LECTURAS CIENTÍFICAS

  • Neurological manifestations of Chikungunya and Zika infections.
    Related ArticlesNeurological manifestations of Chikungunya and Zika infections. Arq Neuropsiquiatr. 2016 Nov;74(11):937-943 Authors: Pinheiro TJ, Guimarães LF, Silva MT, Soares CN Abstract The epidemics of Chikungunya virus (CHIKV) and Zika virus (ZIKV) infections have been considered the most important epidemiological occurrences in the Americas. The clinical picture of CHIKV infection is characterized by high fever, exanthema, myalgia, headaches, and arthralgia. Besides the typical clinical picture of CHIKV, atypical manifestations of neurological complications have been reported: meningo-encephalitis, meningoencephalo-myeloradiculitis, myeloradiculitis, myelitis, myeloneuropathy, Guillain-Barré syndrome and others. The diagnosis is based on clinical, epidemiological, and laboratory criteria. The most common symptoms of ZIKV infection are skin rash (mostly maculopapular), fever, arthralgia, myalgia, headache, and conjunctivitis. Some epidemics that have recently occurred in French Polynesia and Brazil, reported the most severe conditions, with involvement of the nervous system (Guillain-Barré syndrome, transverse myelitis, microcephaly and meningitis). The treatment for ZIKV and CHIKV infections are symptomatic and the management for neurological complications depends on the type of affliction. Intravenous immunoglobulin, plasmapheresis, and corticosteroid pulse therapy are options.PMID: 27901259 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-28
  • What’s in a name? Problems, facts and controversies regarding neurological eponyms.
    Related ArticlesWhat's in a name? Problems, facts and controversies regarding neurological eponyms. Arq Neuropsiquiatr. 2016 May;74(5):423-5 Authors: Teive HA, Lima PM, Germiniani FM, Munhoz RP Abstract The use of eponyms in neurology remains controversial, and important questions have been raised about their appropriateness. Different approaches have been taken, with some eponyms being excluded, others replaced, and new ones being created. An example is Hallervorden-Spatz syndrome, which has been replaced by neurodegeneration with brain iron accuulatium (NBIA). Amiothoplic lateral sclerosys (ALS), for which the eponym is Charcot's disease, has been replaced in the USA by Lou Gehrig's disease. Guillain-Barré syndrome (GBS) is an eponym that is still the subject of controversy, and various different names are associated with it. Finally,restless legs syndrome (RLS), which was for years known as Ekbom's syndrome, has been rechristened as RLS/Willis-Ekbom syndrome. PMID: 27191240 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-28
  • Optimal response to dimethyl fumarate associates in MS with a shift from an inflammatory to a tolerogenic blood cell profile.
    Optimal response to dimethyl fumarate associates in MS with a shift from an inflammatory to a tolerogenic blood cell profile. Mult Scler. 2017 Jun 01;:1352458517717088 Authors: Medina S, Villarrubia N, Sainz de la Maza S, Lifante J, Costa-Frossard L, Roldán E, Picón C, Álvarez-Cermeño JC, Villar LM Abstract BACKGROUND: The precise mechanism of action of dimethyl fumarate (DMF) treatment in MS remains unknown. OBJECTIVE: To identify the changes in the blood lymphocyte profile of MS patients predicting no evidence of disease activity (NEDA) status after DMF treatment. METHODS: We studied blood lymphocyte subsets of 64 MS patients treated with DMF at baseline and after 6 months of treatment by flow cytometry. NEDA (41 patients) or ongoing disease activity (ODA, 23 patients) were monitored after a year of follow-up. RESULTS: During treatment, all patients experienced an increase in the naive T cells and a decrease in effector memory ones. However, only NEDA patients showed a significant reduction in central memory CD4+ and CD8+ T cells, memory B cells, CD4+ T cells producing interferon (IFN)-gamma, CD8+ T cells producing tumor necrosis factor-alpha (TNF-alpha), and IFN-gamma and B cells producing TNF-alpha. Additionally, they had an increase in regulatory CD56bright cells not observed in ODA group. After treatment, there was a negative correlation between CD56bright cells and CD8+ T cells producing IFN-gamma and TNF-alpha. CONCLUSION: A pro-tolerogenic shift in the blood leukocyte profile associates with an optimal response to DMF in MS.PMID: 28653862 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-28
  • Myasthenia gravis: new developments in research and treatment.
    Myasthenia gravis: new developments in research and treatment. Curr Opin Neurol. 2017 Jun 24;: Authors: Evoli A Abstract PURPOSE OF REVIEW: Myasthenia gravis, a rare disorder of the neuromuscular transmission, is increasingly acknowledged as a syndrome more than as a single disease. This review summarizes recent advances in pathophysiology which confirm the disease heterogeneity, and may help find disease-targeted and patient-targeted therapies. RECENT FINDINGS: Antibodies to the acetylcholine receptor, the muscle-specific tyrosine kinase and the lipoprotein receptor protein 4, characterize disease subtypes with distinct clinical traits and immune-pathogenic mechanisms. Genome-wide approaches have identified susceptibility loci within genes that participate in the immune response. Regulatory T and B cells appear to be defective in myasthenia gravis. In patients with acetylcholine receptor antibodies, thymectomy associated with prednisone proved more effective than prednisone alone in a multicenter randomized trial. New therapeutic options target B cells, B-cell growth factors and complement inhibition, and are currently reserved for patients with refractory disease. SUMMARY: In the recent past, there has been an active search for new antigens in myasthenia gravis, whereas clinical and experimental studies have provided new insights of crucial pathways in immune regulation, which might become the targets of future therapeutic interventions.PMID: 28654435 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-28
  • Patients with paediatric-onset multiple sclerosis are at higher risk of cognitive impairment in adulthood: An Italian collaborative study.
    Patients with paediatric-onset multiple sclerosis are at higher risk of cognitive impairment in adulthood: An Italian collaborative study. Mult Scler. 2017 Jun 01;:1352458517717341 Authors: Ruano L, Branco M, Portaccio E, Goretti B, Niccolai C, Patti F, Chisari C, Gallo P, Grossi P, Ghezzi A, Roscio M, Mattioli F, Stampatori C, Simone M, Viterbo RG, Amato MP Abstract BACKGROUND: Patients with paediatric-onset multiple sclerosis (POMS) could be at an increased risk for cognitive impairment (CI), given the potential harmful effects of disease activity in neurodevelopment. However, there is scarce information on their long-term cognitive outcomes. OBJECTIVE: To compare the prevalence and profile of CI between adults with a history of POMS and those with classic, adult-onset multiple sclerosis (AOMS). METHODS: Cognitive performance was assessed through the Brief Repeatable Battery (BRB) and the Stroop Test in consecutive patients referred to six Italian MS centres. CI was defined as impairment in ⩾2 cognitive domains. RESULTS: In all, 119 patients with POMS and 712 with AOMS were included in this analysis. The prevalence of CI was 48.0% in AOMS, 44.5% in POMS; with similar neuropsychological profile between the two groups. However, when adjusting for current age, we found a significantly increased risk for CI (odds ratio (OR) = 1.71; p = 0.02) and for impairment in information processing speed (OR = 1.86; p < 0.01) in patients with POMS. A higher Expanded Disability Status Scale (EDSS) was also identified in POMS ( p = 0.03) compared with AOMS patients. CONCLUSION: Patients with a history of POMS appear to be at higher risk of physical… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-28
  • Genetic factors affecting EBV copy number in lymphoblastoid cell lines derived from the 1000 Genome Project samples.
    Genetic factors affecting EBV copy number in lymphoblastoid cell lines derived from the 1000 Genome Project samples. PLoS One. 2017;12(6):e0179446 Authors: Mandage R, Telford M, Rodríguez JA, Farré X, Layouni H, Marigorta UM, Cundiff C, Heredia-Genestar JM, Navarro A, Santpere G Abstract Epstein-Barr virus (EBV), human herpes virus 4, has been classically associated with infectious mononucleosis, multiple sclerosis and several types of cancers. Many of these diseases show marked geographical differences in prevalence, which points to underlying genetic and/or environmental factors. Those factors may include a different susceptibility to EBV infection and viral copy number among human populations. Since EBV is commonly used to transform B-cells into lymphoblastoid cell lines (LCLs) we hypothesize that differences in EBV copy number among individual LCLs may reflect differential susceptibility to EBV infection. To test this hypothesis, we retrieved whole-genome sequenced EBV-mapping reads from 1,753 LCL samples derived from 19 populations worldwide that were sequenced within the context of the 1000 Genomes Project. An in silico methodology was developed to estimate the number of EBV copy number in LCLs and validated these estimations by real-time PCR. After experimentally confirming that EBV relative copy number remains stable over cell passages, we performed a genome wide association analysis (GWAS) to try detecting genetic variants of the host that may be associated with EBV copy number. Our GWAS has yielded several genomic regions suggestively associated with the number of EBV genomes per cell in LCLs, unraveling promising candidate genes such as CAND1, a known inhibitor of EBV… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-28
  • NB-3 signaling mediates the cross-talk between post-traumatic spinal axons and scar-forming cells.
    Related ArticlesNB-3 signaling mediates the cross-talk between post-traumatic spinal axons and scar-forming cells. EMBO J. 2016 Aug 15;35(16):1745-65 Authors: Huang Z, Gao Y, Sun Y, Zhang C, Yin Y, Shimoda Y, Watanabe K, Liu Y Abstract Little is known about the molecules mediating the cross-talk between post-traumatic axons and scar-forming cells after spinal cord injury. We found that a sustained NB-3 induction was simultaneously present in the terminations of post-traumatic corticospinal axons and scar-forming cells at the spinal lesion site, where they were in direct contact when axons tried to penetrate the glial scar. The regrowth of corticospinal axons was enhanced in vivo with NB-3 deficiency or interruption of NB-3 trans-homophilic interactions. Biochemical, in vitro and in vivo evidence demonstrated that NB-3 homophilically interacted in trans to initiate a growth inhibitory signal transduction from scar-forming cells to neurons by modulating mTOR activity via CHL1 and PTPσ. NB-3 deficiency promoted BMS scores, electrophysiological transmission, and synapse reformation between regenerative axons and neurons. Our findings demonstrate that NB-3 trans-homophilic interactions mediate the cross-talk between post-traumatic axons and scar-forming cells and impair the intrinsic growth ability of injured axons. PMID: 27192985 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-28
  • Plasma exchange for Guillain-Barré syndrome.
    Related ArticlesPlasma exchange for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2017 02 27;2:CD001798 Authors: Chevret S, Hughes RA, Annane D Abstract BACKGROUND: Guillain-Barré syndrome (GBS) is an acute paralysing disease caused by peripheral nerve inflammation. This is an update of a review first published in 2001 and last updated in 2012. OBJECTIVES: To assess the effects of plasma exchange for treating GBS. SEARCH METHODS: On 18 January 2016 we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched clinical trials registries. SELECTION CRITERIA: Randomised and quasi-randomised trials of plasma exchange versus sham exchange or supportive treatment, or comparing different regimens or techniques of plasma exchange. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. MAIN RESULTS: In the first version of this review there were six eligible trials concerning 649 participants comparing plasma exchange with supportive treatment. No new eligible trials have been identified in subsequent updates. Two other studies compared different numbers of plasma exchanges. Overall the included trials had a moderate risk of bias (in general, the studies were at low risk but all had a high risk of bias from lack of blinding).In one trial with 220 severely affected participants, the median time to recover walking with aid was significantly shorter with plasma exchange (30 days) than without plasma exchange (44 days). In another trial with 91 mildly affected participants, the median time to onset of motor recovery was significantly shorter with plasma exchange (six days) than without plasma exchange (10 days).… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-27
  • Comparative effectiveness of rituximab relative to IFN-β or glatiramer acetate in relapsing-remitting MS from the Swedish MS registry.
    Comparative effectiveness of rituximab relative to IFN-β or glatiramer acetate in relapsing-remitting MS from the Swedish MS registry. Mult Scler. 2017 Jun 01;:1352458517713668 Authors: Spelman T, Frisell T, Piehl F, Hillert J Abstract OBJECTIVE: To compare treatment effectiveness and persistence in relapsing-remitting multiple sclerosis patients who initiated rituximab versus glatiramer acetate (GA) or interferon-beta (IFN-β). METHODS: A total of 461 patients from the Swedish MS registry in the rituximab arm were propensity score matched on a 1:2 basis with 922 patients from the IFN-β/GA comparator, between April 2005 and November 2015. Annualised relapse rate (ARR) was compared using the Poisson method. A marginal Cox model was used to analyse time to first relapse, 3-month confirmed disability progression and treatment discontinuation in the matched sample. A signed-rank test was used to compare Expanded Disability Status Scale (EDSS) change from baseline. RESULTS: Rituximab was associated with a reduction in ARR (0.003; 95% confidence interval (CI) = 0.001, 0.009) relative to IFN-β/GA (0.026; 95% CI = 0.020, 0.033) ( p < 0.001). Rituximab was associated with an 87% reduction in the relapse rate (hazard ratio (HR) = 0.13; 95% CI = 0.04, 0.41) and an 85% reduction in the discontinuation rate (HR = 0.15; 95% CI = 0.11, 0.20) relative to IFN-β/GA. EDSS regression from baseline was greater in the rituximab group at 12 and 24 months. CONCLUSION: Rituximab appears to be superior to first-generation disease-modifying treatments (DMTs) with respect to relapse control and tolerability, whereas superiority on disability outcomes is less clear.PMID:… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-27
  • Safety of IV pulse methylprednisolone therapy during breastfeeding in patients with multiple sclerosis.
    Safety of IV pulse methylprednisolone therapy during breastfeeding in patients with multiple sclerosis. Mult Scler. 2017 Jun 01;:1352458517717806 Authors: Boz C, Terzi M, Zengin Karahan S, Sen S, Sarac Y, Emrah Mavis M Abstract BACKGROUND: Women with multiple sclerosis (MS) experience an increased risk of relapse in the postpartum period. High-dose methylprednisolone is the first-line treatment for acute relapses. OBJECTIVES: To determine the transfer of methylprednisolone into human milk in breastfeeding MS patients. METHODS: Methylprednisolone therapy was given for postpartum relapse to nine patients for three consecutive days, and seven patients received a daily infusion once a month. Breast milk samples were obtained before infusion and 1, 2, 4, 8, and 12 hours after completion of infusion. RESULTS: Methylprednisolone concentrations in milk were below detection limits immediately before infusion. Cmax was measured at 1, 2, 4, 8, and 12 hours after infusion and levels of 2.100, 1.659, 0.680, 0.174, and 0.102 µg/mL were determined, respectively. The absolute infant dose was 98.98 µg/kg/day, and the relative infant dose (RID) was 0.71% of the weight-adjusted maternal dose. CONCLUSION: The level of methylprednisolone transfer into breast milk is very low. The RID for methylprednisolone was lower than the generally accepted value. As methylprednisolone therapy is of short duration, infant exposure would be very low should a mother choose to breastfeed 1 hour after infusion. Waiting 2-4 hours after infusion will limit infant exposure still further.PMID: 28649909 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-27
  • Megf10 Is a Receptor for C1Q That Mediates Clearance of Apoptotic Cells by Astrocytes.
    Related ArticlesMegf10 Is a Receptor for C1Q That Mediates Clearance of Apoptotic Cells by Astrocytes. J Neurosci. 2016 May 11;36(19):5185-92 Authors: Iram T, Ramirez-Ortiz Z, Byrne MH, Coleman UA, Kingery ND, Means TK, Frenkel D, El Khoury J Abstract UNLABELLED: Multiple EGF-like domains 10 (Megf10) is a class F scavenger receptor (SR-F3) expressed on astrocytes and myosatellite cells, and recessive mutations in humans result in early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD). Here we report that Megf10-deficient mice have increased apoptotic cells in the developing cerebellum and have impaired phagocytosis of apoptotic cells by astrocytes ex vivo We also report that cells transfected with Megf10 gain the ability to phagocytose apoptotic neurons and that Megf10 binds with high affinity to C1q, an eat-me signal for apoptotic cells. In contrast, cells expressing Megf10 with EMARDD mutations have impaired apoptotic cell clearance and impaired binding to C1q. Our studies reveal that Megf10 is a receptor for C1q and identify a novel role for Megf10 in clearance of apoptotic cells in the mammalian developing brain with potential relevance to EMARDD patients and other CNS disorders. SIGNIFICANCE STATEMENT: Apoptosis is a universal homeostatic process and occurs in many disease conditions. Multiple EGF-like domains 10 (Megf10) is emerging as an essential receptor for synaptic pruning, clearance of neuronal debris, and for muscle differentiation. Here we define a novel Megf10-dependent pathway for apoptotic cell clearance and show that Megf10 is a receptor for C1q, an eat-me signal, that binds phosphatidylserine expressed on the… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-27
  • Assessment of Intrathecal Free Light Chain Synthesis: Comparison of Different Quantitative Methods with the Detection of Oligoclonal Free Light Chains by Isoelectric Focusing and Affinity-Mediated Immunoblotting.
    Related ArticlesAssessment of Intrathecal Free Light Chain Synthesis: Comparison of Different Quantitative Methods with the Detection of Oligoclonal Free Light Chains by Isoelectric Focusing and Affinity-Mediated Immunoblotting. PLoS One. 2016;11(11):e0166556 Authors: Zeman D, Kušnierová P, Švagera Z, Všianský F, Byrtusová M, Hradílek P, Kurková B, Zapletalová O, Bartoš V Abstract OBJECTIVES: We aimed to compare various methods for free light chain (fLC) quantitation in cerebrospinal fluid (CSF) and serum and to determine whether quantitative CSF measurements could reliably predict intrathecal fLC synthesis. In addition, we wished to determine the relationship between free kappa and free lambda light chain concentrations in CSF and serum in various disease groups. METHODS: We analysed 166 paired CSF and serum samples by at least one of the following methods: turbidimetry (Freelite™, SPAPLUS), nephelometry (N Latex FLC™, BN ProSpec), and two different (commercially available and in-house developed) sandwich ELISAs. The results were compared with oligoclonal fLC detected by affinity-mediated immunoblotting after isoelectric focusing. RESULTS: Although the correlations between quantitative methods were good, both proportional and systematic differences were discerned. However, no major differences were observed in the prediction of positive oligoclonal fLC test. Surprisingly, CSF free kappa/free lambda light chain ratios were lower than those in serum in about 75% of samples with negative oligoclonal fLC test. In about a half of patients with multiple sclerosis and clinically isolated syndrome, profoundly increased free kappa/free lambda light chain ratios were found in the CSF. CONCLUSIONS: Our results show that using appropriate method-specific cut-offs, different methods… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-27
  • Galectin-8 as an immunosuppressor in experimental autoimmune encephalomyelitis and a target of human early prognostic antibodies in multiple sclerosis.
    Galectin-8 as an immunosuppressor in experimental autoimmune encephalomyelitis and a target of human early prognostic antibodies in multiple sclerosis. PLoS One. 2017;12(6):e0177472 Authors: Pardo E, Cárcamo C, Uribe-San Martín R, Ciampi E, Segovia-Miranda F, Curkovic-Peña C, Montecino F, Holmes C, Tichauer JE, Acuña E, Osorio-Barrios F, Castro M, Cortes P, Oyanadel C, Valenzuela DM, Pacheco R, Naves R, Soza A, González A Abstract Galectin-8 (Gal-8) is a member of a glycan-binding protein family that regulates the immune system, among other functions, and is a target of antibodies in autoimmune disorders. However, its role in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system (CNS), remains unknown. We study the consequences of Gal-8 silencing on lymphocyte subpopulations and the development of experimental autoimmune encephalitis (EAE), to then assess the presence and clinical meaning of anti-Gal-8 antibodies in MS patients. Lgals8/Lac-Z knock-in mice lacking Gal-8 expression have higher polarization toward Th17 cells accompanied with decreased CCR6+ and higher CXCR3+ regulatory T cells (Tregs) frequency. These conditions result in exacerbated MOG35-55 peptide-induced EAE. Gal-8 eliminates activated Th17 but not Th1 cells by apoptosis and ameliorates EAE in C57BL/6 wild-type mice. β-gal histochemistry reflecting the activity of the Gal-8 promoter revealed Gal-8 expression in a wide range of CNS regions, including high expression in the choroid-plexus. Accordingly, we detected Gal-8 in human cerebrospinal fluid, suggesting a role in the CNS immune-surveillance circuit. In addition, we show that MS patients generate function-blocking anti-Gal-8 antibodies with pathogenic potential. Such antibodies block cell adhesion… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-27
  • Granuloma faciale associated with IgG4-related disease.
    Related ArticlesGranuloma faciale associated with IgG4-related disease. Clin Exp Dermatol. 2017 Jun 25;: Authors: López-Navarro N, Gallego-Dominguez E, Vargas-Nevado A, Castillo-Muñoz R, Herrera E PMID: 28649778 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-27
  • Randomised controlled trial of a baked egg intervention in young children allergic to raw egg but not baked egg.
    Related ArticlesRandomised controlled trial of a baked egg intervention in young children allergic to raw egg but not baked egg. World Allergy Organ J. 2017;10(1):22 Authors: Netting M, Gold M, Quinn P, El-Merhibi A, Penttila I, Makrides M Abstract BACKGROUND: Consumption of baked egg by raw egg allergic children is associated with immune changes suggesting development of tolerance. However, causation has not been tested using a double blind randomized controlled trial (RCT). We aimed to compare clinical and immunological outcomes after baked egg (BE) consumption in young BE tolerant egg allergic children. METHODS: In a double blind RCT, BE tolerant egg allergic children consumed 10 g BE (1.3 g protein) 2 to 3 times per week for 6 months (n = 21 intervention group) or similar egg free baked goods (n = 22 control group) while maintaining an otherwise egg free diet. The final assessment was a raw egg oral food challenge (OFC) 1 month after ceasing the intervention product. Egg specific IgE and IgG4 were assessed at baseline and 7 months. RESULTS: After the intervention there was no difference in raw egg tolerance between groups, (23.5% (4/17) intervention group and 33.3% (6/18) control group). This was independent of age and amount of BE consumed (aOR 0.50 CI 0.11-2.40 p = 0.39). Both groups demonstrated decreased egg specific serum IgE titres and decreased whole egg specific IgE/IgG4 ratios. DISCUSSION: We conducted this trial because inclusion of baked egg protein in the diet of egg allergic children appears to move children towards a more tolerant immune profile. Strengths of our… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-27
  • Investigating the effect of different transducer stiffness values on the contactin complex detachment by steered molecular dynamics.
    Investigating the effect of different transducer stiffness values on the contactin complex detachment by steered molecular dynamics. J Mol Graph Model. 2017 Jun 02;75:340-346 Authors: Kianfar P, Abolfathi N, Karimi NZ Abstract This study investigated the adhesion behavior of Contactin4 (CNTN4), a member of Immunoglobulin Super Family (Ig-SF) of cell adhesion molecules. Contactin4 plays a crucial role in the formation, maintenance, and plasticity of neuronal networks. Contactin in its complex configuration with protein tyrosine phosphatase gamma (PTPRG) was selected for simulation. By utilizing Steered Molecular Dynamics (SMD), the uniaxial force was applied to induce unbinding of the complex, and the force-induced detachment of complex components was probed. Three sets of simulations with three values of transducer stiffness and five pulling speeds were designed. Our results showed the dependence of unbinding force on both accessible parameters of pulling speed and spring stiffness. By increasing the stiffness value and pulling speed the rupture force increased. Accordingly, the dissociation rates due to the Bell's theory based on rupture forces and loading rates were calculated.PMID: 28651183 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-27
  • Influence of type I IFN signaling on anti-MOG antibody-mediated demyelination.
    Influence of type I IFN signaling on anti-MOG antibody-mediated demyelination. J Neuroinflammation. 2017 Jun 24;14(1):127 Authors: Berg CT, Khorooshi R, Asgari N, Owens T Abstract BACKGROUND: Antibodies with specificity for myelin oligodendrocyte glycoprotein (MOG) are implicated in multiple sclerosis and related diseases. The pathogenic importance of anti-MOG antibody in primary demyelinating pathology remains poorly characterized. OBJECTIVE: The objective of this study is to investigate whether administration of anti-MOG antibody would be sufficient for demyelination and to determine if type I interferon (IFN) signaling plays a similar role in anti-MOG antibody-mediated pathology, as has been shown for neuromyelitis optica-like pathology. METHODS: Purified IgG2a monoclonal anti-MOG antibody and mouse complement were stereotactically injected into the corpus callosum of wild-type and type I IFN receptor deficient mice (IFNAR1-KO) with and without pre-established experimental autoimmune encephalomyelitis (EAE). RESULTS: Anti-MOG induced complement-dependent demyelination in the corpus callosum of wild-type mice and did not occur in mice that received control IgG2a. Deposition of activated complement coincided with demyelination, and this was significantly reduced in IFNAR1-KO mice. Co-injection of anti-MOG and complement at onset of symptoms of EAE induced similar levels of callosal demyelination in wild-type and IFNAR1-KO mice. CONCLUSIONS: Anti-MOG antibody and complement was sufficient to induce callosal demyelination, and pathology was dependent on type I IFN. Induction of EAE in IFNAR1-KO mice overcame the dependence on type I IFN for anti-MOG and complement-mediated demyelination.PMID: 28646890 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-26
  • Blink R1 latency utility in diagnosis and treatment assessment of POEMS and CIDP.
    Related ArticlesBlink R1 latency utility in diagnosis and treatment assessment of POEMS and CIDP. Muscle Nerve. 2017 Jun 23;: Authors: Wang W, Litchy WJ, Mauermann ML, Dyck PJB, Dispenzieri A, Mandrekar J, Dyck PJ, Klein CJ Abstract INTRODUCTION: In POEMS and CIDP, limb nerve conduction studies (NCS) are limited in identifying demyelination and detecting treatment effects in severely affected patients. Blink R1-latency may improve these assessments. METHODS: POEMS and CIDP patients having undergone NCS and blink reflex were identified. Correlations between R1-latency, limb NCS and neuropathy impairment scores (NIS) were compared. RESULTS: With182 patients (124 POEMS, 58 CIDP) identified, R1-prolongation (>13ms) occurred in 64.3% (65.3% POEMS, 62.1% CIDP). R1-prolongation correlated with more severely affected NCS in both POEMS (ulnar CMAP 2.6mV vs 4.5mV, p=0.001) and CIDP (2.0mV vs 6.1mV, p< 0.001). In severely affected patients [ulnar CMAP ≤0.5mV (10%:18/182)], R1 (>13ms) helped establish demyelination. In 31 patients (16 POEMS, 15 CIDP), the R1-latency changes were concordant with NIS changes in 94% of POEMS and 60% of CIDP patients. DISCUSSION: Blink R1-latencies are valuable in defining demyelination and detecting improvement in severely affected POEMS and CIDP patients. This article is protected by copyright. All rights reserved.PMID: 28646568 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-25
  • Nogo-A antibodies enhance axonal repair and remyelination in neuro-inflammatory and demyelinating pathology.
    Related ArticlesNogo-A antibodies enhance axonal repair and remyelination in neuro-inflammatory and demyelinating pathology. Acta Neuropathol. 2017 Jun 23;: Authors: Ineichen BV, Kapitza S, Bleul C, Good N, Plattner PS, Seyedsadr MS, Kaiser J, Schneider MP, Zörner B, Martin R, Linnebank M, Schwab ME Abstract Two hallmarks of chronic multiple sclerosis lesions are the absence of significant spontaneous remyelination and primary as well as secondary neurodegeneration. Both characteristics may be influenced by the presence of inhibitory factors preventing myelin and neuronal repair. We investigated the potential of antibodies against Nogo-A, a well-known inhibitory protein for neuronal growth and plasticity, to enhance neuronal regeneration and remyelination in two animal models of multiple sclerosis. We induced a targeted experimental autoimmune encephalomyelitis (EAE) lesion in the dorsal funiculus of the cervical spinal cord of adult rats resulting in a large drop of skilled forelimb motor functions. We subsequently observed improved recovery of forelimb function after anti-Nogo-A treatment. Anterograde tracing of the corticospinal tract revealed enhanced axonal sprouting and arborisation within the spinal cord gray matter preferentially targeting pre-motor and motor spinal cord laminae on lesion level and above in the anti-Nogo-A-treated animals. An important additional effect of Nogo-A-neutralization was enhanced remyelination observed after lysolecithin-induced demyelination of spinal tracts. Whereas remyelinated fiber numbers in the lesion site were increased several fold, no effect of Nogo-A-inhibition was observed on oligodendrocyte precursor proliferation, migration, or differentiation. Enhancing remyelination and promoting axonal regeneration and plasticity represent important unmet medical needs in multiple sclerosis. Anti-Nogo-A antibodies hold promise as… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-25
  • Interferon-β regulates dendritic cell activation and migration in experimental autoimmune encephalomyelitis.
    Interferon-β regulates dendritic cell activation and migration in experimental autoimmune encephalomyelitis. Immunology. 2017 Jun 24;: Authors: Pennell LM, Fish EN Abstract CD11c+ dendritic cells (DCs) exert a critical role as antigen-presenting cells in regulating pathogenic T cells in multiple sclerosis (MS). To determine whether the therapeutic benefit of interferon (IFN)-β treatment for MS is in part influenced by IFN regulation of DC function, we examined the immunophenotype of DCs derived from IFN-β(+/+) and IFN-β(-/-) mice using a myelin oligodendrocyte glycoprotein (MOG) peptide-induced mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Our earlier work identified that IFN-β(-/-) mice exhibit earlier onset and more rapid progression of neurologic impairment compared with IFN-β(+/+) mice. In this study we show that LPS-/MOG peptide-stimulated IFN-β(-/-) DCs secrete cytokines associated with pathologic Th17 rather than Treg polarization and exhibit increased CD80 and MHCII expression when compared to stimulated IFN-β(+/+) DCs. IFN-β(-/-) DCs from mice immunized to develop EAE induce greater proliferation of MOG-transgenic CD4+ T cells and promote IL-17 production by these T cells. Adoptive transfer of MOG peptide-primed IFN-β(-/-) DCs into IFN-β(+/+) and IFN-β(-/-) mice immunized to develop EAE resulted in their rapid migration into the CNS of recipient mice, prior to onset of disease, which we attribute to failed STAT1-mediated inhibition of CCR7. Taken together, our data support immunoregulatory roles for IFN-β in the activation and migration of DCs during EAE. This article is protected by copyright. All rights reserved.PMID: 28646573 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-25
  • Medaka and zebrafish contactin1 mutants as a model for understanding neural circuits for motor coordination.
    Related ArticlesMedaka and zebrafish contactin1 mutants as a model for understanding neural circuits for motor coordination. Genes Cells. 2017 Jun 22;: Authors: Takeuchi M, Inoue C, Goshima A, Nagao Y, Shimizu K, Miyamoto H, Shimizu T, Hashimoto H, Yonemura S, Kawahara A, Hirata Y, Yoshida M, Hibi M Abstract A spontaneous medaka ro mutant shows abnormal wobbling and rolling swimming behaviors. By positional cloning, we mapped the ro locus to a region containing the gene encoding Contactin1b (Cntn1b), which is an immunoglobulin (Ig)-superfamily domain-containing membrane-anchored protein. The ro mutant had a deletion in the cntn1b gene that introduced a premature stop codon. Furthermore, cntn1b mutants generated by the CRISPR/Cas9 system and trans-heterozygotes of the CRISPR mutant allele and ro had abnormal swimming behavior, indicating that the cntn1b gene was responsible for the ro-mutant phenotype. We also established zebrafish cntn1a and cntn1b mutants by transcription activator-like effector nucleases (TALENs). Zebrafish cntn1b but not cntn1a mutants showed abnormal swimming behaviors similar to those in the ro mutant, suggesting that Cntn1b plays a conserved role in the formation or function of the neural circuits that control swimming in teleosts. Although Cntn1-deficient mice have abnormal cerebellar neural circuitry, there was no apparent histological abnormality in the cerebellum of medaka or zebrafish cntn1b mutants. The medaka cntn1b mutants had defective optokinetic response (OKR) adaptation and abnormal rheotaxis (body positioning relative to water flow). Medaka and zebrafish cntn1b mutants are effective models for studying the neural circuits involved in motor learning and motor coordination.PMID: 28639422 [PubMed… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-24
  • Autoimmune episodic ataxia in patients with anti-CASPR2 antibody-associated encephalitis.
    Related ArticlesAutoimmune episodic ataxia in patients with anti-CASPR2 antibody-associated encephalitis. Neurol Neuroimmunol Neuroinflamm. 2017 Jul;4(4):e371 Authors: Joubert B, Gobert F, Thomas L, Saint-Martin M, Desestret V, Convers P, Rogemond V, Picard G, Ducray F, Psimaras D, Antoine JC, Delattre JY, Honnorat J Abstract OBJECTIVE: To report paroxysmal episodes of cerebellar ataxia in a patient with anti-contactin-associated protein-like 2 (CASPR2) antibody-related autoimmune encephalitis and to search for similar paroxysmal ataxia in a cohort of patients with anti-CASPR2 antibody-associated autoimmune encephalitis. METHODS: We report a patient with paroxysmal episodes of cerebellar ataxia observed during autoimmune encephalitis with anti-CASPR2 antibodies. In addition, clinical analysis was performed in a retrospective cohort of 37 patients with anti-CASPR2 antibodies to search for transient episodes of ataxia. Paroxysmal symptoms were further specified from the referral physicians, the patients, or their relatives. RESULTS: A 61-year-old man with limbic encephalitis and anti-CASPR2 antibodies developed stereotyped paroxysmal episodes of cerebellar ataxia, including gait imbalance, dysarthria, and dysmetria, 1 month after the onset of the encephalitis. The ataxic episodes were specifically triggered by orthostatism and emotions. Both limbic symptoms and transient ataxic episodes resolved after treatment with steroids and IV cyclophosphamide. Among 37 other patients with anti-CASPR2 antibodies, we identified 5 additional cases with similar paroxysmal ataxic episodes that included gait imbalance (5 cases), slurred speech (3 cases), limb dysmetria (3 cases), and nystagmus (1 case). All had concomitant limbic encephalitis. Paroxysmal ataxia was not observed in patients with neuromyotonia or Morvan syndrome. Triggering factors (orthostatism or anger) were reported in… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-24
  • Neuropsychiatric manifestations in inflammatory neuropathies: A systematic review.
    Related ArticlesNeuropsychiatric manifestations in inflammatory neuropathies: A systematic review. Muscle Nerve. 2016 Jun;54(1):1-8 Authors: Rajabally YA, Seri S, Cavanna AE Abstract We conducted a systematic literature review on psychological and behavioral comorbidities in patients with inflammatory neuropathies. In Guillain-Barré syndrome (GBS), psychotic symptoms are reported during early stages in 30% of patients. Typical associations include mechanical ventilation, autonomic dysfunction, inability to communicate, and severe weakness. Anxiety and depression are frequent comorbidities. Anxiety may increase post-hospital admissions and be a predictor of mechanical ventilation. Posttraumatic stress disorder may affect up to 20% of ventilated patients. Sleep disturbances are common in early-stage GBS, affecting up to 50% of patients. In chronic inflammatory demyelinating polyradiculoneuropathy, memory and quality of sleep may be impaired. An independent link between depression and pretreatment upper limb disability and ascites was reported in POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin) syndrome, with an association with early death. Hematological treatment of POEMS appears effective on depression. Published literature on psychological/behavioral manifestations in inflammatory neuropathies remains scarce, and further research is needed. Muscle Nerve 54: 1-8, 2016. PMID: 26999767 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-24
  • A Functional and Neuropathological Testing Paradigm Reveals New Disability-Based Parameters and Histological Features for P0180-190-Induced Experimental Autoimmune Neuritis in C57BL/6 Mice.
    Related ArticlesA Functional and Neuropathological Testing Paradigm Reveals New Disability-Based Parameters and Histological Features for P0180-190-Induced Experimental Autoimmune Neuritis in C57BL/6 Mice. J Neuropathol Exp Neurol. 2017 Feb 01;76(2):89-100 Authors: Gonsalvez DG, De Silva M, Wood RJ, Giuffrida L, Kilpatrick TJ, Murray SS, Xiao J Abstract We assessed novel disability-based parameters and neuropathological features of the P0180-190 peptide-induced model of experimental autoimmune neuritis (EAN) in C57BL/6 mice. We show that functional assessments such as running capacity provide a more sensitive method for detecting alterations in disease severity than a classical clinical scoring paradigm. We performed detailed ultrastructural analysis and show for the first time that tomaculous neuropathy is a neuropathological feature of this disease model. In addition, we demonstrate that ultrastructural assessments of myelin pathology are sufficiently sensitive to detect significant differences in both mean G-ratio and mean axon diameter between mice with EAN induced with different doses of pertussis toxin. In summary, we have established a comprehensive assessment paradigm for discriminating variations in disease severity and the extent of myelin pathology in this model. Our findings indicate that this model is a powerful tool to study the pathogenesis of human peripheral demyelinating neuropathies and that this assessment paradigm could be used to determine the efficacy of potential therapies that aim to promote myelin repair and protect against nerve damage in autoimmune neuritides.PMID: 28082327 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-24
  • Frequent laboratory abnormalities in CIDP patients.
    Related ArticlesFrequent laboratory abnormalities in CIDP patients. Muscle Nerve. 2016 Jun;53(6):862-5 Authors: Abraham A, Albulaihe H, Alabdali M, Qrimli M, Breiner A, Barnett C, Katzberg HD, Lovblom LE, Perkins BA, Bril V Abstract INTRODUCTION: The role of screening laboratory tests in chronic inflammatory demyelinating polyneuropathy (CIDP) is currently unknown. The objectives of this study are to explore common laboratory test abnormalities in CIDP patients. METHODS: CIDP subjects attending the Neuromuscular Clinic between 01/2013 and 12/2014 were evaluated. Demographic data, clinical history, physical examination, and laboratory test results were extracted from their charts. RESULTS: Seventy-nine charts were reviewed. Mean age was 61 ± 11 years. Most (84%) CIDP patients had laboratory test abnormalities; the most frequent were paraproteinemia (29%) and elevated HbA1C (28%) and creatine kinase (27%). Additional abnormalities included anemia in 19%, and elevated anti-neutrophil cytoplasmic antibody, erythrocyte sedimentation rate, and urate in 17%, elevated antinuclear antibodies, rheumatoid factor, and thyroid-stimulating hormone in 11%, and abnormal C3 in 10%. CONCLUSIONS: Laboratory test abnormalities were found in most CIDP patients. The most common were paraproteinemia, higher than expected frequency of diabetes, and unexpected CK elevation. Additional abnormalities included anemia, high urate levels, and common biomarkers for vasculitic neuropathies. Muscle Nerve 53: 862-865, 2016.PMID: 26576014 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-24
  • Causes of neuropathy in patients referred as “idiopathic neuropathy”.
    Related ArticlesCauses of neuropathy in patients referred as "idiopathic neuropathy". Muscle Nerve. 2016 Jun;53(6):856-61 Authors: Farhad K, Traub R, Ruzhansky KM, Brannagan TH Abstract INTRODUCTION: The etiology of neuropathy was idiopathic in 20%-30% of patients despite thorough investigation, based on results from the 1980s and 1990s. Since then, new etiologies have been recognized, and skin biopsy has been used to confirm small-fiber neuropathy. METHODS: The authors reviewed the charts of 373 patients with idiopathic neuropathy who were referred to a neuropathy center between 2002 and 2012. RESULTS: Among the 284 eligible patients, 93 (32.7%) remained idiopathic. The most common cause was impaired glucose metabolism (72 patients, 25.3%), including diabetes in 26 and prediabetes in 46. Other etiologies were chronic inflammatory demyelinating polyneuropathy (CIDP) in 57 (20%) and monoclonal gammopathy in 20 (7%), as well as toxic, Sjögren disease, celiac disease, other immune-mediated diseases, vitamin B12 deficiency, amyloidosis, vitamin B1 and B6 deficiency, vasculitis, hypothyroidism, hereditary, Lyme disease, and anti-sulfatide antibody. CONCLUSIONS: The major causes of undiagnosed neuropathies were impaired glucose metabolism, CIDP, and monoclonal gammopathies. Despite thorough evaluation 32.7% remained idiopathic. Muscle Nerve 53: 856-861, 2016.PMID: 26561790 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-24
  • The development of chronic inflammatory demyelinating polyneuropathy during adalimumab treatment in a patient with psoriasis vulgaris.
    Related ArticlesThe development of chronic inflammatory demyelinating polyneuropathy during adalimumab treatment in a patient with psoriasis vulgaris. Eur J Dermatol. 2016 Aug 01;26(4):404-5 Authors: Nakao M, Asano Y, Nakamura K, Shida R, Takahashi T, Yoshizaki A, Mitsui A, Shibata S, Araki M, Watanabe R, Ikawa Y, Toyoda C, Oka H, Sato S PMID: 27086491 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-24
  • Association between acute motor axonal neuropathy and septic shock due to Acinetobacter baumannii.
    Related ArticlesAssociation between acute motor axonal neuropathy and septic shock due to Acinetobacter baumannii. Infez Med. 2015 Dec;23(4):349-52 Authors: Toscani L, Guarducci D, Matà S, Furlan T, Ballo P Abstract In this report, we describe a case of acute motoral axonal neuropathy (AMAN) following septic shock due to Acinetobacter baumannii. The aetiology of AMAN is still not fully clarified. An association with a potential infection by Campylobacter jejuni, resulting in stimulation of autoimmune response against gangliosides mediated by a phenomenon of molecular mimicry, is believed to play a major role. Since the lipopolysaccharide of A. baumannii has a structure that is similar to that of C. jejuni, we hypothesise that the infection by A. baumannii in our patient may have had a pathogenic role in the development of the neurological picture via a mechanism of molecular mimicry. PMID: 26700086 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-24
  • Multifocal Motor Neuropathy Associated With Infliximab: A Case Report and a Literature Review.
    Multifocal Motor Neuropathy Associated With Infliximab: A Case Report and a Literature Review. Neurologist. 2017 Jul;22(4):144-146 Authors: Bayrak AO, Ulusoy H, Bolat N, Doğan B, Ozbenli T Abstract Multifocal motor neuropathy with conduction block (MMN-CB) is purely a motor neuropathy with progressive weakness that is characteristically caused by conduction blocks. Association with antiganglioside antibodies and a good response to immunomodulating therapies suggest an autoimmune etiology. In rare cases, MMN-CB has been reported as an adverse effect of infliximab, a tumor necrosis factor-α blocker. We present a case of MMN-CB due to infliximab in a 45-year-old man with psoriatic arthritis who was exposed to the drug for 2 years because of a delayed diagnosis. We emphasize the possibility of this adverse effect and the importance of detailed electrophysiological examinations, which is supported by a review of the literature.PMID: 28644258 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-24
  • Incomplete Miller-Fisher Syndrome with Advanced Stage Burkitt Lymphoma.
    Related ArticlesIncomplete Miller-Fisher Syndrome with Advanced Stage Burkitt Lymphoma. Indian Pediatr. 2017 May 15;54(5):413-415 Authors: Özdemir ZC, Kar YD, Yarar C, Þaylýsoy S, Bör Ö Abstract BACKGROUND: Lymphoma-associated incomplete Miller-Fisher syndrome is very rare. CASE CHARACTERISTICS: An 11-year-old boy who initially presented with headache, left ptosis, diplopia and weakness. Neurologic examination indicated left sided ptosis with ophthalmoplegia. OBSERVATIONS: Cerebral imaging and cerebrospinal fluid examinations were normal. Magnetic resonance imaging of the abdomen showed a mass lesion in the ileal loops. A bone marrow biopsy showed infiltration by Burkitt's lymphoma. MESSAGE: Burkitt lymphoma may present with incomplete Miller Fisher syndrome.PMID: 28601853 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-06-24