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In today's scientific landscape, research software has evolved from being a supportive tool to becoming a fundamental driver of discovery, particularly in life sciences. Beyond its roots in software engineering, research software now plays a crucial role in facilitating efficient data analysis and enabling the exploration of complex natural phenomena. The advancements in simulations and modeling through research software have significantly accelerated the pace of scientific research while reducing associated costs. This growing reliance underscores the importance of software in ensuring reproducibility - a cornerstone of scientific rigor and trustworthiness. Although verifying reproducibility presents challenges, well-developed and openly accessible research software enhances transparency and aids in the early detection of errors. Although verifying reproducibility can be challenging, well-developed and accessible research software improves transparency and facilitates error detection. This mini-review examines the characteristics of research software and summarizes the key events that have shaped its development, alongside changes in requirements and guidelines. Moreover, we propose two additional principles - reviewability and supportability - complementing the widely accepted FAIR principles (Findability, Accessibility, Interoperability, and Reusability). These new principles aim to improve the efficiency and effectiveness of software evaluation during the peer review process. Through this review, we aim to assist scientists, especially those without extensive software development expertise, in understanding best practices for developing research software and the underlying motivations driving these practices., Competing Interests: The authors have no conflict of interest to declare., (© 2024 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.)

Large-scale genomic studies have significantly increased our knowledge of genetic variability across populations. Regional genetic profiling is essential for distinguishing common benign variants from disease-causing ones. To this end, we conducted a comprehensive characterization of exonic variants in the population of Navarre (Spain), utilizing whole genome sequencing data from 358 unrelated individuals of Spanish origin. Our analysis revealed 61,410 biallelic single nucleotide variants (SNV) within the Navarrese cohort, with 35% classified as common (MAF > 1%). By comparing allele frequency data from 1000 Genome Project (excluding the Iberian cohort of Spain, IBS), Genome Aggregation Database, and a Spanish cohort (including IBS individuals and data from Medical Genome Project), we identified 1069 SNVs common in Navarre but rare (MAF ≤ 1%) in all other populations. We further corroborated this observation with a second regional cohort of 239 unrelated exomes, which confirmed 676 of the 1069 SNVs as common in Navarre. In conclusion, this study highlights the importance of population-specific characterization of genetic variation to improve allele frequency filtering in sequencing data analysis to identify disease-causing variants.

Recent progress in Single-Cell Genomics has produced different library protocols and techniques for molecular profiling. We formulate a unifying, data-driven, integrative, and predictive methodology for different libraries, samples, and paired-unpaired data modalities. Our design of scAEGAN includes an autoencoder (AE) network integrated with adversarial learning by a cycleGAN (cGAN) network. The AE learns a low-dimensional embedding of each condition, whereas the cGAN learns a non-linear mapping between the AE representations. We evaluate scAEGAN using simulated data and real scRNA-seq datasets, different library preparations (Fluidigm C1, CelSeq, CelSeq2, SmartSeq), and several data modalities as paired scRNA-seq and scATAC-seq. The scAEGAN outperforms Seurat3 in library integration, is more robust against data sparsity, and beats Seurat 4 in integrating paired data from the same cell. Furthermore, in predicting one data modality from another, scAEGAN outperforms Babel. We conclude that scAEGAN surpasses current state-of-the-art methods and unifies integration and prediction challenges., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Khan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Circulating tumor cells are the key link between a primary tumor and distant metastases, but once in the bloodstream, loss of adhesion induces cell death. To identify the mechanisms relevant for melanoma circulating tumor cell survival, we performed RNA sequencing and discovered that detached melanoma cells and isolated melanoma circulating tumor cells rewire lipid metabolism by upregulating fatty acid (FA) transport and FA beta-oxidation‒related genes. In patients with melanoma, high expression of FA transporters and FA beta-oxidation enzymes significantly correlates with reduced progression-free and overall survival. Among the highest expressed regulators in melanoma circulating tumor cells were the carnitine transferases carnitine O-octanoyltransferase and carnitine acetyltransferase, which control the shuttle of peroxisome-derived medium-chain FAs toward mitochondria to fuel mitochondrial FA beta-oxidation. Knockdown of carnitine O-octanoyltransferase or carnitine acetyltransferase and short-term treatment with peroxisomal or mitochondrial FA beta-oxidation inhibitors thioridazine or ranolazine suppressed melanoma metastasis in mice. Carnitine O-octanoyltransferase and carnitine acetyltransferase depletion could be rescued by medium-chain FA supplementation, indicating that the peroxisomal supply of FAs is crucial for the survival of nonadherent melanoma cells. Our study identifies targeting the FA-based cross-talk between peroxisomes and mitochondria as a potential therapeutic opportunity to challenge melanoma progression. Moreover, the discovery of the antimetastatic activity of the Food and Drug Administration‒approved drug ranolazine carries translational potential., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Peripheral arterial disease (PAD) is associated with a high risk of cardiovascular events and death and is postulated to be a critical socioeconomic cost in the future. Extracellular vesicles (EVs) have emerged as potential candidates for new biomarker discovery related to their protein and nucleic acid cargo. In search of new prognostic and therapeutic targets in PAD, we determined the prothrombotic activity, the cellular origin and the transcriptomic profile of circulating EVs. This prospective study included control and PAD patients. Coagulation time (Procoag-PPL kit), EVs cellular origin and phosphatidylserine exposure were determined by flow cytometry in platelet-free plasma (n = 45 PAD). Transcriptomic profiles of medium/large EVs were generated using the MARS-Seq RNA-Seq protocol (n = 12/group). The serum concentration of the differentially expressed gene S100A9, in serum calprotectin (S100A8/A9), was validated by ELISA in control (n = 100) and PAD patients (n = 317). S100A9 was also determined in EVs and tissues of human atherosclerotic plaques (n = 3). Circulating EVs of PAD patients were mainly of platelet origin, predominantly Annexin V positive and were associated with the procoagulant activity of platelet-free plasma. Transcriptomic analysis of EVs identified 15 differentially expressed genes. Among them, serum calprotectin was elevated in PAD patients ( p  < 0.05) and associated with increased amputation risk before and after covariate adjustment (mean follow-up 3.6 years, p  < 0.01). The combination of calprotectin with hs-CRP in the multivariate analysis further improved risk stratification ( p  < 0.01). Furthermore, S100A9 was also expressed in femoral plaque derived EVs and tissues. In summary, we found that PAD patients release EVs, mainly of platelet origin, highly positive for AnnexinV and rich in transcripts related to platelet biology and immune responses. Amputation risk prediction improved with calprotectin and was significantly higher when combined with hs-CRP. Our results suggest that EVs can be a promising component of liquid biopsy to identify the molecular signature of PAD patients., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles.)

Meningiomas are primary tumors of the central nervous system composed of both neoplastic and other infiltrating cells. We determined the cellular composition of 51 meningioma samples by multiparameter flow cytometric (MFC) immunophenotyping and investigated the potential relationship between mRNA and protein expression levels of neoplastic cells. For immunophenotypic, morphologic, and cytogenetic characterization of individual cell populations, a large panel of markers was used together with phagocytic/endocytic functional assays and MFC sorting. Overall, our results revealed coexistence of CD45(-) neoplastic cells and CD45(+) immune infiltrating cells in all meningiomas. Infiltrating cells included tissue macrophages, with an HLA-DR(+)CD14(+)CD45(+)CD68(+)CD16(-/+)CD33(-/+) phenotype and high phagocytic/endocytic activity, and a small proportion of cytotoxic lymphocytes (mostly T CD8(+) and natural killer cells). Tumor cells expressed multiple cell adhesion proteins, tetraspanins, HLA-I/HLA-DR molecules, complement regulatory proteins, cell surface ectoenzymes, and growth factor receptors. Noteworthy, the relationship between mRNA and protein levels was variable, depending on the proteins evaluated and the level of infiltration by immune cells. In summary, our results indicate that MFC immunophenotyping provides a reliable tool for the characterization of the patterns of protein expression of different cell populations coexisting in meningioma samples, with a more accurate measure of gene expression profiles of tumor cells at the functional/protein level than conventional mRNA microarray, independently of the degree of infiltration of the tumor by immune cells., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

An actualized revision of the most important aspects of aneurismal subarachnoid hemorrhage is presented from the guidelines previously published by the group of study of cerebrovascular pathology of the Spanish Society of Neurosurgery. The proposed recommendations should be considered as a general guide for the management of this pathological condition. However, they can be modified, even in a significant manner according to the circumstances relating each clinical case and the variations in the therapeutic and diagnostic procedures available in the center attending each patient.

BACKGROUND. The Spanish neurosurgical society created a multicentre data base on spontaneous SAH to analyze the real problematic of this disease in our country. This paper focuses on the group of patients with idiopathic SAH (ISAH). METHODS. 16 participant hospitals collect their spontaneous SAH cases in a common data base shared in the internet through a secured web page, considering clinical, radiological, evolution and outcome variables. The 220 ISAH cases collected from November 2004 to November 2007 were statistically analyzed as a whole and divided into 3 subgroups depending on the CT blood pattern (aneurysmal, perimesencephalic, or normal). RESULTS. The 220 ISAH patients constitute 19% of all 1149 spontaneous SAH collected in the study period. In 46,8% of ISAH the blood CT pattern was aneurysmal, which was related to older age, worse clinical condition, higher Fisher grade, more hydrocephalus and worse outcome, compared to perimesencephalic (42.7%) or normal CT (10.4%) pattern. Once surpassed the acute phase, outcome of ISAH patients is similarly good in all 3 ISAH subgroups, significantly better as a whole compared to aneurysmal SAH patients. The only variable related to outcome in ISAH after a logistic regression analysis was the admission clinical grade. CONCLUSIONS. ISAH percentage of spontaneous SAH is diminishing in Spain. Classification of ISAH cases depending on the blood CT pattern is important to differentiate higher risk groups although complications are not negligible in any of the ISAH subgroups. Neurological status on admission is the single most valuable prognostic factor for outcome in ISAH patients.

Cytogenetic analysis is a powerful tool for predicting recurrence in meningiomas, even among histologically benign/grade I tumors. Despite this, no study has been reported in which the impact of tumor cytogenetics on the gene expression profiles (GEP) has been analyzed in meningiomas. Here, we analyzed the GEP of 47 tumors and correlated them with the most clinical relevant cytogenetic subgroups of meningiomas, as confirmed through the analysis of 172 patients. Additionally three normal meningeal samples were also studied. Overall, our results show a clear association between the clinically relevant cytogenetic subgroups of meningiomas including diploid tumors (n = 18), isolated -22/22q- (n = 12), del(1p36) alone (n = 4) and complex karyotypes associated with del(1p36) and/or -14q (n = 13) and their GEP. Accordingly, based on the expression of 85 genes (40 of which were coded in the altered chromosomes used for patient stratification) the cytogenetic class of the tumor could be predicted with an error of <1%, a clear association being found between the GEP and patient outcome (P = 0.03) but not tumor histopathology. In summary, we show a clear association between GEP of neoplastic cells and clinically relevant cytogenetic subgroups of meningiomas.

Introduction: Subarachnoid haemorrhage is one of the most severe neurosurgical diseases. Its study is crucial for improving the care of these patients in our environment. With this goal the Group for the Study of Neurovascular Pathology of the Spanish Society for Neurosurgery (SENEC) decided to create a multicenter registry for the study of this disease., Materials and Methods: In this database we have prospectively included all cases with spontaneous subarachnoid haemorrhage admitted to the participant hospitals from November 2004 to November 2007. The fields to be included in the database were selected by consensus, including age, past medical history, clinical characteristics at admission, radiological characteristics including presence or absence of an aneurysm and its size and location, type and complications of the aneurysm treatment, outcome assessed by the Glasgow Outcome Scale (GOS) at discharge and six months after the bleeding as well as the angiographic result of the aneurysm treatment. All fields were collected by means of an electronic form posted in secure web page., Results: During the three years of study a total of 1149 patients have been included by 14 Hospitals. The time needed to fill in a patient in the registry is approximately 3.4 minutes. This series of patients with spontaneous SAH is similar to other non-selected in-hospital series of SAH. The mean age of the patients is 55 years and there is a 4:3 female to male ratio. In relation to the severity of the bleeding 32% of the patients were in poor clinical grade at admission (WFNS 4 or 5). 5% of the patients died before angiography could be performed. An aneurysm was confirmed as the origin of the bleeding in 76% of the patients (aSAH), while in 19% of the patients no lesion was found in the angiographic studies and were thus classified as idiopathic subarachnoid hemorrhage (ISAH). Of those patients with aSAH, 47% were treated endovascularly, 39% surgically, 3% received a combined treatment and 11% did not receive any treatment for their aneurysm because of early death. Regarding outcome, there is a 22% mortality in the series. Only 40% of the patients with aSAH reached a good outcome at discharge (GOS = 5)., Conclusions: Spontaneous SAH continues to be a disease with high morbidity and mortality. This database can be an ideal instrument for improving the knowledge about this disease in our environment and to achieve better results. It would be desirable that this database could in the future be the origin of a national registry of spontaneous SAH.

Background: There is general consensus that a successful endoscopic third ventriculostomy is usually followed by a decrease of ventricular size without reaching their normal size. This study was performed to determine how the change related to clinical outcome, how it developed chronologically and whether the change in ventricular size was different in acute and chronic forms of hydrocephalus., Method: Fifty-five of 74 patients who had undergone endoscopic third ventriculostomy during the period 1997-2004 were selected by the criterion that they had both pre-operative and post-operative films and no neurosurgical manoeuvre other than a surgically successful endoscopic third ventriculostomy in the time span between both radiological studies. Ventricular size was measured with the Evans index, third ventricle index, cella media index and ventricular score. Median age was 51 years (interquartile range, 27-65 years)., Results: The change in ventricular size detected shortly after surgery is related to clinical outcome for all ventricular ratios, except the cella media index (p = 0.08). When third ventriculostomy is clinically successful, there is a gradual decrease of ventricular size over a period of more than three months (p < 0.0001 for all ventricular ratios). The reduction is more prominent in acute hydrocephalus than in chronic forms for all ventricular ratios, except the Evans index (p = 0.12). The third ventricle exhibits the greatest reduction (25% with a 95% confidence interval: 15.4-34.5) and determines a different pattern of change in ventricular size after endoscopic third ventriculostomy between acute and chronic hydrocephalus., Conclusions: A decrease of the ventricular size detected soon after endoscopic third ventriculostomy is associated with a satisfactory clinical outcome. This response continues during the first few months after surgery. The reduction is more prominent in acute forms of hydrocephalus.

Tumor recurrence is the major clinical complication in meningiomas, and its prediction in histologically benign/grade I tumors remains a challenge. In this study, we analyzed the prognostic value of specific chromosomal abnormalities and the genetic heterogeneity of the tumor, together with other clinicobiological disease features, for predicting early relapses in histologically benign/grade I meningiomas. A total of 149 consecutive histologically benign/grade I meningiomas in patients who underwent complete tumor resection were prospectively analyzed. Using interphase fluorescence in situ hybridization, we studied the prognostic impact of the abnormalities detected for 11 different chromosomes, together with other relevant clinicobiological and histopathological characteristics of the disease, on recurrence-free survival (RFS) at 2.5, 5, and 10 years. From the prognostic point of view, losses of chromosomes 9, 10, 14, and 18 and del(1p36) were associated with a shorter RFS at 2.5, 5, and 10 years. Similarly, histologically benign/grade I meningiomas showing coexistence of monosomy 14 and del(1p36) in the ancestral tumor cell clone displayed a higher frequency of early relapses. In fact, coexistence of -14 and del(1p36) in the ancestral tumor cell clone, together with tumor size, represented the best combination of independent prognostic factors for the identification of those patients with a high risk of an early relapse. Our results indicate that patients with large histologically benign/grade I meningiomas carrying monosomy 14 and del(1p36) in their ancestral tumor cell clone have a high probability of relapsing early after diagnostic surgery. These findings suggest the need for closer follow-up in this small group of patients.

The female predominance of meningiomas has been established, but how this is affected by hormones is still under discussion. We analyzed the characteristics of meningiomas from male (n = 53) and female (n = 111) patients by interphase fluorescence in situ hybridization (iFISH). In addition, in a subgroup of 45 (12 male and 33 female) patients, tumors were hybridized with the Affymetrix U133A chip. We show a higher frequency of larger tumors (p = .01) and intracranial meningiomas (p = .04) together with a higher relapse rate (p = .03) in male than in female patients. Male patients had a higher percentage of del(1p36) (p < .001), while loss of an X chromosome was restricted to tumors from female patients (p = .008). In turn, iFISH studies showed a higher frequency of chromosome losses, other than monosomy 22 alone, in meningiomas from male patients (p = .002), while female patients displayed a higher frequency of chromosome gains (p = .04) or monosomy 22 alone (p = .03) in the ancestral tumor clone. Interestingly, individual chromosomal abnormalities had a distinct impact on the recurrence-free survival rate of male versus female patients. In turn, gene expression showed that eight genes (RPS4Y1, DDX3Y, JARID1D, DDX3X, EIF1AY, XIST, USP9Y, and CYorf15B) had significantly different expression patterns (R(2) > 0.80; p < .05) in tumors from male and female patients. In summary, we show the existence of different patterns of chromosome abnormalities and gene-expression profiles associated with patient gender, which could help to explain the slightly different clinical behavior of these two patient groups.

Objective: To describe the stage-related clinical features of 8th cranial nerve schwannoma., Material and Method: Descriptive study of 71 patients whose diagnosis and/or treatment have been carried out at our centre between 1997-2003. Gender, age, and symptoms were considered, with special attention to gender. Determination of tumoral stage following Tos and Thomsen image criteria., Results: The mean age was 64.6 (range, 20-87) with a marked incidence between 52 and 70 years (62 % of the whole), slightly higher in females and in the left ear. The main symptoms were those derived from involvement of the 7th and 8th cranial nerves, with other cranial nerves and cerebello-pontine structures being involved in larger tumours, although a high variability was noted in clinical patterns of same-stage cases and in the first symptom. Our study also found a high variability in hearing conservation and a marked frequency of vestibular or facial (motor and sensory) symptoms. There were also very infrequent forms of presentation that are highlighted., Conclusions: There is no typical clinical pattern and no typical first symptom in 8th cranial nerve schwannomas. Any audiovestibular or facial symptom, even the slightest, may be the first expression of 8th cranial nerve schwannoma. There is no stage-specific symptom except for those with involvement of the cerebello-pontine or cerebral structures.

Objective: The aim of this study was to build a preoperative predictive system which could provide reliable information about: 1 degrees which skull base meningiomas can be total or partially removed, and 2 degrees their surgical outcome., Method: Patient histories and imaging data were reviewed retrospectively from 85 consecutive skull base meningiomas patients who underwent surgery from 1990 and 2002. From the preoperative data, nine variables were selected for conventional statistical analysis as regards their relationship with: 1 degrees total vs partial tumor resection and 2 degrees with patients outcome according to the degree of tumour removal., Results: From the nine variables analysed only two had a statistical association with the type of tumour resection performed (total vs partial) and the patient outcome: 1) arteries encasement and 2) cranial nerves involvement. Upon correlating these two variables with the type of tumour resection performed (total vs partial) and with the Karnofsky'scale to evaluate patients surgical outcome, the following grading groups were identified: Grade I: skull base meningiomas which did not involve cranial nerves or artery or only encased one artery or one cranial nerve. In these cases the incidence of gross tumour resection was 98.3% (p< 0.0001) and the perspective to reach 70 points in the Karnofsky'scale was of 96.5% ( p=0.001). Grade II: skull base meningiomas which involved one cranial nerve and encased, at least, two main cerebral arteries. In these cases, the frequency of total resection, decreased to 83.3% (p<0.0001) and the probability to reach 70 points in the Karnofsky'scale was 70.6% (p=0.001). Grade III: skull base meningiomas which involved two or more cranial nerves and encased several arteries In this group, the frequency of a total resection was of 42.9% (p<0.0001) and the probability of reaching 70 points in the Karnofsky'scale was only 60% (p=0.001)., Conclusions: We propose a preoperative grading system for skull base meningiomas that helps predicting both whether total or partial tumor removal will be achieved during surgery and the immediate postsurgical outcome of the patient. In applying this predictive system we will be able to reduce surgical morbidity, to advance the possibility of a radiosurgical treatment and give a more precise information to the patients and their families about our surgical decision-making process.

Purpose: Meningiomas are usually considered benign tumors. However, relapses occur in 10% to 20% of all patients, including both histopathologically aggressive and benign tumors. This study explored the value of numerical abnormalities for 10 different chromosomes in meningiomas for predicting relapse-free survival (RFS)., Patients and Methods: This study prospectively analyzed the frequency of numerical abnormalities of chromosomes 1, 9, 10, 11, 14, 15, 17, 22, X, and Y in 70 meningioma patients by fluorescence in situ hybridization and their relationship with disease characteristics at diagnosis and patients' outcome., Results: Results showed the presence of numerical abnormalities for one or more chromosomes in most patients (77%). Chromosome 22 in the whole series and chromosome Y in males were those more frequently altered, followed by chromosomes 1, 14, and X in females. Patients with abnormalities of chromosomes 1, 9, 10, 11, 14, 15, 17, the sex chromosomes, and gains of chromosome 22 were associated with adverse prognostic features, more frequent relapses, and shorter RFS. Multivariate analysis showed that tumor grade together with chromosome 14 status and age were the best combination of independent variables for predicting RFS. According to these variables, all patients with a score of two or more than two adverse prognostic factors had experienced relapse at 5 years, whereas none of those with a score of zero had experienced relapse 10 years after surgery., Conclusion: In addition to age and histologic grade, abnormalities of chromosome 14 contribute to a better prognostic stratification of meningioma patients at diagnosis. Additional prospective studies in larger series of patients, also including larger numbers of patients who experienced relapse, are necessary to confirm the utility of the proposed predictive model.

Intracerebral hemorrhage ocurring after chronic subdural hematoma evacuation, is a rare and very serious postoperative complication. The sudden increase of cerebral blood flow in the hemisphere beneath the hematoma, is the most likely mechanism responsible for this situation. Two new cases of intracerebral hemorrage after evacuation of chronic subdural hematomas are reported.

Introduction: Hydrocephalus, cerebrospinal fluid (CSF) leak, pseudomeningocele and CSF infection are potential complications related to surgical treatment of posterior fossa tumors. The objectives of this study were to review the incidence of such complications and to identify contributing factors related to them., Material and Methods: This study is based on a retrospective review of the medical records of 71 consecutive patients who underwent posterior fossa surgery for a tumor between the period January 1997 and December 2001. Postoperative hydrocephalus was defined as enlargement of the ventricles and the subsequent clinical worsening requiring surgical treatment. Criteria for CSF leakage were:observed leak of CSF through the wound, rhinorrhea or otorrhea. Pseudomeningocele was determined when there was a large epidural CSF collection diagnosed in the postoperative period or by magnetic resonance imaging performed at least three months after posterior fossa surgery. Finally, CSF infection was defined on clinical ground and positive biochemical examination, but not necessarily positive cultures., Results: The series included 84 operations for resection of posterior fossa tumors on 71 patients. There were CSF related complications in 31% (26/84)with the following detailed incidence: 9.5% (8/84) postoperative hydrocephalus; 14.3% (12/84) CSF leak, 7.1% (6/84) pseudomeningocele; 8.3% (7/84) CSF infection. The mortality rate is 5.9% (5/84). The tumor size was the only statistically significant factor associated with the occurrence of CSF related complications (mean 39.43 mm, SD 18.51 mm vs.29.80 mm, SD 14.12 mm, p=0.015). In the subgroup of patients, in which hydrocephalus was managed preoperatively, the election of an external ventricular drain vs.other strategies (subcutaneous reservoir, definite shunt or endoscopic third ventriculostomy) was associated with a higher occurrence of CSF related complications (p=0.006). The mortality rate was associated with age (mean 63.60 years, SD 5.86 years vs.49.18 years, SD 16.39 years; p=0.002). The occurrence of CSF related complications also influenced mortality (p=0.030), particularly postoperative hydrocephalus (p< 0.001). Inpatient hospital stay was longer in the subgroup of patients who developed CSF related complications (p=0.002)., Conclusions: Tumor size was the only factor associated with the development of CSF related complications after surgery for posterior fossa tumors. In the subgroup of patients in which hydrocephalus was surgically treated preoperatively, the election of an external ventricular drain compared to other surgical modalities was associated with a higher rate of CSF related complications. The development of such complications, particularly hydrocephalus, was related with mortality.

Objective: The results obtained with therapy of intracranial aneurysms, in terms of morbidity and mortality, are very important when the patient has to choose between microsurgical techniques or endovascular management. The aim of this paper is to review the information regarding current microsurgical treatment of intracranial aneurysms, and presenting our experience over the last five years., Material and Methods: We studied 101 consecutive patients with 121 intracranial aneurysms admitted between 1996 and 2000 with the initial diagnosis of subarachnoid hemorrhage. We paid special attention to the day of admission from the onset of the symptomatic hemorrhage to the grade of Hunt&Hess scale and the possibility of early or delayed microsurgical treatment. The diagnosis was based on four vessels cerebral angiography and in a few cases with CT-angiography. All patients were treated by microsurgical technique and such treatment was completed by nimodipine, intensive care unit management and in some cases of postoperative suspected vasospasm, induced arterial hypertension was applied. Post surgical angiography was carried out in all patients to confirm the clipping of the cerebral aneurysm. The 12 months assessment was based on the Glasgow Outcome Scale (GOS)., Results: The 92.1% of the patients were admitted with a grade equal or below III in the Hunt&Hess scale. A 80% were operated within the 72 hours of admission and in the remaining cases, the surgical treatment was delayed due to a grade IV or V or to a medical contraindication. Four patients died (3.9%). At 12 months follow up, 88.9% presented a score I or II in the GOS., Conclusion: According to our results, there are a substantial improvements in the microsurgical treatment of cerebral aneurysms, specially in patients admitted early after the onset of the symptoms of their hemorrhage, who have a grade I to III in the Hunt&Hess scale and showed a good level of consciousness. We think that the improvement of our results are due to: l. the high percentage of patients admitted with grades I to III. 2. the high percentage of patients operated within the first 72 hours from the onset of their symptomatic hemorrhage. 3. surgery was always carried out by the same two experienced vascular neurosurgeons. 4. intraoperative measures taken to prevent the rupture of the aneurysm. 5. early administration of nimodipine, ICU management, doppler studies and in seldom cases, induced hypertension therapy to treat the vasospasm and postoperative hypotension.

Meningeal melanocytomas are infrequent tumors that when located in the spinal cord and because of their close relationship to the nerve root can resemble a neurinoma. The MRl can help to differentiate them from the neurinomas preoperatively. The case of a female patient harboring a cervical meningeal melanocytoma involving the C7 nerve root, and diagnosed preoperatively as an hourglass neurinoma is presented.

Objective: Although information on the cytogenetic characteristics of meningioma tumors has accumulated progressively over the past few decades, information on the genetic heterogeneity of meningiomas is still scanty. The aim of the present study was to analyze by interphase fluorescence in situ hybridization (FISH) the incidence of numerical abnormalities for chromosomes 1, 9, 10, 11, 14, 15, 17, 22, X, and Y in a group of 70 consecutive meningioma tumors. Another goal was to establish the potential associations among the altered chromosomes, as a way to assess both intertumoral and intratumoral heterogeneity., Methods: For the purpose of the study, 70 patients diagnosed with meningioma were analyzed. Interphase FISH for the detection of numerical abnormalities for chromosomes 1, 9, 10, 11, 14, 15, 17, 22, X, and Y was applied to fresh tumor samples from each of the patients studied., Results: The overall incidence of numerical abnormalities was 76%. Chromosome Y in males and chromosome 22 in the whole series were the most common abnormalities (46% and 61%, respectively). Despite the finding that monosomy of chromosome 22/22q(-) deletions are the most frequent individual abnormality (53%), we have observed that chromosome gains are significantly more common than chromosome losses (60% versus 40%). Chromosome gains corresponded to abnormalities of chromosomes 1 (27%), 9 (25%), 10 (23%), 11 (22%), 14 (33%), 15 (22%), 17 (23%), and X in females (35%) and males (23%) whereas chromosome losses apart from chromosome 22 frequently involved chromosomes 14 (19%), X in males (23%), and Y in males (32%). Although an association was found among most gained chromosomes on one side and chromosome losses on the other side, different association patterns were observed. Furthermore, in the latter group, monosomy 22/22q(-) was associated with monosomy X in females and monosomy 14/14q(-) was associated with nulisomy Y in males. In addition, chromosome losses usually involved a large proportion of the tumor cells whereas chromosome gains were restricted to small tumor cell clones, including tetraploid cells., Conclusions: Our results show that meningiomas are genetically heterogeneous tumors that display different patterns of numerical chromosome changes, as assessed by interphase FISH., (Copyright 2002 Wiley-Liss, Inc.)

Stroke is a very uncommon complication of hydatic disease. The case of a pediatric patient who suffered cerebral infarction due to the occlussion of the right middle cerebral artery, and who subsequently developed multiple hydatic cysts in the territory of the occluded vessel, is presented. Even though the diagnostic tests aimed to detect a primary focus of the disease were negative, the existing data support the possibility of a cardiac embolic origin.

Cimino-Brescia performed in 1966 an internal by-pass between an artery and a peripheral vein resulting in an internal arteriovenous fistula (FAVI). Since then, it has been the most used and first chosen vascular access for haemodialysis. Due to the regular use of the access, as well as the patients' chronic condition and the associated pathologies, vascular access can become exhausted, necessitating continuous research and new alternatives to be resorted to.

Using a combined scanning and electron microscope technique, the repercussion on the rostral wall of the III ventricle in a patient affected with a retrochiasmatic craniopharyngioma with growth in the ventricular direction were analysed. The apical surface of the ependymocytes was found to be free of cilia, although there were numerous microvilli. The most striking finding appreciated with the scanning electron microscope was the presence of bulbous protrusions towards the lumen of the ventricle; these were formed of cells with shapes, sizes and surface characteristics different from the rest of the ependyma, which appeared flattened. The ultrastructural study revealed the presence of large numbers of filaments and junction complexes both in the ependymal and subependymal cells. Additionally, the protruded zones corresponded to areas showing different degrees of cellular disorganization.

The natural history of symptomatic adult type I Arnold-Chiari (ACM1) malformation is variable. Patients with this condition frequently develop corticospinal and sensory deficits, together with cerebellar signs and lower cranial nerve palsies in various combinations. In the present report we describe a patient with ACM1 in whom sleep apnea together with disturbances in the central regulation of arterial pressure were a major component of the symptomatology. These paroxysmal blood pressure changes has not been previously reported. The decompression of our patient's medulla, which contains the primary respiratory centers and baroreceptors, resulted in a marked improvement and indicate that the origin may have been on a central basis.

A combined morphological study using transmission and scanning electron microscopy was carried out on the central zone of the rostral wall of the III ventricle from a sample taken during the operation of a patient with a retrochiasmatic craniopharyngioma. Under the scanning electron microscope, the apical cell wall of the ependymocytes generally appeared folded and lack in cilia, but with numerous microvilli developed to different extents. The flat surface cells were scarce and were polygonal in shape and limited by 3-7 prominent edges. Ultrastructural analysis revealed the existence of several types of ependymocytes and subependymal epithelial cells arranged in different layers; in both layers the presence of abundant neurofilaments and intercellular junctions was striking.

Dissecting aneurysms of the intracranial arteries display vascular pathological features that appear sporadically, generally affecting young adults. The clinical features of this condition may involve both ischemic episodes and hemorrhages. Posterior circulation is affected less than the rest of the intracranial arteries, and it is extremely rare to find the posterior cerebral arteries only affected. Mortality is high in patients where the lesion is located in the posterior intracranial circulation, although dissecting aneurysms limited to the posterior cerebral arteries may, to a certain extent, be benign. We report the case of a young woman with ischemia in the territory of the posterior cerebral artery that occurred subsequent to a dissecting aneurysm that resolved spontaneously to a complete remission, both clinically and as demonstrated by angiography. A review of the literature is made, analyzing the pathogenic, clinical, angiographic, and therapeutic characteristics of such lesions.

Meningiomas are uncommon tumors in infancy. Intraventricular meningiomas do occur more frequently in infancy than in adulthood, although the establishment and growth of such tumors in the fourth ventricle is exceptional in children. The occurrence of multiple meningiomas is currently estimated to be less than 8%. We present the case of a girl who displayed two meningiomas in the fourth ventricle. Five years later, the child had four more meningiomas detected and extirpated from the same site. Eighteen months later, a new tumor appeared in the lower third of the clivus; after resection this was found to be another meningioma. The presence in a child of the repeated occurrence of multiple meningiomas, both in the fourth ventricle and in other areas of the posterior fossa, have led the authors to consider that the case is both curious and rare. Twelve similar cases of meningiomas developing exclusively in the fourth ventricle have been published; of these, only 3 occurred during infancy. A discussion is offered concerning the etiology and pathogenesis of these tumors; in which the possibility of unknown neuro-oncogenic factors that might induce meningiomas is postulated.

Based on current controversies on optimal treatment for spontaneous intracerebral haematomas, chronic experiments to investigate the validity of open surgery, stereotactic evacuation and local urokinase administration in these lesions were performed in 52 dogs. Under general anesthesia diverse volumes of autologous blood were intracerebrally injected to produce the haematoma. A catheter was introduced and chronically implanted in the contralateral ventricle for intracranial pressure monitoring. The animals were divided in two groups of 26 dogs each, according to haematoma location in subcortical or basal ganglia structures. The natural history was studied in both groups. Different types of treatment consisting in surgery, stereotactic evacuation, urokinase injection within the clot and both latter techniques combined were carried out 24 or 72 hours following haematoma production. Clinical status, systemic arterial pressure, intracranial pressure and CT scanning were used for result evaluation. Brain specimens were submitted for pathological examination. Our results indicate that stereotactic evacuation performed during the first 24 hours after haematoma occurrence was the most effective and innocuous procedure for basal ganglia lesions. Local urokinase plus stereotactic aspiration showed a high efficacy in controlling delayed basal ganglia and subcortical blood collections. Other therapeutic approaches behaved almost as the natural history.