Project description:Clinical History:A 57-year old woman presented with left hand pain, periodic leg movement during sleep, gradual onset of stiffness, clumsiness, and falls. Neurological examination showed: generalized rigidity and bradykinesia. There was left hand dystonic posturing and ideomotor apraxia, as well as mirror movements of upper limbs and stimulus-sensitive myoclonus. The patient had a high-pitched voice and hypophonia (Video S1). Discussion:Experts discuss localization and the syndromic diagnosis and predict the underlying pathology. The pathological diagnosis is then provided and clinical learning points are considered.
Project description:Prevaccination and 6-week postvaccination samples from the immunogenicity substudy (n = 2269) of the zoster vaccine (ZV) efficacy trial (N = 22 439) in 50-59-year-old subjects were examined for varicella-zoster virus-specific antibody responses to vaccination. The varicella-zoster virus geometric mean titer (GMT) and geometric mean fold rise were higher in ZV recipients than in placebo recipients (GMT, 660.0 vs 293.1 glycoprotein enzyme-linked immunosorbent assay units/mL [P < .001], respectively; geometric mean fold rise, 2.31 vs 1.00 [P < .025]). In each group there was a strong inverse correlation between postvaccination GMT and risk of subsequent herpes zoster. Although these data provide strong evidence that relates ZV-induced antibody and the risk of herpes zoster, a protective threshold was not determined. Clinical Trials Registration. NCT00534248.
Project description:Mutations in the SEPSECS gene are associated with pontocerebellar hypoplasia type 2D. Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare autosomal recessive neurodegenerative disorders, mainly affecting pons and cerebellum. Patients have severe motor and cognitive impairments and often die during infancy. Here, we report a 23-year-old woman with slowly progressive cerebellar ataxia and cognitive impairment, in whom a homozygous missense mutation in the SEPSECS gene (c.1321G>A; p.Gly441Arg) was identified with whole exome sequencing. Our findings underline that defects in selenoprotein synthesis can also result in milder cerebellar atrophy presenting at a later age.
Project description:An 82-year-old woman with a history of LD stage SCLC of her left upper lobe nine years earlier, had been treated with five cycles chemotherapy cyclophosphamide, doxorubicin and etoposide (CDE)) resulting in a complete response. She received prophylactic cranial irradiation. Now she presented with a palpable mass in the right supra-clavicular fossa. Her further medical history revealed coronary vascular disease, for which she underwent PTCA; mild aortic valve stenosis and a pacemaker to treat a third degree AV block. She has NYHA class II. She had a history of cigarette smoking but she stopped when SCLC was diagnosed nine years ago. She had no dyspnea
Project description:An immunocompetent adult received corticosteroids for chest pain, which later was clinically found to be herpes zoster (HZ). She developed severe disease and rapid viral dissemination that elicited an exceptionally strong varicella zoster virus-specific B-cell and CD8 T-cell response. Clinicians should consider atypical HZ presentation prior to corticosteroid administration.
Project description:Herein we describe an episode of focal varicella-zoster virus (VZV) encephalitis in a healthy young man with neither rash nor radicular pain. The symptoms began with headaches and seizures, after which magnetic resonance imaging detected a single hyperintense lesion in the left temporal lobe. Because of the provisional diagnosis of a brain tumor, the lesion was excised and submitted for pathological examination. No tumor was found. But the tissue immunostained positively for VZV antigens, and wild-type VZV sequences were detected. In short, this case represents VZV reactivation, most likely in the trigeminal ganglion, in the absence of clinical herpes zoster.
Project description:The main goal of the study was to measure the epigenetic age (also known as DNA methylation age) of these tissues. Toward this end, we used the epigenetic clock software described in Horvath S (n=2013) DNA methylation age of human tissues and cell types. Genome Biology.2013, 14:R115. DOI: 10.1186/10.1186/gb-2013-14-10-r115 PMID: 24138928
Project description:Primary infection by varicella zoster virus (VZV) typically results in childhood chickenpox, at which time latency is established in the neurons of the cranial nerve, dorsal root and autonomic ganglia along the entire neuraxis. During latency, the histone-associated virus genome assumes a circular episomal configuration from which transcription is epigenetically regulated. The lack of an animal model in which VZV latency and reactivation can be studied, along with the difficulty in obtaining high-titer cell-free virus, has limited much of our understanding of VZV latency to descriptive studies of ganglia removed at autopsy and analogy to HSV-1, the prototype alphaherpesvirus. However, the lack of miRNA, detectable latency-associated transcript and T-cell surveillance during VZV latency highlight basic differences between the two neurotropic herpesviruses. This article focuses on VZV latency: establishment, maintenance and reactivation. Comparisons are made with HSV-1, with specific attention to differences that make these viruses unique human pathogens.