Anti–N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis is the most common autoimmune encephalitis related to autoantibody‐mediated synaptic dysfunction. Cerebrospinal fluid–derived human monoclonal NR1 autoantibodies showed low numbers of somatic hypermutations or were unmutated. These unexpected germline‐configured antibodies showed weaker binding to the NMDAR than matured antibodies from the same patient. In primary hippocampal neurons, germline NR1 autoantibodies strongly and specifically reduced total and synaptic NMDAR currents in a dose‐ and time‐dependent manner. The findings suggest that functional NMDAR antibodies are part of the human naïve B cell repertoire. Given their effects on synaptic function, they might contribute to a broad spectrum of neuropsychiatric symptoms. Ann Neurol 2019;85:771–776

Autoantibodies targeting the GABA(A) receptor (GABA(A)R) hallmark an autoimmune encephalitis presenting with frequent seizures and psychomotor abnormalities. Their pathogenic role is still not well-defined, given the common overlap with further autoantibodies and the lack of patient-derived mAbs. Five GABA(A)R mAbs from cerebrospinal fluid cells bound to various epitopes involving the alpha 1 and gamma 2 receptor subunits, with variable binding strength and partial competition. mAbs selectively reduced GABAergic currents in neuronal cultures without causing receptor internalization. Cerebroventricular infusion of GABA(A)R mAbs and Fab fragments into rodents induced a severe phenotype with seizures and increased mortality, reminiscent of encephalitis patients' symptoms. Our results demonstrate direct pathogenicity of autoantibodies on GABA(A)Rs independent of Fc-mediated effector functions and provide an animal model for GABA(A)R encephalitis. They further provide the scientific rationale for clinical treatments using antibody depletion and can serve as tools for the development of antibody-selective immunotherapies.

Pathology is a discipline that provides the basis of the understanding of disease in medicine. The past decades have seen a decline in the emphasis laid on pathology teaching in medical schools and outdated pathology curricula have worsened the situation. Student opinions and thoughts are central to the questions of whether and how such curricula should be modernized. A survey was conducted among 1018 German medical students regarding their preferences in pathology teaching modalities and their satisfaction with lecture-based courses. A qualitative analysis was performed comparing a recently modernized pathology curriculum with a traditional lecture-based curriculum. The differences in modalities of teaching used were investigated. Student satisfaction with the lecture-based curriculum positively correlated with student grades (spearman’s correlation coefficient 0.24). Additionally, students with lower grades supported changing the curriculum (spearman’s correlation coefficient 0.47). The majority supported virtual microscopy, autopsies, seminars and podcasts as preferred didactic methods. The data supports the implementation of a pathology curriculum where tutorials, autopsies and supplementary computer-based learning tools play important roles.

Background: The Syrian conflict has led to a dramatic increase of Old World cutaneous leishmaniasis (CL), triggered by continuous population displacements, disrupted control programmes, poor shelter and sanitation. Methods: A retrospective patient record study was conducted at the Institute of Tropical Medicine and International Health in Berlin. Records of all refugees from Syria treated for CL between January 2015 and March 2020 were reviewed. Results: Twenty refugees from Syria were treated. Seventeen refugees (85%) had complex lesions, mainly due to previous therapy failure or localization on the face. A long disease duration (50% > 1 year), pronounced facial scarring (20%), recurrences (20%), or worsening of existing lesions (20%) were observed. Nine patients (45%) had been pretreated in Syria. Complete remission was achieved in 10 of 16 patients (63%) treated with perilesional antimony. Eight patients (40%) required systemic treatment, thereof four (20%) repeated systemic treatment. Eight patients (40%) reported a delay of therapy ≥3 months in Germany, thereof one patient with a delay of 12 months and one patient with a delay of 32 months. Conclusion: Between 2015 and 2020, Syrian refugees presented with severe morbidities of CL frequently requiring systemic and even consecutive systemic treatments. We assume a combination of socioeconomic and environmental factors associated with the ongoing Syrian conflict and migration to be responsible for the complex clinical presentations in this case series. More attention should be drawn to the situation of Syrian refugees with CL in countries where they are displaced to.