Background Multiple sclerosis (MS) is an immune-mediated disease that damages myelin in the central nervous system (CNS). We investigated the profile of CCN3, a known regulator of immune function and a potential mediator of myelin regeneration, in multiple sclerosis in the context of disease state and disease-modifying treatment. Methods CCN3 expression was analysed in plasma, immune cells, CSF and brain tissue of MS patient groups and control subjects by ELISA, western blot, qPCR, histology and in situ hybridization. Results Plasma CCN3 levels were comparable between collective MS cohorts and controls but were significantly higher in progressive versus relapsing-remitting MS and between patients on interferon-β versus natalizumab. Higher body mass index was associated with higher CCN3 levels in controls as reported previously, but this correlation was absent in MS patients. A significant positive correlation was found between CCN3 levels in matched plasma and CSF of MS patients which was absent in a comparator group of idiopathic intracranial hypertension patients. PBMCs and CD4+ T cells significantly upregulated CCN3 mRNA in MS patients versus controls. In the CNS, CCN3 was detected in neurons, astrocytes and blood vessels. Although overall levels of area immunoreactivity were comparable between non-affected, demyelinated and remyelinated tissue, the profile of expression varied dramatically. Conclusions This investigation provides the first comprehensive profile of CCN3 expression in MS and provides rationale to determine if CCN3 contributes to neuroimmunological functions in the CNS.

Inflammatory and degenerative neuromuscular conditions can present in acute NMRF. Long-term outcome is good and MR is low, and significantly better than in other neurology patients requiring ICU admission despite longer ICU stay.

Multiple sclerosis (MS) is a chronic, immune-mediated, demyelinating disease of the central nervous system (CNS). The most common form of MS is a relapsing–remitting disease characterised by acute episodes of demyelination associated with the breakdown of the blood–brain barrier (BBB). In the relapsing–remitting phase there is often relative recovery (remission) from relapses characterised clinically by complete or partial resolution of neurological symptoms. In the later and progressive stages of the disease process, accrual of neurological disability occurs in a pathological process independent of acute episodes of demyelination and is accompanied by a trapped or compartmentalised inflammatory response, most notable in the connective tissue spaces of the vasculature and leptomeninges occurring behind an intact BBB. This review focuses on compartmentalised inflammation in MS and in particular, what we know about meningeal tertiary lymphoid structures (TLS; also called B cell follicles) which are organised clusters of immune cells, associated with more severe and progressive forms of MS. Meningeal inflammation and TLS could represent an important fluid or imaging marker of disease activity, whose therapeutic abrogation might be necessary to stop the most severe outcomes of disease.

BackgroundGiven the expanding utility of cerebrospinal fluid biomarkers in clinical practice and research studies, it may become desirable to offer repeat lumbar puncture (LP) beyond diagnosis. Using the United Kingdom Multiple Sclerosis Register (UKMSR), we assessed patient attitude to LP beyond the diagnostic stage.Design/MethodsAn online questionnaire was designed and over 11,000 patients were invited to partici- pate. For specific questions, participants indicated willingness for LP on a Likert scale (0–10).ResultsAlmost 2500 patients completed the questionnaire and over half had relapsing remitting MS. Of the 1089 participants on disease-modifying treatment, almost 60% indicated feeling neutral-to-agreeable to having LP to evaluate treatment efficacy or evidence of relapse. Interestingly, those indicating complete willingness represented the modal point on the scale. Respondents were only slightly less receptive to undergoing LP for research, with just under half still neutral-to-agreeable. We did not observe an influence of age or sex on willingness for LP for either indication.ConclusionsSerial LPs may become informative in evaluating for active MS throughout the disease course. We found that patients on treatment are quite agreeable to considering LP for clinical evaluation. Perhaps understandably, respondents were slightly less willing to have LP solely for research purposes.rrobinson17@qub.ac.uk