Search

Neurosurgery at the University of Oklahoma has played a pivotal role in the development of the specialty in the state. Its history spans nearly 90 years, beginning in 1931 when Dr. Harry Wilkins established the first neurosurgical practice in the state at the University of Oklahoma. Together with his first trainee, Dr. Jess Herrmann, Wilkins established the Division of Neurosurgery and its training program in 1946. Through their tireless work, the division and its residency program gained renown for its patient care and teaching, and this tradition was carried forward by its subsequent leaders. The Department of Neurosurgery was established in 1993. From humble beginnings, neurosurgery at the University of Oklahoma has grown a comprehensive residency program with an intensive curriculum, leveraging the clinical and academic breadth afforded by relationships with the College of Medicine, the University of Oklahoma Health Sciences Center, and allied clinical and research partners. Here, the authors recount the history of neurosurgery at the University of Oklahoma, the flagship academic neurosurgical program in the state.

The purpose of this report is to chronicle a 2-decade period of educational innovation and improvement, as well as governance reform, across the specialty of neurological surgery. Neurological surgery educational and professional governance systems have evolved substantially over the past 2 decades with the goal of improving training outcomes, patient safety, and the quality of US neurosurgical care. Innovations during this period have included the following: creating a consensus national curriculum; standardizing the length and structure of neurosurgical training; introducing educational outcomes milestones and required case minimums; establishing national skills, safety, and professionalism courses; systematically accrediting subspecialty fellowships; expanding professional development for educators; promoting training in research; and coordinating policy and strategy through the cooperation of national stakeholder organizations. A series of education summits held between 2007 and 2009 restructured some aspects of neurosurgical residency training. Since 2010, ongoing meetings of the One Neurosurgery Summit have provided strategic coordination for specialty definition, neurosurgical education, public policy, and governance. The Summit now includes leadership representatives from the Society of Neurological Surgeons, the American Association of Neurological Surgeons, the Congress of Neurological Surgeons, the American Board of Neurological Surgery, the Review Committee for Neurological Surgery of the Accreditation Council for Graduate Medical Education, the American Academy of Neurological Surgery, and the AANS/CNS Joint Washington Committee. Together, these organizations have increased the effectiveness and efficiency of the specialty of neurosurgery in advancing educational best practices, aligning policymaking, and coordinating strategic planning in order to meet the highest standards of professionalism and promote public health.

BACKGROUND: Occipital-cervical fusion (OCF) and ventral decompression (VD) may be used in the treatment of pediatric Chiari-1 malformation (CM-1) with syringomyelia (SM) as adjuncts to posterior fossa decompression (PFD) for complex craniovertebral junction pathology. OBJECTIVE: To examine factors influencing the use of OCF and OCF/VD in a multicenter cohort of pediatric CM-1 and SM subjects treated with PFD. METHODS: The Park-Reeves Syringomyelia Research Consortium registry was used to examine 637 subjects with cerebellar tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and at least 1 yr of follow-up after their index PFD. Comparisons were made between subjects who received PFD alone and those with PFD + OCF or PFD + OCF/VD. RESULTS: All 637 patients underwent PFD, 505 (79.2%) with and 132 (20.8%) without duraplasty. A total of 12 subjects went on to have OCF at some point in their management (PFD + OCF), whereas 4 had OCF and VD (PFD + OCF/VD). Of those with complete data, a history of platybasia (3/10, P = .011), Klippel-Feil (2/10, P = .015), and basilar invagination (3/12, P

OBJECTIVE Scoliosis is common in patients with Chiari malformation type I (CM-I)–associated syringomyelia. While it is known that treatment with posterior fossa decompression (PFD) may reduce the progression of scoliosis, it is unknown if decompression with duraplasty is superior to extradural decompression. METHODS A large multicenter retrospective and prospective registry of 1257 pediatric patients with CM-I (tonsils ≥ 5 mm below the foramen magnum) and syrinx (≥ 3 mm in axial width) was reviewed for patients with scoliosis who underwent PFD with or without duraplasty. RESULTS In total, 422 patients who underwent PFD had a clinical diagnosis of scoliosis. Of these patients, 346 underwent duraplasty, 51 received extradural decompression alone, and 25 were excluded because no data were available on the type of PFD. The mean clinical follow-up was 2.6 years. Overall, there was no difference in subsequent occurrence of fusion or proportion of patients with curve progression between those with and those without a duraplasty. However, after controlling for age, sex, preoperative curve magnitude, syrinx length, syrinx width, and holocord syrinx, extradural decompression was associated with curve progression > 10°, but not increased occurrence of fusion. Older age at PFD and larger preoperative curve magnitude were independently associated with subsequent occurrence of fusion. Greater syrinx reduction after PFD of either type was associated with decreased occurrence of fusion. CONCLUSIONS In patients with CM-I, syrinx, and scoliosis undergoing PFD, there was no difference in subsequent occurrence of surgical correction of scoliosis between those receiving a duraplasty and those with an extradural decompression. However, after controlling for preoperative factors including age, syrinx characteristics, and curve magnitude, patients treated with duraplasty were less likely to have curve progression than patients treated with extradural decompression. Further study is needed to evaluate the role of duraplasty in curve stabilization after PFD.

OBJECTIVE Aneurysmal subarachnoid hemorrhage (aSAH) may be complicated by hydrocephalus in 6.5%–67% of cases. Some patients with aSAH develop shunt dependency, which is often managed by ventriculoperitoneal shunt placement. The objectives of this study were to review published risk factors for shunt dependency in patients with aSAH, determine the level of evidence for each factor, and calculate the magnitude of each risk factor to better guide patient management. METHODS The authors searched PubMed and MEDLINE databases for Level A and Level B articles published through December 31, 2014, that describe factors affecting shunt dependency after aSAH and performed a systematic review and meta-analysis, stratifying the existing data according to level of evidence. RESULTS On the basis of the results of the meta-analysis, risk factors for shunt dependency included high Fisher grade (OR 7.74, 95% CI 4.47–13.41), acute hydrocephalus (OR 5.67, 95% CI 3.96–8.12), in-hospital complications (OR 4.91, 95% CI 2.79–8.64), presence of intraventricular blood (OR 3.93, 95% CI 2.80–5.52), high Hunt and Hess Scale score (OR 3.25, 95% CI 2.51–4.21), rehemorrhage (OR 2.21, 95% CI 1.24–3.95), posterior circulation location of the aneurysm (OR 1.85, 95% CI 1.35–2.53), and age ≥ 60 years (OR 1.81, 95% CI 1.50–2.19). The only risk factor included in the meta-analysis that did not reach statistical significance was female sex (OR 1.13, 95% CI 0.77–1.65). CONCLUSIONS The authors identified several risk factors for shunt dependency in aSAH patients that help predict which patients are likely to require a permanent shunt. Although some of these risk factors are not independent of each other, this information assists clinicians in identifying at-risk patients and managing their treatment.

An understanding of the underlying pathophysiology of tethered cord syndrome (TCS) and modern management strategies have only developed within the past few decades. Current understanding of this entity first began with the understanding and management of spina bifida; this later led to the gradual recognition of spina bifida occulta and the symptoms associated with tethering of the filum terminale. In the 17th century, Dutch anatomists provided the first descriptions and initiated surgical management efforts for spina bifida. In the 19th century, the term “spina bifida occulta” was coined and various presentations of spinal dysraphism were appreciated. The association of urinary, cutaneous, and skeletal abnormalities with spinal dysraphism was recognized in the 20th century. Early in the 20th century, some physicians began to suspect that traction on the conus medullaris caused myelodysplasia-related symptoms and that prophylactic surgical management could prevent the occurrence of clinical manifestations. It was not, however, until later in the 20th century that the term “tethered spinal cord” and the modern management of TCS were introduced. This gradual advancement in understanding at a time before the development of modern imaging modalities illustrates how, over the centuries, anatomists, pathologists, neurologists, and surgeons used clinical examination, a high level of suspicion, and interest in the subtle and overt clinical appearances of spinal dysraphism and TCS to advance understanding of pathophysiology, clinical appearance, and treatment of this entity. With the availability of modern imaging, spinal dysraphism can now be diagnosed and treated as early as the intrauterine stage.

OBJECT The coexistence of Chiari malformation Type I (CM-I) and ventral brainstem compression (VBSC) has been well documented, but the change in VBSC after posterior fossa decompression (PFD) has undergone little investigation. In this study the authors evaluated VBSC in patients with CM-I and determined the change in VBSC after PFD, correlating changes in VBSC with clinical status and the need for further intervention. METHODS Patients who underwent PFD for CM-I by the senior author from November 2005 to January 2013 with complete radiological records were included in the analysis. The following data were obtained: objective measure of VBSC (pB–C2 distance); relationship of odontoid to Chamberlain’s, McGregor’s, McRae’s, and Wackenheim’s lines; clival length; foramen magnum diameter; and basal angle. Statistical analyses were performed using paired t-tests and a mixed-effects ANOVA model. RESULTS Thirty-one patients were included in the analysis. The mean age of the cohort was 10.0 years. There was a small but statistically significant increase in pB–C2 postoperatively (0.5 mm, p < 0.0001, mixed-effects ANOVA). Eleven patients had postoperative pB–C2 values greater than 9 mm. The mean distance from the odontoid tip to Wackenheim’s line did not change after PFD, signifying postoperative occipitocervical stability. No patients underwent transoral odontoidectomy or occipitocervical fusion. No patients experienced clinical deterioration after PFD. CONCLUSIONS The increase in pB–C2 in patients undergoing PFD may occur as a result of releasing the posterior vector on the ventral dura, allowing it to relax posteriorly. This increase appears to be well-tolerated, and a postoperative pB–C2 measurement of more than 9 mm in light of stable craniocervical metrics and a nonworsened clinical examination does not warrant further intervention.

The authors present a case of Chiari type 1.5 malformation with the uncommon presenting symptoms of esotropia and diplopia due to divergence insufficiency in a 12-year-old girl. Imaging at initial diagnosis revealed cerebellar herniation with extension of the tonsils to the C2 vertebral body, a retroflexed odontoid, and a small cervical syrinx. The patient was initially treated with an uncomplicated Chiari malformation decompression without dural opening. Repeat imaging revealed an adequate decompression. Three months postoperatively the patient’s diplopia recurred and she underwent repeat posterior fossa decompression with dural opening and duraplasty. Following repeat decompression with dural opening and duraplasty, the patient’s diplopia had not recurred by the 2-year follow-up.https://thejns.org/doi/abs/10.3171/2018.5.PEDS1886

OBJECTIVEExperience has led us to suspect an association between shunt malfunction and recent abdominal surgery, yet information about this potential relationship has not been explored in the literature. The authors compared shunt survival in patients who underwent abdominal surgery to shunt survival in our general pediatric shunt population to determine whether such a relationship exists.METHODSThe authors performed a retrospective review of all cases in which pediatric patients underwent ventriculoperitoneal shunt operations at their institution during a 7-year period. Survival time in shunt operations that followed abdominal surgery was compared with survival time of shunt operations in patients with no history of abdominal surgery. Univariate and multivariate analyses were used to identify factors associated with failure.RESULTSA total of 141 patients who underwent 468 shunt operations during the period of study were included; 107 of these 141 patients had no history of abdominal surgery and 34 had undergone a shunt operation after abdominal surgery. Shunt surgery performed more than 2 weeks after abdominal surgery was not associated with time to shunt failure (p = 0.86). Shunt surgery performed within 2 weeks after abdominal surgery was associated with time to failure (adjusted HR 3.6, 95% CI 1.3–9.6).CONCLUSIONSUndergoing shunt surgery shortly after abdominal surgery appears to be associated with shorter shunt survival. When possible, some patients may benefit from shunt placement utilizing alternative termini.

Object The authors debate the optimal management for Chiari malformation Type I (CM-I) while sharing their experience with posterior fossa decompression and duraplasty (PFDD). Methods The charts of 48 consecutive pediatric patients surgically treated for CM-I were retrospectively reviewed. Results Patients ranged in age from 2 to 17 years with an average age of 9.8 years. The most common presentations were headache, affecting 34 patients (71%), and pain (neck, back, or extremities), affecting 21 patients (44%). Twenty-seven patients (56%) had a syrinx. All 48 patients underwent PFDD utilizing acellular tissue matrix. The average hospital stay overall was 3.56 days, whereas the average stay for patients with (29 [60%] of 48) or without (19 [40%] of 48) scoliosis and/or syringomyelia was 3.72 and 3.32 days, respectively. The odds of a patient having a hospital stay of 4 or more days was nearly 3 times greater in patients with scoliosis and/or syringomyelia as compared with patients without either condition (OR 2.73, 95% CI 0.74–10.11, p = 0.1330). The average hospital stay for patients 0–8 years of age was 3.29 days; and for those 9–17 years of age, 3.78 days. The odds of a patient having a hospital stay of 4 or more days was nearly 4 times greater in 9- to 17-year-olds as compared with 0- to 8-year-olds (OR 3.73, 95% CI 1.03–13.52, p = 0.0455). Forty patients (89%) experienced early improvement in their signs and symptoms following PFDD. There were 2 revision PFDDs (4%). Conclusions Posterior fossa decompression and duraplasty is a safe and effective surgical option in the management of pediatric CM-I.

Introduction Harvesting autogenous calvarial bone grafts can potentially weaken the donor site and make it more susceptible to trauma. Conversely, restoring the integrity of the cranial vault structure can result in better dissipation of traumatic energy. This study proposes to mathematically model traumatic situations to evaluate the effect of cranioplasty on biomechanical properties of the craniofacial skeleton. Methods Preoperative and 6-month postoperative computed tomography-generated DICOM data were used to extract a tetrahedral volumetric representation of the craniofacial skeleton. These data were then used in finite element solver-simulating traumatic events. Results Deformational stresses accumulate around defect edges and can serve as seed points for calvarial fractures at much lower energy levels in the preoperative models when compared to the postoperative models. Accumulation of stresses in the orbital roof/medial orbital wall areas was observed, similar to fracture patterns observed in the younger pediatric population Conclusions Restoring architectural integrity of the craniofacial skeleton results in significant increased resistance to deformational stresses despite structural weakening caused by harvesting cranial bone.

Ventricular shunt failures and subsequent revisions are a significant source of patient morbidity. We conducted a review of pediatric patients undergoing placement or revision of ventricular shunts at our institution between January 2007 and December 2008. Patients were followed through to July 2014. Data collected included patient demographics, shunt history and indication for procedure, approach taken for shunt placement, and location of shunt tip in relation to the foramen of Monro. Univariate and multivariate analyses were conducted to identify factors associated with proximal failure. A total of 87 procedures were identified in 40 patients, consisting of 23 initial placements and 64 revisions. Thirty-nine proximal catheter malfunctions were identified. Indications for shunt placement included Chiari II malformation (33%) and intraventricular hemorrhage (33%). Mean follow-up period was 5.5 years. Median time to shunt failure was 1.57 years. In the multivariate model, younger age at placement was associated with decreased time to proximal failure (hazard ratio [HR]=0.80 per increasing year of age, 95% confidence interval [CI] 0.64-0.98). Both anterior approach (HR=0.39, 95% CI 0.23-0.67) and farther distance to foramen of Monro (HR=0.02 per increasing 10mm, 95% CI 0.00-0.22) were associated with increased time to proximal failure when the catheter tip was located within the contralateral lateral ventricle. Optimizing outcomes in patients with shunt-dependent hydrocephalus continues to be a challenge. Despite unsatisfactory outcomes, particularly in the pediatric population, few conclusions can be drawn from studies assessing operative variables.

Background Chronic subdural hematoma in the pediatric population often results from trauma. Asymptomatic and benign-appearing subdural collections are generally managed conservatively without operative intervention. Primary intracranial sarcomas are uncommon entities. Diagnosis of sarcoma can be difficult because these lesions often manifest as apparent hematoma. Case Description Presented is the case of a primary intracranial mucoid spindle cell sarcoma that arose in a child with a history of benign-appearing bilateral subdural fluid collections in the setting of nonaccidental trauma. The patient was initially managed conservatively because her neurological examination result was normal and her subdural collections decreased in size on repeated imaging. The collections did not resolve completely. Years later, she exhibited weakness, seizure, and an increase in the size of her subdural fluid collection. Subdural drainage was attempted without significant effect. Cytologic assessment of fluid was negative for malignant cells. Magnetic resonance imaging revealed multiple enhancing masses along the subdural collection. The patient eventually underwent craniotomy in which a diagnosis of sarcoma was obtained. Pathological and radiographic findings as well as oncological management are reviewed. The authors also review the natural history and treatment of primary intracranial sarcoma in the pediatric population. Conclusions Early contrasted magnetic resonance imaging should be obtained in patients with subdural fluid collections that appear asymmetric or do not resolve in the expected time course, despite having a normal neurologic examination result. Negative cytologic assessment does not exclude sarcoma diagnosis.

We discuss the association between tethered cord syndrome (TCS) and Chiari type 1 malformation (CM1), and report on the surgical outcomes of children with CM1 and TCS who underwent sectioning of the filum terminale (SFT). The relationship between TCS and CM1 is unclear. A retrospective review of 170 consecutive spinal cord detetherings between 2008 and 2012 was performed. We identified 17 children with CM1 who underwent SFT. Information regarding clinical presentation, radiographic findings, surgical procedures, and clinical outcomes was analyzed. A mean tonsillar herniation of 10.0mm (range: 5-21) was noted. Children with a fatty or thickened filum terminale demonstrated a greater amount of tonsillar displacement (p

Pediatric epilepsy patients with generalized or multifocal abnormalities on electroencephalogram and developmental delay have not classically been considered surgical candidates, even if neuroimaging revealed a lesion. A new paradigm advocates for early focal epilepsy surgery, despite non-localizing EEG abnormalities. This is an instructive case of curative focal subcortical heterotopia resection in a six-year-old boy with refractory, symptomatic generalized epilepsy who fit criteria for Lennox-Gastaut syndrome. Post-surgery, he had normalization of his EEG, resolution of behavioral problems and developmental delay, and no seizure recurrence off all antiepileptic medications. Literature is reviewed in the context of this demonstrative case supporting that generalized electrographic and clinical expression of focal pathology may occur beyond infancy and the principle of secondary epileptogenesis. Epileptic encephalopathy may be reversible with resection of a focal lesion and there is potential for cure if patients are given early surgical consideration.

Gliomas are primary brain tumors with a complex biology characterized by antigenic and genomic heterogeneity and a propensity for invasion into normal brain tissue. High grade glioma cells possess a voltage-independent, amiloride-inhibitable, inward Na+ current. This current does not exist in normal astrocytes or low grade tumor cells. Inhibition of this conductance decreases glioma growth and cell migration making it a potential therapeutic target. Our previous results have shown that the acid-sensing ion channels (ASICs), members of the epithelial Na+ channel (ENaC)/degenerin (DEG) family of ion channels are part of this current pathway. We hypothesized that one member of the ENaC/DEG family, ASIC2, is retained intracellularly and that it is the lack of functional expression of ASIC2 at the cell surface that results in hyperactivity of this conductance in high grade gliomas. In this study we show that the chemical chaperone, glycerol, and the transcriptional regulator, sodium 4-phenylbutyrate, inhibit the constitutively activated inward current and reduce cell growth and migration in glioblastoma multiforme. The results suggest that these compounds induce the movement of ASIC2 to the plasma membrane, and once there, the basally active inward current characteristic of glioma cells is abolished by inherent negative regulatory mechanisms. This in turn compromises the ability of the glioma cell to migrate and proliferate. These results support the hypothesis that the conductance pathway in high grade glioma cells is comprised of ENaC/DEG subunits and that abolishing this channel activity promotes a reversion of a high grade glioma cell to a phenotype resembling that of normal astrocytes.

Psalmotoxin 1 (a component of the venom of a West Indies tarantula) is a 40-amino acid peptide that inhibits cation currents mediated by acid-sensing ion channels (ASIC). In this study we performed electrophysiological experiments to test the hypothesis that Psalmotoxin 1 (PcTX1) inhibits Na+ currents in high-grade human astrocytoma cells (glioblastoma multiforme, or GBM). In whole cell patch-clamped cultured GBM cells, the peptide toxin quickly and reversibly inhibited both inward and outward current with an IC50 of 36 ± 2 pM. The same inhibition was observed in freshly resected GBM cells. However, when the same experiment was performed on normal human astrocytes, the toxin failed to inhibit the whole cell current. We also determined a cationic selectivity sequence for inward currents in three cultured GBM cell lines (SK-MG-1, U87-MG, and U251-MG). The selectivity sequence yielded a unique biophysical fingerprint with inward K+ conductance approximately fourfold greater than that of Na+, Li+, and Ca2+. These observations suggest that PcTX1 may prove useful in determining whether GBM cells express a specific ASIC-containing ion channel type that can serve as a target for both diagnostic and therapeutic treatments of aggressive malignant gliomas.

PURPOSE: To evaluate the role of diffusion-weighted magnetic resonance imaging (DWIMRI) in the diagnosis and management of children with suspected or confirmed Shaken Baby Syndrome (SBS). METHODS: This was a retrospective interventional case series of all infants and children younger than 2 years of age admitted to a children’s hospital. We retrospectively reviewed medical records and neuroimaging findings of all children younger than 2 years of age with confirmed or suspected SBS admitted to a children’s hospital. Inclusion criteria were documented ocular examination by an ophthalmologist and a brain MRI with DWI. Twenty-six infants and children were included. Other children were excluded. Children with proven SBS were diagnosed with “confirmed SBS,” while children in whom the diagnosis of SBS remained uncertain were diagnosed with “suspected SBS.” RESULTS: Twenty-six infants and children with mean age of 7.1 months (range, 6 weeks–24 months) were included, 18 with confirmed SBS. All 26 patients had a subdural hematoma, 10 had associated occult bone fractures, and 18 had retinal hemorrhages. Seven of the eight cases without retinal hemorrhages had isolated subdural hematoma without parenchymal brain lesions on both conventional MRI and DWIMRI. SBS was confirmed in only one case with a normal fundus. Among the 18 patients with retinal hemorrhages, SBS was confirmed in all but one case. All 18 patients with confirmed SBS had an abnormal DWIMRI. In 13 patients, DWI showed lesions that were larger than on conventional MRI. In patients with brain parenchymal lesions, the DWIMRI characteristics suggested cerebral ischemia, which appears to play a major role in SBS. CONCLUSIONS: In all patients with confirmed SBS, DWIMRI was abnormal and suggested diffuse or posterior cerebral ischemia, in addition to subdural hematomas in the pathogenesis of this disorder.

Hydromechanical brain models often involve constitutive relations which must account for soft tissue deformation and creep, together with the interstitial fluid movement and exchange through capillaries. The interaction of rather unknown mechanisms which produce, absorb, and circulate the cerebrospinal fluid within the central nervous system can further add to their complexity. Once proper models for these phenomena or processes are selected, estimation of the associated parameters could be even more challenging. This paper presents the results of a consistent, coupled poroviscoelastic modeling and characterization of the brain tissue as a dual-porosity system. The model draws from Biot's theory of poroviscoelasticity, and adopts the generalized Kelvin's rheological description of the viscoelastic tissue behavior. While the interstitial space serves as the primary porosity through which the bulk flow of the interstitial fluid occurs, a secondary porosity network comprising the capillaries and venous system allows for its partial absorption into the blood. The correspondence principle is used in deriving a time-dependent analytical solution to the proposed model. It allows for identical poroelastic formulation of the original poroviscoelastic problem in the Laplace transform space. Hydrocephalus generally refers to a class of medical conditions which share the ventricles enlargement as a common feature. A set of published data from induced hydrocephalus and follow-up perfusion of cats' brains is used for quantitative characterization of the proposed model. A selected portion of these data including the ventricular volume and rate of fluid absorption from the perfused brain, together with the forward model solution, is utilized via an inverse problem technique to find proper estimations of the model parameters. Results show significant improvement in model predictions of the experimental data. The convoluted and coupled solution results are presented through the time-dependent plots of the ventricular volume undergoing the perfusion experiment. The plots demonstrate the intricate interplay of viscous and poroelastic diffusive time scales, and their competition in reaching the steady state response of the system.

A variety of mass lesions can arise within or in proximity to the ventricular system in children. These lesions are relatively uncommon, and they present a unique diagnostic and surgical challenge. The differential diagnosis is determined by tumor location in the ventricular system, clinical presentation, age of the patient, and the imaging characteristics of the lesion. In this report the authors provide an introduction to and an overview of the most common pediatric supratentorial intraventricular tumors. The typical radiographic features of each tumor and location preference within the ventricular system are reviewed. Management and treatment considerations are discussed. Examination of tissue samples to obtain diagnosis is usually required for accurate treatment planning, and resection without adjuvant therapies is often curative. The critical management decision frequently involves determining which lesions are appropriate for surgical therapy. Care ful preoperative neuroimaging is extremely useful in planning surgery. Knowledge of the typical imaging characteristics of these tumors can help to determine the diagnosis with relative certainty when a tissue sample has not been obtained, because a small subset of these lesions can be managed expectantly.

Gene expression profiling of three human temporal lobe brain tissue samples (normal) and four primary glioblastoma multiforme (GBM) tumors using oligonucleotide microarrays was done. Moreover, confirmation of altered expression was performed by whole cell patch clamp, immunohistochemical staining, and RT-PCR. Our results identified several ion and solute transport-related genes, such as N-methyl-d-aspartate (NMDA) receptors, α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-2 receptors, GABAA receptor subunits α3, β1, β2, and β3, the glutamate transporter, the glutamate/aspartate transporter II, the potassium channel KV2.1, hKVβ3, and the sodium/proton exchanger 1 (NHE-1), that are all downregulated in the tumors compared with the normal tissues. In contrast, aquaporin-1, possibly aquaporins-3 and -5, and GLUT-3 message appeared upregulated in the tumors. Our results also confirmed previous work showing that osteopontin, nicotinamide N-methyltransferase, murine double minute 2 (MDM2), and epithelin (granulin) are upregulated in GBMs. We also demonstrate for the first time that the cytokine and p53 binding protein, macrophage migration inhibitory factor (MIF), appears upregulated in GBMs. These results indicate that the modulation of ion and solute transport genes and heretofore unsuspected cytokines (i.e., MIF) may have profound implications for brain tumor cell biology and thus may identify potential useful therapeutic targets in GBMs.

Objective: The purpose of this study was to determine if there is a difference in the caudal extent of brain stem herniation and the degree of cervicomedullary deformity between symptomatic and asymptomatic Chiari II patients. Methods: Magnetic resonance imaging and the clinical presentation of 14 symptomatic and 59 asymptomatic patients were analyzed. The level of the cervicomedullary deformity below the foramen magnum was measured in both groups. The level of the deformity was identified by the cervical vertebral body or disc space level. Results and Conclusion: Review of our results shows no obvious relationship between the level of cervicomedullary deformity and the presenting symptoms or the outcome after surgical decompression. We conclude that the level of herniation and the cervicomedullary deformity is not a reliable marker to determine which patients may become symptomatic and require decompression or to determine prognosis.

The authors present a case of migration of a ventricular tapping system into the third ventricle of a 6-year-old boy who is was born prematurely. As an infant, the patient was treated with serial lumbar punctures for hydrocephalus associated with intraventricular hemorrhage. The patient progressed to requiring a ventricular tapping reservoir and eventually a ventriculoperitoneal shunt. The patient presented for suspected shunt malfunction 4 years after placement of his ventriculoperitoneal shunt, and the migrated ventricular tapping system was discovered. The authors discuss several management strategies that could be used to prevent this complication.

Objective We report on 32 neonates treated with ventriculosubgaleal (VSG) shunts to determine VSG shunt survival and associated complications. Methods Between 1993 and 1997, 37 VSG shunts were placed in 32 neonates when the cerebrospinal fluid (CSF) or the abdomen was considered unsuitable for ventriculoperitoneal shunt placement. In each child, a ventricular catheter was attached to 3 cm of a closed-end peritoneal tube via a right-angle connector, which drained into a surgically created subgaleal pocket. Results The causes of hydrocephalus were as follows: intraventricular hemorrhage (IVH) in 20 neonates, meningitis/ventriculitis in 6, IVH and infection in 2, and other causes in 4. The mean postconception age at the time of VSG shunt insertion was 37.2 weeks (33.1 wk in the IVH group), and the mean weight was 2227 g (1724 g in the IVH group). The average preoperative head circumference was 33.6 cm. The average survival of these 37 VSG shunts (five children had two VSG shunts) was 35.1 days. The complications were as follows: one CSF leakage occurred when sutures were removed; one catheter fell into the ventricle and required removal, and one child died immediately after VSG shunt revision. There were no VSG shunt infections. All surviving children followed for a minimum of 4 months after insertion of a VSG shunt (n = 24) have required a ventriculoperitoneal shunt. Mean follow-up from the time of first VSG shunt insertion was 21.6 months. Four children died as a result of causes unrelated to the VSG shunt. Conclusion VSG shunts offer a simple, effective, and relatively safe means of temporizing hydrocephalus, and they avoid the need for external drainage or frequent CSF aspiration in these medically unstable infants until the CSF characteristics and abdomen are acceptable for ventriculoperitoneal shunting.

Introduction. The diagnosis of shunt malfunction can be difficult even for the experienced clinician and may lead to disastrous circumstances when misinterpreted. Less experienced physicians may rely more on radiographic reports as a primary diagnostic modality. In this study, we evaluated the reliability of using these reports without accurate clinical assessment. Methods. All shunt revisions seen at Children's Hospital (Birmingham, AL) between January 1996 and August 1996 were reviewed, excluding patients with brain tumors, supratentorial extraaxial fluid collections, and infections. Sixty-eight patients underwent 100 operations for shunt malfunction. All patients had evidence of shunt blockage, disconnection, catheter malposition, or valve pressure incompatibility. The prospective radiographic interpretation of preoperative computed tomography and magnetic resonance imaging scans was reviewed in each case. Results. Twenty-four percent of the reports made no mention of shunt malfunction. In this group, the ventricular system was described as “unchanged,” “stable,” “normal,” “unremarkable,” “small,” “smaller,” “slit,” “negative,” and “no hydrocephalus,” with no other comment to support a diagnosis of shunt malfunction. An additional 9% of reports contained the same terms, while also hinting at some other clinical or radiographic data that suggest the possibility of shunt failure (eg, a shunt disconnection seen on plain radiographs), despite the scan findings. In all patients in this group, symptoms improved after surgery. Conclusion. We conclude that as many as one third of patients presenting with shunt malfunction will not have the diagnosis of shunt malfunction supported by a prospective radiologic interpretation of brain imaging. Although the neurosurgical community can assess the clinical situation to determine the need for surgery, other clinicians can be easily reassured by a radiographic report that does not mention or diagnose shunt malfunction. Today, more than ever, nonneurosurgeons are being called on to evaluate complex clinical situations and may rely on radiographic reports.

Using a combined search of the Children’s Hospital (Birmingham, Ala., USA) medical records and the Jefferson County Health Department death records, we reviewed all shunt-related deaths that occurred between January 1990 and July 1996. Of these, we excluded patients who died of nonhydrocephalus-related reasons, such as bronchopulmonary dysplasia, as well as patients who had other serious neurological illnesses such as brain tumor and hydranencephaly. Twenty-eight patients died of shunt-related causes in the 6.5-year period. A survival analysis showed that 96% survived 32 months after first shunting. Of 28 patients, 23 were beyond help prior to medical evaluation. However, at least 10 of these patients had symptoms suggestive of shunt failure at least 24 h and as long as 2 weeks prior to their demise. We conclude that hydrocephalic children still die of shunt failure despite the modern technology of the 1990s. Some of these causes may be avoidable through early detection of symptoms. Guidelines to patients, families, and primary caregivers should be emphasized.

Spina bifida and other congenital abnormalities of the spinal cord are relatively common (1 per 1000 births). Early urologic evaluation to determine the extent of neurologic involvement of the lower urinary tract is essential. Urodynamic studies are important in determining voiding pressure and leak pressure and in classifying the type of detrusor and sphincter dysfunction. Therapy is directed toward preservation of the upper tracts. Many nonsurgical (clean intermittent catheterization and anticholinergic drugs) and surgical procedures allow the child to be continent and maintain a normal upper urinary tract. The importance of follow-up is stressed because neurourologic changes frequently occur, and prompt treatment or change of therapy is essential. Today, children with spina bifida are leading healthy, productive lives. A continued multidisciplinary approach to their care is important.

The authors present a case of migration of a ventricular tapping system into the third ventricle of a 6-year-old boy who is was born prematurely. As an infant, the patient was treated with serial lumbar punctures for hydrocephalus associated with intraventricular hemorrhage. The patient progressed to requiring a ventricular tapping reservoir and eventually a ventriculoperitoneal shunt. The patient presented for suspected shunt malfunction 4 years after placement of his ventriculoperitoneal shunt, and the migrated ventricular tapping system was discovered. The authors discuss several management strategies that could be used to prevent this complication.

The pineal gland, located at the roof of the diencephalon, is a cone-shaped structure dorsal to the midbrain tectum. It is composed of a variety of cells, including astrocytes, ganglion cells, blood vessels, and pinocytes. Pineocytes, the parenchymal cells of this organ, are specialized neurons rich in monoaminergic neurotransmitters, including serotonin, norepinepherin, and melatonin. While retinal proteins such as S-antigen are expressed on some pineocytes, the pineal gland is not photosensitive in humans and higher primates. Collateral projections from the retino-thalamic tract as well as sympathetic fibers from the superior cervical ganglion innervate the pineal gland [3]. Its role in humans and higher primates is controversial, but likely related to synchronizing neuro-endocrine responses to sympathetic and circadian light-dark cycles [32].

Neurofibromatosis is a multifaceted disease that often results in tumors of the central nervous system. As our understanding of the molecular biology of the disease improves along with better neuroradiology imaging, surgical instrumentation, and adjunctive care, the management schemes for these patients are evolving. This article reviews what is known about neurofibromatosis, common management problems with respect to the central nervous system, and an approach to the handling of these issues.

Since 1980, 22 patients less than 2 years of age have been treated for intracranial tumors at our institution. The most common presentation was elevated intracranial pressure associated with ventriculomegaly (73%). The diagnosis was made by computed tomography or magnetic resonance imaging and confirmed surgically in every case. In 68% of cases, the tumor involved midline structures in the central nervous system. Tumors were infratentorial in 29% of patients less than 1 year of age and in 60% of those more than 1 year of age. Most tumors were either primitive neuroectodermal tumors (41%, 7 of 9 located in midline posterior fossa structures) or astrocytomas (27%, 5 of 6 located in the hypothalamus, chiasm, or optic nerve). Twenty patients had gross or subtotal tumor resection. Surgical mortality and neurological morbidity were 10% and 5%, respectively. Of 5 patients who underwent a second operation for tumor recurrence, 3 demonstrated a change in the pathological features of the tumor from those of the original diagnosis. Of 10 surgical survivors with malignant tumors, 8 received chemotherapy and 5 radiation therapy. Radiation was not administered before 1 year of age. The overall 1-year survival was 70%, and 2-year survival was 58%. Two-year survival for benign and malignant tumors was not significantly different. We think that the interdisciplinary efforts directed toward the treatment of these tumors has improved survival and that all children should be offered entry to a research protocol and aggressive treatment.

Acid sensing ion channel (ASIC)2 belongs to the amiloride-sensitive Na(+)-channel/ degenerin family. Our previous studies suggested that differential regulation of ASIC2 expression occurs between high-grade glial-derived tumor cells and normal astrocytes. To investigate the mechanisms involved in the regulation of ASIC2 gene expression, the human ASIC2 promoter region (-1551 to +117) was cloned and characterized. The ASIC2 promoter lacked a canonical TATA box, but contained one putative CCAAT box. Nucleotide sequencing of the promoter revealed the presence of a number of transcription factor-binding sites and a 404 bp CpG island upstream the transcription start site. Nested deletion mutants and transfection results showed that the construct between -133 and +117 base pairs conferred basal transcription specific activity. Mutation of Sp1 and CP2 sites in this region resulted in a 70 and 95% decrease in promoter activity, respectively. Gel shift assays demonstrated the existence of specific protein binding to the SP1 and CP2 elements. There was no mutation in the CpG island in six glioma cell lines, but methylation-specific PCR showed methylation in some of glioma cell lines and tumor tissues, and treatment with the methylation inhibitor 5-Aza-2'-deoxycytidine could partially restore ASIC2 expression in cell lines, suggesting that epigenetic mechanisms may contribute to dysregulated ASIC2 expression.

Malignant gliomas have invasive properties that make them nearly impossible to cure surgically. Most physicians agree that the best hope for long-term control lies with adjunctive therapies. One em...

We explored the involvement of protein kinase C (PKC) and its isoforms in the regulation of BNaC2. Reverse transcriptase PCR evaluation of PKC isoform expression at the level of mRNA revealed the presence of alpha and epsilon/epsilon' in all glioma cell lines analyzed; most, but not all cell lines expressed delta and zeta. No messages were found for the betaI and betaII isotypes of PKC in the tumor cells. Normal astrocytes expressed beta but not gamma. The essential features of these results were confirmed at the protein level by Western analysis. This disproportionate pattern of PKC isoform expression in glioma cell lines was further echoed in the functional effects of these PKC isoforms on BNaC2 activity in bilayers. PKC holoenzyme or the combination of PKCbetaI and PKCbetaII isoforms inhibited BNaC2. Neither PKCepsilon nor PKCzeta or their combination had any effect on BNaC2 activity in bilayers. The inhibitory effect of the PKCbetaI and PKCbetaII mixture on BNaC2 activity was abolished by a 5-fold excess of a PKCepsilon and PKCzeta combination. PKC holoenzymes, PKCbetaI, PKCbetaII, PKCdelta, PKCepsilon, and PKCzeta phosphorylated BNaC2 in vitro. In patch clamp experiments, the combination of PKCbetaI and PKCbetaII inhibited the basally activated inward Na(+) conductance. The variable expression of the PKC isotypes and their functional antagonism in regulating BNaC2 activity support the idea that the participation of multiple PKC isotypes contributes to the overall activity of BNaC2.

We describe the resolution of persistent diabetes insipidus after cranioplasty with autogenous bone and bone morphogentic protein 2-infused collagen matrix in a patient who had large bilateral craniectomies for trauma. A potential pathogenic mechanism is presented.

Members of the degenerin/epithelial Na(+) channel superfamily of ion channels subserve many functions, ranging from whole body sodium handling to mechanoelectrical transduction. We studied brain Na(+) channel 2 (BNaC-2) in planar lipid bilayers to examine its single channel properties and regulation by Ca(2+). Upon incorporation of vesicles made from membranes of oocytes expressing either wild-type (WT) BNaC-2 or BNaC-2 with a gain-of-function (GF) point mutation (G433F), functional channels with different properties were obtained. WT BNaC-2 resided in a closed state with short openings, whereas GF BNaC-2 was constitutively activated; a decrease in the pH in the trans compartment of the bilayer activated WT BNaC-2 and decreased its permeability for Na(+) over K(+). Moreover, these maneuvers made the WT channel more resistant to amiloride. In contrast, GF BNaC-2 did not respond to a decrease in pH, and its amiloride sensitivity and selectivity for Na(+) over K(+) were unaffected by this pH change. Buffering the bathing solutions with EGTA to reduce the free [Ca(2+)] to

Human astrocytoma cells were studied using whole cell patch-clamp recording. An inward, amiloride-sensitive Na+ current was identified in four continuous cell lines originally derived from human glioblastoma cells (CH235, CRT, SKMG-1, and U251-MG) and in three primary cultures of cells obtained from glioblastoma multiforme tumors (up to 4 passages). In addition, cells freshly isolated from a resected medulloblastoma tumor displayed this same characteristic inward current. In contrast, amiloride-sensitive currents were not observed in normal human astrocytes, low-grade astrocytomas, or juvenile pilocytic astrocytomas. The only amiloride-sensitive Na+channels thus far molecularly identified in brain are the brain Na+ channels (BNaCs). RT-PCR analyses demonstrated the presence of mRNA for either BNaC1 or BNaC2 in these tumors and in normal astrocytes. These results indicate that the functional expression of amiloride-sensitive Na+ currents is a characteristic feature of malignant brain tumor cells and that this pathway may be a potentially useful target for therapeutic intervention.

OBJECTIVE: The purposes of this study were as follows: 1) to determine the incidence and degree of ventral brain stem compression (VBSC) in pediatric and young adult patients with Chiari I malformations, and 2) to correlate VBSC with other imaging and clinical factors to help determine what amount of VBSC is successfully treated with a posterior decompressive procedure alone. METHODS: The magnetic resonance images and clinical histories of 40 pediatric and young adult patients with Chiari I malformations were analyzed for subjective grade of VBSC, distance of tonsillar descent, odontoid's relation to Chamberlain's and Wackenheim's line, clival length, foramen magnum diameter, syringomyelia, scoliosis, hydrocephalus, presenting clinical status, treatment, and outcome. To objectively measure the amount of ventral cervicomedullary encroachment by the odontoid and its investing tissues into the rostral spinal canal, a line (B-C2) was drawn between the basion and posteroinferior aspect of the C2 body on a sagittal magnetic resonance image. A line perpendicular to this line, pB-C2, was drawn through the odontoid tip to the ventral dura, and a distance (representing the amount of ventral canal encroachment) was measured. RESULTS: Flattening and distortion of the ventral brain stem were present in 48 and 28% of the patients, respectively. Only two patients had basilar invagination by traditional definitions, pB-C2 measurements correlated with the subjective grade of VBSC (P < 0.05), age, and distance of tonsillar descent (P < 0.05). Eye motion abnormalities and upper cervical osseous anomalies were associated with higher pB-C2 measurements. All patients with a pB-C2 measurement of less than 9 mm were treated successfully with posterior fossa decompression alone despite any subjective VBSC. Some patients with pB-C2 measurements greater than 9 mm had either preoperative neurological deficits or neurological worsening after posterior fossa decompression referable to VBSC. CONCLUSION: Patients with a pB-C2 measurement of less than 9 mm do not require treatment directed at VBSC. In select patients with pB-C2 measurements of 9 mm or greater, reduction of VBSC may be prudent before posterior fossa decompression.

A case of ventral brain-stem compression by a congenital subarachnoid ependymal cyst in an infant is presented. Marsupialization of the cyst provided effective decompression and clinical improvement. Immunohistochemical staining demonstrated the glial nature of the epithelium. The fact that these cysts may be congenital, as demonstrated here, supports the hypothesis that they arise from glial elements that have been displaced during development.

Small bowel obstruction and partial enteral loss secondary to entrapment by an incompletely removed ventriculoperitoneal shunt is a previously unreported hazard.