Hemorrhagic stroke, cerebral amyloid angiopathy, Down syndrome and the Boston criteria.

A stroke, or a cerebrovascular accident (CVA) is a life-threatening condition which often results in permanent or significant disability in the adult population. Several classifications of CVAs exist, one of them being based on the mechanism of injury of brain tissue: ischemic (85-90%) and hemorrhagic (10-15%). In a hemorrhagic stroke an intercranial bleeding occurs, leading to the formation of a focal hematoma typically located in the basal ganglia of the brain (approx. 45% of cases). A common yet underestimated cause of intracerebral hemorrhage is cerebral small vessel disease with microhemorrhages, including the cerebral amyloid angiopathy (CAA). This condition is associated with the deposition of amyloid-beta in arterial walls (in soft meninges, subcortical areas and the cerebral cortex). Research has shown that causes of hemorrhagic changes in the brain include genetic disorders, such as Down syndrome. The association is caused by the so-called 'gene dosage effect', as the gene for the precursor protein for amyloid-beta is located in chromosome 21. We wish to present the case of a 60 year old patient with Down syndrome who suffered a hemorrhagic stroke without antecedent hypertension. Based on the history taken, diagnostic imaging and the source literature, a diagnosis of cerebral amyloid angiopathy as the source of the bleeding was made (however it must be noted that without a full post-mortem examination, the Boston criteria allow only for a 'probable cerebral amyloid angiopathy' diagnosis to be made). The authors hereby also report the need to modify the Boston criteria for cerebral amyloid angiopathy.

MicroRNAs as novel regulators of neuroinflammation.

MicroRNAs are relatively recently discovered class of small noncoding RNAs, which function as important regulators of gene expression. They fine-tune protein expression either by translational inhibition or mRNA degradation. MicroRNAs act as regulators of diverse cellular processes, such as cell differentiation, proliferation, and apoptosis. Their defective biogenesis or function has been identified in various pathological conditions, like inflammation, neurodegeneration, or autoimmunity. Multiple sclerosis is one of the predominated debilitating neurological diseases affecting mainly young adults. It is a multifactorial disorder of as yet unknown aetiology. As far, it is suggested that interplay between genetic and environmental factors is responsible for MS pathogenesis. The role of microRNAs in this pathology is now extensively studied. Here, we want to review the current knowledge of microRNAs role in multiple sclerosis.

Selected extracellular microRNA as potential biomarkers of multiple sclerosis activity--preliminary study.

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Four distinct disease courses are known, although approximately 90% of patients are diagnosed with the relapsing-remitting form (RRMS). The name "multiple sclerosis" pertains to the underlying pathology: the presence of demyelinating plaques in the CNS, in particular in the periventricular region, corpus callosum, cervical spine, and the cerebellum. There are ongoing efforts to discover biomarkers that would allow for an unequivocal diagnosis, assess the activity of inflammatory and neurodegenerative processes, or warn of disease progression. At present, small noncoding RNA particles-microRNA (miRNA, miR) seem to be particularly noteworthy, as they take part in posttranscriptional regulation of expression of various genes. Changes in composition as well as function of miRNA found in body fluids of MS patients are subjects of research, in the hope they prove accurate markers of MS activity. This preliminary study aims to evaluate the expression of selected extracellular microRNA particles (miRNA-let-7a, miRNA-92a, miRNA-684a) in patients experiencing MS relapse and remission, with healthy volunteers serving as a control group and to evaluate the correlation between miRNA expression and selected clinical parameters of those patients. Thirty-seven patients suffering from MS formed two examined groups: 20 patients undergoing relapse and 17 in remission. Thirty healthy volunteers formed the control group. All patients who were subjects to peripheral blood sampling had been hospitalized in the Department of Neurology and Stroke(1). Four milliliters of venous whole blood had been collected into EDTA tubes. The basis for the selection of the three particular miRNA investigated in this study (miRNA-let-7a, miRNA-92a, miRNA-684a) was a preliminary bioinformatic analysis of data compiled from several medical databases, including Ovid MEDLINE®, Embase, Cochrane Database of Systematic Reviews (CDSR), miRWalk, and miRBase. The isolation of extracellular microRNA from plasma was carried out using miRNeasy Mini Kit (Qiagen) reagents. The reverse transcription was carried out with TaqMan® MicroRNA Reverse Transcription Kit (Applied Biosystems), as per manufacturers' instructions. Standard microRNA TaqMan® tests (Applied Biosystems) were used for miRNA quantification. The qPCR were performed on a 7900 HT Fast Real-Time PCR System (Applied Biosystems) and analyzed using Sequence Detection System 2.3 software. In addition, all patients at the Department of Neurology and Stroke undergo a routine complete blood count with differential. The main objective of this study was to evaluate the expression of selected microRNA (has-miR-let-7a, miR-92a, and miR-648a) in the plasma of patients with MS during a relapse as well as in remission and attempt to correlate the acquired data with clinically relevant parameters of the disease. Finding such correlations may potentially lead to the use of miRNA as a biomarker of MS, which could help diagnose the disease and assess its severity and the efficacy of treatment. The difference in the expression of has-miR-let-7a in the remission group and the control group was statistically significant (p = 0.002). Similarly, the expression of miRNA-648a in patients in remission was significantly different from the expression in the control group (p = 0.02). Analysis of the correlation between the expression of miRNA-92a and the severity of the disease as measured by the EDSS scale in patients undergoing relapse showed significant negative linear correlation (r = -0.54, p = 0.01). Higher miR-648a expression correlated with more frequent flare-ups in the joint group of patients in remission and relapse (p = 0.03). This study is one of the few that demonstrate significantly changed expression of selected extracellular miRNA in plasma of MS patients and correlate those findings with clinical parameters. These observations may suggest that some miRNA subsets may be potential biomarkers for MS activity.