Background and Objectives To determine the real-world use of rituximab in autoimmune encephalitis (AE) and to correlate rituximab treatment with the long-term outcome. Methods Patients with NMDA receptor (NMDAR)-AE, leucine-rich glioma-inactivated-1 (LGI1)- AE, contactin-associated protein-like-2 (CASPR2)-AE, or glutamic acid decarboxylase 65 (GAD65) disease from the GErman Network for Research on AuToimmune Encephalitis who had received at least 1 rituximab dose and a control cohort of non–rituximab-treated patients were analyzed retrospectively. Results Of the 358 patients, 163 (46%) received rituximab (NMDAR-AE: 57%, CASPR2-AE: 44%, LGI1-AE: 43%, and GAD65 disease: 37%). Rituximab treatment was initiated significantly earlier in NMDAR- and LGI1-AE (median: 54 and 155 days from disease onset) compared with CASPR2-AE or GAD65 disease (median: 632 and 1,209 days). Modified Rankin Scale (mRS) scores improved significantly in patients with NMDAR-AE, both with and without rituximab treatment. Although being more severely affected at baseline, rituximab-treated patients with NMDAR-AE more frequently reached independent living (mRS score ≤2) (94% vs 88%). In LGI1-AE, rituximab-treated and nontreated patients improved, whereas in CASPR2-AE, only rituximab-treated patients improved significantly. No improvement was observed in patients with GAD65 disease. A significant reduction of the relapse rate was observed in rituximab-treated patients (5% vs 13%). Detection of NMDAR antibodies was significantly associated with mRS score improvement. A favorable outcome was also observed with early treatment initiation. Discussion We provide real-world data on immunosuppressive treatments with a focus on rituximab treatment for patients with AE in Germany. We suggest that early and short-term rituximab therapy might be an effective and safe treatment option in most patients with NMDAR-, LGI1-, and CASPR2-AE. Class of Evidence This study provides Class IV evidence that rituximab is an effective treatment for some types of AE.

Ocrelizumab, a humanized monoclonal anti-CD20 antibody, has shown pronounced effects in reduction of disease activity in multiple sclerosis (MS) patients and has recently been approved for the treatment of patients with relapsing MS (RMS) and primary progressive MS (PPMS). CD20 is mainly expressed by B cells, but a subset of T cells (CD3⁺CD20⁺ T cells) also expresses CD20, and these CD20⁺ T cells are known to be a highly activated cell population. The blood of MS patients was analyzed with multicolor flow cytometry before and two weeks after treatment with ocrelizumab regarding the phenotype of peripheral blood mononuclear cells. CD20-expressing CD3⁺ T cells were found in blood samples of all MS patients, accounted for 2.4% of CD45⁺ lymphocytes, and constituted a significant proportion (18.4%) of all CD20⁺ cells. CD3⁺CD20⁺ T cells and CD19⁺CD20⁺ B cells were effectively depleted two weeks after a single administration of 300 mg ocrelizumab. Our results demonstrate that treatment with ocrelizumab does not exclusively target B cells, but also CD20⁺ T cells, which account for a substantial amount of CD20-expressing cells. Thus, we speculate that the efficacy of ocrelizumab might also be mediated by the depletion of CD20-expressing T cells.

Neuroborreliosis represents a relevant infectious disease and can cause a variety of neurological manifestations. Different stages and syndromes are described and atypical symptoms can result in diagnostic delay or misdiagnosis. The aim of this retrospective study was to define the pivotal neurological deficits in patients with neuroborreliosis that were the reason for admission in a hospital. We retrospectively evaluated data of patients with neuroborreliosis. Only patients who fulfilled the diagnostic criteria of an intrathecal antibody production against Borrelia burgdorferi were included in the study. Sixty-eight patients were identified with neuroborreliosis. Cranial nerve palsy was the most frequent deficit (50%) which caused admission to a hospital followed by painful radiculitis (25%), encephalitis (12%), myelitis (7%), and meningitis/headache (6%). In patients with a combination of deficits, back pain was the first symptom, followed by headache, and finally by cranial nerve palsy. Indeed, signs of meningitis were often found in patients with neuroborreliosis, but usually did not cause admission to a hospital. Unusual cases included patients with sudden onset paresis that were initially misdiagnosed as stroke and one patient with acute delirium. Cerebrospinal fluid (CSF) analysis revealed typical changes including elevated CSF cell count in all but one patient, a blood-CSF barrier dysfunction (87%), CSF oligoclonal bands (90%), and quantitative intrathecal synthesis of immunoglobulins (IgM in 74%, IgG in 47%, and IgA in 32% patients). Importantly, 6% of patients did not show Borrelia specific antibodies in the blood. In conclusion, the majority of patients presented with typical neurological deficits. However, unusual cases such as acute delirium indicate that neuroborreliosis has to be considered in a wide spectrum of neurological diseases. CSF analysis is essential for a reliable diagnosis of neuroborreliosis.

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.

Background and Objectives CSF in antibody-defined autoimmune encephalitis (AE) subtypes shows subtype-dependent degrees of inflammation ranging from rare and often mild to frequent and often robust. AEs with NMDA receptor antibodies (NMDAR-E) and leucine-rich glioma-inactivated protein 1 antibodies (LGI1-E) represent opposite ends of this spectrum: NMDAR-E with typically frequent/robust and LGI1-E with rare/mild CSF inflammation. For a more in-depth analysis, we characterized CSF findings in acute, therapy-naive NMDAR-E and LGI1-E in a multicentric, retrospective, cross-sectional setting. Methods Eighty-two patients with NMDAR-E and 36 patients with LGI1-E from the GErman NEtwork for Research of AuToimmune Encephalitis (GENERATE) with lumbar puncture within 90 days of onset and before immunotherapy were included. CSF parameters comprised leukocytes, oligoclonal bands (OCBs), and CSF/serum ratios for albumin, immunoglobulin G (IgG), A (IgA), and M (IgM), the latter 3 converted to Z scores according to Reiber formulas. The MRZ reaction was tested in 14 patients with NMDAR-E and 6 patients with LGI1-E, respectively. Results CSF was abnormal in 94% of NMDAR-E but only in 36% of LGI1-E patients. Robust quantitative intrathecal immunoglobulin synthesis (IIS, IgG > IgM >> IgA) was characteristic for NMDAR-E, but absent in LGI-E. In NMDAR-E, CSF leukocytes were higher when IIS was present or more pronounced. In addition, in NMDAR-E, CSF leukocytes were lower and IIS occurred less often and if so to a lesser degree at older age. Patients with NMDAR-E with severe functional impairment more often had positive OCBs. In CSF obtained later than 3 weeks of onset, leukocytes were lower. In parallel, the correlation of leukocytes with IIS disappeared as IIS was partially independent of disease duration. The MRZ reaction was positive in 5 (36%) patients with NMDAR-E. All these associations were completely absent in LGI1-E. Here, younger patients showed more blood-CSF barrier dysfunction. In LGI1-E, but not in NMDAR-E, the blood-CSF barrier was more dysfunctional when CSF leukocytes were higher. Discussion NMDAR-E and LGI-E differ in their typical extent of CSF inflammation. In addition, the patterns formed by the different inflammatory CSF parameters and their relationship with disease severity, age, and disease duration are subtype-characteristic. Moreover, signs for multiple sclerosis-like chronic inflammation are present in a subgroup of patients with NMDAR-E. These CSF patterns might be markers for the different immunopathogeneses of LGI1-E and NMDAR-E.

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.