Risk of Guillain-Barré syndrome after 2010–2011 influenza vaccination

Influenza vaccination has been implicated in Guillain Barré Syndrome (GBS) although the evidence for this link is controversial. A case–control study was conducted between October 2010 and May 2011 in seven Italian Regions to explore the relation between influenza vaccination and GBS. The study included 176 GBS incident cases aged ≥18 years from 86 neurological centers. Controls were selected among patients admitted for acute conditions to the Emergency Department of the same hospital as cases. Each control was matched to a case by sex, age, Region and admission date. Two different analyses were conducted: a matched case–control analysis and a self-controlled case series analysis (SCCS). Case–control analysis included 140 cases matched to 308 controls. The adjusted matched odds ratio (OR) for GBS occurrence within 6 weeks after influenza vaccination was 3.8 (95 % CI: 1.3, 10.5). A much stronger association with gastrointestinal infections (OR = 23.8; 95 % CI 7.3, 77.6) and influenza-like illness or upper respiratory tract infections (OR = 11.5; 95 % CI 5.6, 23.5) was highlighted. The SCCS analysis included all 176 GBS cases. Influenza vaccination was associated with GBS, with a relative risk of 2.1 (95 % CI 1.1, 3.9). According to these results the attributable risk in adults ranges from two to five GBS cases per 1,000,000 vaccinations

Sex-related differences in cerebrospinal fluid plasma-derived proteins of neurological patients

none11Background and aims: Cerebrospinal fluid (CSF) protein content presents a sexual dimor- phism in humans. We investigated sex-related differences in CSF IgG levels and in the quantification of intrathecal IgG synthesis (IIS). Methods: CSF, serum albumin and IgG were measured in 1519 neurological patients and both linear and hyperbolic formulas were used for the quantification of IIS. CSF-restricted oligoclonal IgG bands (OCBs) were used as “gold standard”. Results: The linear IgG Index showed a weak agreement with OCBs in males and females (k = 0.559, k = 0.587, respectively), while the hyperbolic Reiber’s formulas had a moderate agreement with OCBs in females (k = 0.635) and a weak agreement in males (k = 0.565). Higher CSF albumin and IgG levels were found in men than in women in the whole population and in subjects without IIS after adjusting for age and for serum concentrations of albumin and IgG, respectively (Quade statistics, p < 0.000001). CSF and serum albumin and IgG levels positively correlated to age in both sexes. CSF total protein content did not correlate with CSF leukocyte numbers but was higher in patients with marked pleocytosis. Conclusions: In neurological patients, men have higher levels of CSF serum-derived proteins, such as albumin and IgG.openCastellazzi, Massimiliano; Ferri, Caterina; Alfiero, Sarah; Lombardo, Ilenia; Laudisi, Michele; Tecilla, Ginevra; Boni, Michela; Pizzicotti, Stefano; Fainardi, Enrico; Bellini, Tiziana; Pugliatti, MauraCastellazzi, Massimiliano; Ferri, Caterina; Alfiero, Sarah; Lombardo, Ilenia; Laudisi, Michele; Tecilla, Ginevra; Boni, Michela; Pizzicotti, Stefano; Fainardi, Enrico; Bellini, Tiziana; Pugliatti, Maur

An Extremes of outcome strategy provides evidence that multiple sclerosis severity is determined by alleles at the <i>HLA-DRB1</i> locus

Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system unsurpassed for variability in disease outcome. A cohort of sporadic MS cases (n=63), taken from opposite extremes of the distribution of long-term outcome, was used to determine the role of the HLA-DRB1 locus on MS disease severity. Genotyping sets of benign and malignant MS patients showed that HLA-DRB1*01 was significantly underrepresented in malignant compared with benign cases. This allele appears to attenuate the progressive disability that characterizes MS in the long term. The observation was doubly replicated in (i) Sardinian benign and malignant patients and (ii) a cohort of affected sibling pairs discordant for HLA-DRB1*01. Among the latter, mean disability progression indices were significantly lower in those carrying the HLA-DRB1*01 allele compared with their disease-concordant siblings who did not. The findings were additionally supported by similar transmission distortion of HLA-DRB1*04 subtypes closely related to HLA-DRB1*01. The protective effect of HLA-DRB1*01 in sibling pairs may result from a specific epistatic interaction with the susceptibility allele HLA-DRB1*1501. A high-density (&gt;700) SNP examination of the MHC region in the benign and malignant patients could not identify variants differing significantly between the two groups, suggesting that HLA-DRB1 may itself be the disease-modifying locus. We conclude that HLA-DRB1*01, previously implicated in disease resistance, acts as an independent modifier of disease progression. These results closely link susceptibility to long-term outcome in MS, suggesting that shared quantitative MHC-based mechanisms are common to both, emphasizing the central role of this region in pathogenesis

Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS).We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes.The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85-0.90) was higher than OCB (0.82; 95%CI = 0.79-0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78-0.88) was lower (OCB = 0.92; 95% CI = 0.89-0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB.Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS

Measurement of the atmospheric muon depth intensity relation with the NEMO Phase-2 tower

The results of the analysis of the data collected with the NEMO Phase-2 tower, deployed at 3500 m depth about 80 km off-shore Capo Passero (Italy), are presented. Cherenkov photons detected with the photomultipliers tubes were used to reconstruct the tracks of atmospheric muons. Their zenith-angle distribution was measured and the results compared with Monte Carlo simulations. An evaluation of the systematic effects due to uncertainties on environmental and detector parameters is also included. The associated depth intensity relation was evaluated and compared with previous measurements and theoretical predictions. With the present analysis, the muon depth intensity relation has been measured up to 13 km of water equivalent.Comment: submitted to Astroparticle Physic