The frameshift Leu220Phefs*2 variant in KRIT1 accounts for early acute bleeding in patients affected by cerebral cavernous malformation

Abstract Background and Objectives Cerebral cavernous malformation (CCM) is a neurovascular disease characterized by abnormally expanded and tortuous microvessels with increased predisposition to thrombosis and focal hemorrhage. Its incidence is estimated to range between 0.4% and 0.8%. Sporadic and familial forms of CCM are described. The first one is characterized by single lesion, while the familial form is defined by multiple malformations. In this scenario, more than 300 mutations affecting the CCM genes have been described to date, but the exact pathogenic mechanism is yet unknown. Most of the causative variants of KRIT1 gene are frameshift but there are many missense and nonsense variants and they have been found some splicing mutations. The diagnosis is based on magnetic resonance images (MRI) and genetic testing. Case report A 15-year-old male presented with a two weeks duration worsening headache accompanied by vomiting and three months behavioral changes. Computer tomography revealed a large right temporal lesion with other smaller in left parietal and left cerebellar region. At the time of diagnosis, the two siblings of the proband were asymptomatic. Nevertheless, four months later, the 7-years-old brother was admitted to the emergency room for balance deficit, diplopia, right-hitting nystagmus and stiff neck with deviation of the head. A cerebral CT revealed polylobate hyperdense mass of the middle cerebral pedicle associated to acute bleeding. A genetic testing for hereditary cavernous brain malformation was carried out. Results The molecular analysis identified a 2-bp duplication (NM_194456.1:c.658_659dupTT) as heterozygous within the exon 8 of CCM1/KRIT1 gene (Fig. 1C). This duplication leads to a frameshift variant, resulting in a premature stop codon (p.Leu220Phefs*2). Discussion The clinical data collected confirm the variable phenotypic expression of CCM and suggest a greater severity of symptoms in the youngest patients

amda 2 13 a major update for automated cross platform microarray data analysis

Microarray platforms require analytical pipelines with modules for data pre-processing including data normalization, statistical analysis for identification of differentially expressed genes, cluster analysis, and functional annotation. We previously developed the Automated Microarray Data Analysis (AMDA, version 2.3.5) pipeline to process Affymetrix 3′ IVT GeneChips. The availability of newer technologies that demand open-source tools for microarray data analysis has impelled us to develop an updated multi-platform version, AMDA 2.13. It includes additional quality control metrics, annotation-driven (annotation grade of Affymetrix NetAffx) and signal-driven (Inter-Quartile Range) gene filtering, and approaches to experimental design. To enhance understanding of biological data, differentially expressed genes have been mapped into KEGG pathways. Finally, a more stable and user-friendly interface was designed to integrate the requirements for different platforms. AMDA 2.13 allows the analysis of Affymetrix..

An unusual but possible complication after endoscopic third-ventriculostomy

We present an unusual but possible complication after ETV for the treatment of acute hydrocephalus due to malfunction of a previously implanted V-P shunt. A 12-year-old male patient was urgently operated upon by means of an endoscopic third-ventriculostomy and the positioning of a temporary external ventricular catheter because of the malfunction of a previously implanted V-P shunt; immediately after the operation, the tip of the external catheter caused an obstruction of the ostomy, which was resolved with the withdrawn of catheter for circa 1 cm, left closed and ultimately removed after 4 days. The patient did not present any further symptom and remained shunt-free at the last 2-year follow-up visit. One should consider such occurrence in cases of early ETV failure when a ventricular catheter is left in situ, even though temporarily

Management and treatment of brain tumors during pregnancy: an Italian survey

Purpose: The management of brain tumors during pregnancy is challenging. The clinical rarity and prognostic heterogeneity of such condition makes it difficult to develop standardized guidelines of treatment. The aim of this study was to assess the treatment options used in pregnant women with brain tumors that are currently used in Italy, considering the management of these patients reported in current literature in this field. Methods: A survey addressing the treatments options and management of brain tumors during pregnancy was designed on behalf of an ad-hoc task-force Neuro-Oncology committee of the Società Italiana di Neurochirurgia (SINch) to analyze the management of pregnant patients with brain tumors. We conducted a search of the literature published between January 2011 and September 2021, using MEDLINE (PubMed) in accordance to PRISMA guidelines. Data were discussed to obtain recommendations after evaluation of the selected articles and discussion among the experts. Results: A total of 18 Neurosurgical centers participated in the survey. A total of 31 pregnant women were included in this retrospective study. Meningiomas and gliomas were the two most common types of brain tumors diagnosed during pregnancy. An emergency surgical procedure was required in 12.9% of cases. Conclusion: A multidisciplinary and tailored approach is fundamental. In women showing clinical stability, neurosurgical options should preferably be delayed if possible, and considered during the second trimester or after delivery. In patients with acute neurological symptoms or tumor progression, medical abortion in the first trimester or a C-section in the second and third trimester need to be considered

Management and treatment of brain tumors during pregnancy: an Italian survey

Purpose: The management of brain tumors during pregnancy is challenging. The clinical rarity and prognostic heterogeneity of such condition makes it difficult to develop standardized guidelines of treatment. The aim of this study was to assess the treatment options used in pregnant women with brain tumors that are currently used in Italy, considering the management of these patients reported in current literature in this field. Methods: A survey addressing the treatments options and management of brain tumors during pregnancy was designed on behalf of an ad-hoc task-force Neuro-Oncology committee of the Società Italiana di Neurochirurgia (SINch) to analyze the management of pregnant patients with brain tumors. We conducted a search of the literature published between January 2011 and September 2021, using MEDLINE (PubMed) in accordance to PRISMA guidelines. Data were discussed to obtain recommendations after evaluation of the selected articles and discussion among the experts. Results: A total of 18 Neurosurgical centers participated in the survey. A total of 31 pregnant women were included in this retrospective study. Meningiomas and gliomas were the two most common types of brain tumors diagnosed during pregnancy. An emergency surgical procedure was required in 12.9% of cases. Conclusion: A multidisciplinary and tailored approach is fundamental. In women showing clinical stability, neurosurgical options should preferably be delayed if possible, and considered during the second trimester or after delivery. In patients with acute neurological symptoms or tumor progression, medical abortion in the first trimester or a C-section in the second and third trimester need to be considered