During IFNbeta therapy, the presence of NAb reduced or abolished bioavailability in a relevant percentage of patients. These data could be important for the early detection of patients with MS who are not responsive to IFNbeta therapy.

Background/aimsIn this multicentre study in clinical settings, we assessed the accuracy of optimized procedures for FDG-PET brain metabolism and CSF classifications in predicting or excluding the conversion to Alzheimer's disease (AD) dementia and non-AD dementias.MethodsWe included 80 MCI subjects with neurological and neuropsychological assessments, FDG-PET scan and CSF measures at entry, all with clinical follow-up. FDG-PET data were analysed with a validated voxel-based SPM method. Resulting single-subject SPM maps were classified by five imaging experts according to the disease-specific patterns, as “typical-AD”, “atypical-AD” (i.e. posterior cortical atrophy, asymmetric logopenic AD variant, frontal-AD variant), “non-AD” (i.e. behavioural variant FTD, corticobasal degeneration, semantic variant FTD; dementia with Lewy bodies) or “negative” patterns. To perform the statistical analyses, the individual patterns were grouped either as “AD dementia vs. non-AD dementia (all diseases)” or as “FTD vs. non-FTD (all diseases)”. Aβ42, total and phosphorylated Tau CSF-levels were classified dichotomously, and using the Erlangen Score algorithm. Multivariate logistic models tested the prognostic accuracy of FDG-PET-SPM and CSF dichotomous classifications. Accuracy of Erlangen score and Erlangen Score aided by FDG-PET SPM classification was evaluated.ResultsThe multivariate logistic model identified FDG-PET “AD” SPM classification (Expβ = 19.35, 95% C.I. 4.8–77.8, p < 0.001) and CSF Aβ42 (Expβ = 6.5, 95% C.I. 1.64–25.43, p < 0.05) as the best predictors of conversion from MCI to AD dementia. The “FTD” SPM pattern significantly predicted conversion to FTD dementias at follow-up (Expβ = 14, 95% C.I. 3.1–63, p < 0.001). Overall, FDG-PET-SPM classification was the most accurate biomarker, able to correctly differentiate either the MCI subjects who converted to AD or FTD dementias, and those who remained stable or reverted to normal cognition (Expβ = 17.9, 95% C.I. 4.55–70.46, p < 0.001).ConclusionsOur results support the relevant role of FDG-PET-SPM classification in predicting progression to different dementia conditions in prodromal MCI phase, and in the exclusion of progression, outperforming CSF biomarkers.

BackgroundPregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood.MethodologyWe conducted a genome-wide transcription analysis in peripheral blood mononuclear cells (PBMCs) from 12 women (7 MS patients and 5 healthy controls) followed during their pregnancy. Samples were obtained before, during (i.e. at the third, sixth, and ninth month of gestation) and after pregnancy. A validation of the expression profiles has been conducted by using the same samples and an independent group of 25 MS patients and 11 healthy controls. Finally, considering the total group of 32 MS patients, we compared expression profiles of patients relapsing during pregnancy (n = 6) with those of relapse-free patients (n = 26).Principal FindingsResults showed an altered expression of 347 transcripts in non-pregnant MS patients with respect to non-pregnant healthy controls. Complementary changes in expression, occurring during pregnancy, reverted the previous imbalance particularly for seven inflammation-related transcripts, i.e. SOCS2, TNFAIP3, NR4A2, CXCR4, POLR2J, FAM49B, and STAG3L1. Longitudinal analysis showed that the overall deregulation of gene expression reverted to “normal” already within the third month of gestation, while in the post-partum gene expressions rebounded to pre-pregnancy levels. Six (18.7%) of the 32 MS patients had a relapse during pregnancy, mostly in the first trimester. The latter showed delayed expression profiles when compared to relapse-free patients: in these patients expression imbalance was reverted later in the pregnancy, i.e. at sixth month.ConclusionsSpecific changes in expression during pregnancy were associated with a decrease in disease activity assessed by occurrence of relapses during pregnancy. Findings might help in understanding the pathogenesis of MS and may provide basis for the development of novel therapeutic strategies.

Objective: To evaluate the incidence and the prevalence of neutralising antibodies (NABs) to three interferon beta (IFNβ) products in patients with multiple sclerosis (MS). Methods: Sera were tested from 125 patients with relapsing-remitting MS. Patients were treated with IFNβ-1b (Betaferon, n = 29) 8 MIU subcutaneously every other day, IFNβ-1a (Avonex, n = 44) 30 µg intramuscularly once weekly, or IFNβ-1a (Rebif, n = 36) 22 µg subcutaneously three times weekly for 6 to 18 months. An additional 16 patients were treated with Rebif 22 µg intramuscularly once or twice weekly. NABs were assessed using the cytopathic effect assay before treatment and every three months during treatment. Patients with two or more consecutive positive samples were considered to be persistent NAB positive (NAB+). Results: At baseline, no patients were NAB+. NABs developed during the first three months of treatment and continued to develop until month 18. Over 18 months of treatment, the risk of being persistent NAB+ was 31% for Betaferon, 15% for Rebif, and 2% for Avonex (Betaferon versus Avonex, p = 0.001; Betaferon versus Rebif, p = 0.19; Rebif versus Avonex, p = 0.04). In all patients with one or more NAB+ samples, the risk of becoming NAB+ was 38% for Betaferon, 18% for Rebif, and 7% for Avonex (Betaferon versus Avonex, p = 0.0007; Betaferon versus Rebif, p = 0.10; Rebif versus Avonex, p = 0.07). At month 18, the prevalence of persistent NAB+ patients was 31.6% for Betaferon, 18.7% for Rebif, and 4% for Avonex. Numbers of NAB+ patients observed were similar with intramuscular Rebif and with subcutaneous Rebif. Conclusion: The three IFNβ preparations have different degrees of immunogenicity, with Betaferon producing the highest incidence of NABs and Avonex the lowest. These differences should be considered by neurologists when selecting treatment for their patients with MS because NABs can reduce both bioavailability and clinical efficacy of IFNβ.