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Yuzuru Tashiro, Shushovan Chakrabortty, James M. Drake and Toshiaki Hattori

The authors investigated functional neuronal changes in experimental hydrocephalus using immunohistochemical techniques for glutamic acid decarboxylase (GAD) and two neuronal calcium-binding proteins: parvalbumin (PV) and calbindin D28K (CaBP).

Hydrocephalus was induced in 16 adult Wistar rats by intracisternal injection of a kaolin solution, which was confirmed microscopically via atlantooccipital dural puncture. Four control rats received the same volume of sterile saline. Immunohistochemical staining for GAD, PV, and CaBP and Nissl staining were performed at 1, 2, 3, and 4 weeks after the injection. Hydrocephalus occurred in 90% of kaolin-injected animals with various degrees of ventricular dilation. In the cerebral cortex, GAD-, PV-, and CaBP-immunoreactive (IR) interneurons initially lost their stained processes together with a concomitant loss of homogeneous neuropil staining, followed by the reduction of their total number. With progressive ventricular dilation, GAD- and PV-IR axon terminals on the cortical pyramidal cells disappeared, whereas the number of CaBP-IR pyramidal cells decreased, and ultimately in the most severe cases of hydrocephalus, GAD, PV, and CaBP immunoreactivity was almost entirely diminished. In the hippocampus, GAD-, PV-, and CaBP-IR interneurons demonstrated a reduction of their processes and terminals surrounding the pyramidal cells, with secondary reduction of CaBP-IR pyramidal and granular cells. On the other hand, Nissl staining revealed almost no morphological changes induced by ischemia or neuronal degeneration even in the most severe cases of hydrocephalus.

Hydrocephalus results in the progressive functional impairment of GAD-, PV-, and CaBP-IR neuronal systems in the cerebral cortex and hippocampus, often before there is evidence of morphological injury. The initial injury of cortical and hippocampal interneurons suggests that the functional deafferentation from intrinsic projection fibers may be the initial neuronal event in hydrocephalic brain injury. Although the mechanism of this impairment is still speculative, these findings emphasize the importance of investigating the neuronal pathophysiology in hydrocephalus.

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Sagun Tuli, James Drake, Jerry Lawless, Melanie Wigg and Maria Lamberti-Pasculli

Repeated cerebrospinal fluid (CSF) shunt failures in pediatric patients who have undergone neurosurgical procedures are common, and they are a significant cause of morbidity and occasionally mortality. To date, the risk factors for repeated failure have not been established. By performing survival analysis for repeated events, the authors examined the effects of patient characteristics, shunt hardware, and surgical details in a large cohort of patients.

During a 10-year period all pediatric patients with hydrocephalus requiring CSF diversionary procedures were included in a prospective single-institution observational study. Patient characteristics were defined as age, gender, weight, head circumference; American Society of Anesthesiology class, and the cause of hydrocephalus. Surgical details included whether the procedure was performed on an emergency or nonemergency basis, use of antibiotics, concurrent other surgical procedures, and the duration of surgical procedure. Details on shunt hardware included the type of shunt, the valve system, whether the shunt system included multiple or complex components, the type of distal catheter, site of the shunt, and side on which the shunt was placed.

Repeated shunt failures were assessed with multivariable time-to-event analysis (using the Cox regression model). Conditional models (as established by Prentice, et al.) were formulated for gap times (that is, times between successive shunt failures).

There were 1183 shunt failures in 839 patients. Failure time from the first shunt procedure was an important predictor for the second and third episodes of failures, thus establishing an association between the times to failure within individual patients. Age of less than 40 weeks gestation at time of the first shunt implantion carried a hazard ratio (HR) of 2.49 (95% confidence interval [CI] 1.68-3.68) for the first failure and remained high for subsequent episodes of failure. Age of 40 weeks to 1 year (at the time of the initial surgery) also proved to be an important predictor of first shunt malfunctions (HR 1.77, 95% CI 1.29-2.44). The cause of hydrocephalus was significantly associated with the risk of initial failure and, to a lesser extent, later failures. Concurrent other surgical procedures were associated with an increased risk of failure.

The patient's age at the time of initial shunt placement and the time interval since previous surgical revision are important predictors of repeated shunt failures in the multivariable model. Even after adjusting for age at first shunt insertion as well as the cause of hydrocephalus there is significant association between repeated failure times for individual patients.

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James M. Drake

✓The tethered spinal cord is a fascinating yet controversial condition seen frequently in neurosurgical practice. Treatment decision making is made difficult by the variety of lesions and clinical presentations comprised by this condition and the absence of high-quality clinical outcome data to provide guidance. Clinical presentations may be divided into four general categories or typical scenarios: 1) significant dysraphic abnormality, clear clinical deterioration; 2) significant dysraphic abnormality, clinically normal or stable deficit; 3) incidentally discovered abnormality, other problem; and 4) tethered spinal cord symptomatology, normal imaging. The author provides case examples to illustrate potential treatment approaches and suggests balancing the risks and benefits for each general category.

Clearer diagnostic and treatment strategies for the tethered spinal cord will only result from high-quality clinical and basic research. Until the results of such research are available, surgeons should endeavor to maximize benefit and reduce risk for patients who may have a tethered spinal cord, walking the fine line between over- and undertreatment.

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George M. Ibrahim, Benjamin W. Barry, Aria Fallah, O. Carter Snead III, James M. Drake, James T. Rutka and Mark Bernstein

Epilepsy is a common childhood condition associated with a considerable medical and psychosocial burden. Children in whom medical treatment fails to reduce seizure burden represent an especially vulnerable patient population because prolonged, uncontrolled seizures are associated with poor developmental and neurocognitive outcomes. Surgical treatment in the form of cortical resection, functional disconnection, or neuromodulation may alleviate or significantly reduce the disease burden for a subset of these patients. However, there remains a dichotomy between the perceived benefits of surgery and the implementation of surgical strategies in the management of medically intractable epilepsy. The current paper presents an analysis of the bioethical implications of existing inequities in access to pediatric epilepsy surgery that result from inconsistent referral practices and discrepant evaluation techniques. The authors provide a basic bioethical framework composed of 5 primary expectations to inform public, institutional, and personal policies toward the provision of epilepsy surgery to afflicted children.

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William E. Whitehead, Jay Riva-Cambrin, John C. Wellons III, Abhaya V. Kulkarni, Samuel Browd, David Limbrick, Curtis Rozzelle, Mandeep S. Tamber, Tamara D. Simon, Chevis N. Shannon, Richard Holubkov, W. Jerry Oakes, Thomas G. Luerssen, Marion L. Walker, James M. Drake and John R. W. Kestle

Object

Shunt survival may improve when ventricular catheters are placed into the frontal horn or trigone of the lateral ventricle. However, techniques for accurate catheter placement have not been developed. The authors recently reported a prospective study designed to test the accuracy of catheter placement with the assistance of intraoperative ultrasound, but the results were poor (accurate placement in 59%). A major reason for the poor accurate placement rate was catheter movement that occurred between the time of the intraoperative ultrasound image and the first postoperative scan (33% of cases). The control group of non–ultrasound using surgeons also had a low rate of accurate placement (accurate placement in 49%). The authors conducted an exploratory post hoc analysis of patients in their ultrasound study to identify factors associated with either catheter movement or poor catheter placement so that improved surgical techniques for catheter insertion could be developed.

Methods

The authors investigated the following risk factors for catheter movement and poor catheter placement: age, ventricular size, cortical mantle thickness, surgeon experience, surgeon experience with ultrasound prior to trial, shunt entry site, shunt hardware at entry site, ventricular catheter length, and use of an ultrasound probe guide for catheter insertion. Univariate analysis followed by multivariate logistic regression models were used to determine which factors were independent risk factors for either catheter movement or inaccurate catheter location.

Results

In the univariate analyses, only age < 6 months was associated with catheter movement (p = 0.021); cortical mantle thickness < 1 cm was near-significant (p = 0.066). In a multivariate model, age remained significant after adjusting for cortical mantle thickness (OR 8.35, exact 95% CI 1.20–infinity). Univariate analyses of factors associated with inaccurate catheter placement showed that age < 6 months (p = 0.001) and a posterior shunt entry site (p = 0.021) were both associated with poor catheter placement. In a multivariate model, both age < 6 months and a posterior shunt entry site were independent risk factors for poor catheter placement (OR 4.54, 95% CI 1.80–11.42, and OR 2.59, 95% CI 1.14–5.89, respectively).

Conclusions

Catheter movement and inaccurate catheter placement are both more likely to occur in young patients (< 6 months). Inaccurate catheter placement is also more likely to occur in cases involving a posterior shunt entry site than those involving an anterior shunt entry site. Future clinical studies aimed at improving shunt placement techniques must consider the effects of young age and choice of entry site on catheter location.

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Abhaya V. Kulkarni, Jay Riva-Cambrin, Samuel R. Browd, James M. Drake, Richard Holubkov, John R. W. Kestle, David D. Limbrick, Curtis J. Rozzelle, Tamara D. Simon, Mandeep S. Tamber, John C. Wellons III and William E. Whitehead

Object

The use of endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC) has been advocated as an alternative to CSF shunting in infants with hydrocephalus. There are limited reports of this procedure in the North American population, however. The authors provide a retrospective review of the experience with combined ETV + CPC within the North American Hydrocephalus Clinical Research Network (HCRN).

Methods

All children (< 2 years old) who underwent an ETV + CPC at one of 7 HCRN centers before November 2012 were included. Data were collected retrospectively through review of hospital records and the HCRN registry. Comparisons were made to a contemporaneous cohort of 758 children who received their first shunt at < 2 years of age within the HCRN.

Results

Thirty-six patients with ETV + CPC were included (13 with previous shunt). The etiologies of hydrocephalus were as follows: intraventricular hemorrhage of prematurity (9 patients), aqueductal stenosis (8), myelomeningocele (4), and other (15). There were no major intraoperative or early postoperative complications. There were 2 postoperative CSF infections. There were 2 deaths unrelated to hydrocephalus and 1 death from seizure. In 18 patients ETV + CPC failed at a median time of 30 days after surgery (range 4–484 days). The actuarial 3-, 6-, and 12-month success for ETV + CPC was 58%, 52%, and 52%. Time to treatment failure was slightly worse for the 36 patients with ETV + CPC compared with the 758 infants treated with shunts (p = 0.012). Near-complete CPC (≥ 90%) was achieved in 11 cases (31%) overall, but in 50% (10 of 20 cases) in 2012 versus 6% (1 of 16 cases) before 2012 (p = 0.009). Failure was higher in children with < 90% CPC (HR 4.39, 95% CI 0.999–19.2, p = 0.0501).

Conclusions

The early North American multicenter experience with ETV + CPC in infants demonstrates that the procedure has reasonable safety in selected cases. The degree of CPC achieved might be associated with a surgeon's learning curve and appears to affect success, suggesting that surgeon training might improve results.

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Odeya Bennett-Back, Ayako Ochi, Elysa Widjaja, Shohei Nambu, Akio Kamiya, Cristina Go, Sylvester Chuang, James T. Rutka, James Drake, O. Carter Snead III and Hiroshi Otsubo

Object

Porencephalic cyst/encephalomalacia (PC/E) is a brain lesion caused by ischemic insult or hemorrhage. The authors evaluated magnetoencephalography (MEG) spike sources (MEGSS) to localize the epileptogenic zone in children with intractable epilepsy secondary to PC/E.

Methods

The authors retrospectively studied 13 children with intractable epilepsy secondary to PC/E (5 girls and 8 boys, age range 1.8–15 years), who underwent prolonged scalp video-electroencephalography (EEG), MRI, and MEG. Interictal MEGSS locations were compared with the ictal and interictal zones as determined from scalp video-EEG.

Results

Magnetic resonance imaging showed PC/E in extratemporal lobes in 3 patients, within the temporal lobe in 2 patients, and in both temporal and extratemporal lobes in 8 patients. Magnetoencephalographic spike sources were asymmetrically clustered at the margin of PC/E in all 13 patients. One cluster of MEGSS was observed in 11 patients, 2 clusters in 1 patient, and 3 clusters in 1 patient. Ictal EEG discharges were lateralized and concordant with MEGSS in 8 patients (62%). Interictal EEG discharges were lateralized and concordant with MEGSS hemisphere in 9 patients (69%). Seven patients underwent lesionectomy in addition to MEGSS clusterectomy with (2 patients) and without (5 patients) intracranial video-EEG. Temporal lobectomy was performed in 1 patient and hemispherectomy in another. Eight of 9 patients achieved seizure freedom following surgery.

Conclusions

Magnetoencephalography delineated the extent of the epileptogenic zone adjacent to PC/E in patients with intractable epilepsy. Complete resection of the MEGSS cluster along with PC/E can provide favorable seizure outcomes.

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Gregory W. Albert, George M. Ibrahim, Hiroshi Otsubo, Ayako Ochi, Cristina Y. Go, O. Carter Snead III, James M. Drake and James T. Rutka

Object

Resective surgery is increasingly used in the management of pediatric epilepsy. Frequently, invasive monitoring with subdural electrodes is required to adequately map the epileptogenic focus. The risks of invasive monitoring include the need for 2 operations, infection, and CSF leak. The aim of this study was to evaluate the feasibility and outcomes of resective epilepsy surgery guided by magnetoencephalography (MEG) in children who would have otherwise been candidates for electrode implantation.

Methods

The authors reviewed the records of patients undergoing resective epilepsy surgery at the Hospital for Sick Children between 2001 and 2010. They identified cases in which resections were based on MEG data and no intracranial recordings were performed. Each patient's chart was reviewed for presentation, MRI findings, MEG findings, surgical procedure, pathology, and surgical outcome.

Results

Sixteen patients qualified for the study. All patients had localized spike clusters on MEG and most had abnormal findings on MRI. Resection was carried out in each case based on the MEG data linked to neuronavigation and supplemented with intraoperative neuromonitoring. Overall, 62.5% of patients were seizure free following surgery, and 20% of patients experienced an improvement in seizures without attaining seizure freedom. In 2 cases, additional surgery was performed subsequently with intracranial monitoring in attempts to obtain seizure control.

Conclusions

MEG is a viable alternative to invasive monitoring with intracranial electrodes for planning of resective surgery in carefully selected pediatric patients with localization-related epilepsy. Good candidates for this approach include patients who have a well-delineated, localized spike cluster on MEG that is concordant with findings of other preoperative evaluations and patients with prior brain pathologies that make the implantation of subdural and depth electrodes somewhat problematic.