Hemorrhagic Transformation of Ischemic Strokes.

Ischemic stroke, resulting from insufficient blood supply to the brain, is among the leading causes of death and disability worldwide. A potentially severe complication of the disease itself or its treatment aiming to restore optimal blood flow is hemorrhagic transformation (HT) increasing morbidity and mortality. Detailed summaries can be found in the literature on the pathophysiological background of hemorrhagic transformation, the potential clinical risk factors increasing its chance, and the different biomarkers expected to help in its prediction and clinical outcome. Clinicopathological studies also contribute to the improvement in our knowledge of hemorrhagic transformation. We summarized the clinical risk factors of the hemorrhagic transformation of ischemic strokes in terms of risk reduction and collected the most promising biomarkers in the field. Also, auxiliary treatment options in reperfusion therapies have been reviewed and collected. We highlighted that the optimal timing of revascularization treatment for carefully selected patients and the individualized management of underlying diseases and comorbidities are pivotal. Another important conclusion is that a more intense clinical follow-up including serial cranial CTs for selected patients can be recommended, as clinicopathological investigations have shown HT to be much more common than clinically suspected.

Comparison of Semi-Quantitative Scoring and Artificial Intelligence Aided Digital Image Analysis of Chromogenic Immunohistochemistry.

Semi-quantitative scoring is a method that is widely used to estimate the quantity of proteins on chromogen-labelled immunohistochemical (IHC) tissue sections. However, it suffers from several disadvantages, including its lack of objectivity and the fact that it is a time-consuming process. Our aim was to test a recently established artificial intelligence (AI)-aided digital image analysis platform, Pathronus, and to compare it to conventional scoring by five observers on chromogenic IHC-stained slides belonging to three experimental groups. Because Pathronus operates on grayscale 0-255 values, we transformed the data to a seven-point scale for use by pathologists and scientists. The accuracy of these methods was evaluated by comparing statistical significance among groups with quantitative fluorescent IHC reference data on subsequent tissue sections. The pairwise inter-rater reliability of the scoring and converted Pathronus data varied from poor to moderate with Cohen's kappa, and overall agreement was poor within every experimental group using Fleiss' kappa. Only the original and converted that were obtained from Pathronus original were able to reproduce the statistical significance among the groups that were determined by the reference method. In this study, we present an AI-aided software that can identify cells of interest, differentiate among organelles, protein specific chromogenic labelling, and nuclear counterstaining after an initial training period, providing a feasible and more accurate alternative to semi-quantitative scoring.

Pathological and clinical comparison of Parkinson's disease dementia and dementia with Lewy bodies. / [A Parkinson-kórhoz társuló demencia és a Lewy-testes demencia patológiai és klinikai összehasonlítása].

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are two major neurodegenerative diseases sharing common clinical, pathophysiological and morphologic features. The pathological hallmark of both diseases is the presence of Lewy-bodies (LB). The main constituent of these inclusions is the pathologically aggregated α-synuclein protein. In DLB, LBs are predominantly located in the cortex, whereas in PDD, the subcortical regions are predominantly affected. Furthermore, in DLB, coexisting Alzheimer's disease (AD), pathology with ß-amyloid plaques and neurofibrillary tangles are more common. It is still debated whether DLB and PDD are two distinct entities or different phenotypes of the same disease. Clinical diagnosis is based on the temporal sequence of motor and cognitive symptoms. Dementia often precedes parkinsonism in DLB, while in PDD, cognitive decline generally appears after the onset of motor symptoms. Also, fluctuation of cognitive functions and neuroleptic sensitivity is more severe in DLB than PDD. The recent advancements of imaging techniques revealed that cortical damage, cholinergic deficit and concomitant AD pathology are more severe in DLB compared to PDD. The analysis of cerebrospinal fluid biomarkers shows higher oligomeric α-synuclein burden in PDD. Levodopa is less effective in DLB than in PDD and may increase the risk of psychosis. In this review, we comprehensively analyse the pathological, radiological and clinical features of DLB and PDD, highlighting the overlaps and differences. Orv Hetil. 2020; 161(18): 727-737.

Lemur Tyrosine Kinase 2 (LMTK2) Level Inversely Correlates with Phospho-Tau in Neuropathological Stages of Alzheimer's Disease.

: Alzheimer's disease (AD) is the most common neurodegenerative dementia. Mapping the pathomechanism and providing novel therapeutic options have paramount significance. Recent studies have proposed the role of LMTK2 in AD. However, its expression pattern and association with the pathognomonic neurofibrillary tangles (NFTs) in different brain regions and neuropathological stages of AD is not clear. We performed chromogenic (CHR) LMTK2 and fluorescent phospho-tau/LMTK2 double-labelling (FDL) immunohistochemistry (IHC) on 10-10 postmortem middle frontal gyrus (MFG) and anterior hippocampus (aHPC) samples with early and late neuropathological Braak tau stages of AD. MFG in early stage was our 'endogenous control' region as it is not affected by NFTs. Semiquantitative CHR-IHC intensity scoring revealed significantly higher (p < 0.001) LMTK2 values in this group compared to NFT-affected regions. FDL-IHC demonstrated LMTK2 predominance in the endogenous control region, while phospho-tau overburden and decreased LMTK2 immunolabelling were detected in NFT-affected groups (aHPC in early and both regions in late stage). Spearman's correlation coefficient showed strong negative correlation between phospho-tau/LMTK2 signals within each group. According to our results, LMTK2 expression is inversely proportionate to the extent of NFT pathology, and decreased LMTK2 level is not a general feature in AD brain, rather it is characteristic of the NFT-affected regions.

Neuropathological characterization of Lemur tyrosine kinase 2 (LMTK2) in Alzheimer's disease and neocortical Lewy body disease.

Alzheimer's disease (AD) and neocortical Lewy body disease (LBD) are the most common neurodegenerative dementias, with no available curative treatment. Elucidating pathomechanism and identifying novel therapeutic targets are of paramount importance. Lemur tyrosine kinase 2 (LMTK2) is involved in several physiological and pathological cellular processes. Herewith a neuropathological characterization is presented in AD and neocortical LBD samples using chromogenic and fluorescent LMTK2 immunohistochemistry on post-mortem brain tissues and compared them to age-matched controls (CNTs). LMTK2 immunopositivity was limited to the neuronal cytoplasm. Neurons, including tau-positive tangle-bearing ones, showed decreased chromogenic and immunofluorescent labelling in AD in every cortical layer compared to CNT and neocortical LBD. Digital image analysis was performed to measure the average immunopositivity of groups. Mean grey values were calculated for each group after measuring the grey scale LMTK2 signal intensity of each individual neuron. There was significant difference between the mean grey values of CNT vs. AD and neocortical LBD vs. AD. The moderate decrease in neocortical LBD suggests the effect of coexisting AD pathology. We provide neuropathological evidence on decreased neuronal LMTK2 immunolabelling in AD, with implications for pathogenesis.

Biological function of Lemur tyrosine kinase 2 (LMTK2): implications in neurodegeneration.

Neurodegenerative disorders are frequent, incurable diseases characterised by abnormal protein accumulation and progressive neuronal loss. Despite their growing prevalence, the underlying pathomechanism remains unclear. Lemur tyrosine kinase 2 (LMTK2) is a member of a transmembrane serine/threonine-protein kinase family. Although it was described more than a decade ago, our knowledge on LMTK2's biological functions is still insufficient. Recent evidence has suggested that LMTK2 is implicated in neurodegeneration. After reviewing the literature, we identified three LMTK2-mediated mechanisms which may contribute to neurodegenerative processes: disrupted axonal transport, tau hyperphosphorylation and enhanced apoptosis. Moreover, LMTK2 gene expression is decreased in an Alzheimer's disease mouse model. According to these features, LMTK2 might be a promising therapeutic target in near future. However, further investigations are required to clarify the exact biological functions of this unique protein.