Aγγειῒτιδα Churg-Strauss σε 64χρονη γυναίκα με διαταραχή βάδισης

Peripheral neuropathy is often a feature of systemic diseases. We report a case of a 64-year-old woman with gait difficulty due to multifocal sensorimotor polyneuropathy which was diagnosed as Churg-Strauss syndrome and presented clinical improvement after oral prednisolone administration. The clinical suspicion of this condition is crucial to early and correct diagnosis.Η περιφερική πολυνευροπάθεια αποτελεί συχνά εύρημα συστηματικών παθήσεων. Παρουσιάζουμε περιστατικό μιας 64χρονης γυναίκας με διαταραχή βάδισης λόγω πολυεστιακής αισθητικοκινητικής πολυνευροπάθειας που διεγνώσθη ως σύνδρομο Churg-Strauss και παρουσίασε βελτίωση μετά την από του στόματος χορήγηση πρεδνιζολόνης. Η κλινική υποψία του συνδρόμου αυτού είναι κρίσιμη για την έγκαιρη διάγνωση και την σωστή θεραπεία του

Immunization with recombinant prion protein leads to partial protection in a murine model of TSEs through a novel mechanism.

Transmissible spongiform encephalopathies are neurodegenerative diseases, which despite fervent research remain incurable. Immunization approaches have shown great potential at providing protection, however tolerance effects hamper active immunization protocols. In this study we evaluated the antigenic potential of various forms of recombinant murine prion protein and estimated their protective efficacy in a mouse model of prion diseases. One of the forms tested provided a significant elongation of survival interval. The elongation was mediated via an acute depletion of mature follicular dendritic cells, which are associated with propagation of the prion infectious agent in the periphery and in part to the development of humoral immunity against prion protein. This unprecedented result could offer new strategies for protection against transmissible encephalopathies as well as other diseases associated with follicular dendritic cells

Correction: Immune Parameters That Distinguish Multiple Sclerosis Patients from Patients with Other Neurological Disorders at Presentation.

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system. Effector T helper cells, mainly Th1 and Th17, cytotoxic T-cells, B-cells, macrophages, microglia, and the cytokines they secrete, are implicated in the initiation and maintenance of a deregulated immune response to myelin antigens and the ensuing immune-mediated demyelination. In this study, we investigated whether signature cytokines exist in MS patients at presentation to gain an insight into the underlying immunopathogenic processes at the early stage of the disease.We collected serum and cerebrospinal fluid (CSF) samples from 123 patients at presentation, eventually diagnosed with MS or non-inflammatory (NIND) or inflammatory neurological diseases (IND) or symptomatic controls (SC). The levels of cytokines IFN-γ, TNF-α, TGF-β1, IL-2, IL-4, IL-6, IL-10 and IL-17 were measured, and cytokine ratios, such as Th1/Th2, Th1/Th17, and Type-1/Type-2, were calculated. All parameters were tested for their correlations with the intrathecal IgG synthesis.Cytokine levels in CSF were lower than in serum in all the patients, with the exception of IL-6. Serum or CSF cytokine levels of MS patients did not differ significantly from NIND or SC, with the exception of serum IFN-γ and TNF-α that were significantly higher in NIND. IND patients presented with the highest levels of all cytokines in serum and CSF, with the exception of serum IL-10 and CSF IL-17. MS patients had a significantly lower serum Th1/Th2 ratio compared to the NIND and IND groups, and significantly lower serum Type-1/Type-2, IFN-γ/IL-10 and CSF Th1/Th17 ratios compared to IND patients. MS patients had a significantly higher CSF IL-17/IL-10 ratio compared to IND patients. The IgG index was higher in MS patients compared to the control groups; the differences reached statistical significance between the MS and the NIND and SC groups. Reiber-Felgenhauer analysis of the QIgG and QAlb indices revealed higher intrathecal IgG synthesis in MS patients, and higher blood-CSF barrier dysfunction in IND patients. The IgG index correlated with CSF IL-4 in MS patients only.We found no signature cytokines or profiles thereof in MS patients at presentation. Only IND patients presented with a clear Th1 cytokine polarization in serum and CSF. The parameters that distinguished MS patients from patients with other neurological disorders were IgG intrathecal synthesis, the IgG index and its correlation with CSF IL-4 levels

New horizons in schizophrenia treatment: autophagy protection is coupled with behavioral improvements in a mouse model of schizophrenia: Autophagy protection is coupled to behavioral improvements in a mousemodel of schizophrenia

International audienceAutophagy plays a key role in the pathophysiology of schizophrenia as manifested by a 40% decrease in BECN1/Beclin 1 mRNA in postmortem hippocampal tissues relative to controls. This decrease was coupled with the deregulation of the essential ADNP (activity-dependent neuroprotector homeobox), a binding partner of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 beta) another major constituent of autophagy. The drug candidate NAP (davunetide), a peptide fragment from ADNP, enhanced the ADNP-LC3B interaction. Parallel genetic studies have linked allelic variation in the gene encoding MAP6/STOP (microtubule-associated protein 6) to schizophrenia, along with altered MAP6/STOP protein expression in the schizophrenic brain and schizophrenic-like behaviors in Map6-deficient mice. In this study, for the first time, we reveal significant decreases in hippocampal Becn1 mRNA and reversal by NAP but not by the antipsychotic clozapine (CLZ) in Map6-deficient (Map6+/-) mice. Normalization of Becn1 expression by NAP was coupled with behavioral protection against hyperlocomotion and cognitive deficits measured in the object recognition test. CLZ reduced hyperlocomotion below control levels and did not significantly affect object recognition. The combination of CLZ and NAP resulted in normalized outcome behaviors. Phase II clinical studies have shown NAP-dependent augmentation of functional activities of daily living coupled with brain protection. The current studies provide a new mechanistic pathway and a novel avenue for drug development

Recognition of PrP on the cell surface.

<p>Transgenic DT40 cells expressing PrP on their surface were stained with sera from 4 mice immunized with agPrP+FA (red, green, purple and cyan histograms) (A) or from 6 mice immunized with sPrP+DnaK+FA (red, green, purple, cyan, orange and brown histograms) (B), to evaluate recognition of PrP on the cell surface. Indigo; 6H4 staining, red negative control (secondary antibody only). Differences in the modes of the histograms between agPrP+FA and sPrP+DnaK+FA mice are statistically significant (T-test, P = 0.330).</p

Sera from sPrP+DnaK mice recognize total PrPSc and sPrP in western blots.

<p>A. 2.5 mg brain equivalent from terminally ill mice were blotted with 6H4 (lanes 1, 2), serum from a mouse immunized with sPrP+DnaK (lanes 3, 4) or with the secondary antibody alone (lanes 5, 6), prior (lanes 1, 3, 5) or ensuing (lanes 2, 4, 6) PrP^Sc enrichment. B. sPrP (1 µg) was blotted with serum from a mouse immunized with sPrP+DnaK (lane 7) or the secondary antibody alone (lane 8).</p

Survival curves of immunized mice.

<p>Naive mice and mice immunized with sPrP+FA, agPrP+FA, PrP-DnaK+FA, sPrP+DnaK+FA or FA alone were challenged with a mouse adapted scrapie strain and sacrificed at terminal point. Mice immunized with agPrP+FA survive significantly longer than naive mice (Mantel-Cox test, P = 0.0033).</p

Cytokines and cytokine ratios measured in patients and controls.

<p>Cytokines and cytokine ratios measured in patients and controls.</p

IgG index (A), QAlb (B) and QIgG (C) values of MS patients and control groups.

<p>The data are presented as box plots with whiskers, showing the median with the upper (75) and lower (25) percentiles. The uncorrected p values are shown where statistical significance was reached. The asterisk (*) denotes statistical significance retained after controlling for type I error.</p