The incidence rate ratios (IRRs) of transient global amnesia after cancer diagnosis according to time since cancer diagnosis and by different cancer types, a cohort study in Sweden, 2001–2009.

<p>The incidence rate ratios (IRRs) of transient global amnesia after cancer diagnosis according to time since cancer diagnosis and by different cancer types, a cohort study in Sweden, 2001–2009.</p

Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression

<div><p>Pathology studies of progressive multiple sclerosis (MS) indicate a major role of inflammation including Th17-cells and meningeal inflammation with ectopic lymphoid follicles, B-cells and plasma cells, the latter indicating a possible role of the newly identified subset of follicular T-helper (T_FH) cells. Although previous studies reported increased systemic inflammation in progressive MS it remains unclear whether systemic inflammation contributes to disease progression and intrathecal inflammation. This study aimed to investigate systemic inflammation in progressive MS and its relationship with disease progression, using flow cytometry and gene expression analysis of CD4⁺ and CD8⁺T-cells, B-cells, monocytes and dendritic cells. Furthermore, gene expression of cerebrospinal fluid cells was studied. Flow cytometry studies revealed increased frequencies of ICOS⁺T_FH-cells in peripheral blood from relapsing-remitting (RRMS) and secondary progressive (SPMS) MS patients. All MS subtypes had decreased frequencies of Th1 T_FH-cells, while primary progressive (PPMS) MS patients had increased frequency of Th17 T_FH-cells. The Th17-subset, interleukin-23-receptor⁺CD4⁺T-cells, was significantly increased in PPMS and SPMS. In the analysis of B-cells, we found a significant increase of plasmablasts and DC-SIGN⁺ and CD83⁺B-cells in SPMS. ICOS⁺T_FH-cells and DC-SIGN⁺B-cells correlated with disease progression in SPMS patients. Gene expression analysis of peripheral blood cell subsets substantiated the flow cytometry findings by demonstrating increased expression of <i>IL21</i>, <i>IL21R</i> and <i>ICOS</i> in CD4⁺T-cells in progressive MS. Cerebrospinal fluid cells from RRMS and progressive MS (pooled SPMS and PPMS patients) had increased expression of T_FH-cell and plasmablast markers. In conclusion, this study is the first to demonstrate the potential involvement of activated T_FH-cells in MS. The increased frequencies of Th17-cells, activated T_FH- and B-cells parallel findings from pathology studies which, along with the correlation between activated T_FH- and B-cells and disease progression, suggest a pathogenic role of systemic inflammation in progressive MS. These observations may have implications for the treatment of progressive MS.</p> </div

Missing data.

<p>The amount of missing data was low and was imputed using multiple imputations.</p><p>Missing data.</p

Baseline characteristics of study participants in a cohort study of cancer diagnosis and transient global amnesia (TGA) in Sweden, 2001–2009.

<p>Baseline characteristics of study participants in a cohort study of cancer diagnosis and transient global amnesia (TGA) in Sweden, 2001–2009.</p

The crude incidence rates (IRs, per 1000 person-years) and incidence rate ratios (IRRs) of transient global amnesia (TGA) after cancer diagnosis, according to sex, calendar period of follow-up, age at follow-up, and previous TGA, a cohort study in Sweden, 2001–2009.

<p>The crude incidence rates (IRs, per 1000 person-years) and incidence rate ratios (IRRs) of transient global amnesia (TGA) after cancer diagnosis, according to sex, calendar period of follow-up, age at follow-up, and previous TGA, a cohort study in Sweden, 2001–2009.</p

Cerebrospinal fluid cell and peripheral blood mononuclear cell gene expression data.

<p>Gene expression data cerebrospinal fluid cell (CSF) and peripheral blood mononuclear cell (PBMC) are expressed as normalization ratio (NR). Values are expressed as means with standard error (SE). Parametric (ANOVA and T-test) and non-parametric analyses (Kruskal-Wallis and Mann-Whitney) were used when appropriate. Post-hoc analyses was done when ANOVA or Kruskal-Wallis tests were significant (p = 0.05) and values for post-hoc tests are indicated (T-tests: ^∧ p<0.05 and Mann-Whitney ∼ p<0.05; ≈ p<0.01).Relapsing-remitting multiple sclerosis (RRMS) group consists of 10 patients in clinical remission and 10 patients with clinical relapse. Progressive multiple sclerosis (MS) consists of 10 secondary progressive and 10 primary progressive MS patients. Abbreviations: Non-inflammatory neurological disease = NIND.</p

Demographic and clinical characteristics of MS patients, healthy controls and non-inflammatory neurological controls included in the studies.

<p>Values for age, MS disease duration, EDSS and EDSS change are medians with interquartile ranges in brackets. EDSS change represents the change in EDSS the two previous years prior to blood sampling. Abbreviations: CSF = cerebrospinal fluid; EDSS = expanded disability status scale; HC = healthy control; MS = multiple sclerosis; NIND = non-inflammatory neurological disease; RRMS = relapsing-remitting multiple sclerosis; SPMS = secondary progressive multiple sclerosis; PPMS = primary progressive multiple sclerosis.</p

Case-only analysis investigating prescription (ATC) history during the vaccination period and before index date and diagnosis (ICD10) history before index date on risk of developing narcolepsy.

<p>Case-only analysis investigating prescription (ATC) history during the vaccination period and before index date and diagnosis (ICD10) history before index date on risk of developing narcolepsy.</p

Gene expression studies of whole blood in secondary progressive multiple sclerosis with and without mitoxantrone treatment.

<p>Mean plots show mean normalization ratios (NR) with error bars representing 95% confidence intervals. Parametric (T-test) or non-parametric (Mann-Whitney (MW)) statistic tests were applied when suitable. Comparing untreated secondary progressive multiple sclerosis (SPMS) patients to SPMS patient treated with mitoxantrone (SPMS MTX) whole blood expression of <i>IL21</i> significantly decreased while no significant changes were observed for <i>ICOS</i> and <i>IGJ</i>.</p

Gene expression studies of peripheral blood CD4⁺ and CD8⁺T-cells from multiple sclerosis patients and healthy controls.

<p>Mean plots show mean normalization ratios (NR) with error bars representing 95% confidence intervals. Parametric (ANOVA and post-hoc T-tests) or non-parametric (Kruskal-Wallis (KW) and Mann-Whitney (MW)) statistic tests were applied when suitable. (A) Gene expression analysis in CD4⁺T-cells shows increased expression of <i>ICOS</i>, <i>IL21R</i> and <i>LTB</i> in secondary progressive (SPMS) and primary progressive (PPMS) multiple sclerosis patients as compared to healthy controls (HC) and increased expression of <i>IL21</i> and <i>IFNG</i> in SPMS patients compared to HCs. (B) Gene expression analysis in CD8⁺T-cells shows increased expression of <i>GATA3</i>, <i>LTB</i> and <i>LTBR</i> in SPMS and PPMS compared to HCs. <i>HLX</i>, <i>TGFB</i>, <i>TNFA</i> and <i>TNFSF14</i> were increased in SPMS compared to HCs.</p