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Background: This study addresses the challenging characterisation and differentiation of CIDP versus CIDP in association with Sjögren's syndrome to facilitate the process in clinical routine., Methods: Patients with both CIDP and Sjögren's syndrome and CIDP without Sjögren's syndrome were compared concerning relevant differences in clinical, laboratory and electrophysiological findings. 154 patients who fulfilled the diagnostic EFNS/PNS criteria for CIDP were included in the analysis. 54 of these patients additionally fulfilled the ACR/EULAR classification criteria for Sjögren's syndrome., Results: The frequency of female patients was higher in patients with CIDP and Sjögren's syndrome (52%) versus CIDP patients without Sjögren's syndrome (28%). Furthermore, the occurrence of cranial nerve impairment was significantly higher in patients with Sjögren's syndrome (39% versus 14%). There were no significant group differences in the evaluation of initial symptoms, severity of disability judged by INCAT disability scale score, presence or distribution of sensory deficits, limb weakness and the presence of ataxia, pain or dysautonomia, CSF laboratory or electrophysiological findings., Conclusions: In conclusion, our data indicate that cranial nerve impairment and female gender might represent red flags for an additional Sjögren's syndrome in patients with CIDP. The patterns of clinical disabilities and electrophysiological findings due to peripheral nerve damage are similar in both CIDP entities., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Background: Cognitive impairment (CI) affects approximately one-third of the patients with early multiple sclerosis (MS) and clinically isolated syndrome (CIS). Little is known about factors predicting CI and progression after initial diagnosis., Methods: Neuropsychological screening data from baseline and 1-year follow-up of a prospective multicenter cohort study (NationMS) involving 1123 patients with newly diagnosed MS or CIS were analyzed. Employing linear multilevel models, we investigated whether demographic, clinical and conventional MRI markers at baseline were predictive for CI and longitudinal cognitive changes., Results: At baseline, 22% of patients had CI (impairment in ≥2 cognitive domains) with highest frequencies and severity in processing speed and executive functions. Demographics (fewer years of academic education, higher age, male sex), clinical (EDSS, depressive symptoms) but no conventional MRI characteristics were linked to baseline CI. At follow-up, only 14% of patients showed CI suggesting effects of retesting. Neither baseline characteristics nor initiation of treatment between baseline and follow-up was able to predict cognitive changes within the follow-up period of 1 year., Conclusions: Identification of risk factors for short-term cognitive change in newly diagnosed MS or CIS is insufficient using only demographic, clinical and conventional MRI data. Change-sensitive, re-test reliable cognitive tests and more sophisticated predictors need to be employed in future clinical trials and cohort studies of early-stage MS to improve prediction.

The majority of patients presenting with a first clinical symptom suggestive of multiple sclerosis (MS) do not fulfill the MRI criteria for dissemination in space and time according to the 2010 revision of the McDonald diagnostic criteria for MS and are thus classified as clinically isolated syndrome (CIS). To re-evaluate the utility of cerebrospinal fluid (CSF) analysis in the context of the revised McDonald criteria from 2010, we conducted a retrospective multicenter study aimed at determining the prevalence and predictive value of oligoclonal IgG bands (OCBs) in patients with CIS. Patients were recruited from ten specialized MS centers in Germany and Austria. We collected data from 406 patients; at disease onset, 44/406 (11 %) fulfilled the McDonald 2010 criteria for MS. Intrathecal IgG OCBs were detected in 310/362 (86 %) of CIS patients. Those patients were twice as likely to convert to MS according to McDonald 2010 criteria as OCB-negative individuals (hazard ratio = 2.1, p = 0.0014) and in a shorter time period of 25 months (95 % CI 21-34) compared to 47 months in OCB-negative individuals (95 % CI 36-85). In patients without brain lesions at first attack and presence of intrathecal OCBs (30/44), conversion rate to MS was 60 % (18/30), whereas it was only 21 % (3/14) in those without OCBs. Our data confirm that in patients with CIS the risk of conversion to MS substantially increases if OCBs are present at onset. CSF analysis definitely helps to evaluate the prognosis in patients who do not have MS according to the revised McDonald criteria., Competing Interests: Compliance with ethical standards Conflicts of interest The authors declare that they have no conflict of interest. Ethical approval This procedure and sample analysis for the purpose of this study was approved by the local Ethics Committees of each participating center in accordance with the Declaration of Helsinki. Informed consent All patients gave written informed consent for the use of remaining samples for research.

Current treatments for multiple sclerosis (MS) include immunomodulatory or immunosuppressive agents but no neuroprotective or regenerative therapy is available. From various animal models, we have learned that remyelination in the CNS is a potent neuroprotective mechanism. The knowledge about oligodendrocyte biology and the process of remyelination has greatly increased in recent years; however, the precise mechanisms are far from being understood. Although remyelination is, in principle, also possible in the diseased MS brain, it is not clear why it fails in many MS patients. The clinical trials performed so far either failed to show an effect or were insufficient in design. Thus, further knowledge about the molecular mechanisms of the repair processes and MS pathophysiology is required to achieve the ultimate goal of a neuroprotective and neuroregenerative treatment in MS.

The original rationale for the therapeutic application of immunoglobulins was prevention and treatment of infectious diseases. With the description of agammaglobulinemia, substitution therapy became the primary indication for the use of immunoglobulins. Limitations and side effects of the intramuscular administration of immunoglobulins led to the development of preparations for intravenous use (IVIg). In the early 1980s an immunomodulatory effect of IVIg was described. Since then, the efficacy of IVIg has been established in controlled trials for diseases like idiopathic thrombocytopenic purpura, Kawasaki disease, Guillain-Barré syndrome, dermatomyositis, and many others. There is a large body of evidence that IVIg can modulate an immune reaction at the level of T cells, B cells, and macrophages, interferes with antibody production and degradation, modulates the complement cascade, and has effects on the cytokine network. However, the precise mechanism of action is not yet clear.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

The increased use of intravenous immunoglobulins (IVIg) in the treatment of neurological autoimmune diseases has led to more awareness of adverse reactions. We studied prospectively the side effects of IVIg during 84 treatment courses with a total of 341 infusions under routine clinical conditions. Mild reactions were common. Headache was noted most often, occurring during 30% of treatment courses. There were three severe adverse events (3.6% of all treatment courses) that led to discontinuation of the treatment, namely thrombosis of the jugular vein, allergic reaction and retrosternal pressure. Significant changes in laboratory findings were seen for leucocytes, erythrocytes, haematocrit, haemoglobin, ALAT and ASAT. None of these changes were clinically relevant. The elevation of liver enzymes was dependent on the IVIg preparation used, while there was no association with the underlying disease, age, or gender of the patient. In conclusion, this prospective study confirms the high frequency of mild, self-limited side effects of IVIg. Elevation of liver enzymes may possibly be associated with certain IVIg preparations. Bearing these complications in mind, this prospective study supports the notion that IVIg can generally be regarded as safe, leading to severe adverse events during only 3 (0.9%) of 341 infusions (or 3 of 84 treatment courses, 3.6 %). However, careful monitoring for severe side effects remains mandatory, and we propose that laboratory findings like full blood count, renal and liver function should be monitored routinely.