Spinal cord lipomas: lessons learned in the era of total resection.

PURPOSE: Recent years have seen a paradigm shift towards total/near-total resection in spinal cord lipoma surgery. As this procedure is technically challenging, surgical candidates need to be selected appropriately through accurate image assessment and classification. The purpose of this paper is to describe a surgical series of paediatric spinal cord lipomas, their diagnosis, results and complications. METHODS: We undertook a retrospective review of paediatric patients with spinal cord lipomas who underwent surgery between 2008 and 2022. The variables studied were age, gender, preoperative symptoms according to the Necker Functional Score (NFS), type of lipoma according to Morota's classification, functional and radiological surgical outcomes using the cord-sac ratio (CSR), need for re-operation, complications and follow-up. RESULTS: A total of 25 patients (average age 36 months) underwent surgery. According to Morota's classification, MRI showed 13 type 1 lipomas, two type 2, two type 3 and eight type 4. The preoperative NFS was 16.06, with urological abnormalities being the most frequent manifestation. Total/near-total resection was attempted since 2015. Five patients with type 1 lipoma required re-operation due to clinical deterioration with suspected retethering, all of them with a CSR > 0.3. The series average CSR was 0.417. CONCLUSIONS: This paper highlights the importance of proper classification for a correct surgical approach to obtain favourable results and minimise possible complications. Based on our experience, given our results regarding the percentage of fistulae and retethering rates, we limited radical resection to symptomatic type 1 lipomas. Our future aim is to obtain better CSR rates and to decrease the retethering percentage.

Neuroendoscopic septostomy in unilateral and bilateral ventricular hydrocephalus.

PURPOSE: This study describes the results of septostomy (SPT) in terms of success and analysis of follow-up in a series of pediatric patients diagnosed with unilateral ventricular hydrocephalus (UHV) and biventricular hydrocephalus (BVH). METHODS: A total of 29 pediatric patients diagnosed with UVH or BVH were included in this study. In UVH, a neuroendoscopic SPT was performed (sometimes accompanied by NEFPFMO). In those diagnosed with BVH, an SPT combined with VPS was carried out. Demographic, etiological, clinical, and diagnostic variables and percentage of treatment success were collected. RESULTS: SPT was successful during follow-up when no VPS was required in UVH and only unilateral VPS was implanted in BVH. At the time of surgery, 16 patients needed a ventriculoperitoneal shunt. The first SPT was successful in 22 patients, requiring a second surgery in 7 patients, from the oncology group diagnosed with BHV. CONCLUSIONS: The surgical management of UVH and BVH still has some disclosure points to be reviewed. However, SPT seems to be a secure, non-traumatic, and efficient procedure.

FURIN gene variants (rs6224/rs4702) as potential markers of death and cardiovascular traits in severe COVID-19.

Furin is a protease that plays a key role in the infection cycle of SARS-CoV-2 by cleaving the viral proteins during the virus particle assembly. In addition, Furin regulates several physiological processes related to cardio-metabolic traits. DNA variants in the FURIN gene are candidates to regulate the risk of developing these traits as well as the susceptibility to severe COVID-19. We genotyped two functional FURIN variants (rs6224/rs4702) in 428 COVID-19 patients in the intensive care unit. The association with death (N = 106) and hypertension, diabetes, and hyperlipidaemia was statistically evaluated. The risk of death was associated with age, hypertension, and hypercholesterolemia. The two FURIN alleles linked to higher expression (rs6224 T and rs4702 A) were significantly increased in the death cases (odds ratio= 1.40 and 1.43). Homozygosis for the two high expression genotypes (rs6224 TT and rs4702 AA) and for the T-A haplotype was associated with an increased risk of hypercholesterolemia. In the multiple logistic regression both, hypercholesterolemia and the TT + AA genotype were significantly associated with death. In conclusion, besides its association with hypercholesterolemia, FURIN variants might be independent risk factors for the risk of death among COVID-19 patients.

The APOB polymorphism rs1801701 A/G (p.R3638Q) is an independent risk factor for early-onset coronary artery disease: Data from a Spanish cohort.

BACKGROUND AND AIMS: Apoliprotein B (ApoB) has been associated with hypercholesterolemia and ischemic coronary disease. This study was aimed to determine the effect of two APOB gene variants in the risk of developing early-onset coronary artery disease (EO-CAD) in a Spanish population. The association of these polymorphisms with hypercholesterolemia was also analysed. METHODS AND RESULTS: The study involved a total of 889 healthy population controls (397 male) and 790 EO-CAD cases (636 male; EO-CAD was defined as male <60 years and women <65 years). All the patients had at least one vessel with angiography documented atherosclerotic lesion. Patients and controls were genotyped for the APOB variants rs1801701 A/G (p.R3638Q) and rs1367117 C/T (p.T98I). Allele and genotype frequencies were compared between the groups (patients vs. controls, hyper-vs. normo-cholesterolemia) by logistic regression. The rs1801701 was significantly associated with EO-CAD in male (OR = 1.44, 95%CI = 1.05-1.99) and female (OR = 2.22, 95%CI = 1.58-3.14). This SNP was significantly associated with hypercholesterolemia in female, with a trend in male. The association with EO-CAD was independent of hypercholesterolemia (multiple logistic regression). CONCLUSION: A common APOB polymorphism (rs1801701) was an independent risk factor for EO-CAD in our population. The risk-effect was more significant in female than in male.

Conventional posterior cranial vault expansion: indications and results-review of the literature.

In the late 1980s, craniofacial surgery units reported suboptimal cosmetic results, cranial volume restriction, and intracranial hypertension after anterior cranial vault remodeling in bilateral coronal synostosis associated with severe brachyturricephaly. A possible explanation was a severe associated growth restriction of the posterior calvaria with radiological synostosis at the lambda sutures. "Conventional" or "fixed" posterior cranial vault expansion techniques were developed to address these limitations, sometimes as the first surgical step in a two-staged protocol of total calvarial reconstruction, combined with suboccipital decompression in cases of symptomatic cerebellar tonsillar herniation or, more easily, to resolve the characteristic occipital flattening of lambdoid synostosis. Various surgical approaches have been described; however, the indications for and timing of surgical treatment and postoperative evaluation of results still remain controversial. Although more invasive, conventional posterior cranial vault expansion has proven to be safe and offers a remodeled and protective bony vault immediately after surgery, but the underlying cranial base malformation remained untreated, with implications in the postoperative growth of the facial skeleton. Overcorrection, rigid stabilization, and grafting are also concerns to be addressed.

Quality of life in school-age children with shunt implantation due to neonatal posthemorrhagic hydrocephalus.

PURPOSE: To assess the functional outcome in school-age children shunted in the neonatal period due to post-hemorrhagic hydrocephalus (PHH), using the HOQ-Spanish version (HOQ-sv), and to analyze predictors of quality of life in this group. METHODS: A cross-sectional study was performed between 2015 and 2018. Parents of pediatric patients with PHH attending our neurosurgery outpatient clinic were invited to complete the HOQ-sv and to enroll in the study. Clinical variables regarding the patients' neonatal course and surgical outcome were recorded. A descriptive analysis was done, and independent variables related to the HOQ scores were studied in univariate and multivariate analyses with regression trees. RESULTS: The study comprised a total of 52 patients. The mean overall HOQ score was 0.67 (on a scale from 0 [worse] to 1 [best]). The quality of life for the PHH children at school age was related to perinatal factors (gestational age at birth, time until shunt surgery, length of hospitalization at the time of shunt implantation, and comorbidity), shunt complications (symptomatic overdrainage, number of shunt revisions, and shunt revisions related to infection during the first year after treatment), and clinical background (seizures, spasticity, Gross Motor Function Classification System level or visual impairment). CONCLUSION: HOQ dimension scores in school-age children shunted due to PHH in our center were similar to those of referral centers for other etiologies of pediatric hydrocephalus. Future goals should be the prevention of complications related to worse outcomes at the time of diagnosis and to try to improve shunt performance later.

Cervical myelomeningocele with CSF leakage: a case-based review.

BACKGROUND: The cystic spinal dysraphism of the cervical and upper thoracic region (CDCT) accounts for only 3.9 to 8% of spina bifida cystica lesions. The presence of external cerebrospinal fluid (CSF) leakage is infrequent and very few authors have reported about surgical complications. CASE REPORT: We present the case of a new born diagnosed of CDCT C1-C3 with a stalk of fibrovascular tissue, CSF leakage, hydrocephalus, and type Chiari II malformation, discuss about the chosen surgical technique and the associated complications, and make a review of the literature focusing on the main aspects of CDCT. CONCLUSIONS: The CDCT with a stalk of neuroglial and/or fibrovascular tissue originates from the dorsal surface of the spinal cord and penetrates into a cervical cystic sac. The presence of CSF leakage, hydrocephalus, and/or type Chiari II malformation can influence to decide the most appropriate surgical technique.

Suprasellar ganglioglioma presenting as a middle cerebral artery infarction.

BACKGROUND: Gangliogliomas are a relatively rare neoplasm with a major incidence in the pediatric population. As the temporal lobes are the most common site, patients usually present with seizures. CASE REPORT: We report the case of a 9-year-old child with an extensive suprasellar ganglioglioma presenting with a cerebral infarction due to direct compression of the medium cerebral artery. CONCLUSIONS: Suprasellar lesions can compress adjacent vascular structures, so an accurate diagnosis is necessary for an early treatment.

Shunt independence in paediatric hydrocephalus: our 16-year experience and review.

PURPOSE: Shunt independence remains a matter of debate for neurosurgeons, and little information on this subject is available in the literature. The aims of the study were to analyse the incidence of shunt removal in a series of paediatric patients and to describe our experience with attempts at shunt removal. METHODS: Thirty of 212 paediatric patients shunted between 2000 and 2016 at our institution were studied for shunt independence. Variables related to hydrocephalus aetiology, shunt complications, independence trial peculiarities and follow-up were recorded and a descriptive analysis of the data was performed. RESULTS: Two patients (0.94%) refused to be included in a shunt independence trial and were analysed separately. In the other 28 patients, 29 shunt independence trials were performed, of which 19 (65.52%) were successful, giving a global rate of shunt independence of 8.96% (19/212) in our population. Secondary endoscopic third ventriculostomy was the most frequent type of independence trial and achieved the highest success rate (75%). Spontaneous independence was achieved in just 4/7 cases (57.14%). Planned removal of the shunt in overdrainage cases had a 50% success rate, with transient measures to control intracranial pressure frequently required. CONCLUSIONS: Shunt independence trials should be considered for selected patients in a closely monitored setting. Secondary endoscopic third ventriculostomy at the time of shunt malfunction has the highest success rate whereas planned removal of the shunt in overdrainage is an invasive procedure with more likelihood of failure. Shunt independence should not be presumed.

Shunt overdrainage syndrome: review of the literature.

Shunt overdrainage in patients with hydrocephalus still represents a challenge for neurosurgeons, in part due to the lack of agreement or uniformity concerning the entity. Important problems exist relating to the real incidence of the entity, its definition, classification, and the pathophysiological theories behind the various treatment strategies proposed. Recent reports have suggested that the evidence about overdrainage and its consequences is not so robust as presumed. Consequently, the topic requires more detailed examination. In this review, we comment on all the main facets related with shunt overdrainage.

An elderly Jervell and Lange-Nielsen patient heterozygous compound for two new KCNQ1 mutations.

We present the case of a 66-year-old female with early onset deafness and seizures, who was diagnosed with epilepsy at the age of 2 years. She received antiepileptic drugs and was free of syncope episodes for 32 years. After a syncope at the age of 34, the ECG was characteristic of long-QT syndrome and was treated with antiarrhythmic drugs. Sequencing of the KCNQ1 gene identified two novel KCNQ1 variants interpreted to be pathogenic, and the patient was finally diagnosed with Jervell and Lange-Nielsen syndrome. © 2016 Wiley Periodicals, Inc.

Factors related to shunt survival in paediatric hydrocephalus. Could failure be avoided?

BACKGROUND: Improved shunt survival and a better understanding of factors related to failure in paediatric hydrocephalus still pose a challenge for neurosurgeons, in order to avoid morbidity and mortality, as well as the economic impact of repeated revision surgeries. For these reasons, an analysis is performed on the factors related to the first shunt failure in the long-term follow-up of a series in a single centre. METHODS: A retrospective review was conducted on 166 hydrocephalic paediatric patients shunted for the first time between 2000 and 2014. An analysis was made of the statistical relationships between first shunt failure and the demographic, aetiological, surgical and clinical variables. RESULTS: Of the 166 shunts implanted in our centre during the study period, 111 required revision over a mean follow-up period of 93 months. Factors significantly related to failure were post-haemorrhagic and post-infectious hydrocephalus, meningitis episode, posterior burr hole, differential pressure valve, standard catheter in first surgery, and symptomatic over-drainage. Multivariable analysis showed that previous meningitis and symptomatic over-drainage were risk factors for shunt failure, whereas frontal burr hole location and antibiotic-impregnated catheters were protective factors. Cox regression determined that independent factors significantly related to a worse shunt survival, were shunt infection and symptomatic over-drainage. CONCLUSIONS: Meningitis, symptomatic over-drainage, frontal burr hole, and antibiotic impregnated catheters are significant prognostic factors for shunt survival. Shunt infection and symptomatic over-drainage are independent factors significantly related to a shorter shunt survival. Prospective, randomised, controlled trials are required to validate these results.

Surgical outcome of the shunt: 15-year experience in a single institution.

PURPOSE: Surgical outcome after shunt insertion in pediatric hydrocephalus can vary greatly. Although first shunt survival rates and complications have been studied by several teams, much less is known about survival and complications of subsequent systems. The goals of this study were to evaluate the surgical outcome in a series of pediatric patients followed for a long time and establish the differences between first and subsequent extracranial shunt survival and complications. METHODS: We undertook a retrospective study in pediatric patients treated with ventriculoperitoneal shunts between 2000 and 2015 at our institution. Surgical outcome was assessed, and different shunt survival curves were studied with Kaplan-Meier. Complications related to each shunt failure were examined and compared. RESULTS: A total of 166 patients underwent 425 procedures, with a mean follow-up period of 93 months. The median number of shunt revision surgeries was 2. Shunt survival rates were better with the first shunt compared to those with the subsequent shunts. The main complication necessitating system revision surgery was overdrainage, the frequency of proximal and distal dysfunctions was similar in all the shunt failures, and isolated ventricle and infection were more frequent in younger patients. Shunt-related infections accounted for 7 % of the procedures, and the shunt independence rate was 10 %. CONCLUSIONS: The frequency of complications related to shunt failure in pediatric patients changes during follow-up. A strict protocol of overdrainage detection and active treatment could explain the need for repeat surgeries and the progressively shorter shunt survival time in our series.

ABCB1 (MDR-1) pharmacogenetics of tacrolimus in renal transplanted patients: a Next Generation Sequencing approach.

BACKGROUND: A CYP3A5 gene polymorphism is the main determinant of Tacrolimus (Tac) dose requirements among renal transplanted patients. In spite of the utility of CYP3A5 genotyping to predict the Tac-dose, many patients exhibit an out of range blood Tac level and it is thus likely that other genes/polymorphisms contribute to define Tac bioavailability. To address this issue we searched for coding sequence variants in the ABCB1/MDR1 gene in renal transplanted patients treated with Tac and who had out of the range blood levels. METHODS: We studied 100 renal transplanted patients treated with Tac, 60 of whom had Tac blood levels below (n=39) and above (n=21) the target range (10-15 ng/mL) at 1 week post-transplant. The DNA was subjected to multiplex amplification followed by massive parallel semiconductor sequencing in the Ion Torrent personal genome machine. RESULTS: We found four missense changes, all reported and present in cases above and below the blood Tac target. In addition, we did not find differences in the allele and genotype frequencies for the common rs1045642 polymorphism (p.I1145I) between the groups. CONCLUSIONS: Our results suggested that the ABCB1 variants had no effect on the risk of showing out of range Tac blood levels among renal transplanted patients.

Next generation sequencing search for uromodulin gene variants related with impaired renal function.

Uromodulin gene (UMOD) mutations have been linked to rare forms of mendelian dominant medullary cystic kidney disease and familial hyperuricemia. In addition, common single nucleotide polymorphisms in the UMOD promoter have been associated with the risk for impaired renal function and chronic kidney disease. Our main purpose was to identify UMOD variants related with impaired renal function in an elderly population. The UMOD gene was next generation sequenced in a total of 100 healthy individuals with normal or reduced renal function [measured as the rate of estimated glomerular filtration (eGFR)]. The identified missense changes and the common promoter rs12917707 polymorphism were determined in individuals with reduced (n = 88) and normal (n = 442) eGFR values. Allele and genotype frequencies were compared between the groups. We only identified a rare UMOD misense change, p.V458L, and the rare leu allele was significantly more frequent in a cohort of individuals with reduced (eGFR < 60) compared to normal eGFR (P = 0.02). The common rs12917707 polymorphism previously linked to renal function and kidney disease was not associated with impaired filtration rate in our cohort. We found a significant effect of the rare p.V458L variant on the value of estimated glomerular filtration. This finding deserves further validation in larger cohorts.

Mutation analysis of the main hypertrophic cardiomyopathy genes using multiplex amplification and semiconductor next-generation sequencing.

BACKGROUND: Mutations in at least 30 genes have been linked to hypertrophic cardiomyopathy (HCM). Due to the large size of the main HCM genes, Sanger sequencing is labor intensive and expensive. The purpose was to develop a next-generation sequencing (NGS) procedure for the main HCM genes. METHODS AND RESULTS: Multiplex amplification of the coding exons of MYH7,MYBPC3,TNNT2,TNNI3,ACTC1,TNNC1,MYL2,MYL3, and TPM1 was designated, followed by NGS with the Ion Torrent PGM (Life Technologies). A total of 8 pools containing DNA from HCM patients were sequenced in a 2-step approach. First, a total of 60 patients (validation cohort) underwent both PGM and Sanger sequencing for the 9 genes. No false-negative variants were found on NGS (100% sensitivity), and a specificity of 97% and 80% was achieved for single-nucleotide and insertion/deletion variants, respectively. Second, the PGM was used to search for mutations in a total of 76 cases not previously studied (discovery cohort). A total of 19 putative mutations were identified in the discovery pools, which were confirmed and assigned to specific patients on Sanger sequencing. CONCLUSIONS: An NGS procedure has been developed for the main sarcomeric genes that would facilitate the screening of large cohorts of patients. In addition, this procedure would facilitate the uncovering of rare gene variants on a population scale.

The surface charge of electroactive materials governs cell behaviour through its effect on protein deposition.

The precise mechanisms underlying the cellular response to static electric cues remain unclear, limiting the design and development of biomaterials that utilize this parameter to enhance specific biological behaviours. To gather information on this matter we have explored the interaction of collagen type-I, the most abundant mammalian extracellular protein, with polyvinylidene fluoride (PVDF), an electroactive polymer with great potential for tissue engineering applications. Our results reveal significant differences in collagen affinity, conformation, and interaction strength depending on the electric charge of the PVDF surface, which subsequently affects the behaviour of mesenchymal stem cells seeded on them. These findings highlight the importance of surface charge in the establishment of the material-protein interface and ultimately in the biological response to the material. STATEMENT OF SIGNIFICANCE: The development of new tissue engineering strategies relies heavily on the understanding of how biomaterials interact with biological tissues. Although several factors drive this process and their driving principles have been identified, the relevance and mechanism by which the surface potential influences cell behaviour is still unknown. In our study, we investigate the interaction between collagen, the most abundant component of the extracellular matrix, and poly(vinylidenefluoride) with varying surface charges. Our findings reveal substantial variations in the binding forces, structure and adhesion of collagen on the different surfaces, which collectively explain the differential cellular responses. By exposing these differences, our research fills a critical knowledge gap and paves the way for innovations in material design for advanced tissue regeneration strategies.

[Factors related to endoscopic third ventriculostomy prognosis in the paediatric population]. / Factores relacionados con el pronóstico de la ventriculostomía premamilar endoscópica en pacientes pediátricos.

Endoscopic third ventriculostomy (ETV) for paediatric patients has different success rates between the published series, making its recommendation controversial. Different definitions of ETV success, hydrocephalus aetiology or patient age at diagnosis may influence the outcome of the ETV procedure. The aim of this work was to analyse our clinical series and to examine the influence of different factors on ETV outcome. This was a retrospective study of 45 patients who had undergone ETV at our Paediatric Hospital between 2003 and 2009. Successful outcome was defined as a combination of features including clinical improvement or stability, with at least 1 positive radiological parameter. The influence of age, hydrocephalus aetiology, existence or not of previous shunt and the type of endoscopic procedure were analysed in relation to ETV outcome. Up to 29% of patients were younger than 1 year. The most frequent causes of hydrocephalus were: brain tumour, aqueductal stenosis and myelomeningocele. The overall success rate was 69%, with a mean follow-up period of 26 months and mean ETV survival of 14 months. We obtained statistically significant differences in ETV success between patients aged over and under 6 moths. Our ETV success rate can be considered safe and effective for the treatment of paediatric hydrocephalus. To our knowledge, ETV is most effective in patients aged 6 months and over.

Multicentric and collaborative study of Spanish neurosurgical management of pediatric craniopharyngiomas: S-PedCPG.co.

PURPOSE: To present a descriptive analysis of pediatric craniopharyngiomas (PedCPG) treated in various Spanish hospitals, defining factors related to recurrence and performing a critical analysis of the results. METHODS: We undertook a multicenter retrospective review of PedCPG treated between 2000 and 2017. Data collected included epidemiological variables, clinical and radiological characteristics, goal of first surgery, rate of recurrence and its approach, adjuvant treatment, complications and permanent morbidity. Associations were studied between progression and number of progressions and independent variables. RESULTS: The study involved 69 children from 8 Spanish hospitals. Most of the tumors invaded several intracranial compartments at diagnosis, with the hypothalamus involved in 41.3% of cases. The first treatment strategy was usually gross total resection (GTR) (71%), with some patients treated with radiotherapy or intracystic chemotherapy. The progression rate after first surgery was 53% in a mean follow-up of 88.2 months (range 7-357). In the GTR group 38.8% of tumors recurred, 40% in the group of subtotal resection or biopsy and 93.3% in the cyst fenestration±Ommaya reservoir group. Mortality was 7.2%. Follow-up period, size of the tumor and goal of first surgery were significantly related with progression. CONCLUSIONS: Our results in terms of disease control, hormonal or visual impairment and mortality were acceptable, but there are several areas for improvement. Our short-term goals should be to create a national register of PedCPG, reach a consensus about a treatment algorithm, and improve diagnosis of hypothalamic dysfunction to avoid preventable morbidity.