Data-Driven Analysis Reveals Cortical Infarction Patterns Correlated With Inflammation and Prognosis: A Retrospective, Multicenter Cohort Study.

BACKGROUND: We aim to identify the distinct lesion patterns and regions associated with functional outcome and inflammation in patients with acute ischemic stroke, and investigate whether the association between lesion patterns and functional outcome was mediated by inflammation. METHODS AND RESULTS: We performed nonnegative matrix factorization to derived low-dimensional lesion patterns (atoms), and Bayesian linear regression models were applied to explore the associations of lesion patterns with inflammatory factors including high-sensitivity C-reactive protein and interleukin-6, as well as functional outcome (defined as modified Rankin Scale score at 3 months). The difference distribution mean and 95% highest probability density interval (HPDI) were calculated. Mediation analysis was used to examine the mediating effects of inflammation on the relationships between lesion patterns and functional outcome. Seven lesion patterns were derived from 5914 patients with acute ischemic stroke. Lesion patterns distributed in the cortical regions were associated with inflammatory response, including atom 1 (interleukin-6: mean, 0.113 [95% HPDI, 0.073-0.162]; high-sensitivity C-reactive protein: mean, 0.082 [95% HPDI, 0.038-0.123]) and atom 4 (interleukin-6: mean, 0.113 [95% HPDI, 0.071-0.167]; high-sensitivity C-reactive protein: mean, 0.108 [95% HPDI, 0.058-0.165]). These lesion patterns were also significantly associated with functional outcome (atom 1: mean, 1.958 [95% HPDI, 1.538-2.383]; atom 4: mean, 2.245 [95% HPDI, 1.773-2.741]). Mediation analysis suggested that interleukin-6 explained 15.34% and 7.47% in the association of atom 1 and atom 4 with functional outcome, respectively. CONCLUSIONS: Certain lesion patterns that are associated with both inflammation and functional outcome of acute ischemic stroke, especially cortical infarction, may play a role in functional outcome through modulating inflammatory reactions.

Sex-specific lesion pattern of functional outcomes after stroke.

Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale >2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men - women) = -0.295 (90% highest posterior density interval = -0.556 to -0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.

Distribution patterns of saprolegniosis cutaneous lesions in wild and farmed brown trout (Salmo trutta L.) obtained using a geographic information system (GIS).

A retrospective study was conducted using 250 clinical records of brown trout (Salmo trutta L.) with saprolegniosis by Saprolegnia parasitica, which had been collected from 8 rivers and 1 fish farm in the province of León (Spain). A geographic information system (GIS) was used to obtain skin lesion distribution patterns in males and females. Lesions in wild brown trout affected 15.31 ± 13.33% of the body surface, with a mean of 12.76 ± 6.56 lesions per fish. In addition, 51.23% of wild trout presented lesions with necrosis of the skin or fins. The pattern obtained when not distinguishing between sexes indicated that saprolegniosis lesions are mainly located above the lateral line and most frequently affect the dorsal cephalic region, the adipose fin, the peduncle and the caudal fin. However, differences were observed between males and females. Farmed trout presented a lower percentage of affected body surface (2.06 ± 4.36) and a lower number of lesions with and without necrosis because they received preventive treatment for saprolegniosis.

Aspectos macroscópicos e histológicos da cisticercose bovina / Macroscopic and histological findings of bovine cysticercosis

Cisticercose bovina é uma importante doença parasitária de caráter zoonótico, com elevada ocorrência em algumas regiões do Brasil. Considerando a possibilidade de erro na identificação das lesões, bem como a dificuldade de classificação dos cistos e a necessidade de melhorar o diagnóstico, o objetivo desse trabalho foi caracterizar e correlacionar as lesões macroscópicas e microscópicas da cisticercose bovina, além de utilizar a técnica da PCR para auxiliar na identificação do agente. Amostras de lesões císticas e nodulares de bovinos, compatíveis macroscopicamente com cisticercose, foram coletadas em abatedouros frigoríficos do Estado do Rio Grande do Sul. Os cistos foram divididos em três grupos: Grupo 1, cisticercos vivos (viáveis); Grupo 2 (subdividido em 2a e 2b), cisticercos degenerados com potencial escólex viável; e Grupo 3 cisticercos mortos (mineralizados). Após a obtenção das lâminas histológicas dos cisticercos de cada grupo, foi realizada a correlação macroscópica e microscópica. Para a realização da técnica da PCR foram utilizadas lesões císticas de 26 bovinos. Foram analisados cisticercos de 127 bovinos, totalizando 232 cistos. Dos 127, 46 bovinos (36,2%) apresentaram mais de um cisticerco e 81 (63,8%) um cisticerco cada. Em relação a localização anatômica dos cistos, o coração demonstrou o maior envolvimento (55,9%), seguido do músculo masseter (22,8%). Quando houve o envolvimento de dois órgãos em um mesmo bovino, coração e músculo masseter juntos, totalizaram 11 casos (8,6%). De maneira geral a média da frequência de cisticercose foi de 10% a 15% de bovinos acometidos por lote. Entretanto, a média isolada de alguns lotes demonstrou condenações acima de 50%, 80% e 90%. Morfologicamente, os 232 cisticercos foram classificados dentro de três grupos. No Grupo 1, 23 cistos (9,9%) foram considerados como vivos (viáveis), e eram caracterizados por lesões císticas com parede translúcida ou levemente opaca, contendo líquido claro e um ponto esbranquiçado no interior (escólex). Na histologia, os cistos eram compostos por uma membrana de onde invaginava um escólex de Taenia saginata. No segundo grupo (Grupo 2), foram incluídos 156 (67,2%) cisticercos degenerados com potencial escólex viável e macroscopicamente os cistos demonstraram dois padrões morfológicos distintos. No primeiro deles (Grupo 2a), visualizado em 111 casos (71,1%), observaram-se lesões nodulares com aspecto caseoso. Microscopicamente, os cistos caracterizavam-se por formações nodulares compostas por área central contendo escólex e membrana, ambos degenerados, e necrose caseosa. No segundo padrão (Grupo 2b), observado em 45 cisticercos (28,9%), as lesões também eram caseosas, entretanto ao corte os cistos demonstravam na área central um orifício em meio ao material caseoso. Os aspectos microscópicos dos 45 cistos incluídos no segundo padrão macroscópico assemelhavam-se aos cisticercos do primeiro padrão. Entretanto, oito cistos (17,8%) demonstraram somente a membrana parasitária viável e em um cisto notou-se a membrana com o escólex viável. No restante dos 36 cistos (80%), observou-se área central contendo escólex e membrana, ambos degenerados, e necrose caseosa. No terceiro grupo de classificação morfológica dos cisticercos (Grupo 3), foram inseridos os cistos mineralizados (mortos), totalizando 53 cistos (22,9%). O aspecto macroscópico desses cisticercos caracterizava-se por lesões nodulares, amarelas, firmes ao corte, que se fragmentavam. Histologicamente observaram-se formações nodulares com área central de acentuada mineralização, rodeadas por infiltrado inflamatório granulomatoso. Dos 127 bovinos, foi realizado PCR a partir do DNA extraído dos cisticercos de 26 bovinos, no qual 24 foram positivos para cisticercose. Em relação aos dois cisticercos negativos, um deles fazia parte do Grupo 2a e o outro do Grupo 3. A correlação entre os aspectos macroscópicos e microscópicos do segundo padrão morfológico observado dentro do Grupo 2, demonstrou que esse subgrupo representa o maior problema na interpretação, pois alguns cistos apresentaram características de viabilidade. Macroscopicamente esses cisticercos podem ser identificados quando cortados, porque possuem um orifício na área central que pode auxiliar no diagnóstico.(AU)

Bovine cysticercosis is an important zoonotic parasitic disease with high prevalence in several regions of Brazil. Considering the need of improvement of the accuracy of diagnosis of these lesions, as well as the difficulty of classification of the cysts, this study aimed to correlate gross and histopathological changes of bovine cysticercosis and to use polymerase chain reaction (PCR) as an aid in their identification. Cystic and nodular lesions from cattle, grossly compatible with cysticercosis, were sampled in slaughterhouses from Rio Grande do Sul State. Lesions were allotted in one of the following groups. Group 1: viable cysticercus; Group 2 (subdivided 2a e 2b): degenerating cysticercus with a potentially viable scolex; and Group 3: dead cysticercus (mineralized). The gross and microscopic aspects of every cysticerci of each group were compared. Two hundred and thirty two cysts and nodules compatible with cysticercus were sampled from 127 bovine. Twenty six of those lesions were tested with PCR. Out of 127 cattle, 46 (36.2%) had more than one cyst and the remaining 81 (63.8%) had on cyst each. Myocardium was the most frequently involved anatomical site (55.9%), followed by masseter muscle (22.8%). When there was more than one organ involved in the same bovine, myocardium a master muscle sum up 11 cases (8.6%). In general, the average of cysticercosis frequency was 10-15%. However the average in some cattle lots was in excess of 50%, 80% and 90%. Morphologically, 232 cysticerci were classified in three groups. In Group 1, 23 cysticerci (9.9%) were considered viable and were characterized by cysts of translucent or slightly opaque wall, containing clear and a white point (scolex) within the cyst. Histologically, the cysts consisted of a membrane from which a scolex of Taenia saginata invaginated. One hundred and fifty six cysts (67.2%) were allotted in Group 2; grossly these cysts revealed two different morphological patterns. In 111 (71.1%) cases of Group 2 (Group 2a) nodular caseous lesions were observed. Histologically, the cysts were characterized by nodules consisting by a central area containing the scolex and membrane, both degenerated, and caseous necrosis. In the remaining 45 (28.9%) cases of Group 2 (Group 2b), lesions were also caseous; however, at cut surface the cysts had a central hole amidst the caseous material. The microscopic aspect of the 45 cysts included in the second was similar to that of the first pattern. However in eight (17.8%) of the 45 cysts only a viable parasitic membrane was observed and in one cyst the membrane and viable scolex were observed. In the remaining 36 cases (80%), the cysts consisted of a central area containing both degenerated membrane and scolex, and caseous necrosis. In Group 3, 53 dead cysts (mineralized) (22.9%) were found among the total of 232 cysts. The gross aspect of these cysticerci was characterized by yellow form nodules which crumbled when cut. Histologically nodules were observed with marked central area of mineralization surrounded by granulomatous inflammatory response. Twenty four of the twenty cysts examined by PCR were positive for Cysticercus bovis and two of them were negative. One of the negatives was part of Group 2 (degenerated cysts) and the other one of the Group 3 (dead mineralized cysts). The correlation between gross and microscopic aspects of the second morphologic aspect of the Group 2 demonstrated that this subset represents a major complicating factor in interpretation, since a large number of these cysts reveal characteristics of viability. Grossly, these cysticerci might be identified when cut, since a hole in the central area will be observed aiding in recognizing his lesions.(AU)

Risk factors, topographic patterns and mechanism analysis of intracranial atherosclerotic stenosis ischemic stroke.

BACKGROUND: The association between topographic patterns, risk factors and stroke mechanisms of ICAS in first-ever stroke remains unknown. METHODS: A large sample sized retrospective study was performed on first-ever ICAS ischemic stroke using DWI and MRA. RESULTS: Hypertension (60.92%), cigarette smoking (26.82%), MCA (76.65%) and multiple vessels (65.37%) stenosis, were the major factors favoring different mechanisms. Subcortical lesions were the most occurring topographic patterns (41.4%). The common mechanism was LBO (66.3%). Statistical analysis showed a significant relationship between lesion patterns and mechanisms (r = 0.384, P = 0.001). Single mechanism had the higher apoB/apoAI ratio (P = 0.005) and levels of plasma apoB (P = 0.007) compared with multiple mechanisms. The anterior circulation stroke were more multiple mechanisms as compared to the posterior circulation stroke (P = 0.001). LBO was more prevalent in posterior circulation stroke than in anterior circulation stroke (P = 0.001). CONCLUSIONS: The topographic patterns of ischemic lesions is helpful in early identification of different mechanisms of ICAS. Monitoring apoB and apoB/apoA1 may help to predict the mechanism of stroke with ICAS. The prevalence of mechanisms differ between anterior and posterior circulation stroke with ICAS.

Decoding post-stroke motor function from structural brain imaging.

Clinical research based on neuroimaging data has benefited from machine learning methods, which have the ability to provide individualized predictions and to account for the interaction among units of information in the brain. Application of machine learning in structural imaging to investigate diseases that involve brain injury presents an additional challenge, especially in conditions like stroke, due to the high variability across patients regarding characteristics of the lesions. Extracting data from anatomical images in a way that translates brain damage information into features to be used as input to learning algorithms is still an open question. One of the most common approaches to capture regional information from brain injury is to obtain the lesion load per region (i.e. the proportion of voxels in anatomical structures that are considered to be damaged). However, no systematic evaluation has yet been performed to compare this approach with using patterns of voxels (i.e. considering each voxel as a single feature). In this paper we compared both approaches applying Gaussian Process Regression to decode motor scores in 50 chronic stroke patients based solely on data derived from structural MRI. For both approaches we compared different ways to delimit anatomical areas: regions of interest from an anatomical atlas, the corticospinal tract, a mask obtained from fMRI analysis with a motor task in healthy controls and regions selected using lesion-symptom mapping. Our analysis showed that extracting features through patterns of voxels that represent lesion probability produced better results than quantifying the lesion load per region. In particular, from the different ways to delimit anatomical areas compared, the best performance was obtained with a combination of a range of cortical and subcortical motor areas as well as the corticospinal tract. These results will inform the appropriate methodology for predicting long term motor outcomes from early post-stroke structural brain imaging.