Objective To evaluate the clinical consequences of extended interval dosing (EID) of ocrelizumab in relapsing-remitting multiple sclerosis (RRMS) during the coronavirus disease 2019 (COVID-19) pandemic. Methods In our retrospective, multicenter cohort study, we compared patients with RRMS on EID (defined as ≥4-week delay of dose interval) with a control group on standard interval dosing (SID) at the same period (January to December 2020). Results Three hundred eighteen patients with RRMS were longitudinally evaluated in 5 German centers. One hundred sixteen patients received ocrelizumab on EID (median delay [interquartile range 8.68 [5.09–13.07] weeks). Three months after the last ocrelizumab infusion, 182 (90.1%) patients following SID and 105 (90.5%) EID patients remained relapse free (p = 0.903). Three-month confirmed progression of disability was observed in 18 SID patients (8.9%) and 11 EID patients (9.5%, p = 0.433). MRI progression was documented in 9 SID patients (4.5%) and 8 EID patients (6.9%) at 3-month follow-up (p = 0.232). Multivariate logistic regression showed no association between treatment regimen and no evidence of disease activity status at follow-up (OR: 1.266 [95% CI: 0.695–2.305]; p = 0.441). Clinical stability was accompanied by persistent peripheral CD19⁺ B-cell depletion in both groups (SID vs EID: 82.6% vs 83.3%, p = 0.463). Disease activity in our cohort was not associated with CD19⁺ B-cell repopulation. Conclusion Our data support EID of ocrelizumab as potential risk mitigation strategy in times of the COVID-19 pandemic. Classification of Evidence This study provides Class IV evidence that for patients with RRMS, an EID of at least 4 weeks does not diminish effectiveness of ocrelizumab.

More than 10 disease-modifying therapies (DMT) are approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of multiple sclerosis (MS) and new therapeutic options are on the horizon. Due to different underlying therapeutic mechanisms, a more individualized selection of DMTs in MS is possible, taking into account the patient's current situation. Therefore, concomitant treatment of various comorbid conditions, including autoimmune mediated disorders such as rheumatoid arthritis, should be considered in MS patients. Because the pathomechanisms of autoimmunity partially overlap, DMT could also treat concomitant inflammatory diseases and simplify the patient's treatment. In contrast, the exacerbation and even new occurrence of several autoimmune diseases have been reported as a result of immunomodulatory treatment of MS. To simplify treatment and avoid disease exacerbation, knowledge of the beneficial and adverse effects of DMT in other autoimmune disorders is critical. Therefore, we conducted a literature search and described the beneficial and adverse effects of approved and currently studied DMT in a large number of comorbid autoimmune diseases, including rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel diseases, cutaneous disorders including psoriasis, Sjögren´s syndrome, systemic lupus erythematosus, systemic vasculitis, autoimmune hepatitis, and ocular autoimmune disorders. Our review aims to facilitate the selection of an appropriate DMT in patients with MS and comorbid autoimmune diseases.

Varicella zoster virus (VZV) reactivation is a common infectious disease in neurology and VZV the second most frequent virus detected in encephalitis. This study investigated characteristics of clinical and laboratory features in patients with VZV infection. Two hundred eighty two patients with VZV reactivation that were hospitalized in the department of neurology in the time from 2005 to 2013 were retrospectively evaluated. Results from cerebrospinal fluid (CSF) analysis were available from 85 patients. Trigeminal rash was the most common clinical manifestation, followed by segmental rash, CNS infection, facial nerve palsy, postherpetic neuralgia, and radiculitis. MRI of the brain performed in 25/33 patients with encephalitis/meningitis did not show any signs of infection in the brain parenchyma. Only one patient showed contrast enhancement in the hypoglossal nerve. General signs of infection such as fever or elevated CRP values were found in only half of the patients. Furthermore, rash was absent in a quarter of patients with CNS infection and facial nerve palsy, and thus, infection could only be proven by CSF analysis. Although slight inflammatory CSF changes occurred in few patients with isolated rash, the frequency was clearly higher in patients with CNS infection and facial nerve palsy. Monosegmental herpes zoster is often uncomplicated and a diagnostic lumbar puncture is not essential. In contrast, CSF analysis is an essential diagnostic tool in patients with skin lesions and cranial nerve or CNS affection. In patients with neuro-psychiatric symptoms and inflammatory CSF changes analysis for VZV should be performed even in the absence of skin lesions.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic is a challenge for all participants in the healthcare system. At the beginning of the pandemic, many physicians asked themselves what risk their patients, especially those with chronic diseases, were exposed to. We present an overview of all patients with multiple sclerosis (MS) and SARS-CoV-2 infection published in the literature so far. In total, there are publications on 873 SARS-CoV-2 positive MS patients and information on the outcome can be given for 700 patients. With regard to the different disease modifying therapies (DMTs), by far the most cases were described under anti-CD20 treatment (n = 317). The mortality rate of all MS patients was 4% and a further 3% required invasive or non-invasive ventilation. When looking at the severe and fatal cases, it is particularly noticeable that patients without DMTs, with previous cardiovascular diseases, or with a severe degree of disability are at risk. Immunosuppressive therapy itself does not appear to be a substantial risk factor. Rather, it is reasonable to assume that the therapies could be protective, either directly, by mitigating the cytokine storm, or indirectly, by reducing the disease activity of MS.

The latest revision of the McDonald criteria of 2017 considers the evidence of an intrathecal immunoglobulin (IgG) synthesis as a diagnostic criterion for dissemination in time in multiple sclerosis. While the detection of oligoclonal bands is considered as the gold standard, determination of kappa free light chains might be a promising tool as a less technically demanding and cost saving method. However, data on the direct comparison between kappa free light chains and oligoclonal bands are limited and no study to date has used the highly sensitive method of polyacrylamide gels with consecutive silver staining for the demonstration of oligoclonal bands. Furthermore, the impact of the revised McDonald criteria of 2017 on the role of kappa free light chains as a biomarker has not been investigated. Nephelometry was used to determine kappa free light chains in cerebrospinal fluid (CSF) and serum from 149 patients with their first demyelinating event between 2010 and 2015. Clinical data, kappa free light chains, and oligoclonal band status were compared at the time of initial diagnosis and after follow-up to identify converters from clinically isolated syndrome to multiple sclerosis. An elevated kappa free light chain index (>5.9) was found in 79/83 patients (95%) with multiple sclerosis diagnosed at baseline, slightly less frequent than oligoclonal bands (98.8%). 18/25 (72%) patients who converted from clinically isolated syndrome to multiple sclerosis showed an elevated kappa free light chain index compared to 20/25 (80%) patients with positive oligoclonal bands. In patients with stable clinically isolated syndrome 7/41 (17%) displayed an elevated kappa free light chain index against 11/41 (27%) oligoclonal band positive patients. Only two patients with stable clinically isolated syndrome showed an elevated kappa free light chain index but were oligoclonal bands negative. In conclusion, determination of the kappa free light chain index is a promising diagnostic approach to assess intrathecal immunoglobulin synthesis in multiple sclerosis. Nevertheless, oligoclonal bands are highly prevalent in multiple sclerosis and can detect an intrathecal synthesis of IgG even when the kappa free light chain index is below the threshold. We consider sequential use of both methods as reasonable.

Attack prevention is crucial in managing neuromyelitis optica spectrum disorders (NMOSDs). Eculizumab (ECU), an inhibitor of the terminal complement cascade, was highly effective in preventing attacks in a phase III trial of aquaporin-4 (AQP4)-IgG seropositive(+) NMOSDs. In this article, we evaluated effectiveness and safety of ECU in routine clinical care. We retrospectively evaluated patients with AQP4-IgG+ NMOSD treated with ECU between December 2014 and April 2022 at 20 German and 1 Austrian university center(s) of the Neuromyelitis Optica Study Group (NEMOS) by chart review. Primary outcomes were effectiveness (assessed using annualized attack rate [AAR], MRI activity, and disability changes [Expanded Disability Status Scale {EDSS}]) and safety (including adverse events, mortality, and attacks after meningococcal vaccinations), analyzed by descriptive statistics. Fifty-two patients (87% female, age 55.0 ± 16.3 years) received ECU for 16.2 (interquartile range [IQR] 9.6 – 21.7) months. Forty-five patients (87%) received meningococcal vaccination before starting ECU, 9 with concomitant oral prednisone and 36 without. Seven of the latter (19%) experienced attacks shortly after vaccination (median: 9 days, IQR 6–10 days). No postvaccinal attack occurred in the 9 patients vaccinated while on oral prednisone before starting ECU and in 25 (re-)vaccinated while on ECU. During ECU therapy, 88% of patients were attack-free. The median AAR decreased from 1.0 (range 0–4) in the 2 years preceding ECU to 0 (range 0–0.8; p < 0.001). The EDSS score from start to the last follow-up was stable (median 6.0), and the proportion of patients with new T2-enhancing or gadolinium-enhancing MRI lesions in the brain and spinal cord decreased. Seven patients (13%) experienced serious infections. Five patients (10%; median age 53.7 years) died on ECU treatment (1 from myocardial infarction, 1 from ileus with secondary sepsis, and 3 from systemic infection, including 1 meningococcal sepsis), 4 were older than 60 years and severely disabled at ECU treatment start (EDSS score ≥ 7). The overall discontinuation rate was 19%. Eculizumab proved to be effective in preventing NMOSD attacks. An increased risk of attacks after meningococcal vaccination before ECU start and potentially fatal systemic infections during ECU—particularly in patients with comorbidities—must be considered. Further research is necessary to explore optimal timing for meningococcal vaccinations. This study provides Class IV evidence that eculizumab reduces annualized attack rates and new MRI lesions in AQP4-IgG+ patients with NMOSD.