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Paul Gross, Gavin T. Reed, Rachel Engelmann and John R. W. Kestle

Object

Funding of hydrocephalus research is important to the advancement of the field. The goal of this paper is to describe the funding of hydrocephalus research from the National Institutes of Health (NIH) over a recent 10-year period.

Methods

The NIH online database RePORT (Research Portfolio Online Reporting Tools) was searched using the key word “hydrocephalus.” Studies were sorted by relevance to hydrocephalus. The authors analyzed funding by institute, grant type, and scientific approach over time.

Results

Over $54 million was awarded to 59 grantees for 66 unique hydrocephalus proposals from 48 institutions from 2002 to 2011. The largest sources of funding were the National Institute of Neurological Disease and Stroke and the National Institute of Child Health and Human Development. Of the total, $22 million went to clinical trials, $15 million to basic science, and $10 million to joint ventures with small business (Small Business Innovation Research or Small Business Technology Transfer). Annual funding varied from $2.3 to $8.1 million and steadily increased in the second half of the observation period. The number of new grants also went from 15 in the first 5 years to 27 in the second 5 years. A large portion of the funding has been for clinical trials. Funding for shunt-device development grew substantially. Support for training of hydrocephalus investigators has been low.

Conclusions

Hydrocephalus research funding is low compared with that for other conditions of similar health care burden. In addition to NIH applications, researchers should pursue other funding sources. Small business collaborations appear to present an opportunity for appropriate projects.

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Heather S. Spader, Dean A. Hertzler, John R. W. Kestle and Jay Riva-Cambrin

OBJECT

Intraventricular hemorrhage in premature infants often leads to progressive ventricular dilation and the need for ventricular reservoir placement. Unfortunately, these reservoirs have a higher rate of infection than ventriculoperitoneal shunts in premature babies. The authors analyzed the risk factors for infection in this population and studied whether the implementation of an institutional protocol for shunt placement had a corollary effect on ventricular access device (VAD) infection rates in premature neonates with intraventricular hemorrhage.

METHODS

The authors conducted a retrospective cohort review of consecutive premature neonates in whom VADs were inserted in the operating room at Primary Children's Hospital between June 2003 and June 2011 to identify risk factors for infection. Medical records were reviewed for information on infection (culture proven or eroded hardware at 90 days), gestational age at birth, weight, gestational age at surgery, intrathecal antibiotics, hemorrhage, death, and surgeon. The institution used a pilot protocol for shunt infection reduction in 2006–2007, and then the full Hydrocephalus Clinical Research Network protocol from June 2007 to 2011, and the rates of infection during these periods were analyzed. Confounding factors such as sepsis, necrotizing enterocolitis, and a history of meningitis were also analyzed.

RESULTS

The overall infection rate was 10.5% (11 patients) in the 105 patients identified. Gestational age at procedure was a significant risk factor for infection (p = 0.05). Meningitis was significantly associated with infection, with 63% of the infected group having had prior meningitis compared with 7% for the noninfected group (p < 0.001). Concurrent with the implementation of the protocol to reduce shunt infection, the VAD infection rate decreased from 14.7% to 5.4% (p = 0.2).

CONCLUSIONS

Gestational age at procedure and previous meningitis were significant risk factors for VAD infections. In addition, the implementation of an institutional standardized shunt protocol for ventriculoperitoneal shunts may have altered the operating room team's behavior, indicated by a nonmandated use of intrathecal antibiotics in VAD surgeries, contributing to a reduced VAD infection rate. Although the observed difference was not statistically significant with the small sample size, the authors believe that these findings deserve further study.

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Hugh J. L. Garton, John R. W. Kestle and James M. Drake

Object. In evaluating pediatric patients for shunt malfunction, predictive values for symptoms and signs are important in deciding which patients should undergo an imaging study, whereas determining clinical findings that correlate with a low probability of shunt failure could simplify management.

Methods. Data obtained during the recently completed Pediatric Shunt Design Trial (PSDT) were analyzed. Predictive values were calculated for symptoms and signs of shunt failure. To refine predictive capability, a shunt score based on a cluster of signs and symptoms was derived and validated using multivariate methods.

Four hundred thirty-one patient encounters after recent shunt insertions were analyzed. For encounters that took place within 5 months after shunt insertion (early encounters), predictive values for symptoms and signs included the following: nausea and vomiting (positive predictive value [PPV] 79%, likelihood ratio [LR] 10.4), irritability (PPV 78%, LR 9.8), decreased level of consciousness (LOC) (PPV 100%), erythema (PPV 100%), and bulging fontanelle (PPV 92%, LR 33.1). Between 9 months and 2 years after shunt insertion (late encounters), only loss of developmental milestones (PPV 83%, LR 36.7) and decreased LOC (PPV 100%) were strongly associated with shunt failure. However, the absence of a symptom or sign still left a 15 to 29% (early encounter group) or 9 to 13% (late encounter group) chance of shunt failure. Using the shunt score developed for early encounters, which sums from 1 to 3 points according to the specific symptoms or signs present, patients with scores of 0, 1, 2, and 3 or greater had shunt failure rates of 4%, 50%, 75%, and 100%, respectively. Using the shunt score derived from late encounters, patients with scores of 0, 1, and 2 or greater had shunt failure rates of 8%, 38%, and 100%, respectively.

Conclusions. In children, certain symptoms and signs that occur during the first several months following shunt insertion are strongly associated with shunt failure; however, the individual absence of these symptoms and signs offers the clinician only a limited ability to rule out a shunt malfunction. Combining them in a weighted scoring system improves the ability to predict shunt failure based on clinical findings.

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Paul Steinbok, Stephen Hentschel, D. Douglas Cochrane and John R. W. Kestle

✓ The rationale for obtaining surveillance computerized tomography (CT) scans or magnetic resonance (MR) images in pediatric patients with brain tumors is that early detection of recurrence may result in timely treatment and better outcome. The purpose of this study was to investigate the value of surveillance cranial images in a variety of common pediatric brain tumors managed at a tertiary care pediatric hospital.

A retrospective chart review was performed of children with astrocytoma of the cerebral hemisphere, cerebellum, optic chiasm/hypothalamus, or thalamus; cerebellar or supratentorial high-grade glioma; supratentorial ganglioglioma; posterior fossa or supratentorial primitive neuroectodermal tumor (PNET); and posterior fossa ependymoma. Data were analyzed to determine the frequency with which recurrences were identified on a surveillance image and how the type of image at which recurrence was identified related to outcome.

In 159 children, 17 of 44 recurrences were diagnosed by surveillance imaging. The percentage of recurrences identified by surveillance imaging was 64% for ependymoma, 50% for supratentorial PNET, 43% for optic/hypothalamic astrocytoma, and less than 30% for other tumors. The rate of diagnosis of recurrence per surveillance image varied from 0% to 11.8% for different tumor types. Only for ependymomas did there appear to be an improved outcome when recurrence was identified prior to symptoms.

Our results indicate that, using the protocols outlined in this study, surveillance imaging was not valuable in identifying recurrence of cerebellar astrocytoma or supratentorial ganglioglioma during the study period, but was probably worth-while in identifying recurrence of posterior fossa ependymoma and optic/hypothalamic astrocytoma and, possibly, medulloblastoma. Surveillance protocols could be made more effective by individualizing them for each type of tumor, based on current data on the patterns of recurrence.

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Paul Steinbok, Bengt Gustavsson, John R. W. Kestle, Ann Reiner and D. Doug Cochrane

✓ At British Columbia's Children's Hospital, the criteria used in selective functional posterior rhizotomy (SFPR) evolved in three distinct phases. In Phase 1 the electrophysiological criteria for abnormality included a low threshold to a single stimulation, a sustained response to 50-Hz stimulation, and spread outside the segmental level being stimulated. In Phase 2 the electrophysiological criteria were unchanged, but fewer L3–4 nerve roots were cut. In Phase 3, fewer L3–4 nerve roots were cut, as in Phase 2, but based on the results of posterior nerve root stimulation in nonspastic controls, the only electrophysiological criterion used was contralateral and suprasegmental spread. The present study examined the relationship between the criteria used in each phase and patient outcome.

The records of 77 consecutive children who underwent SFPR and had a minium follow-up period of 1 year were reviewed, comprising 25, 19, and 33 patients in Phases 1, 2, and 3, respectively. Outcome parameters included quantitative assessments of lower-limb spasticity and range of motion, and qualitative assessments of lower-limb function.

In Phase 3, 52% of the nerve roots were cut, compared to 66% in Phases 1 and 2. In all three phases there was a significant decrease in lower-limb spasticity and an increase in range of movement, with the smallest decrease in spasticity in Phase 3. Over 90% of children in each phase improved with respect to lower-limb function, and excluding independent walkers and quadriplegics confined to a wheelchair, improvement in the level of ambulation occurred in 87.5%, 71.4%, and 73.7% of patients, in Phases 1, 2, and 3, respectively.

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Paul Klimo Jr., Clinton J. Thompson, James Drake and John R. W. Kestle

Object. Most surgical procedures are associated with a learning curve in which the success rate is lower early in the experience before mistakes have been identified and modifications made to the procedure. Negative results obtained early in a trial's learning curve may be a matter of timing rather than a reflection of the procedure's effectiveness. The recently published results of the Endoscopic Shunt Insertion Trial (ESIT) represent the notion that endoscopically placed shunts were no more likely to survive than conventionally placed shunts. This negative result may be due to inexperience in performing endoscopic surgeries.

Methods. Surgical experience was assessed in two ways. Shunt survival rates were compared between cases treated endoscopically in the 1st and last years of the ESIT. The effect of center volume was evaluated using a Cox proportional hazard model in which the following variables were analyzed: age at registration, the diagnosis of myelomeningocele, head size, method of shunt placement (endoscopic compared with conventional), and center volume.

There was no difference in survival (endurance) of the shunt between patients enrolled in the 1st and last years (log rank = 0.08, p = 0.77). Likewise, no variable in the Cox multivariate model, including center volume, was a significant factor in predicting shunt survival.

Conclusions. The primary result of the ESIT was found to be internally valid. The fact that endoscopic shunt placement did not benefit patients evaluated in the study was not due to early timing of the trial. Any learning curve among the participating surgeons did not adversely affect the results.

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James K. Liu, Chad D. Cole, Gregory T. Sherr, John R. W. Kestle and Marion L. Walker

✓Extradural arachnoid cysts in the spine are relatively uncommon causes of spinal cord compression in the pediatric population that are thought to arise from congenital defects in the dura mater. Most reports describe such cysts communicating with the intrathecal subarachnoid space through a small defect in the dura. The authors describe the case of a child who presented with spinal cord compression caused by a large spinal extradural arachnoid cyst that did not communicate with the intradural subarachnoid space. An 11-year-old girl presented with urinary urgency, progressive lower-extremity weakness, myelopathy, and severe gait ataxia. Magnetic resonance imaging of the spine demonstrated a large extradural arachnoid cyst extending from T-8 to T-12. The patient underwent a thoracic laminoplasty for en bloc resection of the spinal extradural arachnoid cyst. Intraoperatively, the dura was intact and there was no evidence of communication into the intradural subarachnoid space. Postoperatively, the patient's motor strength and ambulation improved immediately, and no subsequent cerebrospinal fluid leak occurred.

Noncommunicating spinal extradural arachnoid cysts are extremely rare lesions that can cause spinal cord compression in children. Because the dura remains intact, they can be removed entirely without subsequent dural repair. The authors review the literature and discuss the proposed underlying mechanisms of formation of these arachnoid cysts.

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Paul Klimo Jr., John R. W. Kestle, Joel D. MacDonald and Richard H. Schmidt

Object

Cerebral vasospasm after subarachnoid hemorrhage (SAH) continues to be a major source of morbidity in patients despite significant clinical and basic science research. Efforts to prevent vasospasm by removing spasmogens from the subarachnoid space have produced mixed results. The authors hypothesize that lumbar cisternal drainage can remove blood from the basal subarachnoid spaces more effectively than an external ventricular drain (EVD). This nonrandomized, controlled-cohort study was undertaken to evaluate the effectiveness of a lumbar drain in patients with SAH compared with those in whom an EVD or no form of cerebrospinal fluid (CSF) drainage was used to prevent the development of clinical vasospasm and its sequelae.

Methods

The authors collected data on 266 patients with nontraumatic SAH who were admitted to the University of Utah Health Sciences Center between January 1994 and January 2003. Of these, 167 met the study entry criteria. The treatment group consisted of 81 patients in whom a lumbar drain had been placed for CSF shunting, whereas the control group was composed of 86 patients who received no form of CSF drainage or who were treated solely with an EVD. Primary outcome measures were as follows: 1) clinically evident vasospasm; 2) the need for endovascular intervention; 3) vasospasm-induced infarction; 4) disposition at time of discharge; and 5) Glasgow Outcome Scale (GOS) score at 1 to 3 months postdischarge. Secondary outcomes included length of stay and the need for CSF shunting.

The presence of a lumbar drain conferred a statistically significant protective and beneficial effect across all outcome measures, reducing the incidence of clinical vasospasm from 51 to 17%, the need for angioplasty from 45 to 17%, and the occurrence of vasospastic infarction from 27 to 7% (all p ≤ 0.001–0.008). Patients in the treatment group were more likely to be discharged home (54% compared with 25%, p = 0.002) and to have a GOS score of 5 at follow up (71% compared with 35%, p < 0.001). The mean number of days spent in the intensive care unit and in the hospital overall was also fewer in the treatment group. A similar degree of benefit was found in patients with different Fisher grades and regardless of whether an EVD was needed on presentation, both by subgroup analysis and multivariate logistic regression modeling. There was no statistical difference between the groups in terms of patients requiring a shunt. Complications with lumbar drains were rare and yielded no permanent sequelae.

Conclusions

Shunting of CSF through a lumbar drain after an SAH markedly reduces the risk of clinically evident vasospasm and its sequelae, shortens hospital stay, and improves outcome. Its beneficial effects are probably mediated through the removal of spasmogens that exist in the CSF. The results of this study warrant a randomized clinical trial, which is currently under way.

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Peter Kan, Marion L. Walker, James M. Drake and John R. W. Kestle

Object

Slit ventricle syndrome (SVS) is a delayed complication of shunt insertion and occurs only in children with slitlike ventricles after shunt placement. Although SVS appears to be related to early shunt placement, its predisposing factors are largely unknown.

Methods

Baseline data in 737 children who had received shunts were obtained from the databases of two previous clinical trials. Ventricular size before shunt placement and at the last routine follow up was measured using the fronto-occipital horn ratio (FOHR). Ventricles with an FOHR less than or equal to 0.2 at follow up were classified as slitlike ventricles. A univariate analysis was performed on data obtained in children with more than 1 year of clinical and radiographic follow up to identify risk factors for developing slitlike ventricles. These results were entered into a multivariate analysis to identify independent predictors of slitlike ventricles.

Two hundred forty-four children had more than 1 year of clinical and radiographic follow-up data. The 23 patients (9.4%) who developed slitlike ventricles had shunts inserted at a younger age (42 compared with 134 days, p = 0.09) and were more likely to have developed hydrocephalus secondary to infection (37.5%), head injury (25.0%), or aqueductal stenosis (22.2%). Slitlike ventricles were seen in 10.8% of patients with differential-pressure valves, 10.5% of patients with Delta valves, and 3.6% of patients with Orbis-Sigma valves (p = 0.007). Regression analysis supported the role of the valve type in developing slitlike ventricles.

Conclusions

Age at shunt insertion and valve type appear to be the modifiable risk factors for developing slitlike ventricles. If the authors of subsequent studies can further validate these conclusions, slow-draining valves and delayed shunt insertion might be used to decrease the incidence of slitlike ventricles and SVS.