Objective To develop a model to predict the probability of endoscopic third ventriculostomy (ETV) success in the treatment for hydrocephalus on the basis of a child's individual characteristics. ...Study design We analyzed 618 ETVs performed consecutively on children at 12 international institutions to identify predictors of ETV success at 6 months. A multivariable logistic regression model was developed on 70% of the dataset (training set) and validated on 30% of the dataset (validation set). Results In the training set, 305/455 ETVs (67.0%) were successful. The regression model (containing patient age, cause of hydrocephalus, and previous cerebrospinal fluid shunt) demonstrated good fit (Hosmer-Lemeshow, P = .78) and discrimination (C statistic = 0.70). In the validation set, 105/163 ETVs (64.4%) were successful and the model maintained good fit (Hosmer-Lemeshow, P = .45), discrimination (C statistic = 0.68), and calibration (calibration slope = 0.88). A simplified ETV Success Score was devised that closely approximates the predicted probability of ETV success. Conclusions Children most likely to succeed with ETV can now be accurately identified and spared the long-term complications of CSF shunting.
Neural stem cells are currently being investigated as potential therapies for neurodegenerative diseases, stroke, and trauma. However, concerns have been raised over the safety of this experimental ...therapeutic approach, including, for example, whether there is the potential for tumors to develop from transplanted stem cells.
A boy with ataxia telangiectasia (AT) was treated with intracerebellar and intrathecal injection of human fetal neural stem cells. Four years after the first treatment he was diagnosed with a multifocal brain tumor. The biopsied tumor was diagnosed as a glioneuronal neoplasm. We compared the tumor cells and the patient's peripheral blood cells by fluorescent in situ hybridization using X and Y chromosome probes, by PCR for the amelogenin gene X- and Y-specific alleles, by MassArray for the ATM patient specific mutation and for several SNPs, by PCR for polymorphic microsatellites, and by human leukocyte antigen (HLA) typing. Molecular and cytogenetic studies showed that the tumor was of nonhost origin suggesting it was derived from the transplanted neural stem cells. Microsatellite and HLA analysis demonstrated that the tumor is derived from at least two donors.
This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.
Introduction
The IIHS is an international, prospective, multicenter study to compare endoscopic third ventriculostomy (ETV) and shunt in infants (<24 months old) with symptomatic triventricular ...hydrocephalus from aqueductal stensosis. Recruitment started in 2004, and here, we present the first results of IIHS.
Methods
IIHS utilized a prospective comprehensive cohort design, which contained both a randomized and a non-randomized arm. Patients received either an ETV or shunt, based on randomization or parental preference. Patients were followed prospectively for time to treatment failure, defined as the need for repeat CSF diversion procedure (shunt or ETV) or death due to hydrocephalus. Survival analysis was used to compare time to failure for ETV versus shunt. The trial was registered at
clinicaltrials.gov
(NCT00652470).
Results
A total of 158 patients met eligibility criteria (median age at surgery 3.6 months, IQR 1.6–6.6 months) across 27 centers in 4 continents. Since only 52 patients (32.9 %) were randomized, all 158 patients were analyzed together (115 ETV, 43 shunt). Actuarial success rates for ETV vs shunt at 3, 6, and 12 months were as follows: 68 vs 95 %, 66 vs 88 %, and 66 vs 83 %. The 6-month ETV success rate of 66 % was slightly higher than would have been predicted by the ETV Success Score (57 %).The hazard ratio for time to treatment failure favored shunt over ETV (3.17, 95 % CI 1.45–6.96,
p
= 0.004), after adjusting for age at surgery, history of previous hemorrhage or infection, continent, and randomization status. Patients younger than 6 months of age appeared to do relatively worse with ETV than older patients.
Conclusions
The IIHS has provided the first prospective direct comparison of ETV and shunt for infant hydrocephalus. These initial results suggest that shunting has a superior success rate compared to ETV, although the success rate for both was relatively high. This patient cohort continues to be followed, and we will await the results of the important primary outcome of health status at 5 years of age.
Introduction
One of the most important unanswered questions in pediatric hydrocephalus is determining whether treatment with endoscopic third ventriculostomy (ETV) versus shunt results in improved ...health status and quality of life (QOL). To answer this, the International Infant Hydrocephalus Study (IIHS) was started in 2005 as a prospective, multicenter study to compare ETV and shunt in infants (< 24 months old) with symptomatic triventricular hydrocephalus from aqueductal stenosis. Herein, we present the 5-year primary outcome results.
Methods
IIHS utilized a prospective comprehensive cohort design, in which patients received ETV or shunt, based on either randomization or parental preference. For this analysis, we pooled the randomized arm and the parental preference arm, analyzing them together. At 5 years of age, children were assessed with the Health Utilities Index Mark 2 (HUI-2) (primary outcome) and the Hydrocephalus Outcome Questionnaire (HOQ), a measure of QOL. Results were compared in an analysis of covariance, adjusting for baseline variables including age at surgery and baseline development status.
Results
From a total of 158 patients who met eligibility criteria, complete 5-year outcomes were available on 78 (19 treated initially with shunt, 61 treated initially with ETV), assessed at a mean age of 62.1 months (SD 6.3). The mean 5-year HUI-2 utility score was 0.90 (SD 0.19) for ETV and 0.94 (SD 0.10) for shunt (
p
= 0.21). The mean 5-year HOQ overall score was 0.81 (SD 0.15) for ETV and 0.85 (SD 0.12) for shunt (
p
= 0.42). Similarly, there were no significant differences noted between 5-year HOQ subscores (cognitive, social-emotional, physical) or developmental measures at 1, 2, and 3 years.
Conclusions
This is the first prospective direct comparison of long-term outcomes of ETV and shunt for infant hydrocephalus. These results suggest that overall health status and quality of life in this cohort of infants treated for aqueductal stenosis are high, with no significant difference between those treated initially with ETV or shunt.
Trial registration
NCT00652470
Children with the autosomal dominant single gene disorder, neurofibromatosis type 1 (NF1), display multiple structural and functional changes in the central nervous system, resulting in ...neuropsychological cognitive abnormalities. Here we assessed the pathological functional organization that may underlie the behavioral impairments in NF1 using resting-state functional connectivity MRI. Coherent spontaneous fluctuations in the fMRI signal across the entire brain were used to interrogate the pattern of functional organization of corticocortical and corticostriatal networks in both NF1 pediatric patients and mice with a heterozygous mutation in the Nf1 gene (Nf1+/−). Children with NF1 demonstrated abnormal organization of cortical association networks and altered posterior-anterior functional connectivity in the default network. Examining the contribution of the striatum revealed that corticostriatal functional connectivity was altered. NF1 children demonstrated reduced functional connectivity between striatum and the frontoparietal network and increased striatal functional connectivity with the limbic network. Awake passive mouse functional connectivity MRI in Nf1+/− mice similarly revealed reduced posterior-anterior connectivity along the cingulate cortex as well as disrupted corticostriatal connectivity. The striatum of Nf1+/− mice showed increased functional connectivity to somatomotor and frontal cortices and decreased functional connectivity to the auditory cortex. Collectively, these results demonstrate similar alterations across species, suggesting that NF1 pathogenesis is linked to striatal dysfunction and disrupted corticocortical connectivity in the default network.
•Cross-species comparative analysis of a model of autism and learning disabilities.•Brain organization comparison of NF1 children and mice using resting-state fMRI.•NF1 children demonstrate disrupted organization of cortical association networks.•Reduced posterior-anterior connectivity along the cingulate cortex in both NF1 children and mice.•Altered corticostriatal connectivity in both NF1 children and mice.
Purpose
Optic pathway gliomas (OPG) are low‐grade pilocytic astrocytomas accounting for 3‐5% of pediatric intracranial tumors. Accurate and quantitative follow‐up of OPG using magnetic resonance ...imaging (MRI) is crucial for therapeutic decision making, yet is challenging due to the complex shape and heterogeneous tissue pattern which characterizes these tumors. The aim of this study was to implement automatic methods for segmentation and classification of OPG and its components, based on MRI.
Methods
A total of 202 MRI scans from 29 patients with chiasmatic OPG scanned longitudinally were retrospectively collected and included in this study. Data included T2 and post‐contrast T1 weighted images. The entire tumor volume and its components were manually annotated by a senior neuro‐radiologist, and inter‐ and intra‐rater variability of the entire tumor volume was assessed in a subset of scans. Automatic tumor segmentation was performed using deep‐learning method with U‐Net+ResNet architecture. A fivefold cross‐validation scheme was used to evaluate the automatic results relative to manual segmentation. Voxel‐based classification of the tumor into enhanced, non‐enhanced, and cystic components was performed using fuzzy c‐means clustering.
Results
The results of the automatic tumor segmentation were: mean dice score = 0.736 ± 0.025, precision = 0.918 ± 0.014, and recall = 0.635 ± 0.039 for the validation data, and dice score = 0.761 ± 0.011, precision = 0.794 ± 0.028, and recall = 0.742 ± 0.012 for the test data. The accuracy of the voxel‐based classification of tumor components was 0.94, with precision = 0.89, 0.97, and 0.85, and recall = 1.00, 0.79, and 0.94 for the non‐enhanced, enhanced, and cystic components, respectively.
Conclusion
This study presents methods for automatic segmentation of chiasmatic OPG tumors and classification into the different components of the tumor, based on conventional MRI. Automatic quantitative longitudinal assessment of these tumors may improve radiological monitoring, facilitate early detection of disease progression and optimize therapy management.
Summary
Objective
Drug‐resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in ...infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on “ultra‐early” epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study's goal is to review the safety and efficacy of ultra‐early epilepsy surgery performed before the age of 3 months.
Methods
To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications.
Results
Sixty‐four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty‐five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy ILAE grade I) was achieved in 66% of cases over a median follow‐up of 41 months (19–104 interquartile range IQR). The number of antiseizure medications was significantly reduced (median 2 drugs, 1–3 IQR, p < .0001). Outcome was not significantly associated with the type of surgery (hemispheric or more limited resections).
Significance
Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. Thus surgical treatment should not be postponed to treat DRE in very young infants based on their age.
Background
The aim of this study was to identify independent risk factors for cerebrospinal fluid shunt infection.
Methods
The medical records of all patients aged 0–18 years who underwent ...shunt‐related surgery for the treatment of hydrocephalus at the present institution between January 1996 and December 2015 were reviewed. For each case, two randomly selected controls with no shunt infection, matched for year of surgery, were chosen. Demographic clinical and microbiological data were ed.
Results
A total of 1,570 shunt‐related procedures met the inclusion criteria, yielding 68 infections (in 63 patients). The control group consisted of 132 infection‐free patients. The average annual infection rate was 4.2% cases per year. The median time between shunt procedures to infection was 19 days (range, 1–2,181). On multivariate analysis, risk factors associated with increased risk for developing an infection included a history of two or more previous revisions (OR, 4.8; 95%CI: 1.5–15.9); and age <5 years (OR, 4.5; 95%CI 1.5–13.4). A neoplastic etiology for hydrocephalus was found to be a protective factor for shunt infection (P = 0.001).
Conclusions
A history of shunt revision was the most significant risk factor in the development of subsequent shunt infection. Age >5 years was a protective factor. Future efforts should focus on modalities to optimize revision procedures and reduce the risk of subsequent infection.
Introduction
Among children with hydrocephalus, neonates with intraventricular hemorrhage (IVH) and posthemorrhagic hydrocephalus (PH) are considered a group with one of the highest complication ...rates of treatment. Despite continued progress in neonatal care, a standardized and reliable guideline for surgical management is missing for this challenging condition. Thus, further research is warranted to compare common methods of surgical treatment. The introduction of neuroendoscopic lavage has precipitated the establishment of an international registry aimed at elaborating key elements of a standardized surgical treatment.
Methods
The registry is designed as a multicenter, international, prospective data collection for neonates aged 41 weeks gestation, with an indication for surgical treatment for IVH with ventricular dilatation and progressive hydrocephalus. The following initial temporizing surgical interventions, each used as standard treatment at participating centers, will be compared: external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). Type of surgery, perioperative data including complications and mortality, subsequent shunt surgeries, ventricular size, and neurological outcome will be recorded at 6, 12, 36, and 60 months.
Results
An online, password-protected website will be used to collect the prospective data in a synchronized manner. As a prospective registry, data collection will be ongoing, with no prespecified endpoint. A prespecified analysis will take place after a total of 100 patients in the NEL group have been entered. Analyses will be performed for safety (6 months), shunt dependency (12, 24 months), and neurological outcome (60 months).
Conclusion
The design and online platform of the TROPHY registry will enable the collection of prospective data on different surgical procedures for investigation of safety, efficacy, and neurodevelopmental outcome of neonates with IVH and hydrocephalus. The long-term goal is to provide valid data on NEL that is prospective, international, and multicenter. With the comparison of different surgical treatment modalities, we hope to develop better therapy guidelines for this complex neurosurgical condition.
A hydraulic energy redirection and release technology has been developed for mitigating the effects of blast shock waves on protected objects. The technology employs a liquid-filled plastic tubing as ...a blast overpressure transformer to transfer kinetic energy of blast shock waves into hydraulic energy in the plastic tubings. The hydraulic energy is redirected through the plastic tubings to the openings at the lower ends, and then is quickly released with the liquid flowing out through the openings. The samples of the specifically designed body armor in which the liquid-filled plastic tubings were installed vertically as the outer layer of the body armor were tested. The blast test results demonstrated that blast overpressure behind the body armor samples was remarkably reduced by 97% in 0.2 msec after the liquid flowed out of its appropriate volume through the openings. The results also suggested that a volumetric liquid surge might be created when kinetic energy of blast shock wave was transferred into hydraulic energy to cause a rapid physical movement or displacement of the liquid. The volumetric liquid surge has a strong destructive power, and can cause a noncontact, remote injury in humans (such as blast-induced traumatic brain injury and post-traumatic stress disorder) if it is created in cardiovascular system. The hydraulic energy redirection and release technology can successfully mitigate blast shock waves from the outer surface of the body armor. It should be further explored as an innovative approach to effectively protect against blast threats to civilian and military personnel.
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