Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a recently identified variant of primitive neuroectodermal tumor, with fewer than 50 cases reported in the literature to date. Histologically, this tumor has features of ependymoblastoma and neuroblastoma, demonstrating areas of fine fibrillary neuropil intermingled with ependymoblastic rosettes and zones of undifferentiated neuroepithelial cells. However, ETANTR is distinguished pathologically from other embryonal tumors by the striking abundance of neuropil. Clinically, ETANTRs have shown high malignant potential and poor clinical outcome despite aggressive treatment. The authors describe 2 illustrative surgical cases of ETANTR, one involving the longest reported survival in the literature to date. The other had a poor outcome despite high-dose adjuvant chemotherapy with sequential autologous hematopoietic stem cell rescue. The authors review the natural history and treatment strategies available for this unusual malignant pediatric brain tumor.
Sunil Manjila, Abhishek Ray, Yin Hu, Dan X. Cai, Mark L. Cohen and Alan R. Cohen
Nima Alan, Sunil Manjila, Nori Minich, Nancy Bass, Alan R. Cohen, Michele Walsh and Shenandoah Robinson
Although survival for extremely low gestational age newborns (ELGANs) has improved in the past 3 decades, these infants remain prone to complications of prematurity, including intraventricular hemorrhage (IVH). The authors reviewed the outcomes for an entire cohort of ELGANs who suffered severe IVH at their institution during the past 12 years to gain a better understanding of the natural history of IVH and frequency of ventriculoperitoneal (VP) shunt placement in this population.
Data from the neonatal ICU (NICU) database, neurosurgery operative log, and medical records were used to identify and follow up all ELGANs who suffered a severe IVH between 1997 and 2008. Trends between Period 1 (1997–2001) and Period 2 (2004–2008) were analyzed using the Pearson chi-square test.
Between 1997 and 2008, 1335 ELGANs were admitted to the NICU at the authors' institution within 3 days of birth, and 111 (8.3%) of these infants suffered a severe IVH. Survival to 2 years, incidence of severe IVH, neonatal risk factors (gestational age, birth weight, and incidence of necrotizing enterocolitis), ventriculomegaly on cranial ultrasonography, and use of serial lumbar punctures for symptomatic hydrocephalus were all stable. Infants from Period 2 had a significantly lower incidence of bronchopulmonary dysplasia and sepsis than infants from Period 1 (both p < 0.001). All ELGANs with severe IVH and ventriculomegaly underwent long-term follow-up to identify shunt status at late follow-up. Twenty-two ELGANs (20%) with severe IVH required a temporary ventriculosubgaleal (VSG) shunt. Three infants with VSG shunts showed spontaneous hydrocephalus resolution, and 2 infants died of unrelated causes during the neonatal admission. The temporary VSG shunt complication rate was 20% (12% infection and 8% malfunction). Sixteen percent of all ELGANs (18 of 111) with severe IVH eventually required permanent ventricular shunt insertion. Six (35%) of 17 infants with a permanent VP shunt required at least 1 permanent shunt revision during the 1st year. The proportion of ELGANs with severe IVH who required a temporary VSG (35%) or permanent VP shunt (30%) during Period 1 decreased by more than 60% in Period 2 (10% [p = 0.005] and 8.3% [p = 0.009], respectively).
The authors report for the first time a marked reduction over the past 12 years in the proportion of ELGANs with severe IVH who required surgical intervention for hydrocephalus. Using the NICU database, the authors were able to identify and follow all ELGANs with severe IVH and ventriculomegaly. They speculate that the reduction in ventricular shunt rate results from improved neonatal medical care, including reduced infection, improved bronchopulmonary dysplasia, and postnatal steroid avoidance, which may aid innate repair mechanisms. Multicenter prospective trials and detailed analyses of NICU parameters of neonatal well-being are needed to understand how perinatal factors influence the propensity to require ventricular shunting.
Sumit Jhas and Mark Bernstein
Sunil Manjila, Harvey Chim, Sylvia Eisele, Shakeel A. Chowdhry, Arun K. Gosain and Alan R. Cohen
The history and evolution of surgical strategies for the treatment of Kleeblattschädel deformity are not well described in the medical literature. Kleeblattschädel anomaly is one of the most formidable of the craniosynostoses, requiring a multidisciplinary team for surgical treatment. The initial descriptions of this cloverleaf deformity and the evolution of surgical treatment are detailed in the present report. Two illustrative cases of Kleeblattschädel deformity, syndromic and nonsyndromic craniosynostoses treated by the senior authors, are also described along with insights into operative strategies.
Peter Weinstock, Roberta Rehder, Sanjay P. Prabhu, Peter W. Forbes, Christopher J. Roussin and Alan R. Cohen
Recent advances in optics and miniaturization have enabled the development of a growing number of minimally invasive procedures, yet innovative training methods for the use of these techniques remain lacking. Conventional teaching models, including cadavers and physical trainers as well as virtual reality platforms, are often expensive and ineffective. Newly developed 3D printing technologies can recreate patient-specific anatomy, but the stiffness of the materials limits fidelity to real-life surgical situations. Hollywood special effects techniques can create ultrarealistic features, including lifelike tactile properties, to enhance accuracy and effectiveness of the surgical models. The authors created a highly realistic model of a pediatric patient with hydrocephalus via a unique combination of 3D printing and special effects techniques and validated the use of this model in training neurosurgery fellows and residents to perform endoscopic third ventriculostomy (ETV), an effective minimally invasive method increasingly used in treating hydrocephalus.
A full-scale reproduction of the head of a 14-year-old adolescent patient with hydrocephalus, including external physical details and internal neuroanatomy, was developed via a unique collaboration of neurosurgeons, simulation engineers, and a group of special effects experts. The model contains “plug-and-play” replaceable components for repetitive practice. The appearance of the training model (face validity) and the reproducibility of the ETV training procedure (content validity) were assessed by neurosurgery fellows and residents of different experience levels based on a 14-item Likert-like questionnaire. The usefulness of the training model for evaluating the performance of the trainees at different levels of experience (construct validity) was measured by blinded observers using the Objective Structured Assessment of Technical Skills (OSATS) scale for the performance of ETV.
A combination of 3D printing technology and casting processes led to the creation of realistic surgical models that include high-fidelity reproductions of the anatomical features of hydrocephalus and allow for the performance of ETV for training purposes. The models reproduced the pulsations of the basilar artery, ventricles, and cerebrospinal fluid (CSF), thus simulating the experience of performing ETV on an actual patient. The results of the 14-item questionnaire showed limited variability among participants' scores, and the neurosurgery fellows and residents gave the models consistently high ratings for face and content validity. The mean score for the content validity questions (4.88) was higher than the mean score for face validity (4.69) (p = 0.03). On construct validity scores, the blinded observers rated performance of fellows significantly higher than that of residents, indicating that the model provided a means to distinguish between novice and expert surgical skills.
A plug-and-play lifelike ETV training model was developed through a combination of 3D printing and special effects techniques, providing both anatomical and haptic accuracy. Such simulators offer opportunities to accelerate the development of expertise with respect to new and novel procedures as well as iterate new surgical approaches and innovations, thus allowing novice neurosurgeons to gain valuable experience in surgical techniques without exposing patients to risk of harm.
Alan R. Cohen, David W. Leifer, Marc Zechel, Daniel P. Flaningan, Jonathan S. Lewin and W. David Lust
Object. The purpose of this study was to elucidate the pathophysiological characteristics of hydrocephalus in a new transgenic model of mice created to overproduce the cytokine transforming growth factor—β1 (TGFβ1) in the central nervous system (CNS).
Methods. Galbreath and colleagues generated transgenic mice that overexpressed TGFβ1 in the CNS in an effort to examine the role of this cytokine in the response of astrocytes to injury. Unexpectedly, the animals developed severe hydrocephalus and died. The authors have perpetuated this transgenic colony to serve as a model of congenital hydrocephalus, breeding asymptomatic carrier males that are heterozygous for the transgene with wild-type females.
One hundred twelve (49.6%) of 226 mice developed clinical manifestations of hydrocephalus, characterized by dorsal doming of the calvaria, spasticity, limb tremors, ataxia, and, ultimately, death. The presence of the TGFβ1 transgene was determined by performing polymerase chain reaction (PCR) analysis of sample tail slices. Animals with the hydrocephalic phenotype consistently carried the transgene, although some animals with the transgene did not develop hydrocephalus. Animals without the transgene did not develop hydrocephalus.
Alterations in brain structure were characterized using magnetic resonance (MR) imaging, gross and light microscopic analysis, and immunocytochemical studies. Magnetic resonance imaging readily distinguished hydrocephalic animals from nonhydrocephalic controls and demonstrated an obstruction at the outlets of the fourth ventricle. Gross and light microscopic examination confirmed the MR findings. The results of immunofluorescent staining of brain tissue slices revealed the presence of the TGFβ1 cytokine and its receptor preferentially in the meninges and subarachnoid space in both hydrocephalic and control mice. Reverse transcriptase—PCR analysis demonstrated tissue-specific expression of the TGFβ1 gene in the brains of transgenic mice, and enzyme-linked immunosorbent assay confirmed overexpression of the TGFβ1 cytokine in brain, cerebrospinal fluid, and plasma.
Conclusions. The transgenic murine model provides a reproducible representation of congenital hydrocephalus. The authors hypothesize that overexpression of TGFβ1 in the CNS causes hydrocephalus by altering the environment of the extracellular matrix and interfering with the circulation of cerebrospinal fluid. A model of hydrocephalus in which the genetic basis is known should be useful for evaluating hypotheses regarding the pathogenesis of this disorder and should also help in the search for new treatment strategies.
Mary I. Huang, Mary Ann O'Riordan, Ellen Fitzenrider, Lolita McDavid, Alan R. Cohen and Shenandoah Robinson
Nonaccidental head trauma (NAHT) is a major cause of death in infants. During the current economic recession, the authors noticed an anecdotal increase in infants with NAHT without an increase in the overall number of infants admitted with traumatic injuries. An analysis was performed to determine whether there was an association between economic recession and NAHT.
With Institutional Review Board approval, the trauma database was searched for NAHT in infants 0–2 years old during nonrecession (December 2001 to November 2007) and recession (December 2007 to June 2010) periods. Incidence is reported as infants with NAHT per month summarized over time periods. Continuous variables were compared using Mann-Whitney U-tests, and proportions were compared using the Fisher exact test.
Six hundred thirty-nine infant traumas were observed during the study time period. From the nonrecession to the recession period, there was an 8.2% reduction in all traumas (458 in 72 months [6.4 /month] vs 181 in 31 months [5.8/month]) and a 3.5% reduction in accidental head traumas (142 in 72 months [2.0/month] vs 59 in 31 months [1.9/month]). Nonaccidental head trauma accounted for 14.6% of all traumas (93/639). The median patient age was 4.0 months and 52% were boys. There were no significant differences in the representative counties of referral or demographics between nonrecession and recession populations (all p > 0.05). The monthly incidence rates of NAHT doubled from nonrecession to recession periods (50 in 72 months [0.7/month] vs 43 in 31 months [1.4/month]; p = 0.01). During this recession, at least 1 NAHT was reported in 68% of the months compared with 44% of the months during the nonrecession period (p = 0.03). The severity of NAHTs also increased, with a greater proportion of deaths (11.6% vs 4%, respectively; p = 0.16) and severe brain injury (Glasgow Coma Scale score ≤ 8: 19.5% vs 4%, respectively; p = 0.06) during the recession.
In the context of an overall reduction in head trauma, the significant increase in the incidence of NAHT appears coincident with economic recession. Although the cause is likely multifactorial, a full analysis of the basis of this increase is beyond the scope of this study. This study highlights the need to protect vulnerable infants during challenging economic times.