In neuromyelitis optica (NMO), astrocytes become targets for pathogenic aquaporin 4 (AQP4)-specific antibodies which gain access to the central nervous system (CNS) in the course of inflammatory processes. Since these antibodies belong to a T cell-dependent subgroup of immunoglobulins, and since NMO lesions contain activated CD4+ T cells, the question arose whether AQP4-specific T cells might not only provide T cell help for antibody production, but also play an important role in the induction of NMO lesions. We show here that highly pathogenic, AQP4-peptide-specific T cells exist in Lewis rats, which recognize AQP4268–285 as their specific antigen and cause severe panencephalitis. These T cells are re-activated behind the blood–brain barrier and deeply infiltrate the CNS parenchyma of the optic nerves, the brain, and the spinal cord, while T cells with other AQP4-peptide specificities are essentially confined to the meninges. Although AQP4268–285-specific T cells are found throughout the entire neuraxis, they have NMO-typical “hotspots” for infiltration, i.e. periventricular and periaqueductal regions, hypothalamus, medulla, the dorsal horns of spinal cord, and the optic nerves. Most remarkably, together with NMO-IgG, they initiate large astrocyte-destructive lesions which are located predominantly in spinal cord gray matter. We conclude that the processing of AQP4 by antigen presenting cells in Lewis rats produces a highly encephalitogenic AQP4 epitope (AQP4268–285), that T cells specific for this epitope are found in the immune repertoire of normal Lewis rats and can be readily expanded, and that AQP4268–285-specific T cells produce NMO-like lesions in the presence of NMO-IgG.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-015-1501-5) contains supplementary material, which is available to authorized users.

Introduction Recently, a novel hypothesis has been proposed concerning the origin of craniovertebral junction (CVJ) abnormalities. Commonly found in patients with these entities, atlantoaxial instability has been suspected to cause both Chiari malformation type I and basilar invagination, which renders the tried and tested surgical decompression strategy ineffective. In turn, C1-2 fusion is proposed as a single solution for all CVJ abnormalities, and a revised definition of atlantoaxial instability sees patients both with and without radiographic evidence of instability undergo fusion, instead relying on the intraoperative assessment of the atlantoaxial joints to confirm instability. Methods The authors conducted a comprehensive narrative review of literature and evidence covering this recently emerged hypothesis. The proposed pathomechanisms are discussed and contextualized with published literature. Conclusion The existing evidence is evaluated for supporting or opposing sole posterior C1-2 fusion in patients with CVJ abnormalities and compared with reported outcomes for conventional surgical strategies such as posterior fossa decompression, occipitocervical fusion, and anterior decompression. At present, there is insufficient evidence supporting the hypothesis of atlantoaxial instability being the common progenitor for CVJ abnormalities. Abolishing tried and tested surgical procedures in favor of a single universal approach would thus be unwarranted.

Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine expressed at barrier surfaces of the skin, gut, nose, lung, and the maternal/fetal interphase. At these sites, it is important for the generation and maintenance of non-inflammatory, tissue-resident dendritic cell responses. We show here that TSLP is also expressed in the central nervous system (CNS) where it is produced by choroid plexus epithelial cells and astrocytes in the spinal cord. Under conditions of low-grade myelin degeneration, the numbers of TSLP-expressing astrocytes increase, and microglia express transcripts for the functional TSLP receptor dimer indicating that these cells are targets for TSLP in the myelin-degenerative CNS.

IntroductionRobotic guidance (RG) and computer-assisted navigation (NV) have seen increased adoption in instrumented spine surgery over the last decade. Although there exists some evidence that these techniques increase radiological pedicle screw accuracy compared with conventional freehand (FH) surgery, this may not directly translate to any tangible clinical benefits, especially considering the relatively high inherent costs. As a non-randomised, expertise-based study, the European Robotic Spinal Instrumentation Study aims to create prospective multicentre evidence on the potential comparative clinical benefits of RG, NV and FH in a real-world setting.Methods and analysisPatients are allocated in a non-randomised, non-blinded fashion to the RG, NV or FH arms. Adult patients that are to undergo thoracolumbar pedicle screw instrumentation for degenerative pathologies, infections, vertebral tumours or fractures are considered for inclusion. Deformity correction and surgery at more than five levels represent exclusion criteria. Follow-up takes place at 6 weeks, as well as 12 and 24 months. The primary endpoint is defined as the time to revision surgery for a malpositioned or loosened pedicle screw within the first postoperative year. Secondary endpoints include patient-reported back and leg pain, as well as Oswestry Disability Index and EuroQOL 5-dimension questionnaires. Use of analgesic medication and work status are recorded. The primary analysis, conducted on the 12-month data, is carried out according to the intention-to-treat principle. The primary endpoint is analysed using crude and adjusted Cox proportional hazards models. Patient-reported outcomes are analysed using baseline-adjusted linear mixed models. The study is monitored according to a prespecified monitoring plan.Ethics and disseminationThe study protocol is approved by the appropriate national and local authorities. Written informed consent is obtained from all participants. The final results will be published in an international peer-reviewed journal.Trial registration numberClinical Trials.gov registryNCT03398915; Pre-results, recruiting stage.