Multiple Sclerosis Research Repository

1. “Association of intrathecal pleocytosis and IgG synthesis with axonal damage in early MS” by Sinah Engel et al

-typical CSF findings in MS include: slightly elevated leukocyte count; presence of mononuclear cells; OCBs; elevated IgG synthesis; increased synthesis of intrathecally produced immunoglobulins against measles, rubella and varicella zoster (MRZ) viruses

-an increase in the CSF/serum IgG ratio (QIgG) and the presence of OCBs reflect chronic CNS-intrinsic immune reactions whereas the CSF leukocyte count is a dynamic parameter of acute inflammatory activity.

-we hypothesized that both chronic and acute inflammation influence sNfL levels in patients with MS

-we did not observe an association between clinical prognostic factors (sensory 

compared with motor symptoms and complete compared with incomplete remission) and sNfL levels in patients with cerebral relapses.  SNfL levels also demonstrated no significant correlation with EDSS, independent of whether the cohort was stratified for disease activity at the time of sample collection.  There was no significant correlation between any of the inflammation-related CSF parameters and the EDSS, except for Qalb

-CSF leukocyte count was higher during relapse than in clinically stable patients and correlated with sNfL levels

-presence of OCBs was significantly related to increased sNfL levels

-intrathecal fraction of the Ig subclasses IgA and IgM and their CSF/serum ratios and QIgM were unrelated to sNfL levels

-unclear whether the sNfL level increase rather reflects acute focal inflammatory activity or chronic widespread diffuse neurodegenerative processes

-IgG synthesis (intrathecal) is an established marker of chronic CSF inflammation; it can be detected by an elevation of QIgG, the presence of OCBs, or by positive MRZ reaction

-sNfL levels were significantly higher in OCB-positive patients and correlated with CSF IgG levels and QIgG

-significant correlation between sNfL levels and CSF leukocyte count

-snFL levels increase during relapses compared with stable disease phases and correlate with the number of CELs in MRI which suggests exacerbated acute focal inflammation as the underlying cause

-in CSF, acute inflammation is reflected by an increase in the leukocyte count and Qalb

-ocrelizumab appears to reduce CSF leukocyte count and sNfL

-in progressive MS, no correlation of CSF NfL with CSF count; indicates a less pronounced acute inflammatory activity in progressive MS

-albumin is exclusively of extrathecal origin; is a reliable indicator of BBB integrity; majority of MS patients have normal albumin levels

-we suggest that NfL levels in blood will only be affected by severe disruption of BBB Integrity

-the effect of acute inflammatory activity on sNfL may outweigh the effect of underlying chronic inflammation

-lower SNfL concentrations in patients presenting with ON than in patients with symptoms suggestive of cerebral or spinal inflammation