Asymmetric posterior reversible encephalopathy syndrome in patient with hyperplastic anterior choroidal artery

We describe a case of asymmetric PRES due to the presence of hyperplastic anterior choroidal artery (AChA) in a man affected by sever hypertension. Posterior reversible encephalopathy syndrome (PRES) has become synonymous with a unique pattern of brain vasogenic edema and predominates in the parietal and occipital regions, accompanied by clinical neurological alterations. Sever hypertension is a risk factor that exceeds the limits of brain autoregulation, leading to breakthrough brain edema. In our knowledge this is the first case reported in literature, in which a similar vascular abnormality is linked to a PRES syndrome

Genome-Wide Multiple Sclerosis Association Data and Coagulation

The emerging concept of a crosstalk between hemostasis, inflammation, and immune system prompt recent works on coagulation cascade in multiple sclerosis (MS). Studies on MS pathology identified several coagulation factors since the beginning of the disease pathophysiology: fibrin deposition with breakdown of blood brain barrier, and coagulation factors within active plaques may exert pathogenic role, especially through the innate immune system. Studies on circulating coagulation factors showed complex imbalance involving several components of hemostasis cascade (thrombin, factor X, factor XII). To analyze the role of the coagulation process in connection with other pathogenic pathways, we implemented a systematic matching of genome-wide association studies (GWAS) data with an informative and unbiased network of coagulation pathways. Using MetaCore (version 6.35 build 69300, 2018) we analyzed the connectivity (i.e., direct and indirect interactions among two networks) between the network of the coagulation process and the network resulting from feeding into MetaCore the MS GWAS data. The two networks presented a remarkable over-connectivity: 958 connections vs. 561 expected by chance; z-score = 17.39; p-value < 0.00001. Moreover, genes coding for cluster of differentiation 40 (CD40) and plasminogen activator, urokinase (PLAU) shared both networks, pointed to an integral interplay between coagulation cascade and main pathogenic immune effectors. In fact, CD40 pathways is especially operative in B cells, that are currently a major therapeutic target in MS field. The potential interaction of PLAU with a signal of paramount importance for B cell pathogenicity, such as CD40, suggest new lines of research and pave the way to implement new therapeutic targets

Tako tsubo and ischemic stroke in a patient with Alzheimer’s disease

Background Tako-tsubo cardiomyopathy (TTC), also known as "stress induced cardiomyopathy", is an acute cardiac condition characterized by transient myocardial dysfunction associated with a peculiar pattern of reversibile left ventricular ballooning that mimics myocardial infarction, but with normal coronary arteries. Tako-tsubo cardiomyopathy typically occurs in postmenopausal women and it is often triggered by physical or emotional stressful events. We report on a patient with Alzheimer's disease, who presented with TTC and an ischemic stroke. © 2014 Springer International Publishing Switzerland

Cerebral ischemia in young patients (under 45 years of age): clinical and neuroradiological follow-up.

Ischemic stroke in young patients is a relatively rare event. Few studies have examined the long-term prognosis. The aim of this study was to evaluate the long-term outcome to identify clinical, laboratory and radiologic patterns as possible predictors for mortality, recurrence and functional recovery. We prospectively evaluated 94 patients (42 males and 52 females, aged 14-45 years, mean age 35.5 years, SD 8.4) admitted to our Neurological Department, for first acute ischemic stroke. A 48-month follow-up was performed. The patients were classified according to TOAST and Baltimore classification and Bamford criteria. The severity of the neurological deficit on admission was assessed using the NIHSS. The follow-up included a clinical visit, the modified Ranking scale (mRs) score, Barthel index (BI), and magnetic resonance imaging and intra-extracranial vessel Angio MRI. A good functional outcome (mRS 0-1) was found in 74 patients and unfavourable outcome (mRS 2-6) in 20 patients. 16 patients had a recurrent cerebral ischemic event: 5 patients had stroke and 11 patients had TIA. The average incidence annual rate of recurrence was 4.5% and a mortality rate was of 1.06%. Our study does not demonstrate any predictive factor related to clinical outcome. The relevant data of neuroradiological follow-up is the presence of clinically silent lesions in nine patients, considered as a recurrent stroke. To attribute a prognostic role to these lesions, clinical and neuroradiological follow-up needs to be continued

Lineage switch from pro-B acute lymphoid leukemia to acute myeloid leukemia in a case with t(12;17)(p13;q11)/TAF15-ZNF384 rearrangement

[No abstract available

A novel germline mutation in CDK4 codon 24 associated to familial melanoma

Germline mutations of the CDK4 gene have been reported in 18 familial cutaneous melanoma (CM) cases worldwide, with only 2 substitutions, the c.70C>T,p.Arg24Cys and c.71G>A,p.Arg24His, described to date. Moreover, the acquired CDK4 p.Asn41Ser variant has been related to sporadic metastatic malignant melanoma. we report the molecular studies of a familial case of CM carrying the new germline CDK4 c.71G>T,p.Arg24Leu. modulators

A novel germline mutation in CDK4

Germline mutations of the CDK4 gene have been reported in 18 familial cutaneous melanoma (CM) cases worldwide, with only 2 substitutions, the c.70C>T,p.Arg24Cys and c.71G>A,p.Arg24His, described to date. Moreover, the acquired CDK4 p.Asn41Ser variant has been related to sporadic metastatic malignant melanoma. we report the molecular studies of a familial case of CM carrying the new germline CDK4 c.71G>T,p.Arg24Leu. modulators

Combined interphase fluorescence in situ hybridization elucidates the genetic heterogeneity of T-cell acute lymphoblastic leukemia in adults

Background Molecular lesions in T-cell acute lymphoblastic leukemias affect regulators of cell cycle, proliferation, differentiation, survival and apoptosis in multi-step pathogenic pathways. Full genetic characterization is needed to identify events concurring in the development of these leukemias. Design and Methods We designed a combined interphase fluorescence in situ hybridization strategy to study 25 oncogenes/tumor suppressor genes in T-cell acute lymphoblastic leukemias and applied it in 23 adult patients for whom immunophenotyping, karyotyping, molecular studies, and gene expression profiling data were available. The results were confirmed and integrated with those of multiplex-polyrnerase chain reaction analysis and gene expression profiling in another 129 adults with T-cell acute lymphoblastic leukemias. Results The combined hybridization was abnormal in 21/23 patients (91%), and revealed multiple genomic changes in 13 (56%). It found abnormalities known to be associated with T-cell acute lymphoblastic leukemias, i.e. CDKN2A-B/9p21 and GRIK2/6q16 deletions, TCR and TLX3 rearrangements, SIL-TAL1, CALM-AF10, MLL-translocations, del(17)(q12)/NF1 and other cryptic genomic imbalances, i.e. 9q34, 11p, 12p, and 17q11 duplication, del(5)(q35), del(7)(q34), del(9)(q34), del(12)(p13), and del(14)(q11). It revealed new cytogenetic mechanisms for TCRB-driven oncogene activation and C-MYB duplication. In two cases with cryptic del(9)(q34), fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction detected the TAF_INUP214 fusion and gene expression profiling identified a signature characterized by HOXA and NUP214 upregulation and TAF_I, FNBP1, C9orf78, and USP20 down-regulation. Multiplex-polymerase chain reaction analysis and gene expression profiling of 129 further cases found five additional cases of TAF_INUP214-positive T-cell acute lymphoblastic leukemia. Conclusions Our combined interphase fluorescence in situ hybridization strategy greatly improved the detection of genetic abnormalities in adult T-cell acute lymphoblastic leukemias. It identified new tumor suppressor genes/oncogenes involved in leukemogenesis and highlighted concurrent involvement of genes. The estimated incidence of TAF_I-NUP214, a new recurrent fusion in adult T-cell acute lymphoblastic leukemias, was 4.6% (7/152)