neuritis (P = 0.0258).Conclusion: Due to the limited concordance, high rate of samples with insufficient material, and the unknown origin of tear IgG we cannot recommend that tear OCB detection may replace CSF OCB detection in MS patients. The detection of unique OCB in tears might offer new insights in ophthalmological diseases

Regenerative Effects of CDP-Choline: A Dose-Dependent Study in the Toxic Cuprizone Model of De- and Remyelination

Inflammatory attacks and demyelination in the central nervous system (CNS) are the key factors responsible for the damage of neurons in multiple sclerosis (MS). Remyelination is the natural regenerating process after demyelination that also provides neuroprotection but is often incomplete or fails in MS. Currently available therapeutics are affecting the immune system, but there is no substance that might enhance remyelination. Cytidine-S-diphosphate choline (CDP-choline), a precursor of the biomembrane component phospholipid phosphatidylcholine was shown to improve remyelination in two animal models of demyelination. However, the doses used in previous animal studies were high (500 mg/kg), and it is not clear if lower doses, which could be applied in human trials, might exert the same beneficial effect on remyelination. The aim of this study was to confirm previous results and to determine the potential regenerative effects of lower doses of CDP-choline (100 and 50 mg/kg). The effects of CDP-choline were investigated in the toxic cuprizone-induced mouse model of de- and remyelination. We found that even low doses of CDP-choline effectively enhanced early remyelination. The beneficial effects on myelin regeneration were accompanied by higher numbers of oligodendrocytes. In conclusion, CDP-choline could become a promising regenerative substance for patients with multiple sclerosis and should be tested in a clinical trial