Infeção fetal não primária por citomegalovírus

Cytomegalovirus (CMV) is the most common congenital viral infection, causing hearing, visual and psychomotor impairment. Preexisting maternal CMV immunity substantially reduces, but not eliminates, the risk of fetal infection and affectation. This article is about a case of nonprimary maternal CMV infection during pregnancy, with vertical transmission, resulting in severe fetal affectation. Preconceptional analysis indicated maternal CMV past infection. Pregnancy progressed uneventfully until the 20th week ultrasound (US), which revealed cerebral abnormalities: thin and hyperechogenic cerebral cortex with prominent lateral ventricles, bilateral periventricular hyperechogenicities, cerebellar vermis hypoplasia and absent corpus callosum. The MRI suggested these findings were compatible with congenital infection rather than primary brain malformation.The fetal karyotype was normal. The title of CMV's IgG antibodies almost tripled. Since the first semester, analysis of the polymerase chain reaction (PCR) for CMV DNA in the amniotic fluid was negative. The pregnancy was terminated at 23 weeks. Neuropathological findings at autopsy showed severe brain lesions associated with CMV infection.O citomegalovírus (CMV) é a infeção viral congénita que mais comumente causa deficiência auditiva, visual e psicomotora. A preexistência de imunidade materna reduz substancialmente, mas não elimina, o risco de infeção e afetação fetal. Trata-se de um caso de infeção materna não primária por CMV durante a gravidez, com transmissão vertical, resultando em afetação fetal severa. As análises preconcepção indicavam infecção passada por CMV. A gravidez decorreu sem intercorrências até a ecografia efetuada na 20ª semana, que revelou alterações cerebrais: córtex cerebral fino e hiperecogénico com ventrículos laterais proeminentes, hiperecogenecidades periventriculares bilaterais, hipoplasia do vérmis cerebeloso e ausência de corpo caloso. A ressonância magnética sugeriu que estes achados eram mais favoráveis a uma infeção congénita do que com uma malformação cerebral primária. O cariótipo fetal era normal. O título de anticorpos IgG para CMV havia triplicado desde a dosagem do primeiro trimestre. O PCR para o DNA do CMV no líquido amniótico foi negativo. A gravidez foi interrompida na 23ª semana. Os achados neuropatológicos na autópsia mostraram lesões cerebrais severas associadas a infeção por CMV.info:eu-repo/semantics/publishedVersio

McArdle disease presenting with rhabdomyolisis and acute kidney injury

A doença de McArdle apresenta-se tipicamente por mialgias, intolerância aos esforços, cãibras e mioglobinúria na infância ou jovens adultos. A deficiência hereditária da enzima miofosforílase incapacita a degradação de glicogénio, com consequente acumulação no tecido muscular e défice energético. A rabdomiólise pode ocorrer e complicar-se de lesão renal aguda mas raramente, em cerca de 11% dos casos, é manifestação inicial da doença. Apresentamos um caso de Doença de McArdle num paciente de 38 anos de idade. Tinha antecedentes de mialgias, intolerância aos esforços e episódio isolado de mioglobinúria. A doença foi diagnosticada num episódio de rabdomiólise grave complicada de lesão renal aguda oligúrica, com necessidade de hemodiálise. A biópsia renal demonstrou necrose tubular aguda. Apesar da recuperação renal, os marcadores de lise muscular permaneceram elevados. Na suspeita de miopatia metabólica realizou biópsia muscular que revelou deposição subsarcolémica de glicogénio e ausência de atividade da miofosforilase. As miopatias metabólicas devem ser consideradas na abordagem de LRA associada a rabdomiólise severa

Specific configuration of dendritic degeneration in pyramidal neurons of the medial prefrontal cortex induced by differing corticosteroid regimens

We previously demonstrated that hypercorticalism induces pronounced volumetric reductions in the rat medial prefrontal cortex (mPFC) and that these structural changes correlate with deficits in executive function. By applying 3-dimensional analysis of Golgi- Cox--stained material, we now demonstrate that corticosteroids can exert differential effects on dendritic arborizations of pyramidal neurons in lamina II/III of the mPFC. Treatment with the glucocorticoid receptor--selective agonist dexamethasone and with the natural adrenosteroid, corticosterone (CORT), results in significant reductions in the total length of apical dendrites in the pyramidal neurons in lamina II/III of the anterior cingulate/prelimbic and infralimbic cortices. Interestingly, although these treatments do not affect the number of dendritic branches, they are associated with impoverished arborizations in their distal portions and, in CORTtreated animals, with increased branching in the middle portions of the apical dendritic tree. Deprivation of corticosteroids by adrenalectomy leads to decreases in total apical dendritic length and spine number, but in this case, dendritic impoverishment was restricted to the middle/proximal segments of the dendritic trees. None of the treatments influenced the architecture of the basal dendrites. These results add to our knowledge of the morphological substrates through which corticosteroids may disrupt mPFC-dependent behaviors

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Ryanodine myopathies without central cores-clinical, histopathologic, and genetic description of three cases.

BACKGROUND: Mutations in ryanodine receptor 1 gene (RYR1) are frequent causes of myopathies. They classically present with central core disease; however, clinical variability and histopathologic overlap are being increasingly recognized. PATIENTS: Patient 1 is a 15-year-old girl with mild proximal, four-limb weakness from age 5, presenting with a progressive scoliosis starting at age 10. Patient 2 is an 18-year-old girl with progressively worsening muscle hypotrophy and mild proximal, four-limb weakness. She developed a rapidly progressive scoliosis from age 11 and needed surgical treatment at age 14 years. Patient 3 is an 11-year-old boy with moderate proximal limb weakness and progressive neck flexor weakness, first noticed at age 2. Muscle biopsies revealed type 1 fiber predominance (Patients 1 and 2) or abnormal type 1 fiber uniformity (Patient 3). Different RYR1 variants were identified in all patients. In Patients 1 and 3, these changes were validated as being pathogenic. CONCLUSIONS: These patients illustrate early-onset, progressive myopathies with predominant axial involvement. Histopathologic findings were abnormal but not specific for a diagnosis, particularly central core myopathy. Genetic testing helped broaden the range of phenotypes included in the RYR1-related myopathies. Our patients reinforce the need to recognize the broad histopathologic variability of RYR1-related myopathies and sometimes lack of pathognomonic findings that may reduce the diagnostic threshold of this disease. We suggest that the predominance of type 1 fibers and involvement of axial muscles may be an important element to consider the RYR1 gene as candidate

Acute ischemic stroke secondary to glioblastoma. A case report

Glioblastoma is a malignant infiltrative glial tumor occurring most often over 50 years of age, with diverse clinical presentations. We describe a case of temporal lobe glioblastoma with a rare presentation as an acute ischemic stroke, discussing the imaging and histopathological findings, and reviewing the literature. A 77-year-old woman had sudden onset of left hemiparesis and hemihypoesthesia. The neuroradiological studies revealed an acute ischemic lesion in the right lenticulostriate arteries territory and a right anterior temporal lobe tumor, enhancing heterogeneously after contrast with enhancement of the right middle cerebral artery wall. Histopathological analysis of the resected temporal lesion revealed a glioblastoma multiforme with tumoral infiltration of the vascular wall. Glioblastoma should be considered in the etiology of acute ischemic stroke, where neuroimaging plays an important diagnostic role, enabling a more immediate therapeutic approach, with a consequent impact on survival

Exonization of an Intronic LINE-1 Element Causing Becker Muscular Dystrophy as a Novel Mutational Mechanism in Dystrophin Gene

A broad mutational spectrum in the dystrophin (DMD) gene, from large deletions/duplications to point mutations, causes Duchenne/Becker muscular dystrophy (D/BMD). Comprehensive genotyping is particularly relevant considering the mutation-centered therapies for dystrophinopathies. We report the genetic characterization of a patient with disease onset at age 13 years, elevated creatine kinase levels and reduced dystrophin labeling, where multiplex-ligation probe amplification (MLPA) and genomic sequencing failed to detect pathogenic variants. Bioinformatic, transcriptomic (real time PCR, RT-PCR), and genomic approaches (Southern blot, long-range PCR, and single molecule real-time sequencing) were used to characterize the mutation. An aberrant transcript was identified, containing a 103-nucleotide insertion between exons 51 and 52, with no similarity with the DMD gene. This corresponded to the partial exonization of a long interspersed nuclear element (LINE-1), disrupting the open reading frame. Further characterization identified a complete LINE-1 (~6 kb with typical hallmarks) deeply inserted in intron 51. Haplotyping and segregation analysis demonstrated that the mutation had a de novo origin. Besides underscoring the importance of mRNA studies in genetically unsolved cases, this is the first report of a disease-causing fully intronic LINE-1 element in DMD, adding to the diversity of mutational events that give rise to D/BMD.The authors are grateful to the patient and his family for accepting to collaborate in this work. The authors also wish to thank Dr. Stefan White and Yavuz Ariyurek from the Leiden University Medical Center (Netherlands) for facilitating the Single Molecule Real Time (PacBio) sequencing work. A research grant was attributed to J.O. by “Fundo para a Investigação e Desenvolvimento do Centro Hospitalar do Porto” (Grant ref.: 336-13(196-DEFI/285-CES)). The work was also supported by the authors’ Institutions and in part by UMIB, which is funded by “Fundação para a Ciência e Tecnologia (FCT)” under the Pest-OE/SAU/UI0215/2014.info:eu-repo/semantics/publishedVersio

Cadherin expression and emt: A focus on gliomas

Cadherins are calcium-binding proteins with a pivotal role in cell adhesion and tissue homeostasis. The cadherin-dependent mechanisms of cell adhesion and migration are exploited by cancer cells, contributing to tumor invasiveness and dissemination. In particular, cadherin switch is a hallmark of epithelial to mesenchymal transition, a complex development process vastly described in the progression of most epithelial cancers. This is characterized by drastic changes in cell polarity, adhesion, and motility, which lead from an E-cadherin positive differentiated epithelial state into a dedifferentiated mesenchymal-like state, prone to metastization and defined by N-cadherin expression. Although vastly explored in epithelial cancers, how these mechanisms contribute to the pathogenesis of other non-epithelial tumor types is poorly understood. Herein, the current knowledge on cadherin expression in normal development in parallel to tumor pathogenesis is reviewed, focusing on epithelial to mesenchymal transition. Emphasis is taken in the unascertained cadherin expression in CNS tumors, particularly in gliomas, where the potential contribution of an epithelial-to-mesenchymal-like process to glioma genesis and how this may be associated with changes in cadherin expression is discussed.This work was funded by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by FCT—Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia e Ensino Superior under the project FCT/02/SAICT/2017/030625

Neuropathology of central nervous system involvement in TTR amyloidosis

Hereditary transthyretin amyloidosis (ATTRv) is a systemic disease caused by the accumulation of misfolded transthyretin (TTR). It usually presents with an adult-onset progressive axonal peripheral neuropathy and cardiomyopathy. In the central nervous system (CNS), variant TTR is produced by the choroid plexus and accumulates in the leptomeninges. CNS symptoms have been increasingly recognized in this population, including transient focal neurological episodes and stroke, particularly in patients with the V30M mutation and longstanding disease. The prevalence, pathophysiology, and progression of CNS involvement remain to be clarified. The present work explores if there is a recognizable sequence of CNS TTR deposition in ATTRv. We studied the topographical and severity distribution of TTR deposition in 16 patients with ATTRv, aged 27–69 years and with a mean disease duration of 10.9 years (range: 3–29). Our results suggest that CNS pathological involvement in V30M ATTRv occurs early in the disease course, probably starting in pre-symptomatic phases, and follows a distinct sequence. Leptomeninges and subarachnoid meningeal vessels are affected earlier, then followed by perforating cortical vessels and subpial deposition, and finally by deposition in the subependymal and basal ganglia vessels near the ependymal lining. Brainstem and spinal cord show early and severe involvement, with amyloid subpial deposition already seen in initial stages. Despite massive superficial amyloid deposition, no parenchymal deposition outside subpial or subependymal regions was found. Additionally, vascular lesions or superficial cortical siderosis were not frequent. Future studies with more patients from different populations and TTR mutations will be important to confirm these findings. Defining stages of TTR pathology in the CNS may be useful to better understand pathogenic mechanisms leading to symptoms and to interpret neuroimaging biomarkers.Unit for Multidisciplinary Research in Biomedicine (UMIB) is funded by the Foundation for Science and Technology (FCT) Portugal (Grant Numbers UIDB/00215/2020, and UIDP/00215/2020). We acknowledge Portuguese Brain Bank for tissue samples supply. The authors thank José Ferreira for the help in editing the manuscript figures

Evidence of amyloid-β cerebral amyloid angiopathy transmission through neurosurgery

Amyloid-β (Aβ) is a peptide deposited in the brain parenchyma in Alzheimer’s disease and in cerebral blood vessels, causing cerebral amyloid angiopathy (CAA). Aβ pathology is transmissible experimentally in animals and through medical procedures in humans, such as contaminated growth hormone or dura mater transplantation in the context of iatrogenic prion disease. Here, we present four patients who underwent neurosurgical procedures during childhood or teenage years and presented with intracerebral haemorrhage approximately three decades later, caused by severe CAA. None of these patients carried pathogenic mutations associated with early Aβ pathology development. In addition, we identified in the literature four patients with a history of neurosurgical intervention and subsequent development of CAA. These findings raise the possibility that Aβ pathology may be transmissible, as prion disease is, through neurosurgical procedures