New prognostic score for the prediction of 30-day outcome in spontaneous supratentorial cerebral haemorrhage.

Aims. The purpose of the present study was to evaluate predictors of outcome in primary supratentorial cerebral haemorrhage. Furthermore, we aimed to develop a prognostic model to predict 30-day fatality. Methods. We retrospectively analyzed a database of 156 patients with spontaneous supratentorial haemorrhage to explore the relationship between clinical and CT characteristics and fatal outcome within 30 days using multiple logistic regression analysis. The analyzed factors included volumetric data assessed by neuropathological and CT volumetry. A second CT scan in survivors or neuropathological ABC/2 volumetry in nonsurvivors was used along with the baseline CT to assess the growth index of haematoma. Results. Systolic blood pressure, serum potassium and glucose levels, platelet count, absolute and relative haematoma volumes, and presence and size of intraventricular haemorrhage statistically significantly predicted the fatal outcome within 30 days. Based on our results we formulated a six-factor scoring algorithm named SUSPEKT to predict outcome. Conclusions. After validation the SUSPEKT score may be applicable in general clinical practice for early patient selection to optimize individual management or for assessment of eligibility for treatment trials

Gamma-synuclein pathology in amyotrophic lateral sclerosis

Objective: The prominent histopathological feature of the amyotrophic lateral sclerosis (ALS) is the presence of intracellular inclusions in degenerating neurons and their axons. The appearance and localization of these pathological structures depend on an aggregated protein that forms their scaffold. We investigated if c-synuclein, an aggregation-prone protein highly expressed in healthy motor neurons, and predominantly localized in their axons and synaptic terminals is involved in ALS pathology. Methods: Immunostaining of histological sections and sequential protein extraction from postmortem neural samples followed by immunoblotting. Results: Immunohistochemical screening revealed a subset of sporadic (9 of 31) and familial (8 of 23) ALS cases with a novel type of pathology characterized by the accumulation of c-synuclein in distinct profiles within the dorsolateral column. Sequential fractionation of proteins from the spinal cord tissues revealed detergent-insoluble c-synuclein species specifically in the dorsolateral corticospinal tracts of a ALS patient with c-synuclein-positive profiles in this region. These profiles are negative for protein markers commonly found in pathological inclusions in the spinal cord of ALS patients and most probably represent degenerated axons of upper motor neurons that have lost their neurofilaments. A subset of these profiles was found in association with phagocytic cells positive for Mac-2/Galectin-3. A smaller subset of studied ALS cases (4 of 54) contained large cytoplasmic inclusions in the cell body of remaining spinal motor neurons. Interpretation: Our observations suggest that pathological aggregation of c-synuclein might contribute to the pathogenesis of ALS

Tyrosine Kinase Inhibitor Imatinib Mesylate Alters DMBA-Induced Early Onco/Suppressor Gene Expression with Tissue-Specificity in Mice

Tyrosine kinases play crucial roles in cellular development and tumorigenesis. Tyrosine kinase inhibitors (TKIs) are effective and widely used drug molecules in targeted cancer therapies. Altered expressions of protooncogenes and tumor suppressor genes after DMBA (7,12-dimethylbenz[a]anthracene) treatment have been described as early markers of tumor induction; however their tissue-specific effects remain still unclear. Our study was aimed at examining the short-term possible antineoplastic and chemopreventive effects of a TKI compound (imatinib mesylate) on a DMBA-induced mouse tumor model. In addition, we also investigated the tissue-specific expressions of Hras, Kras, Myc, and Trp53 genes in the brain, bone marrow, spleen, liver, abdominal lymph nodes, thymus, lungs, and kidneys, respectively. 24 hours after the imatinib mesylate injection, we observed significant Kras downregulation in the bone marrow and lung of the DMBA-treated mice. Moreover, the mRNA expression of Myc was also found to be decreased significantly in the spleen. Interestingly, while Trp53 expression was significantly increased in the lung, it was decreased in the other tissues. However, there was also a tendency in the decreased Myc level in the bone marrow, brain, kidneys, lungs, and lymph nodes and in the decreased Hras level in the bone marrow, kidneys, and lungs, although no significant differences were observed. Our findings indicate rapid tissue-specific impact of imatinib mesylate on DMBA-induced gene expression in vivo, supporting the chemopreventive potential of imatinib mesylate in cancer.K

Prognostic role of the expression of invasion-related molecules in glioblastoma.

Background Glioblastoma multiforme (GBM) is the most common malignant disease of the central nervous system. Its prognosis is unfavorable, and the median overall survival of patients is 16 to 24 months. The main cause of the poor survival data are the extensive invasion of cancer cells to the neighboring parenchyma, thus leading to inevitable local recurrence. The extracellular matrix (ECM) is a known factor in tumor invasion, and differences in the ECM of nontumor brain and glioblastoma has been proven. Methods In this research, 20 invasion-related expressions of ECM components were determined in 26 GBM flash-frozen samples using quantitative reverse transcription-polymerase chain reaction and proteomic measurements. Expression data were then set against the survival data of the patients. Results Significant alterations between groups with different survival rates could not be established in the individual evaluation of the expression level of the selected molecules. However, statistical analysis of the expression pattern of invasion-related molecules revealed a correlation with prognosis. The positive predictive values of the messenger RNA (mRNA) and the proteomic expression studies were 0.85 and 0.89, respectively. The receiver operation characteristic value was 0.775 for the mRNA expression data and 0.875 for the protein expression data. Furthermore, a group of molecules, including brevican, cadherin-12, integrin β1, integrin α3, laminin α4, and laminin β1, that play a prominent role in invasion were identified. Conclusions Joint assessment of the expression of invasion-related molecules provides a specific invasion spectrum of the tumor that correlates with the survival of glioblastoma patients. Using statistical classifiers enables the adoption of an invasion spectrum as a considerably accurate prognostic factor while gaining predictive information on potential molecular oncotherapeutic targets at the same time

Amyotrophic lateral sclerosis - frontotemporal spectrum disorder (ALS-FTSD): Revised diagnostic criteria

This article presents the revised consensus criteria for the diagnosis of frontotemporal dysfunction in amyotrophic lateral sclerosis (ALS) based on an international research workshop on frontotemporal dementia (FTD) and ALS held in London, Canada in June 2015. Since the publication of the Strong criteria, there have been considerable advances in the understanding of the neuropsychological profile of patients with ALS. Not only is the breadth and depth of neuropsychological findings broader than previously recognised – – including deficits in social cognition and language – but mixed deficits may also occur. Evidence now shows that the neuropsychological deficits in ALS are extremely heterogeneous, affecting over 50% of persons with ALS. When present, these deficits significantly and adversely impact patient survival. It is the recognition of this clinical heterogeneity in association with neuroimaging, genetic and neuropathological advances that has led to the current re-conceptualisation that neuropsychological deficits in ALS fall along a spectrum. These revised consensus criteria expand upon those of 2009 and embrace the concept of the frontotemporal spectrum disorder of ALS (ALS-FTSD)