Search

Background The enlargement of the posterior cranial fossa volume is considered one of the main steps of the surgical management of children with multiple sutures craniosynostosis. Different management options have been proposed including fixed expansive craniotomy, free bone flap craniotomy, and distraction osteogenesis. Objectives To review indications to “free bone flap” craniotomy for the posterior fossa expansion, detailing advantages, disadvantages, and complications related to the technique. Results and conclusions A review of the literature shows that “free bone flap” posterior expansion cranioplasty still has a role, particularly in infants with thin and “honeycomb” structure of the bone, allowing to gain adequate intracranial volume increases and to postpone to a more adequate time surgery aimed at anterior cranial fossa expansion.

In spite of the significant technical and technological progress in neurosurgery and the continuous discoveries by the basic research, adamantinomatous craniopharyngioma remains a significant clinical challenge. Actually, the huge size of the tumor, its multiple cystic components, the encasement of Willis' circle and optic pathways, and the invasion of the hypothalamus often prevent its safe surgical resection. Moreover, the local aggressiveness of the tumor accounts for a high risk of recurrence even after a gross total resection. For these reasons, more and more efforts are being dedicated to enhance the knowledge about AC and improve the tools for its treatment.This paper is dedicated to the most recent advances concerning the AC management. Promising, new insights come for the basic research, thanks to the updates on the role of the WNT-β-catenin pathway (important for the tumor genesis and progression, not yet developed enough for a safe target therapy in children but useful for determining the prognosis) and the inflammatory mediators (widely overexpressed, especially by the cyst of the tumor, and for which target therapies are being developed). Moreover, further factors and pathways are under investigation.Also the development of new treatment strategies accounts for the improvement of the prognosis and the quality of life of AC patients. The enhancement of the experience with the endoscopic techniques (both transsphenoidal and transventricular approaches) actually allows to perform a less invasive but effective surgery that can be coupled with new modalities of radiation therapy aiming at obtaining a reliable control of the disease and protecting the endocrinological, ophthalmological, and neurological functions. A special mention is finally deserved by the techniques specifically designed for the intracystic therapy (as cyst fenestration alone or in combination with administration of radionuclides or bleomycin or interferon-α) that are here analyzed together with the aforementioned advances.

To investigate the current practice of neurosurgeons and their perception of complications related to the securement of external drainage (ED) to the skin.We created a 24-points English language questionnaire on Google Forms covering the five main domains of care. The survey was distributed among members of the European Society for Pediatric Neurosurgery (ESPN) in April 2020.The results were entirely self-reported, without any independent validation. Fifty-one neurosurgeons practising in different centres worldwide participated in this survey. Despite well-known complications and drawbacks, sutures are still the most commonly used method to secure cerebrospinal fluid (CSF) ventricular ED (49 out of 51 respondents) and spinal ED (37 out of 51) to the skin. Perception of the risk of pullout is estimated as1% by 25.5% of the respondents, 1-5% by 39.2%, 5-10% by 17.6% and 10% by 11.8%. Twenty out of fifty-one respondents acknowledge that their method of securement has drawbacks, and 49% believe that it may also affect the risk of infection. Factors eventually affecting the risk of pullout are young age (62.7%), aetiology (25.5%), neurological status (90.2%), occipital exit site (37.3%), inadequate length of the subcutaneous tunnel (58%), the duration of ED (70.6%), and hospital stay in service (84.3%). 39.2% of respondents agree that the paediatric population deserves a different device or technique to secure ED to the skin. 21.6% of respondents underestimate the risk of accidental pullout. 86.3% of respondents have never read about the 'sutureless subcutaneous anchoring device'.Complications associated with the securement method, such as the risk of pullout and infection, are most likely underestimated. More research is needed to implement effective guidelines in this field.

BackgroundDuring the first SARS-CoV-2 pandemic phase, the sudden closure of schools was one of the main measures to minimize the spread of the virus. In the second phase, several safety procedures were implemented to avoid school closure.To evaluate if the school is a safe place, students and staff of two school complexes of Rome were monitored to evaluate the efficacy of prevention measures inside the school buildings.MethodsOral secretions specimens were collected from 1262 subjects for a total of 3431 samples, collected over a 3 months period.Detection of Coronavirus SARS-CoV-2 was performed by real-time PCR. Target genes were represented by E gene, RdRP/S gene and N gene.ResultsAmong the 3431 samples analyzed, just 16 sample resulted as positive or low positive: 1 sample in the first month, 12 samples in the second month and 3 in the third month.In each period of evaluation, all positive children attended different classes.ConclusionsEven if the school has the potential for spreading viruses, our preliminary results show the efficacy of the implementations undertaken in this setting to minimize virus diffusion.Our evidence suggests that school does not act as an amplifier for transmission of SARS-CoV-2 and can be really considered a safe place for students.

Ultrafine particles (UFPs) usually explosive growth during new particle formation (NPF) events. However, the risk of exposure to UFPs on NPF days has been ignored due to the prevalence of mass-based air quality standards. In this study, the daily deposited doses, i.e., the daily deposited particle number dose (D-PNd), mass dose (D-PMd), and surface area dose (D-PSd), of ambient particles in the human respiratory tract in Beijing were evaluated based on the particle number size distribution (3 nm-10 mu m) from June 2018 to May 2019 utilizing a Multiple-Path Particle Dosimetry Model (MPPD) after the hygroscopic growth of particles in the respiratory tract had been accounted for. Our observations showed a high frequency (72.6%) of NPF on excellent air quality days, with daily mean PM2.5 concentrations less than 35 mu g m(-3). The daily D-PNd on excellent air quality days was com-parable with that on polluted days, although the D-PMd on excellent air quality days was as low as 15.6% of that on polluted days. The D-PNd on NPF days was similar to 1.3 times that on non-NPF days. The D-PNd in respiratory tract regions decreased in the order: tracheobronchial (TB) > pulmonary (PUL) > extrathoracic (ET) on NPF days, while it was PUL > TB > ET on non-NPF days. The number of deposited nucleation mode particles, which were deposited mainly in the TB region (45%), was 2 times higher on NPF days than that on non-NPF days. Our results demonstrated that the deposition potential due to UFPs in terms of particle number concentrations is high in Beijing regardless of the aerosol mass concentration. More toxicological studies related to UFPs on NPF days, especially those targeting tracheobronchial and pulmonary impairment, are required in the future.

Background A comparison of clinical and radiological outcomes after two different variants of open door laminoplasty for cervical spondylotic myelopathy (CSM) is described. Methods Fifty-five patients underwent cervical laminoplasty for CSM. Between 2005 to 2009, 32 patients underwent open-door laminoplasty (Group A) performed with a monolateral exposure with contralateral "green stick" laminar fracture. A technical variant consisting in bilateral exposure, spinous process removal and symmetrical muscular closure was applied in the other 23 (Group B), from 2009 to 2016. A retrospective analysis of surgical results between the two groups was performed. Results In group B, the mean operative time was longer and the mean volume of intraoperative blood loss was much higher than in group A. Both differences were not significant (p=0.1601 and p=0.0884, respectively). The average hospitalization was nonsignificantly longer in group B (7.3±1.8 vs. 6.5±1.6 d; p= 0.0947). Postoperatively, axial neck pain was more severe in group A at last follow-up than preoperatively (P>0.05). mJOA scores and Nurick grades improved significantly in both groups at last follow-up; in group A, the mean recovery rates were 41.5 % by mJOA scores and 29.4 % by Nurick grades, whereas in group B they were 52.7 % and 36.8 %, respectively. Conclusions Applying some few variations to a standard monolateral approach, although slightly more time and blood consuming, could reduce the incidence of long term axial symptoms and, in our experience, are not burdened by worsening of outcomes. A prospective, multicentric study with a longer follow-up should be conducted in order to confirm our findings.

G-quadruplexes (G4s) are noncanonical forms of DNA involved in many key genome functions. Here, we exploited UV Resonance Raman scattering to simultaneously explore the vibrational behavior of a human telomeric G4 (Tel22) and its aqueous solvent as the biomolecule underwent thermal melting. We found that the OH stretching band, related to the local hydrogen-bonded network of a water molecule, was in strict relation with the vibrational features of the G4 structure as a function of temperature. In particular, the modifications to the tetrahedral ordering of the water network were strongly coupled to the DNA rearrangements, showing changes in temperature that mirrored the multi-step melting process of Tel22. The comparison between circular dichroism and Raman results supported this view. The present findings provide novel insights into the impact of the molecular environment on G4 conformation. Improving current knowledge on the solvent structural properties will also contribute to a better understanding of the role played by water arrangement in the complexation of G4s with ligands.

In spite of literature data stating that children with single-suture craniosynostosis have an increased risk for neuropsychological deficits, no data are present clarifying the potential risk factors. All children with non-syndromic single-suture craniosynostosis operated on from January 2014 to January 2017 were enrolled. A comprehensive neurocognitive and neuro-ophthalmological evaluation was performed before surgery and 6 months after surgery. A further neurocognitive evaluation was performed 12 months after surgery. All children had a preoperative CT/MR study. One hundred forty-two patients were enrolled; 87 are affected by sagittal craniosynostosis, 38 by trigonocephaly, and 17 by plagiocephaly. A global neurocognitive impairment was documented in 22/87 children with scaphocephaly, 5/38 children with trigonocephaly, and 6/17 children with anterior plagiocephaly. There was a significant relationship between results of the ophthalmological evaluation, global IQ, and CT findings at diagnosis (r = 0.296, p

Background Causes of the nonaneurysmal subarachnoid hemorrhage (na-SAH) are still debated. Many studies confirmed the possible involvement of the intracranial venous system, in particular variants of the basal vein of Rosenthal. Study Object The aim of this study is to investigate the role of extracranial venous system, in particular the jugular drainage, in the na-SAH pathophysiology. Materials and Methods This is a multicenter retrospective study including patients suffering from na-SAH who were radiologically screened to exclude vascular malformations. The course of the internal jugular veins was evaluated to reveal any stenosis (caliber reduction >80%). Particular attention was paid at the passage between the styloid process and the arch of C1 to detect possible compression. As a control group, we enrolled patients who underwent CT angiograms and/or cerebral DSAs in the past 2 years. Results We included 194 patients. The na-SAH group consisted of 94 patients, whereas the control group consisted of 100 patients. Fifty patients of the control group underwent a CT angiography for an ischemic cerebrovascular disease or trauma and 50 patients for an SAH due to a ruptured aneurysm. A significant jugular stenosis was found in 49 (52.1%) patients in the na-SAH group and in 18 (18%) patients in the control group. At univariate and multivariate analysis, the difference was statistically significant (p Conclusions This is the first study investigating the correlation between jugular stenosis and the occurrence of na-SAH. The impaired venous outflow due to reduced venous caliber could result in an engorgement of the upstream intracranial veins with transient hypertensive phases facilitating ruptures. Further larger prospective studies are necessary to confirm these data.

Background Autism spectrum disorder is a complex condition with wide variation in type and severity that involves persistent challenges in social interaction, speech and nonverbal communication, restricted/repetitive behaviours and adaptive behaviours. In recent years, research has deepened the study of the predictive factors of optimal outcome, intended as indicators of positive trajectory in children with a previous diagnosis of autism who, after a therapeutic path, show a significant reduction in the “core” symptoms of autism and a positive evolution in social, adaptive, affective, and relational skills. Methods The study included 40 children aged 21 to 66 months, enrolled between 2015 and 2016 for an autism spectrum disorder clinical suspicious. Children were re-evaluated after at least 2 years of therapy and they were divided into two groups: the ASD-ASD group included children with a confirmed diagnosis of ASD, and the ASD-OO comparison group included children who no longer met the criteria for an autism classification. The aim of this retrospective study was to investigate the presence of cognitive, emotional and relational predictors capable of predicting the presence of optimal outcome in with a diagnosis of autism; the predictors taken into consideration were the intelligence quotient, the play, the emotional contagion and the understanding of other’s intentions. In this way, it is possible to support clinicians in defining a more complete diagnostic framework of autism, using assessment tools that can be administered quickly and therefore suitable for short observation sessions in paediatric patients. Results The findings showed that 15 out of 40 children, after at least for 2 years, no longer fell into the diagnostic ASD category based on the ADOS-2, DSM-5 and clinical criteria. The children in the ASD-OO group initially had a higher IQ than those in the ASD-ASD group, lower severity of autistic symptoms, greater understanding of intentions, more emotional contagion, and better quality of play. The results suggest that the initial coexistence of skills in these areas at the time of the first diagnostic assessment may allow us to predict the possibility of achieving optimal outcome after 2 years of therapy. Conclusions The data of this study highlight the importance of considering, during assessment, intelligence quotient, play, emotional contagion, and understanding of the intentions of others as potential prognostic predictors that can become useful tools for clinicians and paediatricians. This allows us to focus attention, in both the diagnostic and prognostic phases, on emotional-relational variables that can support the clinician in defining a more complete diagnostic framework and in planning a more personalized therapeutic path.

Carbonaceous aerosol is one of the main components of atmospheric particulate matter, which is of great significance due to its role in climate change, earth's radiation balance, visibility, and human health. In this work, carbonaceous aerosols were measured in Shijiazhuang and Beijing using the OC/EC analyzer from December 1, 2019 to March 15, 2020, which covered the Coronavirus Disease 2019 (COVID-19) pandemic. The observed results show that the gas-phase pollutants, such as NO, NO2, and aerosol-phase pollutants (Primary Organic Compounds, POC) from anthropogenic emissions, were significantly reduced during the lockdown period due to limited human activities in North China Plain (NCP). However, the atmospheric oxidation capacity (Ox/CO) shows a significantly increase during the lockdown period. Meanwhile, additional sources of nighttime Secondary Organic Carbon (SOC), Secondary Organic Aerosol (SOA), and babs, BrC(370 nm) are observed and ascribed to the nocturnal chemistry related to NO3 radical. The Potential Source Contribution Function (PSCF) analysis indicates that the southeast areas of the NCP region contributed more to the SOC during the lockdown period than the normal period. Our results highlight the importance of regional nocturnal chemistry in SOA formation., Graphical abstract Potential source of SOC during COVID-19 pandemic.Unlabelled Image

Aim To describe the epidemiological aspects of nocturnal enuresis (NE). In this study we identify the prevalence and the familial conditions in a large, representative sample of children with monosymptomatic NE (MNE) and nonmonosyptomatic NE (NMNE). Material and methods In this descriptive-analytic study the Italian Society of Pediatrics (SIP) promoted a prevalence study of NE using a questionnaire involved 320 primary care Pediatricians from Northern, Central and Southern Italy, from January 2019 to July 2019, with a total of 130,000 children analyzed by questionnaire related to epidemiology and type of NE, familiarity, quality of sleep, eating and drinking habits, pharmacological and psychological/behavioural interventions and family involvement. Results 270/320 (84.4%) Paediatrician replied to our questionnaire. We enrolled a total of 9307/130,000 (7.2%) children with NE, aged between 5 and 14 years: 2141 diagnosed with MNE and 7176 qualified as NMNE. Poor quality of sleep were reported in 7064 patients; 90% of children did not consider a dietary and drinking recommendation. Pediatrician reported a total of 54.1% of parents who declared to have a negative reaction to their children because of the bedwetting. A percentage of 71.4% of parents declared to use or to have used alternative therapies and not to prefer, at first, a pharmacological intervention. Conclusion The choice of treatment should include psychological/behavioural interventions in all cases to improve the therapeutic outcome. All primary care Pediatricians should be aware of the all aspects of NE to choose the best way to treat every patient.

Background Piezosurgery (PS) has gained increasing dispersion in neurosurgery. In pediatric neurosurgery, the experience is limited to craniosynostosis surgery. The present study assesses PS in the pediatric population, also considering outcomes and complications in cranial and spinal procedures. Methods All consecutive craniotomies and laminotomies, performed with PS (group A) or conventional osteotomes (group B) in the 2014–2017 period were reviewed. The following variables were analyzed: dural tears, estimated blood loss and need of transfusion, cosmetic outcome (Sloan score), and operative times. A review of the pertinent literature is included. Results 172 children were enrolled, 90 in group A and 82 in group B. The mean follow-up time was 2.1 years. A statistically significant difference in favor of group A was found about EBL (105 vs. 113 ml) and late outcome (Sloan class A 98.5% vs. 91.5%). PS also reduced the risk of dural tears (1 vs. 7 cases in groups A and B, respectively) and blood transfusion (52% vs. 55.5%) but without statistical significance. The operative times were significantly shorter in group B (13 vs. 23 minutes), although the newer PS plus (PSP) was demonstrated to significantly shorten these times compared with the traditional PS (3.5 vs. 6.5 minutes for orbitotomy and 7.5 vs. 9.5 minutes for hemicraniotomy). Conclusions PS is a safe and effective tool that can be specifically recommended for bone splitting and graft, laminotomy, and craniotomy in cosmetically eloquent areas. The limit of operation times can be overcome by a learning curve in neurosurgery and PSP.

In this study, we use temporally aligned word embeddings and a large diachronic corpus of English to quantify language change in a data‐driven, scalable way, which is grounded in language use. We show a unique and reliable relation between measures of language change and age of acquisition (AoA) while controlling for frequency, contextual diversity, concreteness, length, dominant part of speech, orthographic neighborhood density, and diachronic frequency variation. We analyze measures of language change tackling both the change in lexical representations and the change in the relation between lexical representations and the words with the most similar usage patterns, showing that they capture different aspects of language change. Our results show a unique relation between language change and AoA, which is stronger when considering neighborhood‐level measures of language change: Words with more coherent diachronic usage patterns tend to be acquired earlier. The results support theories positing a link between ontogenetic and ethnogenetic processes in language.

Background The optimal management of neonatal post-hemorrhagic hydrocephalus (PHH) is still debated, though several treatment options have been proposed. In the last years, ventriculosubgaleal shunt (VSgS) and neuroendosdcopic lavage (NEL) have been proposed to overcome the drawbacks of more traditional options, such as external ventricular drainage and ventricular access device. Methods We retrospectively reviewed neonates affected by PHH treated at our institution since September 2012 to September 2020. Until 2017 patients received VSgS as initial treatment. After the introduction of NEL, this treatment option was offered to patients with large intraventricular clots. After NEL, VSgS was always placed. Primary VSgS was reserved to patients without significant intraventricular clots and critically ill patients that could not be transferred to the operating room and undergo a longer surgery. Results We collected 63 babies (38 males and 25 females) with mean gestational age of 27.8 ± 3.8SD weeks (range 23–38.5 weeks) and mean birthweight of 1199.7 ± 690.6 SD grams (range 500–3320 g). In 6 patients, hemorrhage occurred in the third trimester of gestation, while in the remaining cases hemorrhage complicated prematurity. This group included 37 inborn and 26 outborn babies. Intraventricular hemorrhage was classified as low grade (I–II according to modified Papile grading scale) in 7 cases, while in the remaining cases the grade of hemorrhage was III to IV. Mean age at first neurosurgical procedure was 32.2 ± 3.6SD weeks (range 25.4–40 weeks). Death due to prematurity occurred in 5 patients. First-line treatment was VSgS in 49 patients and NEL in the remaining 14 cases. Mean longevity of VSgS was 30.3 days (range 10–97 days) in patients finally requiring an additional treatment of hydrocephalus. Thirty-two patients required one to three redo VSgS. Interval from initial treatment to permanent shunt ranged from 14 to 312 days (mean 70.9 days). CSF infection was observed in 5 patients (7.9%). Shunt dependency was observed in 51 out of 58 surviving patients, while 7 cases remained shunt-free at the last follow-up. Multiloculated hydrocephalus was observed in 14 cases. Among these, only one patient initially received NEL and was complicated by isolated trapped temporal horn. Conclusions VSgS and NEL are two effective treatment options in the management of PHH. Both procedures should be part of the neurosurgical armamentarium to deal with PHH, since they offer specific advantages in selected patients. A treatment algorithm combining these two options may reduce the infectious risk and the risk of multiloculated hydrocephalus.

Parents of children with autism spectrum disorder (ASD) have to address various challenges mainly due to their children’s atypia related to communication, emotion regulation and behaviors, arising also within the relationship with their caregivers. Several studies have pointed out that children with ASD can exhibit many difficulties regarding initiating and maintaining meaningful relationships with others. To date, little research has explored the interactions between children with ASD and their fathers, focusing more on mothers. In the context of parent–child interactions in the presence of autism, recent studies have highlighted the importance of parental attunement but there is little research considering solely the affective-bodily dimension. Therefore, the aim of the present study was to explore the parental attunement in fathers of children with ASD observed during play interactions and to investigate the relationship between paternal attunement and the perception of their psychological characteristics related to care relationships. The results highlight that fathers who describe themselves as better in affective care and sensitivity toward others more likely have an absence of paternal attunement during play interactions. The data presented are discussed in the light of intervention hypotheses, aimed at improving the relationship between fathers and children with autism.

Introduction Electrical source imaging (ESI) and especially hdEEG represent a noninvasive, low cost and accurate method of localizing epileptic zone (EZ). Such capability can greatly increase seizure freedom rate in surgically treated drug resistant epilepsy cases. Furthermore, ESI might be important in intracranial record planning. Case report We report the case of a 15 years old boy suffering from drug resistant epilepsy with a previous history of DNET removal. The patient suffered from heterogeneous seizure semiology characterized by anesthesia and loss of tone in the left arm, twisting of the jaw to the left and dysarthria accompanied by daze; lightheadedness sometimes associated with headache and dizziness and at a relatively short time distance negative myoclonus involving the left hand. Clinical evidence poorly match scalp and video EEG monitoring thus requiring hdEEG recording followed by SEEG to define surgical target. Surgery was also guided by ECoG and obtained seizure freedom. Discussion ESI offers an excellent estimate of EZ, being hdEEG and intracranial recordings especially important in defining it. We analyzed our results together with the data from the literature showing how in children hdEEG might be even more crucial than in adults due to the heterogeneity in seizures phenomenology. The complexity of each case and the technical difficulties in dealing with children, stress even more the importance of a noninvasive tool for diagnosis. In fact, hdEEG not only guided in the presented case SEEG planning but may also in the future offer the possibility to replace it.

Aim To analyze the current literature on neurocutaneous melanosis (NCM), as well as, our cases, in order to better define the prognosis and the presence of risk factors affecting it, thus, offering better information to the parents. Material and methods Two cases observed at the Pediatric Neurosurgery Unit of the Catholic University Medical School in Rome are described. Both of them had cutaneous stigmata and cerebral MR evidence of intracranial melanin deposits. These two children showed a very different clinical course. Results The present study enlighten the differences among the two cases and review the literature on the subject, with the attempt to understand which are clinical and disease related factors that might influence the prognosis. Conclusion Beside malignant features of cutaneous melanotic lesions, the presence of hydrocephalus at diagnosis and the early appearance of clinical symptoms, when appearing contemporarily, are predicting the rapid progression of the disease and a worse prognosis.

Securing the catheter to the skin either with sutures or staples and to the skull with bolt system still represents the most common options in the management of CSF external drainage. However, these options bear an unavoidable risk of complications. This problem is common to vascular accesses and has been successfully overcome with the introduction of device for subcutaneous anchoring (SecurAcath®, Interrad Medical, Inc., Plymouth, Minnesota), which has rapidly become the standard of care in this field. We report our experience with the use of SecurAcath® to secure CSF drainage, either ventricular or spinal. Results were compared with literature data. Since 2015, SecurAcath® was used in 209 patients (mean age 7 years) to secure 195 external cranial catheters (either ventricular or subdural or intralesional) and 16 spinal drainages. Indwell time ranged from 5 to 30 days. No complication related to the use of the device was observed. In particular, there was no case of dislocation or accidental pullout of the catheter. Rate of infection, or superinfection in case of ventricular catheter implanted for CSF infection, was null. SecurAcath® is a safe and effective device to secure CSF external catheters, with several relevant advantages, including easy placement and maintenance. Moreover, it may stay in place for the whole duration of the catheter without any skin tissue trauma and allows a complete antisepsis of the exit site, thus reducing local skin complications. This factor has significant impact on the reduction of infection rate of external CSF catheters.

Purpose Sturge-Weber syndrome (SWS) is a neurocutaneous facomatosis characterized by facial and leptomeningeal angioma, glaucoma, seizures, and neurological disability. Therefore, a challenging multidisciplinary interaction is required for its management. The goal of this paper is to review the main aspects of SWS and to present an illustrative pediatric series. Methods The pertinent literature has been analyzed, focused mainly on etiopathogenesis, pathology, clinical features, diagnostic tools, management, and outcome of the disease. Moreover, a series of 11 children operated on for refractory epilepsy between 2005 and 2015 (minimum follow-up 5 years, mean follow-up 9.6 years) is reported. The series consists of six boys and five girls with 6.5-month and 16.2-month mean age at seizure onset and at surgery, respectively. Seizures affected all children, followed by hemiparesis and psychomotor delay (81%), glaucoma (54%), and other neurological deficits (45%). Results All children underwent hemispherectomy (anatomical in three cases, functional in two cases, hemispherotomy in six cases); one patient needed a redo hemispherotomy. Mortality was nil; disseminated intravascular coagulation and interstitial pneumonia occurred in one patient each; three children had subdural fluid collection. Eight patients (72%) are in the ILAE Class 1 (completely seizure and aura free), two in Class 2 (only auras, no seizure), and one in Class 3 (1-3 seizure days per year). AEDs discontinuation was possible in 73% of cases. The most important news from the literature concerned the pathogenesis (role of the mutation of the GNAQ gene in the abnormal SWS vasculogenesis), the clinical findings (the features and pathogenesis of the stroke-like episodes are being understood), the diagnostic tools (quantitative MRI and EEG), and both the medical (migraine, seizures) and surgical management (epilepsy). The epileptic outcome of SWS patients is very good (80% are seizure-free), if compared with other hemispheric syndromes. The quality of life is affected by the neurological and cognitive deficits. Conclusions SWS still is an etiological and clinical challenge. However, the improvements over the time are consistent. In particular, the neurosurgical treatment of refractory epilepsy provides very good results as long as the indication to treatment is correct.

A multi-technique approach, combining circular dichroism spectroscopy, ultraviolet resonance Raman spectroscopy and small angle scattering techniques, has been deployed to elucidate how the structural features of the human telomeric G-quadruplex d[A(GGGTTA)3GGG] (Tel22) change upon thermal unfolding. The system is studied both in the free form and when it is bound to Actinomycin D (ActD), an anticancer ligand with remarkable conformational flexibility. We find that at room temperature binding of Tel22 with ActD involves end-stacking upon the terminal G-tetrad. Structural evidence for drug-driven dimerization of a significant fraction of the G-quadruplexes is provided. When the temperature is raised, both free and bound Tel22 undergo melting through a multi-state process. We show that in the intermediate states of Tel22 the conformational equilibrium is shifted toward the (3+1) hybrid-type, while a parallel structure is promoted in the complex. The unfolded state of the free Tel22 is consistent with a self-avoiding random-coil conformation, whereas the high-temperature state of the complex is observed to assume a quite compact form. Such an unprecedented high-temperature arrangement is caused by the persistent interaction between Tel22 and ActD, which stabilizes compact conformations even in the presence of large thermal structural fluctuations.

CustomBone Service (CBS) is a patient-specific, biocompatible, and osteoconductive device made of porous hydroxyapatite, indicated for cranial reconstruction in adults and children. Adult literature data report a failure rate of about 8%. The aim of this Post-Marketing Surveillance study is to verify the hypothesis that CBS in children aged 7–13 years old shows a failure rate not superior to adults. Inclusion criteria were age at implantation ranging 7–13 years old, with at least 1 year elapsed from the date of surgery. The degree of satisfaction of surgeons and patients was assessed. Data about 76 implants in 67 patients (M:F = 41:26) were obtained from 28 centers across 7 European countries. The mean age at surgery was 10.03 ± 1.72 years, with age stratification almost equally distributed. Fifty-nine subjects received one CBS, 7 subjects two and one subject received three CBS. Main etiologies were trauma (60.5%), malformation (11.8%), bone tumor (10.5%), and cerebral tumor (7.9%). Main indications to CBS were decompression (47.4%), autologous bone resorption (18.4%), tumor resection (11.8%), malformation (9.2%), comminuted fracture (5.3%), and other materials rejection (5.3%). Main implantation sites were fronto-parieto-temporal (26.3%), parietal (23.7%), frontal (11.8%), fronto-temporal (10.5%), and parieto-temporal (7.9%). CBS was chosen as first line of treatment in 63.1% of the cases. Mean follow-up was about 36 months. Eleven adverse events (14.5%) were reported in nine devices. Five CBS required explantation (three cases of infection, one fracture, and one mobilization). Failure rate was 6.58%, which is statistically not superior to the explantation rate recorded in adults (two-sided 95%, CI 2.2–14.7%). Satisfaction of surgeons and patients was of about 95%. CBS is a safe and effective solution for cranial repair in pediatric patients. In particular, over the age of 7, CBS shows a rate of failure as low as in adults.

Primary central nervous system (CNS) neuroblastoma is a rare intracranial tumor affecting children mainly in the first years of life. It is usually a supratentorial tumor with a wide spectrum of clinical presentation, seizures, and focal neurological deficits being the most common presenting signs. A 2-year-old child was admitted to our ward after a generalized seizure. Neurological examination was normal. Radiological studies showed a small DWI hyperintense lesion of the right rectus gyrus. Follow-up brain MRI 8 months later showed a huge growth of the tumor (90 × 80 × 65 mm) with polycyclic and apparently defined margins, cystic components, and diffuse contrast enhancement. Complete tumor removal was performed in two planned surgical steps. Histological diagnosis was CNS neuroblastoma. At a follow-up of 8 months, the child is in good clinical and neurological condition and is completing chemotherapy treatment according to the SIOP PNET 4 protocol. A thorough review of the literature confirms that primary CNS neuroblastoma has to be considered a distinct entity. The disease related mortality is 12.5%, lower than the one usually reported for other previously described as PNETs tumors. The most relevant factors influencing prognosis are the possibility of obtaining a complete tumor removal and age more than 3 years, which allows to include radiotherapy among treatment options.

Residual and recurrent intracranial aneurysms after surgical clipping present a persistent risk of bleeding. Secondary coiling after incomplete clipping represents a strategy to occlude the residual sac: feasibility, bleeding risk and outcome were evaluated through a systematic review of literature along with the series of two tertiary referral neurovascular centres. Demographics, ruptured status, aneurysm morphology, topography, exclusion at surgery, timing of secondary coiling, complications, occlusion rate and outcome were analysed. Percentage of incidence and 95% CI were calculated for all variables. T test was used for continue variables, whereas Fisher's test (two-sided) is for categorical ones. Overall, 102 patients (92 cases from literature and 10 cases from institutional series) were included. Mean age at diagnosis was 52.94 ± 12.17 years, and male/female ratio 0.5; 3/4 of aneurysms involved the anterior circulation, whereas ¼ the posterior circulation. An aneurysmal neck remnant was described in 58.43% of cases, an aneurysmal sac remnant in 29.21% and a regrowth in 12.36%. Residual aneurysm rupture was reported in 22% of cases. Complete/near-complete occlusion after secondary coiling was observed in 70% of cases, a partial in 25.56% and a failure in 4.44%. Only one case of perforation was reported. Complications were comparable to standard endovascular procedures. Aneurysms remnants after clipping are often observed in cases difficult anatomical locations. Their bleeding risk is not negligible. Secondary coiling is a rescue strategy to effectively and safely secure the aneurysm remnant. Only in a minority of cases, it is a staged treatment after 'remodelling' of the aneurysm neck.

Background Postoperative seizures (PSs) after neurosurgical operations are common but little is known about the role of surgical brain incision on their genesis. This topic has not been addressed so far. Objective To verify if the corticotomy affects the risk of PSs and postoperative epilepsy (PE) in children. Methods One hundred forty-three consecutive pediatric cases operated on for supratentorial lesions at the same institution in the last 15 yr have been retrospectively reviewed by dividing them into group A, 68 children who required brain corticotomy mainly for hemispheric tumors, and group B, 75 children treated through extracortical approaches mainly for suprasellar and optic tumors. Patients with possible "epileptic" biases, like preoperative seizures, were excluded. Results No significant differences have been found between group A and B as far as incidence of PSs (11.7% vs 14.5%) and PE (4.5% vs 6.5%), timing, and type of seizures are concerned after a mean 6.8 yr follow-up. The size of corticotomy in group A ( 3 cm2) had no impact on epileptogenesis as well as the other variables considered in both groups (age, sex, extent of lesion resection). Conclusion This study shows that the surgical cortical "trauma" would not represent a risk factor for PSs and PE. According to the present analysis and the literature, other causes seem to be involved (namely, electrolytic imbalance and brain gliosis). This information is important for preoperative surgical planning and postoperative management. A validation by both adult series and prospective studies is needed.

Postnatal growth of neurocranium is prevalently completed in the first years of life, thus deeply affecting the clinical presentation and surgical management of pediatric neurosurgical conditions involving the skull. This paper aims to review the pertinent literature on the normal growth of neurocranium and critically discuss the surgical implications of this factor in cranial repair. A search of the electronic database of Pubmed was performed, using the key word “neurocranium growth”, thus obtaining 217 results. Forty-six papers dealing with this topic in humans, limited to the English language, were selected. After excluding a few papers dealing with viscerocranium growth or pathological conditions not related to normal neurocranium growth 18 papers were finally included into the present review. The skull growth is very rapid in the first 2 years of life and approximates the adult volume by 7 years of age, with minimal further growth later on, which is warranted by the remodeling of the cranial bones. This factor affects the outcome of cranioplasty. Thus, it is essential to consider age in the planning phase of cranial repair, choice of the material, and critical comparison of results of different cranioplasty solutions.

Cranioplasty aims at restoring the physiological integrity and volume of the skull. Any disproportion between the intracranial content and the volume of the container may favor the occurrence of complications. A classification of volume mismatches is proposed. A negative mismatch, consisting of intracranial content minor to skull volume, is well represented by the sinking flap. On the other side, a positive mismatch, consisting of intracranial content higher than skull volume, usually depends on CSF collection or hydrocephalus once the brain edema is regressed. Though, in children, this condition may result from physiological brain growth after decompressive craniectomy. Treatment algorithm based on this classification is presented. A 1-year-old boy with a severe traumatic brain injury underwent right decompressive craniectomy, evacuation of subdural hematoma, and dural expansion at another institution. After failure of autologous bone-assisted cranioplasty for infection, a helmet was recommended in order to postpone the cranial repair. Patient was admitted to our institution 3 years later. CT scan showed brain herniation through the cranial defect, associated to a condition of acquired craniocerebral disproportion, due to the condition of “open skull”. Augmented hydroxyapatite cranioplasty (CustomBone, Finceramica, Faenza, Italy) was performed in order to manage this rare condition of positive volume mismatch. Subsequent course was uneventful and no complication was recorded at 30-month follow-up. This illustrative case highlights the possible occurrence of a positive structural mismatch between the skull and the intracranial content after decompressive craniectomy, thus configuring a condition of acquired craniocerebral disproportion, aside of other brain or CSF complications. We firstly recognize this condition in the literature and propose it as a possible factor affecting the outcome of cranioplasty in infants and young children.

Treatment of intraosseous meningiomas is a two-staged procedure including tumor resection and cranial reconstruction. Several are the potential pitfall of this kind of surgery such as the conspicuous dimensions usually reached by the tumor and the peculiar involvement of irregular and deep bony structures. For these reasons, a surgical accurate virtual planning and a careful removal followed by tailored reconstruction are mandatory to achieve satisfactory results. We analyzed six patients operated on for intraosseous meningiomas between September 2014 and June 2018. Resection strategy was planned beforehand and shared with the manufacturer who provided the PEEK cranioplasty used in the reconstructive phase. Between September 2014 and April 2018, six patients affected by intraosseous meningioma were operated on. Female/male ratio was 5:1 and mean age was 54 ± 10.8 years. Mean FU was 20.3 ± 16.4 months. Mean dimension was 73.9 ± 24.8 mm × 69.2 ± 16.2 mm. Mean surgical time was 5.1 ± 1.1 h. The resection of intraosseous meningiomas requires the earliest and finest reconstructive phase. Custom-made implants should be considered the gold-standard for cranioplasty, especially in large skull and in frontal or hairless areas of the skull. The described technique is simple, accurate, and effective in achieving good results in disease control as well as cosmetic and functional restoration.

Desmoplastic infantile gangliogliomas (DIGs) and desmoplastic infantile astrocytomas (DIAs) are tumors typical of the infantile age. A large size, with a mixed solid and cystic component, clinical presentation with progressing signs of increased intracranial pressure, a prominent benign desmoplastic structure at histological examination, and a favorable clinical course in the majority of cases are the prominent features of these tumors. The objective of the present paper was to review the pertinent literature on the topic together with our personal experience, with the aim of an updated review of the subject. Only 28 papers are present in the literature devoted to DIGs and DIAs, most of them reporting on single cases or small series, with a total of 107 patients aged from 5 days to 48 months with a slight male prevalence. Most of the reported cases refer to supratentorial and hemispheric locations, a few cases involving the hypothalamic region, the posterior fossa, and the spinal cord. The typical MRI appearance is of large mixed solid and cystic tumors with a spontaneous hyperintense T2 appearance of the solid part which also shows a strong contrast enhancement. Mixed ganglionic and astrocytic cells are identifiable in DIGs, whereas DIAs are typically featured by the exclusive presence of glial cells. In both cases, more primitive cells may be observed, which present a higher number of mitoses and these areas can mimic the features of malignant astrocytomas. Surgery represents the treatment of choice; however, radical removal has been reported as possible only in around 30 % of the cases: the low age of the patients together with their low weight and the large size of and the hyper-vascularized structure of the tumors represent the main factors limiting surgery. Pure observation is considered as first choice in children undergoing a partial/subtotal tumor resection, chemotherapic regimens being considered in cases of recurrences after a second look surgery. Long-term prognosis is favorable with mortality being related mostly to the rare midline (i.e., hypothalamic) locations, which beyond the functionally relevant site, tend to have an unusually more aggressive histological behavior.

OBJECT Only a few published studies of the surgical treatment of benign peripheral nerve sheath tumors (BPNSTs), malignant peripheral nerve sheath tumors (MPNSTs), and peripheral non–neural sheath tumors (PNNSTs) have analyzed the results and possible prognostic factors using multivariate analysis. The authors report on their surgical series of cases of BPNSTs, MPNSTs, and PNNSTs with long-term follow-up and analyze the role of selected factors with respect to the prognosis and risk of recurrence of these tumors using multivariate analysis. They also review the pertinent literature and discuss their results in its context. METHODS The authors retrospectively reviewed data from cases involving patients who underwent resection of a peripheral nerve tumor between January 1983 and December 2013 at their institution. Of a total of 200 patients, 150 patients (with 173 surgically treated tumors) had adequate follow-up data available for analysis. Pain was assessed using a visual analog scale (VAS), and motor and sensory function were assessed by means of the Louisiana State University grading system. They also analyzed the relationship between tumor recurrence and patient sex, patient age, diagnosis of neurofibromatosis (NF), tumor histopathology, tumor size, tumor location, and extent of resection (subtotal vs gross-total resection), using univariate and multivariate analyses. RESULTS There was a statistically significant improvement in the mean VAS pain score (preoperative 3.96 ± 2.41 vs postoperative 0.95 ± 1.6, p = 0.0001). Motor strength and sensory function were significantly improved after resection of tumors involving the brachial plexus (p = 0.0457 and p = 0.0043, respectively), tumors involving the upper limb (p = 0.0016 and p = 0.0016, respectively), BPNSTs (p = 0.0011 and p < 0.0001, respectively), and tumors with dimensions less than 5 cm (motor strength: p = 0.0187 and p = 0.0021 for ≤ 3 cm and 3–5 cm tumors, respectively; sensory function: p = 0.0003 and p = 0.0001 for ≤ 3 cm and 3–5 cm tumors, respectively). Sensory function showed a statistically significant improvement also in patients who had undergone resection of tumors involving the lower limb (p = 0.0118). Total resection was associated with statistically significant improvement of motor strength (p = 0.0251) and sensory function (p < 0.0001). In univariate analysis, a history of NF (p = 0.0034), a diagnosis of MPNST or PNNST (p < 0.0001), and subtotal resection (p = 0.0042) were associated with higher risk of tumor recurrence. In multivariate analysis (logistic regression analysis), a history of NF (OR 9.28%, 95% CI 1.62–52.94, p = 0.0121) and a diagnosis of MPNST (OR 0.03%, 95% CI 0.002–0.429, p = 0.0098) or PNNST (OR 0.081%, 95% CI 0.013–0.509, p = 0.0077) emerged as independent prognostic factors for tumor recurrence. CONCLUSIONS A total resection should be attempted in all cases of peripheral nervous system tumors (irrespective of the supposed diagnosis and tumor dimensions) because it is associated with better prognosis in term of functional outcome and overall survival. Moreover, a total resection predicts a lower risk of tumor recurrence. Patients with a history of NF and tumors with malignant histology remain a challenge both for neurosurgeons and oncologists due to higher recurrence rates and the lack of standardized adjuvant therapies.

The aim of this paper is to review the current knowledge on the management of local infections in posterior cranial fossa (PCF) and spinal surgery; the center of our paper will be the diagnosis and management of infections of the wound, the subcutaneous tissue, and muscle strata. Very few papers address the problem of local infections in posterior cranial fossa and spinal surgery. The largest amount of the literature data is indeed centered on how to deal with deep infections, CSF leak, and secondary meningitis or hardware infection. Concerning PCF surgery, a higher rate of local infections has been reported, compared with supratentorial surgery. To prevent such complications, prophylaxis remains the most important tool in dealing with local infections; a careful surgical planning and patient selection are also important. On the other hand, in dealing with local infection in spinal setting, there are several evidences that local vancomycin might help reducing them in adults as well as in children. The treatment protocol consists in antibiotic therapy and, whenever needed, wound revision to remove infectious material or to obtain a microbiological diagnosis. Prognosis has overall to be considered favorable both in the short term as well as in the long term.

We have simplified the published procedure (5) for measuring sweat rates in individual human sweat glands. Sweat secretion rates were obtained from sweat drops secreted on the forearm by multiple individual glands. We computed a ratio between CFTR-dependent (by intradermal microinjection of a β adrenergic cocktail) and CFTR-independent (by methacoline as cholinergic stimulus) sweat secretion rates. We obtained a reproducible, approximately linear readout of CFTR function with measurements performed by two different independent teams. We considered three groups (CF subjects, CF carriers and non-CF controls, n=22 in each group); their mean ratios was respectively 0.000, 0.104 and 0.205 The average ratio of CF subjects was consistent with diagnosis in 3 additional cases clinically resembling CF. All groups were clearly discriminated, with sensibility and specificity ranging from 82% to 100%. A software was developed for detecting sweat droplets. This bioassay is suitabile for multicentre studies focusing on CFTR targeted therapies, controversial diagnosis and functional relevance of rare CFTR mutations.

The management of obstructive hydrocephalus associated to posterior cranial fossa tumor remains a controversial issue. In this context, the role of endoscopic third ventriculostomy (ETV) performed before tumor removal (the so-called preoperative ETV) is debated and its success rate is reported as being largely variable in the literature. We describe two children who experienced the closure of a preoperatively performed ETV after the surgical resection of their posterior fossa tumor. In both cases tumor removal was performed in the prone position. Radiological investigations and intraoperative evidence documented that the failure of the ETV was due to a blood clot which directly occluded the stoma. We speculate that the prone position favored the migration of blood, through the aqueduct, thereafter, clotting on the most declivous part of the third ventricle once the patient assumed the upright position, with the consequent occlusion of the stoma. Based on a gravitational hypothesis, we named this mechanism the "snow globe effect."

Shunt malfunction represents one of the most common problem to deal with in the daily neurosurgical practice. Among the variety of possible presentations, the cyst-like dilatation of the brain around the proximal catheter is one of the most rare and misleading type. The case of a boy with a 'tumour-like' proximal shunt malfunction is described and the pertinent literature is analysed.

Although the c-Myc oncogene is frequently deregulated in human cancer, its involvement in the pathogenesis of glioblastoma is not clear. We conducted immunohistochemical analysis of the expression of c-Myc, polycomb ring finger oncogene (BMI1), and acetylation of the lysine 9 (H3K9Ac) of histone 3 in 48 patients with glioblastoma who underwent surgery followed by radiotherapy and temozolomide treatment. The expression of c-Myc, BMI1, and H3K9ac was correlated with clinical characteristics and outcome. We found that overexpression of c-Myc was significantly associated with that of BMI1 (P = .009), and that patients who harbored glioblastomas overexpressing c-Myc and BMI1 showed significantly longer overall survival (P < .0001 and P = .0009, respectively). Our results provide the first evidence of the prognostic value of c-Myc and associated genes in patients with glioblastoma. The favorable effect of c-Myc and BMI1 expression on survival is likely mediated by the sensitization of cancer cells to radiotherapy and temozolomide through the activation of apoptotic pathways.Although the c-Myc oncogene is frequently deregulated in human cancer, its involvement in the pathogenesis of glioblastoma is not clear. We conducted immunohistochemical analysis of the expression of c-Myc, polycomb ring finger oncogene (BMI1), and acetylation of the lysine 9 (H3K9Ac) of histone 3 in 48 patients with glioblastoma who underwent surgery followed by radiotherapy and temozolomide treatment. The expression of c-Myc, BMI1, and H3K9ac was correlated with clinical characteristics and outcome. We found that overexpression of c-Myc was significantly associated with that of BMI1 (P = .009), and that patients who harbored glioblastomas overexpressing c-Myc and BMI1 showed significantly longer overall survival (P < .0001 and P = .0009, respectively). Our results provide the first evidence of the prognostic value of c-Myc and associated genes in patients with glioblastoma. The favorable effect of c-Myc and BMI1 expression on survival is likely mediated by the sensitization of cancer cells to radiotherapy and temozolomide through the activation of apoptotic pathways.

Polycythemia associated with acromegaly is usually caused by the systemic manifestations of the disease, such as sleep-apnea or concomitant erythropoietin-secreting kidney tumors. The recognition of underlying pathologies requires a thorough diagnostic process. We report a unique case of acromegaly with polycythemia, not caused by commonly described manifestations of the disease, and receding with octreotide therapy. The medical history of 141 acromegalic patients followed by the Endocrinology Unit of the San Martino University Hospital in Genoa has been also reviewed, together with the literature evidence for similar cases. The diagnostic workflow and 2-years follow-up of a 43-years old acromegalic, polycythemic man with a history of past smoking, moderate hypertension, and mental retardation are described. The hematological parameters of our cohort was retrospectively compared with those of a healthy, age/gender-related control group as well. Therapy with octreotide LAR, 20 mg i.m. q28d was begun soon after diagnosis of acromegaly in the polycythemic patient. Haematocrit level, hormonal setting, as well as pituitary tumor size and visual perimetry during treatment were recorded. Octreotide LAR treatment normalized hormonal alterations, as well as hematological parameters. Polycythemia has not recurred after 2 years of therapy. The median hemoglobin and hematocrit levels of the retrospectively analyzed cohort of acromegalic were significantly lower than normal ranges of a healthy, age/sex- related control population. In conclusions, polycythemia can be a direct, albeit rare, secondary manifestation of acromegaly, that must be considered during the diagnostic work-up of acromegalic patients presenting with such disorder.

This paper presents an On-Demand Indoor Navigation System (ODINS) based on RFID technology. ODINS is a distributed infrastructure where a set of information points (Fixed Stations - FS) provides the direction to a user who has to reach the destination point he/she has previously selected. ODINS system is proposed for residencies hosting people with mild cognitive disabilities and elderly but it can be also applied to structures where people could be disoriented. The destination is configured at some reception points or it is a predefined (e.g. the bed room or a selected "safe" point). The destination is associated with a RFID disposable bracelet assigned to her/him. The path is algorithmically computed and spread to all FSs. Every time the user is disoriented, she/he can search for the closest FS that displays the right directition. FSs should be located in strategic positions and provide a user-friendly interface such as bright arrows. The complexity is "system-side" making ODINS usable for everyone.

90 Italian children (72 boys, 18 girls) with a diagnosis of infantile autism (age range = 2.5–16.5 yr.) were assessed with a non-verbal intelligence test (Leiter–R). The test was repeated 3 times in four years. The measures used were IQ and Fluid Reasoning (FR), as evaluation of inductive and deductive reasoning, and the Autism Diagnostic Observation Schedule (ADOS), indicative of the severity of autistic symptoms at the beginning and at the end of therapy. The increase in the average IQ and FR scores at retests demonstrates the effectiveness of a treatment that emphasizes the centrality of the relationship-based approach. Moreover, the FR score at intake was predictive of a significant decrease of ADOS scores after four years of treatment, and of the increase in IQ observed in later evaluations. The data support the hypothesis that a relationship-based intervention allows cognitive improvement regardless of the autism severity expressed in the ADOS score.

Background In the large-scale trial, Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-3 (GISSI-3), patients receiving the combination of lisinopril and glyceryl trinitrate benefited most from experimental therapy. Therefore, a multicenter, randomized, double-blind study, Delapril Remodeling After Acute Myocardial Infarction (DRAMI), was designed to assess (1) the possible additive beneficial effect on left ventricular remodeling of nitrates when combined with an angiotensin-converting enzyme inhibitor (ACEI), and (2) the tolerability of a new ACEI, delapril, in respect to lisinopril in patients with large myocardial infarction (MI). Methods A total of 177 patients were randomized to receive delapril plus isosorbide-5-mononitrate (IS5MN) placebo, delapril plus IS5MN, lisinopril plus IS5MN placebo, or lisinopril plus IS5MN starting within the first 36 hours after the onset of symptoms and continuing for 3 months. Results More than 80% of the patients showed extensive ST-segment changes and 36.7% had signs or symptoms of heart failure during the first 36 hours. Over 3 months, IS5MN reduced, by 76%, the increase in LVEDV (17.4 ± 5.0 mL placebo vs 4.2 ± 4.4 mL IS5MN, P = .0439), reversed the increase in LVESV (7.5 ± 3.9 mL placebo vs −5.5 ± 2.9 mL IS5MN, P = .0052), and increased the recovery of LVEF (1.9% ± 1.3% placebo vs 6.7% ± 1.2% IS5MN, P = .0119). Overall, 3-month mortality was 10.2%; the most frequent clinical events were new episodes of severe heart failure (18.1%), persistent hypotension (10.7%), and post-MI angina (18.1%), with no differences between treatment groups. Conclusions Administration for 3 months of IS5MN combined with an ACEI, both started within 36 hours from the onset of symptoms, was safe and effective in reducing LV dilation and dysfunction after MI. The 2 ACEIs, delapril and lisinopril, appeared to be equally well tolerated.

Objective Duraplasty can be performed both by means of autologous tissues (such as galea-pericranium, temporal muscle, fascia lata) or by commercially available dural patches. Nowadays many neurosurgeons consider galea-pericranium duraplasty time-consuming, technically demanding or not adequate, thus dural surrogates are increasingly popular. In this prospective research we compared duraplasty using autologous galea-pericranium vs. dural patches in terms of postoperative long term results, ease/time required and costs. Patients and methods Research has been designed as prospective cohort study, that included 185 patients undergoing supratentorial elective neurosurgery with galea-pericranium or non-autologous duraplasty (minimum follow-up 12 months). Variables taken into account were: wound infection, CSF fistula, subcutaneous CSF collection, bone flap osteitis, brain abscess, empyema and tardive wound dehiscence (particularly after postoperative radiotherapy). Time for galea-pericranium collection, size of galea-pericranium harvest and dural defects were recorded in each case. Costs for non-autologous duroplasty were calculated. Results No statistically significant differences were evident in long term postoperative results between the two groups. Mean time of galea-pericranium collection is less than 2 min and enough galea-pericranium can be harvested in supratentorial approach to cover almost any dural defect. The only difference between the two groups is costs: an average of 268.7€/patient spent just for duraplasty. This figure is surely substantial if considered for the entire amount of surgeries performed in a department. Conclusions Considering that in our study long term results are equivalent, that galea-pericranium duraplasty is feasible and rapid, our indications are in favor of saving a considerable amount of money since an ideal autologous dural substitute is available and “free”.

Transient left ventricular apical ballooning syndrome is a new entity in the field of acute coronary syndromes and percutaneous coronary intervention. A 92-year-old patient presented with an intriguing, previously undescribed finding: the 'migrant' nature of the wall motion abnormalities, first involving the inferior wall and, subsequently, the apical region of the left ventricle. We add a small piece to the complicated puzzle represented by this syndrome.

Advances in comprehension of molecular biology of glioblastoma (GBM) have led to the development of targeted therapies. The aim of the present study was to evaluate the efficacy and safety of a targeted therapeutic approach in which administration of bevacizumab and erlotinib was tailored on the molecular profile of recurrent GBM. We prospectively enrolled ten adult patients suffering from recurrent GBM who had undergone surgical resection and standard chemo-radiotherapy. Tumor tissue was assessed for the expression of EGFRvIII and MGMT promoter methylation by RT-PCR, and for PTEN and VEGF expression by immunohistochemistry. Normal PTEN status was required for inclusion. Patients with VEGF overexpressing tumors (10/10) were treated with bevacizumab (10 mg/kg iv every 2 weeks in 6-week cycles); patients whose tumor expressed EGFRvIII (4/10) added erlotinib (150 mg/day orally; 300 mg/day if on enzyme-inducing antiepileptic drugs). Therapy was continued until disease progression or unacceptable toxicity. Primary endpoints of the study were response rate (RR), 6-month progression-free survival (PFS-6), and safety profile. The RR and PFS-6 were 100 % (4/4) and 50 % (3/6) in patients treated with bevacizumab+erlotinib (n = 4) and bevacizumab (n = 6), respectively. In the whole cohort (n = 10), RR and PFS-6 were both 70 % (7/10); median PFS and overall survival (OS) were 8.0 (3.0–31.0) and 9.5 (5.0–31.0) months, respectively. No grade 3/4 adverse events were observed; three patients treated with bevacizumab+erlotinib displayed grade 1/2 rash not requiring dose reduction; one patient treated with bevacizumab developed intratumoral hemorrhage requiring treatment discontinuation. To our knowledge, this is the first study on recurrent GBM in which administration of bevacizumab and erlotinib was tailored on the molecular profile of the patient’s tumor. Although we treated a limited number of patients, we obtained significantly higher RR and PFS-6 than those reported in a previous trial lacking molecular tumor analysis.

Primary empty sella syndrome (ESS) shares with idiopathic intracranial hypertension (IIH) high intracranial pressure (ICP) and association with obesity. Bariatric surgery is effective in IIH treatment; no data, however, exist about ESS. We report two overweight ESS patients in whom bariatric surgery resolved obesity but failed in curing ESS, requiring cerebrospinal fluid (CSF) shunt placement.

Communicating hydrocephalus is an uncommon complication in patients treated for glioblastoma multiforme (GBM). Its pathogenesis remains unclear. The authors evaluated the clinical and radiological factors associated with the onset of communicating hydrocephalus and the impact of ventriculoperitoneal (VP) shunt surgery on the outcome of these patients.One hundred twenty-four patients harboring GBM, who had undergone craniotomy for tumor resection and adjuvant radiochemotherapy, were retrospectively assessed. Seven of them developed communicating hydrocephalus and were treated with VP shunt surgery. Clinical and radiological estimates included Karnofsky Performance Scale (KPS) score, previous surgery, overall survival (OS), CSF pressure and components, tumor location, and leptomeningeal dissemination.All 7 patients who developed communicating hydrocephalus had undergone at least 2 craniotomies for tumor resection before the onset of hydrocephalus (p = 0.0006; Fisher exact test). Six cases showed high levels of CSF proteins. There was a highly significant relationship between ventricular opening at surgery for tumor recurrence and onset of hydrocephalus (p = 0.0002; Fisher exact test). In these patients, VP shunt surgery was followed by a significant improvement of KPS score (p = 0.0180; Wilcoxon signed-rank test). The median OS after VP shunt insertion was 5 ± 2.9 months.Ventricular opening after radiochemotherapy and high CSF protein levels are significant predictors of communicating hydrocephalus in patients with GBM. The VP shunt surgery improves quality of life in these patients.

Object Communicating hydrocephalus is an uncommon complication in patients treated for glioblastoma multiforme (GBM). Its pathogenesis remains unclear. The authors evaluated the clinical and radiological factors associated with the onset of communicating hydrocephalus and the impact of ventriculoperitoneal (VP) shunt surgery on the outcome of these patients. Methods One hundred twenty-four patients harboring GBM, who had undergone craniotomy for tumor resection and adjuvant radiochemotherapy, were retrospectively assessed. Seven of them developed communicating hydrocephalus and were treated with VP shunt surgery. Clinical and radiological estimates included Karnofsky Performance Scale (KPS) score, previous surgery, overall survival (OS), CSF pressure and components, tumor location, and leptomeningeal dissemination. Results All 7 patients who developed communicating hydrocephalus had undergone at least 2 craniotomies for tumor resection before the onset of hydrocephalus (p = 0.0006; Fisher exact test). Six cases showed high levels of CSF proteins. There was a highly significant relationship between ventricular opening at surgery for tumor recurrence and onset of hydrocephalus (p = 0.0002; Fisher exact test). In these patients, VP shunt surgery was followed by a significant improvement of KPS score (p = 0.0180; Wilcoxon signed-rank test). The median OS after VP shunt insertion was 5 ± 2.9 months. Conclusions Ventricular opening after radiochemotherapy and high CSF protein levels are significant predictors of communicating hydrocephalus in patients with GBM. The VP shunt surgery improves quality of life in these patients.

Falls and fall related injuries are a significant cause of morbidity, disability, and health care utilization, particularly among the age group of 65 years and over. The ability to detect falls events in an unsupervised manner would lead to improved prognoses for falls victims. Several wearable accelerometry and gyroscope-based falls detection devices have been described in the literature; however, they all suffer from unacceptable false positive rates. This paper investigates the augmentation of such systems with a barometric pressure sensor, as a surrogate measure of altitude, to assist in discriminating real fall events from normal activities of daily living. The acceleration and air pressure data are recorded using a wearable device attached to the subject's waist and analyzed offline. The study incorporates several protocols including simulated falls onto a mattress and simulated activities of daily living, in a cohort of 20 young healthy volunteers (12 male and 8 female; age: 23.7 ±3.0 years). A heuristically trained decision tree classifier is used to label suspected falls. The proposed system demonstrated considerable improvements in comparison to an existing accelerometry-based technique; showing an accuracy, sensitivity and specificity of 96.9%, 97.5%, and 96.5%, respectively, in the indoor environment, with no false positives generated during extended testing during activities of daily living. This is compared to 85.3%, 75%, and 91.5% for the same measures, respectively, when using accelerometry alone. The increased specificity of this system may enhance the usage of falls detectors among the elderly population.

A falls detection system, employing a Bluetooth-based wearable device, containing a triaxial accelerometer and a barometric pressure sensor, is described. The aim of this study is to evaluate the use of barometric pressure measurement, as a surrogate measure of altitude, to augment previously reported accelerometry-based falls detection algorithms. The accelerometry and barometric pressure signals obtained from the waist-mounted device are analyzed by a signal processing and classification algorithm to discriminate falls from activities of daily living. This falls detection algorithm has been compared to two existing algorithms which utilize accelerometry signals alone. A set of laboratory-based simulated falls, along with other tasks associated with activities of daily living (16 tests) were performed by 15 healthy volunteers (9 male and 6 female; age: 23.7 +/- 2.9 years; height: 1.74 +/- 0.11 m). The algorithm incorporating pressure information detected falls with the highest sensitivity (97.8%) and the highest specificity (96.7%).

We have previously demonstrated peripheral nerve enlargement in acromegaly.The aim of this study was to use ultrasound (US) to assess any changes in the peripheral nerves of patients with acromegaly 1 year after the first evaluation.We prospectively examined the median and ulnar nerve cross-sectional area (CSA) in 34 non-diabetic, patients with acromegaly (18 females and 16 males; 18-79 years) and 34 age-, sex-, BMI-matched controls, using a 17-5 MHz US probe.The median nerve was examined at the mid-forearm (MN-f) and at the carpal tunnel (MN-Ct) levels; the ulnar nerve at mid-forearm (UN-f) and at distal arm (UN-a). Patients were grouped according to the clinical control of the disease: 'improved'; 'always controlled'; 'always uncontrolled'; and 'worsened'.The median nerve at mid-forearm (MN-f), the ulnar nerve at mid-forearm (UN-f) and at distal arm (UN-a) were significantly reduced after 1-year follow-up in all patients (P0.001, P0.008, P0.012, respectively). In the 'improved' group, there was a significant reduction of median nerve CSA examined at mid-forearm (MN-f) (P = 0.02), and distal arm ulnar nerve CSA (UN-a) (P = 0.002). In the other groups no statistically significant differences in ultrasound parameters were recorded. However, UN-a, UN-f, MN-f, MN-ct were still significantly higher in all groups compared with controls (P0.001).These data demonstrate that median and ulnar nerves CSA are reduced after 1 year follow-up, in line with the reduction of GH/IGF-I levels. However, as the control of the disease incompletely reverts nerve enlargement, this phenomenon could be only partially reversible.

Acromegalic patients may complain of sensory disturbances in their hands.Our objective was to examine median (MN) and ulnar nerves (UN) of acromegalic patients with ultrasound (US) and to determine whether nerve abnormalities correlate with clinical parameters and nerve conduction studies (NCS).We prospectively examined the MN and UN in 34 nondiabetic, acromegalic patients (18 females and 16 males; age range 18-79 yr) and 34 sex-, age-, and body mass index-matched controls with 17-5 MHz US.The MN was examined at the carpal tunnel (MN-Ct) and at mid-forearm (MN-f) levels; the UN at the mid-forearm (UN-f) and distal arm (UN-a). A total of 272 nerve cross-sectional areas (CSA) were recorded from both patients and controls. In addition, 22 patients underwent NCS.Nerves of acromegalic patients (MN-Ct=16.5+/-4.4 mm2; MN-f=10.5+/-2.4 mm2; UN-f=9.5+/-3.0 mm2; UN-a=13.1+/-3.7 mm2) had significantly (P0.0001) greater CSA compared with controls (MN-Ct=7.4+/-1.7 mm2; MN-f=5.5+/-1.4 mm2; UN-f=5.3+/-1.4 mm2; UN-a=6.6+/-1.7 mm2). NCS displayed at least one abnormality in 59% of patients. Acromegalic patients, grouped according to disease activity (14 controlled, 8 partially controlled, 12 uncontrolled), had significantly (P0.0001) greater CSA compared with controls. Nerve CSA were significantly greater in uncontrolled patients compared to controlled, both at MN-Ct and at UN-f levels (P0.01). Abnormal NCS were observed in five of seven uncontrolled patients and four of nine controlled patients. IGF-I levels, but not GH levels, were correlated with CSA (r=0.34), whereas disease duration correlated with both nerve CSA and NCS (r=0.33 and r=0.31).US identified a significantly increased volume of MN and UN in acromegalic patients. Peripheral nerve enlargement in acromegaly seems to be an intrinsic feature of the disease related to clinical control, disease duration, and IGF-I levels.

Criteria to define the response to somatostatin (SS) analogs (SSA) in acromegaly are based on biochemical control of the disease. However, the mechanisms of action of SSAs in inhibiting tumor growth and hormonal secretion are only partially understood, and the two effects may occur independently.The objective of the study was to investigate the dissociation between antiproliferative and antisecretive effects of SSA in an octreotide-resistant patient displaying dramatic tumor shrinkage during primary therapy with octreotide LAR.We characterized somatostatin and dopamine D(2) receptor expression by immunohistochemistry and real-time RT-PCR. The effects of different receptor-selective, bispecific analogs, and chimeric somatostatin/dopamine compounds on GH secretion and cell proliferation in primary cell cultures of the tumor were assessed.The expression of SS receptor subtypes (sst)(5) and D(2) receptor was higher, compared with the other receptor subtypes. GH inhibition by SS-14 and the two chimeric somatostatin/dopamine compounds was scant but greater than subtype-selective and sst(2)/sst(5) bispecific agonists. Conversely, cell growth was potently inhibited by all test substances. However, SS-14, sst(2)/sst(5) bispecific agonist, and chimeric molecules were more potent than the other compounds.The significant antiproliferative effect of octreotide seems to be related to the higher expression of sst(5) and the negligible antihormonal effect to the lower expression of sst(2). However, activation of multiple receptors by new analogs may produce better control of tumor cell activities. The dissociation between antisecretive and antiproliferative effects observed in vivo and in vitro confirms that SSAs may induce tumor shrinkage despite the lack of effect on GH secretion.