Eosinophilic Fasciitis: an Atypical Presentation of a Rare Disease

Objectives: We report an atypical presentation of eosinophilic fasciitis and provide a concise overview of the literature. Materials and Methods: Clinical and laboratory findings in a patient presenting with fever and skin induration were recorded. A deep muscle biopsy was performed in order to confirm the diagnosis. Results: A spontaneous favourable clinical and radiological evolution was observed. Conclusion: The diagnosis of eosinophilic fasciitis is challenging due to the lack of pathognomonic signs and symptoms. As spontaneous resolution has been described, watchful waiting is defendable depending on the clinical presentation. Although magnetic resonance imaging (MRI) can be useful in establishing the diagnosis, a deep muscle biopsy remains the gold standard diagnostic tool

Loss of DPP6 in neurodegenerative dementia : a genetic player in the dysfunction of neuronal excitability

Emerging evidence suggested a converging mechanism in neurodegenerative brain diseases (NBD) involving early neuronal network dysfunctions and alterations in the homeostasis of neuronal firing as culprits of neurodegeneration. In this study, we used paired-end short-read and direct long-read whole genome sequencing to investigate an unresolved autosomal dominant dementia family significantly linked to 7q36. We identified and validated a chromosomal inversion of ca. 4Mb, segregating on the disease haplotype and disrupting the coding sequence of dipeptidyl-peptidase 6 gene (DPP6). DPP6 resequencing identified significantly more rare variants-nonsense, frame-shift, and missense-in early-onset Alzheimer's disease (EOAD, p value = 0.03, OR = 2.21 95% CI 1.05-4.82) and frontotemporal dementia (FTD, p = 0.006, OR = 2.59, 95% CI 1.28-5.49) patient cohorts. DPP6 is a type II transmembrane protein with a highly structured extracellular domain and is mainly expressed in brain, where it binds to the potassium channel K(v)4.2 enhancing its expression, regulating its gating properties and controlling the dendritic excitability of hippocampal neurons. Using in vitro modeling, we showed that the missense variants found in patients destabilize DPP6 and reduce its membrane expression (p < 0.001 and p < 0.0001) leading to a loss of protein. Reduced DPP6 and/or K(v)4.2 expression was also detected in brain tissue of missense variant carriers. Loss of DPP6 is known to cause neuronal hyperexcitability and behavioral alterations in Dpp6-KO mice. Taken together, the results of our genomic, genetic, expression and modeling analyses, provided direct evidence supporting the involvement of DPP6 loss in dementia. We propose that loss of function variants have a higher penetrance and disease impact, whereas the missense variants have a variable risk contribution to disease that can vary from high to low penetrance. Our findings of DPP6, as novel gene in dementia, strengthen the involvement of neuronal hyperexcitability and alteration in the homeostasis of neuronal firing as a disease mechanism to further investigate

Characterisation of irradiated thin silicon sensors for the CMS phase II pixel upgrade

The high luminosity upgrade of the Large Hadron Collider, foreseen for 2026, necessitates the replacement of the CMS experiment's silicon tracker. The innermost layer of the new pixel detector will be exposed to severe radiation, corresponding to a 1 MeV neutron equivalent fluence of up to Phi(eq) = 2x10(16) cm(-2), and an ionising dose of approximate to 5 MGy after an integrated luminosity of 3000 fb(-1). Thin, planar silicon sensors are good candidates for this application, since the degradation of the signal produced by traversing particles is less severe than for thicker devices. In this paper, the results obtained from the characterisation of 100 and 200 mu m thick p-bulk pad diodes and strip sensors irradiated up to fluences of Phi(eq) = 1.3 x 10(16) cm(-2) are shown.Peer reviewe

TBK1 Mutation Spectrum in an Extended European Patient Cohort with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

We investigated the mutation spectrum of the TANK-Binding Kinase 1 (TBK1) gene and its associated phenotypic spectrum by exonic resequencing of TBK1 in a cohort of 2,538 patients with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), or FTD plus ALS, ascertained within the European Early-Onset Dementia Consortium. We assessed pathogenicity of predicted protein-truncating mutations by measuring loss of RNA expression. Functional effect of in-frame amino acid deletions and missense mutations was further explored in vivo on protein level and in vitro by an NFκB-induced luciferase reporter assay and measuring phosphorylated TBK1. The protein-truncating mutations led to the loss of transcript through nonsense-mediated mRNA decay. For the in-frame amino acid deletions, we demonstrated loss of TBK1 or phosphorylated TBK1 protein. An important fraction of the missense mutations compromised NFκB activation indicating that at least some functions of TBK1 are lost. Although missense mutations were also present in controls, over three times more mutations affecting TBK1 functioning were found in the mutation fraction observed in patients only, suggesting high-risk alleles (P = 0.03). Total mutation frequency for confirmed TBK1 LoF mutations in the European cohort was 0.7%, with frequencies in the clinical subgroups of 0.4% in FTD, 1.3% in ALS, and 3.6% in FTD-ALS

Polymorphous low-grade neuroepithelial tumor of the young: case report of a newly described histopathological entity.

INTRODUCTION : Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described pathological entity featured by a specific histological, immunohistochemical and molecular profile combining an oligodendroglial-like component, a diffuse CD34 expression, and an alteration of the MAP-kinase signalling pathway. That entity was so far rarely described. We would like to report an additional case. [...

Focal neurological deficit with sudden onset as the first manifestation of sarcoidosis: A case report with MRI follow-up

Stroke as a presenting manifestation of sarcoidosis has rarely been reported. This contrasts with the frequent anatomopathological findings of cerebrovascular involvement in neurosarcoidosis. We present a patient who developed acutely a right brachiofacial weakness and dysarthria. Pulmonary sarcoidosis was found. A brain CT and magnetic resonance imaging (MRI) scan disclosed multiple bilateral ischemic, mainly subcortical lesions. Despite a favorable clinical evolution under adequate corticotherapy, an MRI performed 3 months later showed an increased number of the previously observed lesions. This observation suggests that in some cases the evolution of central nervous system sarcoid lesions occurs independently from corticotherapy, and that MRI, in spite of its known great sensitivity in detecting those lesions, may not play a role in the follow-up of some patients with neurosarcoidosis.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Ataxia as the only delayed neurotoxic manifestation of organophosphate insecticide poisoning

A patient is reported presenting a cerebellar disorder developing about 5 weeks after acute exposure to an organophosphate insecticide. Initially no major cholinergic features were observed. The ataxia of delayed onset was not accompanied by clinical or electrophysiological signs of polyneuropathy. The possible pathogenetic mechanisms are reviewed and discussed. This case illustrates the need to closely monitor all patients intoxicated with such chemicals for at least 5 weeks. One should not only keep in mind the well-known late-onset polyneuropathy, but also the less frequent delayed central nervous system effects, even in the milder cases where initial signs of acetylcholine excess are only minimally present or lacking.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Differentiating primary central nervous system (CNS) lymphoma from "butterfly glioma": A case report

SCOPUS: ar.jinfo:eu-repo/semantics/publishe