Impact of Different Thymic Pathologies on the Clinical Course of Myasthenia Gravis : A Population Wide Study in Latvia

Publisher Copyright: © 2015 by Anete Zieda.Myasthenia gravis (MG) is an autoimmune disease characterized by autoantibody mediated postsynaptic failure of neuromuscular transmission. The thymus gland has a role in the pathogenesis of MG. The aim of this study was to determine (1) the prevalence of different thymic pathologies in the MG patient population of Latvia; (2) the potential impact of different thymus pathologies on the clinical course of MG; and (3) the effectiveness of surgical treatment of thymic pathologies in Latvia. The results showed that the most common thymus pathology among the patients with MG in Latvia is thymoma. Compared to the published data, the proportion of MG patients diagnosed with thymus hyperplasia in Latvia is very small. Thymus hyperplasia is uncommon among patients 60 years of age and older. MG onset for patients with thymoma is significantly later than that of patients with thymus hyperplasia. Almost all patients with thymoma or thymus hyperplasia develop a generalised form of MG. The presence of a thymus pathology does not significantly affect the electrophysiological test results, clinical symptom severity, frequency of disability or hospitalisation of the patients with MG. Thymectomy in patients with thymoma or thymus hyperplasia has no significant effect on relieving MG symptoms.publishersversionPeer reviewe

Structural and ultrastructural alterations in human olfactory pathways and possible associations with herpesvirus 6 infection

Publisher Copyright: © 2017 Skuja et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Structural and ultrastructural alterations in human olfactory pathways and putative associations with human herpesvirus 6 (HHV-6) infection were studied. The olfactory bulb/tract samples from 20 subjects with an unspecified encephalopathy determined by pathomorphological examination of the brain autopsy, 17 healthy age-matched and 16 younger controls were used. HHV-6 DNA was detected in 60, 29, and 19% of cases in these groups, respectively. In the whole encephalopathy group, significantly more HHV-6 positive neurons and oligodendrocytes were found in the gray matter, whereas, significantly more HHV-6 positive astrocytes, oligodendrocytes, microglia/macrophages and endothelial cells were found in the white matter. Additionally, significantly more HHV-6 positive astrocytes and, in particular, oligodendrocytes were found in the white matter when compared to the gray matter. Furthermore, when only HHV-6 PCR+ encephalopathy cases were studied, we observed similar but stronger associations between HHV-6 positive oligodendrocytes and CD68 positive cells in the white matter. Cellular alterations were additionally evidenced by anti-S100 immunostaining, demonstrating a significantly higher number of S100 positive cells in the gray matter of the whole encephalopathy group when compared to the young controls, and in the white matter when compared to both control groups. In spite the decreased S100 expression in the PCR+ encephalopathy group when compared to PCR- cases and controls, groups demonstrated significantly higher number of S100 positive cells in the white compared to the gray matter. Ultrastructural changes confirming the damage of myelin included irregularity of membranes and ballooning of paranodal loops. This study shows that among the cellular targets of the nervous system, HHV-6 most severely affects oligodendrocytes and the myelin made by them.publishersversionPeer reviewe

Diagnostic Bias in the COVID-19 Pandemic: A Series of Short Cases

During the COVID-19 pandemic, healthcare systems have faced unprecedented pressures. One challenge has been to promptly recognise non-COVID-19 conditions. Cognitive bias due to the availability heuristic may cause difficulties in reaching the correct diagnosis. Confirmation bias may also affect imaging interpretation. We report three cases with an alternative final diagnosis in whom COVID-19 was initially suspected: (a) Pneumocystis jirovecii pneumonia with unrecognised HIV infection; (b) pulmonary lymphangitis carcinomatosis; and (c) ST elevation myocardial infarction causing acute pulmonary oedema. To help mitigate bias, there is no substitute for thoughtful clinical assessment and critical appraisal when evaluating new information and formulating the differential diagnosis

TEM.

<p><b>Ultrastructural changes observed in the olfactory pathways of HHV-6 positive subjects.</b> (A) A fragment of neuron revealing irregularly dilated perinuclear space (white arrow), remarkable decrease of rough endoplasmic reticulum, polyribosomes (black arrows), mitochondria and vacuoles (arrowhead). (B) A fragment of astrocyte nucleus, an electron-lucent perinuclear cytoplasm (white arrow) with scanty intermediate filaments (black arrow). (C) Two oligodendrocytes with characteristically structured nuclear chromatin, dilated perinuclear space (white arrow) surrounded by a narrow rim of cytoplasm containing some swollen mitochondria (black arrows), cisternae of rough endoplasmic reticulum, and ribosomes. Myelin layer surrounding axons is thin; profiles of the paranodal loops are greatly varying. (D) Some myelinated axons and dendritic processes. Myelin layer of axons shows irregularity and ballooning of paranodal loops (black arrows).</p

Quantitative comparison of the IHC results between the gray and the white matter.

<p>(A) Distribution of HHV-6 positive glial cells in the encephalopathy group. (B) Distribution of S100 positive glial cells in the encephalopathy group. (C) Distribution of CD68 positive activated microglial cells/macrophages in the encephalopathy group and both control groups.</p

IHC.

<p>(A) Immunoreactivity observed in the olfactory tract of HHV-6 positive subjects: HHV-6 immunopositivity in the astrocytes (white arrow) and oligodendrocytes (black arrow), × 250. Confocal microscopy, representative image of HHV-6, insert, × 1000. (B) S100 immunopositivity in the cells of the olfactory bulb: positive neurons (white arrows), negative neurons (arrowheads), astrocytes (black arrows), × 200. (C) S100 and GFAP immunopositivity in the astrocytes (white arrows) and S100 positive oligodendrocytes (black arrows) of the olfactory tract, × 250; insert, × 200. (D) CD68 immunopositivity in the activated microglial cells/macrophages close to the neurons (black arrows) and oligodendrocytes (white arrow) of the olfactory bulb, × 200. (E) CD68 immunopositivity in the activated microglial cells/macrophages (black arrows) and MBP expression (white arrows) of the olfactory tract, × 250; insert, × 100.</p

Cellular localization of S100 antigen in the olfactory pathways.

<p>Cellular localization of S100 antigen in the olfactory pathways.</p

Prevalence of the CD68 positive activated microglial cells/macrophages.

<p>Prevalence of the CD68 positive activated microglial cells/macrophages.</p

Quantitative comparison of the IHC results between PCR⁺ and PCR^- cases.

<p>(A) Distribution of HHV-6 positive astrocytes and oligodendrocytes in the white matter of the encephalopathy group. (B) Distribution of HHV-6 positive oligodendrocytes in the white matter of the encephalopathy group compared to controls.</p