Positron emission tomography (PET) studies have shown that cortical cerebral metabolic rate of glucose (CMRglc) is reduced in multiple sclerosis (MS). Quantitative magnetic resonance spectroscopy (MRS) measures of N-acetyl-aspartate (NAA) normalized to creatine (NAA/Cr) assess neuronal deterioration, and several studies have shown reductions in MS. Furthermore, both PET and MRS reductions correlate with cognitive dysfunction in MS. Our aim was to determine if changes in cortical CMRglc in early MS correlate with NAA/Cr measurements of neuronal deterioration, as well as cognitive dysfunction and neurological disability.We studied 20 recently diagnosed, clinically definite, relapsing-remitting MS patients. Global and cortical CMRglc was estimated using PET with 18-F-deoxyglucose and NAA/Cr ratio was measured using multislice echo-planar spectroscopic imaging. All subjects were neuro-psychologically tested and a cognitive dysfunction factor (CDF) was calculated.Cortical CMRglc correlated with cortical NAA/Cr (r = 0.45; P < 0.05), but there were no correlation between CMRglc and other NAA/Cr measurements, conventional magnetic resonance imaging measurements, or CDF. Stepwise regression analysis showed association between cortical NAA/Cr and CMRglc of the left ventrolateral prefrontal cortex (P < 0.001), left putamen (P = 0.010), and left hippocampus (P = 0.011). Furthermore, CDF was related to CMRglc in the left cerebellum (P = 0.001) and the left caudate nucleus (P = 0.013). The results of the statistical analysis should be regarded as exploratory, since we did not correct for multiple comparisons.Our findings suggest that reductions in cortical CMRglc are associated with reductions in cortical NAA/Cr in early MS. These changes affect cortical and subcortical neural circuits of importance to cognitive function.
To study the intrathecal synthesis of anti-myelin basic protein (MBP) and anti-proteolipid protein (PLP) antibodies in patients in the early stages of multiple sclerosis.A study of consecutive patients with acute optic neuritis (ON) who were undergoing lumbar punctures in an ambulatory unit.Eleven patients with acute idiopathic ON and 14 patients with acute ON as a symptom of definite multiple sclerosis (the diagnosis of which was supported by clinical or laboratory findings). Nineteen patients with other neurological diseases (10 with inflammatory diseases) served as controls.Numbers of anti-MBP and anti-PLP antibody-secreting cells in peripheral blood and cerebrospinal fluid samples that were enumerated with an immunospot assay.Cerebrospinal fluid cells that secreted anti-MBP or anti-PLP antibodies were detected in 10 of 15 and in 21 of 23 patients with acute ON, while they were detected in nine of 18 and in six of 18 patients with other neurological diseases, respectively. Patients with ON had significantly more anti-PLP-secreting cells than did patients with other neurological diseases (P < .01). No difference was observed for anti-MBP-secreting cells. A significant correlation between the time from onset and the number of anti-PLP-secreting cells was found in patients with idiopathic ON (P < .02).These data suggest that anti-PLP antibodies are a more specific finding in demyelinating disease than anti-MBP antibodies. Furthermore, they suggest that anti-PLP antibodies may arise as a consequence of the demyelinating process.
This chapter contains section titled: Introduction Search strategy Quantitative analysis of total protein and albumin Quantitative intrathecal immunoglobulin synthesis Qualitative (oligoclonal) intrathecal IgG synthesis CSF glucose concentration, CSF/serum glucose ratio and lactate Cytological examination Investigation of infectious CSF
To evaluate the associations of serum neurofilament light chain (sNfL) concentrations and disease activity, disability progression and response to natalizumab treatment in participants with secondary progressive multiple sclerosis (SPMS).
Background: Previous studies of multiple sclerosis (MS) have indicated differences in the pathogenesis in relapsing–remitting (RRMS), secondary progressive (SPMS) and primary progressive (PPMS) disease. Objective: We hypothesized that different MS subtypes would show differences in gene expression that could be traced to specific subsets of peripheral blood mononuclear cells (PBMCs). Methods: Gene expression in RRMS, SPMS, PPMS and healthy control (HC) PBMCs was analyzed on Affymetrix arrays. In addition, we studied gene expression in pools of purified PBMC subsets. Results: We found 380 genes that were differentially expressed in RRMS, PPMS, SPMS and HCs (false discovery rate < 5%). There were no major differences between the subtypes of MS. The genes showing most prominent expression changes in RRMS were associated with adaptive immune pathways, while genes in PPMS were associated with innate immune system pathways. SPMS patients shared pathways with RRMS and PPMS patients. Gene expression changes were most prominent in B cells, CD8+ T cells and monocytes. Conclusion: Differences in gene expression, which could be traced to B cells, CD8+ T cells and monocytes, were found between MS patients and HCs but only minor differences were observed between MS subgroups.
Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.
The number of patients with relapsing remitting multiple sclerosis (RRMS) who convert to secondary progressive (SP) MS is uncertain, and with emerging treatment options for SPMS, it is important to identify RRMS patients in transition to the SP phase. The objective of the present study was to characterize clinical parameters and use of disease modifying therapies in patients diagnosed with SPMS and RRMS patients already entered the SP phase by use of the Danish Multiple Sclerosis Registry (DMSR).We used a cross-sectional design, including all living patients with MS as of June 30, 2020 from DMSR. First, we applied the MSBase definition of SPMS on all RRMS patients. Second, we applied the slightly modified inclusion criteria from the EXPAND clinical trial on patients with clinically confirmed SPMS and patients with RRMS fulfilling the MSBase definition of SPMS to identify SPMS patients recently progressed who may benefit from treatment with disease modifying therapy. We compared clinical characteristics and disease-modifying therapy use in the different patient groups.Among patients with clinically confirmed SPMS, application of a slightly modified EXPAND trial inclusion criteria for SPMS (m-EXPAND) captured patients who had converted to SPMS more recently and who had relapsed and initiated high-efficacy treatment more frequently. Moreover, our RRMS patients fulfilling the "SPMS"-criteria according to MSBase and recently progression according to m-EXPAND had similar characteristics and remarkably resembled the SPMS population in the EXPAND trial.Our results indicate that data-driven diagnostic definitions might help identify RRMS patients at risk for SPMS and we highlight the challenges and reluctance in diagnosing SPMS in clinical practice.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
