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Mandeep S. Tamber and James T. Rutka

The purpose of this review is to highlight some of the pertinent concepts and controversies surrounding the diagnosis and treatment of pediatric supratentorial high-grade gliomas. Unlike the adult counterparts, pediatric high-grade gliomas are likely derived from distinct cytogenetic and molecular alterations. Surgery has been shown to play a role in extending patient survival. Some success is associated with the provision of chemotherapy. Radiotherapy remains an important adjunct in children older than age 3 years. The challenges involved in improving the poor prognosis of children in whom these very aggressive tumors have been diagnosed will be discussed, as well as some of the novel approaches being investigated to improve patient survival and quality of life.

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Ann Marie Flannery, Ann-Christine Duhaime, Mandeep S. Tamber and Joanna Kemp

Object

This systematic review was undertaken to answer the following question: Do technical adjuvants such as ventricular endoscopic placement, computer-assisted electromagnetic guidance, or ultrasound guidance improve ventricular shunt function and survival?

Methods

The US National Library of Medicine PubMed/MEDLINE database and the Cochrane Database of Systematic Reviews were queried using MeSH headings and key words specifically chosen to identify published articles detailing the use of cerebrospinal fluid shunts for the treatment of pediatric hydrocephalus. Articles meeting specific criteria that had been delineated a priori were then examined, and data were abstracted and compiled in evidentiary tables. These data were then analyzed by the Pediatric Hydrocephalus Systematic Review and Evidence-Based Guidelines Task Force to consider evidence-based treatment recommendations.

Results

The search yielded 163 abstracts, which were screened for potential relevance to the application of technical adjuvants in shunt placement. Fourteen articles were selected for full-text review. One additional article was selected during a review of literature citations. Eight of these articles were included in the final recommendations concerning the use of endoscopy, ultrasonography, and electromagnetic image guidance during shunt placement, whereas the remaining articles were excluded due to poor evidence or lack of relevance.

The evidence included 1 Class I, 1 Class II, and 6 Class III papers. An evidentiary table of relevant articles was created.

Conclusions

Recommendation: There is insufficient evidence to recommend the use of endoscopic guidance for routine ventricular catheter placement. Strength of Recommendation: Level I, high degree of clinical certainty.

Recommendation: The routine use of ultrasound-assisted catheter placement is an option. Strength of Recommendation: Level III, unclear clinical certainty.

Recommendation: The routine use of computer-assisted electromagnetic (EM) navigation is an option. Strength of Recommendation: Level III, unclear clinical certainty.

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Joanna Kemp, Ann Marie Flannery, Mandeep S. Tamber and Ann-Christine Duhaime

Object

The objective of this guideline was to answer the following question: Do the entry point and position of the ventricular catheter have an effect on shunt function and survival?

Methods

Both the US National Library of Medicine/MEDLINE database and the Cochrane Database of Systematic Reviews were queried using MeSH headings and key words specifically chosen to identify published articles detailing the use of CSF shunts for the treatment of pediatric hydrocephalus. Articles meeting specific criteria that had been delineated a priori were then examined, and data were abstracted and compiled in evidentiary tables.

Results

The search yielded 184 abstracts, which were screened for potential relevance to the clinical question of the effect of ventricular catheter entry site on shunt survival. An initial review of the abstracts identified 14 papers that met the inclusion criteria, and these were recalled for full-text review. After review of these articles, only 4 were noted to be relevant for an analysis of the impact of entry point on shunt survival; an additional paper was retrieved during the review of full-text articles and was included as evidence to support the recommendation. The evidence included 1 Class II paper and 4 Class III papers. An evidentiary table was created including the relevant articles.

Conclusion

Recommendation: There is insufficient evidence to recommend the occipital versus frontal point of entry for the ventricular catheter; therefore, both entry points are options for the treatment of pediatric hydrocephalus. Strength of Recommendation: Level III, unclear degree of clinical certainty.

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Mandeep S. Tamber, Paul Klimo Jr., Catherine A. Mazzola and Ann Marie Flannery

Object

The objective of this systematic review was to answer the following question: What is the optimal treatment strategy for CSF shunt infection in pediatric patients with hydrocephalus?

Methods

The US National Library of Medicine and the Cochrane Database of Systematic Reviews were queried using MeSH headings and key words relevant to the objective of this systematic review. Abstracts were reviewed, after which studies meeting the inclusion criteria were selected and graded according to their quality of evidence (Classes I–III). Evidentiary tables were constructed that summarized pertinent study results, and based on the quality of the literature, recommendations were made (Levels I–III).

Results

A review and critical appraisal of 27 studies that met the inclusion criteria allowed for a recommendation for supplementation of antibiotic treatment using partial (externalization) or complete shunt hardware removal, with a moderate degree of clinical certainty. However, a recommendation regarding whether complete shunt removal is favored over partial shunt removal (that is, externalization) could not be made owing to severe methodological deficiencies in the existing literature. There is insufficient evidence to recommend the use of intrathecal antibiotic therapy as an adjunct to systemic antibiotic therapy in the management of routine CSF shunt infections. This also holds true for other clinical scenarios such as when an infected CSF shunt cannot be completely removed, when a shunt must be removed and immediately replaced in the face of ongoing CSF infection, or when the setting is ventricular shunt infection caused by specific organisms (for example, gram-negative bacteria).

Conclusions

Supplementation of antibiotic treatment with partial (externalization) or complete shunt hardware removal are options in the management of CSF shunt infection. There is insufficient evidence to recommend either shunt externalization or complete shunt removal as the preferred surgical strategy for the management of CSF shunt infection. Therefore, clinical judgment is required. In addition, there is insufficient evidence to recommend the combination of intrathecal and systemic antibiotics for patients with CSF shunt infection when the infected shunt hardware cannot be fully removed, when the shunt must be removed and immediately replaced, or when the CSF shunt infection is caused by specific organisms. The potential neurotoxicity of intrathecal antibiotic therapy may limit its routine use.

Recommendation: Supplementation of antibiotic treatment with partial (externalization) or with complete shunt hardware removal is an option in the management of CSF shunt infection. Strength of Recommendation: Level II, moderate degree of clinical certainty.

Recommendation: There is insufficient evidence to recommend either shunt externalization or complete shunt removal as a preferred surgical strategy for the management of CSF shunt infection. Therefore, clinical judgment is required. Strength of Recommendation: Level III, unclear degree of clinical certainty.

Recommendation: There is insufficient evidence to recommend the combination of intrathecal and systemic antibiotics for patients with CSF shunt infection in whom the infected shunt hardware cannot be fully removed or must be removed and immediately replaced, or when the CSF shunt infection is caused by specific organisms. The potential neurotoxicity of intrathecal antibiotic therapy may limit its routine use. Strength of Recommendation: Level III, unclear degree of clinical certainty.

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Xiao Zhu, Michael M. McDowell, William C. Newman, Gary E. Mason, Stephanie Greene and Mandeep S. Tamber

Nivolumab is an immune checkpoint inhibitor (ICI) currently undergoing Phase III clinical trials for the treatment of glioblastoma. The authors present the case of a 10-year-old girl with glioblastoma treated with nivolumab under compassionate-use guidelines. After the first dose of nivolumab the patient developed hemiparesis, cerebral edema, and significant midline shift due to severe tumor necrosis. She was managed using intravenous dexamethasone and discharged on a dexamethasone taper. The patient's condition rapidly deteriorated after the second dose of nivolumab, demonstrating hemiplegia, seizures, and eventually unresponsiveness with a fixed and dilated left pupil. Computed tomography of her brain revealed malignant cerebral edema requiring emergency decompressive hemicraniectomy. Repeat imaging demonstrated increased size of the lesion, reflecting immune-mediated inflammation and tumor necrosis. The patient remained densely hemiplegic, but became progressively more interactive and was ultimately extubated. She resumed nivolumab several weeks later, but again her condition deteriorated with headache, vomiting, swelling at the craniectomy site, and limited right-sided facial movement following the sixth dose. MRI demonstrated severe midline shift and uncal herniation despite her craniectomy. Her condition gradually declined, and she died several days later under “do not resuscitate/do not intubate” orders. To the authors' knowledge, this represents the first case of malignant cerebral edema requiring operative intervention following nivolumab treatment for glioblastoma in a pediatric patient.

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James M. Drake, Jay Riva-Cambrin, Andrew Jea, Kurtis Auguste, Mandeep Tamber and Maria Lamberti-Pasculli

Object

Complications of specific pediatric neurosurgical procedures are well recognized. However, focused surveillance on a specific neurosurgical unit, for all procedures, may lead to better understanding of the most important complications, and allow targeted strategies for quality improvement.

Methods

The authors prospectively recorded the morbidity and mortality events at a large pediatric neurosurgical unit over a 2-year period. Morbidity was defined as any significant adverse outcome or death (for obstructive shunt failure, within 30 days). Multiple and unrelated complications in the same patient were recorded as separate events.

Results

There were 1082 surgical procedures performed during the evaluation period. One hundred seventy-seven complications (16.4%) occurred in 147 patients. By procedure, the most common complications occurred in vascular surgery (41.7%) and brain tumor surgery (27.9%). The most common complications were CSF leakage (31 cases), a new neurological deficit (27 cases), early shunt or endoscopic third ventriculostomy obstruction (27 cases), and shunt infection (24 cases). Meningitis occurred in 19 cases: in 58% of shunt infections, 13% of CSF leaks, and 10% of wound infections. Sixty-four percent of adverse events required a second procedure, most commonly an external ventricular drain placement or shunt revision.

Conclusions

Complications in pediatric neurosurgical procedures are common, result in significant morbidity, and more than half the time require a repeat surgical procedure. Targeted strategies to prevent common complications, such as shunt infections or CSF leaks, might significantly reduce this burden.

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John R. W. Kestle, Amy Lee, Richard C. E. Anderson, Barbu Gociman, Kamlesh B. Patel, Matthew D. Smyth, Craig Birgfeld, Ian F. Pollack, Jesse A. Goldstein, Mandeep Tamber, Thomas Imahiyerobo, Faizi A. Siddiqi and for the Synostosis Research Group

OBJECTIVE

The authors created a collaborative network, the Synostosis Research Group (SynRG), to facilitate multicenter clinical research on craniosynostosis. To identify common and differing practice patterns within the network, they assessed the SynRG surgeons’ management preferences for sagittal synostosis. These results will be incorporated into planning cooperative studies.

METHODS

The SynRG consists of 12 surgeons at 5 clinical sites. An email survey was distributed to SynRG surgeons in late 2016, and responses were collected through early 2017. Responses were collated and analyzed descriptively.

RESULTS

All of the surgeons—7 plastic/craniofacial surgeons and 5 neurosurgeons—completed the survey. They varied in both experience (1–24 years) and sagittal synostosis case volume in the preceding year (5–45 cases). Three sites routinely perform preoperative CT scans. The preferred surgical technique for children younger than 3 months is strip craniectomy (10/12 surgeons), whereas children older than 6 months are all treated with open cranial vault surgery. Pre-incision cefazolin, preoperative complete blood count panels, and an arterial line were used by most surgeons, but tranexamic acid was used routinely at 3 sites and never at the other 2 sites. Among surgeons performing endoscopic strip craniectomy surgery (SCS), most create a 5-cm-wide craniectomy, whereas 2 surgeons create a 2-cm strip. Four surgeons routinely send endoscopic SCS patients to the intensive care unit after surgery. Two of the 5 sites routinely obtain a CT scan within the 1st year after surgery.

CONCLUSIONS

The SynRG surgeons vary substantially in the use of imaging, the choice of surgical procedure and technique, and follow-up. A collaborative network will provide the opportunity to study different practice patterns, reduce variation, and contribute multicenter data on the management of children with craniosynostosis.

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

OBJECTIVE

Endoscopic third ventriculostomy (ETV) is now established as a viable treatment option for a subgroup of children with hydrocephalus. Here, the authors report prospective, multicenter results from the Hydrocephalus Clinical Research Network (HCRN) to provide the most accurate determination of morbidity, complication incidence, and efficacy of ETV in children and to determine if intraoperative predictors of ETV success add substantially to preoperative predictors.

METHODS

All children undergoing a first ETV (without choroid plexus cauterization) at 1 of 7 HCRN centers up to June 2013 were included in the study and followed up for a minimum of 18 months. Data, including detailed intraoperative data, were prospectively collected as part of the HCRN's Core Data Project and included details of patient characteristics, ETV failure (need for repeat hydrocephalus surgery), and, in a subset of patients, postoperative complications up to the time of discharge.

RESULTS

Three hundred thirty-six eligible children underwent initial ETV, 18.8% of whom had undergone shunt placement prior to the ETV. The median age at ETV was 6.9 years (IQR 1.7–12.6), with 15.2% of the study cohort younger than 12 months of age. The most common etiologies were aqueductal stenosis (24.8%) and midbrain or tectal lesions (21.2%). Visible forniceal injury (16.6%) was more common than previously reported, whereas severe bleeding (1.8%), thalamic contusion (1.8%), venous injury (1.5%), hypothalamic contusion (1.5%), and major arterial injury (0.3%) were rare. The most common postoperative complications were CSF leak (4.4%), hyponatremia (3.9%), and pseudomeningocele (3.9%). New neurological deficit occurred in 1.5% cases, with 0.5% being permanent.

One hundred forty-one patients had documented failure of their ETV requiring repeat hydrocephalus surgery during follow-up, 117 of them during the first 6 months postprocedure. Kaplan-Meier rates of 30-day, 90-day, 6-month, 1-year, and 2-year failure-free survival were 73.7%, 66.7%, 64.8%, 61.7%, and 57.8%, respectively. According to multivariate modeling, the preoperative ETV Success Score (ETVSS) was associated with ETV success (p < 0.001), as was the intraoperative ability to visualize a “naked” basilar artery (p = 0.023).

CONCLUSIONS

The authors' documented experience represents the most detailed account of ETV results in North America and provides the most accurate picture to date of ETV success and complications, based on contemporaneously collected prospective data. Serious complications with ETV are low. In addition to the ETVSS, visualization of a naked basilar artery is predictive of ETV success.

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Jay Riva-Cambrin, John R. W. Kestle, Richard Holubkov, Jerry Butler, Abhaya V. Kulkarni, James Drake, William E. Whitehead, John C. Wellons III, Chevis N. Shannon, Mandeep S. Tamber, David D. Limbrick Jr., Curtis Rozzelle, Samuel R. Browd, Tamara D. Simon and The Hydrocephalus Clinical Research Network

OBJECT

The rate of CSF shunt failure remains unacceptably high. The Hydrocephalus Clinical Research Network (HCRN) conducted a comprehensive prospective observational study of hydrocephalus management, the aim of which was to isolate specific risk factors for shunt failure.

METHODS

The study followed all first-time shunt insertions in children younger than 19 years at 6 HCRN centers. The HCRN Investigator Committee selected, a priori, 21 variables to be examined, including clinical, radiographic, and shunt design variables. Shunt failure was defined as shunt revision, subsequent endoscopic third ventriculostomy, or shunt infection. Important a priori–defined risk factors as well as those significant in univariate analyses were then tested for independence using multivariate Cox proportional hazard modeling.

RESULTS

A total of 1036 children underwent initial CSF shunt placement between April 2008 and December 2011. Of these, 344 patients experienced shunt failure, including 265 malfunctions and 79 infections. The mean and median length of follow-up for the entire cohort was 400 days and 264 days, respectively. The Cox model found that age younger than 6 months at first shunt placement (HR 1.6 [95% CI 1.1–2.1]), a cardiac comorbidity (HR 1.4 [95% CI 1.0–2.1]), and endoscopic placement (HR 1.9 [95% CI 1.2–2.9]) were independently associated with reduced shunt survival. The following had no independent associations with shunt survival: etiology, payer, center, valve design, valve programmability, the use of ultrasound or stereotactic guidance, and surgeon experience and volume.

CONCLUSIONS

This is the largest prospective study reported on children with CSF shunts for hydrocephalus. It confirms that a young age and the use of the endoscope are risk factors for first shunt failure and that valve type has no impact. A new risk factor—an existing cardiac comorbidity—was also associated with shunt failure.

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

OBJECT

In a previous report by the same research group (Kestle et al., 2011), compliance with an 11-step protocol was shown to reduce CSF shunt infection at Hydrocephalus Clinical Research Network (HCRN) centers (from 8.7% to 5.7%). Antibiotic-impregnated catheters (AICs) were not part of the protocol but were used off protocol by some surgeons. The authors therefore began using a new protocol that included AICs in an effort to reduce the infection rate further.

METHODS

The new protocol was implemented at HCRN centers on January 1, 2012, for all shunt procedures (excluding external ventricular drains [EVDs], ventricular reservoirs, and subgaleal shunts). Procedures performed up to September 30, 2013, were included (21 months). Compliance with the protocol and outcome events up to March 30, 2014, were recorded. The definition of infection was unchanged from the authors' previous report.

RESULTS

A total of 1935 procedures were performed on 1670 patients at 8 HCRN centers. The overall infection rate was 6.0% (95% CI 5.1%–7.2%). Procedure-specific infection rates varied (insertion 5.0%, revision 5.4%, insertion after EVD 8.3%, and insertion after treatment of infection 12.6%). Full compliance with the protocol occurred in 77% of procedures. The infection rate was 5.0% after compliant procedures and 8.7% after noncompliant procedures (p = 0.005). The infection rate when using this new protocol (6.0%, 95% CI 5.1%–7.2%) was similar to the infection rate observed using the authors' old protocol (5.7%, 95% CI 4.6%–7.0%).

CONCLUSIONS

CSF shunt procedures performed in compliance with a new infection prevention protocol at HCRN centers had a lower infection rate than noncompliant procedures. Implementation of the new protocol (including AICs) was associated with a 6.0% infection rate, similar to the infection rate of 5.7% from the authors' previously reported protocol. Based on the current data, the role of AICs compared with other infection prevention measures is unclear.