Complement activation and increased anaphylatoxin receptor expression are associated with cortical grey matter lesions and the compartmentalised inflammatory response of multiple sclerosis.

Background: The extent of cortical pathology is an important determinant of multiple sclerosis (MS) severity. Cortical demyelination and neurodegeneration are related to inflammation of the overlying leptomeninges, a more inflammatory CSF milieu and with parenchymal microglia and astroglia activation. These are all components of the compartmentalised inflammatory response. Compartmentalised inflammation is a feature of progressive MS, which is not targeted by disease modifying therapies. Complement is differentially expressed in the MS CSF and complement, and complement receptors, are associated with demyelination and neurodegeneration. Methods: To better understand if complement activation in the leptomeninges is associated with underlying cortical demyelination, inflammation, and microglial activation, we performed a neuropathological study of progressive MS (n = 22, 14 females), neuroinflammatory (n = 8), and non-neurological disease controls (n = 10). We then quantified the relative extent of demyelination, connective tissue inflammation, complement, and complement receptor positive microglia/macrophages. Results: Complement was elevated at the leptomeninges, subpial, and within and around vessels of the cortical grey matter. The extent of complement C1q immunoreactivity correlated with connective tissue infiltrates, whilst activation products C4d, Bb, and C3b associated with grey matter demyelination, and C3a receptor 1+ and C5a receptor 1+ microglia/macrophages closely apposed C3b labelled cells. The density of C3a receptor 1+ and C5a receptor 1+ cells was increased at the expanding edge of subpial and leukocortical lesions. C5a receptor 1+ cells expressed TNFα, iNOS and contained puncta immunoreactive for proteolipid protein, neurofilament and synaptophysin, suggesting their involvement in grey matter lesion expansion. Interpretation: The presence of products of complement activation at the brain surfaces, their association with the extent of underlying pathology and increased complement anaphylatoxin receptor positive microglia/macrophages at expanding cortical grey matter lesions, could represent a target to modify compartmentalised inflammation and cortical demyelination.

The Learning Styles Neuromyth Is Still Thriving in Medical Education.

Learning Styles theory promises improved academic performance based on the identification of a personal, sensory preference for informational processing. This promise is not supported by evidence, and is in contrast to our current understanding of the neuroscience of learning. Despite this lack of evidence, prior research shows that that belief in the Learning Styles "neuromyth" remains high amongst educators of all levels, around the world. This perspective article is a follow up on prior research aimed at understanding why belief in the neuromyth of Learning Styles remains so high. We evaluated current research papers from the field of health professions education, to characterize the perspective that an educator would be given, should they search for evidence on Learning Styles. As in earlier research on Higher Education, we found that the use of Learning Style frameworks persist in education research for the health professions; 91% of 112 recent research papers published on Learning Styles are based upon the premise that Learning Styles are a useful approach to education. This is in sharp contrast to the fundamental principle of evidence-based practice within these professions. Thus any educator who sought out the research evidence on Learning Styles would be given a consistent but inaccurate endorsement of the value of a teaching technique that is not evidence based, possibly then propagating the belief in Learning Styles. Here we offer perspectives from both research and student about this apparent mismatch between educational practice and clinical practice, along with recommendations and considerations for the future.