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Catherine Miller and Daniel Guillaume

OBJECT

External ventricular drains (EVDs) are regularly used in pediatric neurosurgery for diagnostic and therapeutic purposes. Hemorrhage caused by placing an EVD is a common complication noted in the adult literature. In the pediatric literature, on the other hand, only a few articles have assessed the risk of hemorrhage with placement, and none have reported the occurrence of hemorrhage with removal of an EVD. The authors investigated the incidence of hemorrhage with both placement and removal of the EVD in a pediatric population.

METHODS

After obtaining institutional review board approval, a comprehensive database was created to include all pediatric patients who required EVD placement between March 2008 and June 2014 at the authors’ institution. A retrospective chart review was completed, and all imaging was reviewed for evidence of hemorrhage with placement and removal of the EVD.

RESULTS

During the designated time period, 73 EVDs were placed in 63 patients (ages 2 weeks–17 years). Indications for EVD placement were as follows: shunt infection/malfunction (21), tumor (12), hydrocephalus (18), hemorrhage (12), edema (4), trauma (1), and other (5). Hemorrhage with placement was noted in 5 of the 50 patients who underwent imaging, with a volume ranging from 0.48 cm3 to 7.7 cm3. Thirty-two patients had imaging after EVD removal, and 7 of these patients were noted to have hemorrhage (volume range 0.012 cm3 to 81.5 cm3).

CONCLUSIONS

The authors found the incidence of hemorrhage at EVD placement to be 10%, and the incidence of hemorrhage on EVD removal to be 21.9% in those patients who underwent imaging after each event. Although none of the hemorrhages were of obvious clinical significance, these data can be useful in decision making, and in discussing the risks of EVDs with the patient’s family.

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David Satzer and Daniel J. Guillaume

Object

Brainstem dysfunction occurs in a minority of patients with myelomeningocele (MMC), most of whom have Chiari Type II malformation. Some surgeons advocate early identification of these patients for craniocervical decompression to avoid significant mortality. The auditory brainstem response has been found to be abnormal in most children with MMC. The present study examines whether failure of routine newborn hearing screening (NHS) predicts brainstem dysfunction in MMC patients.

Methods

The charts of 40 newborns with MMC and 50 newborns without MMC who stayed in the neonatal intensive care unit were reviewed. Results of NHS, brainstem symptoms, birth demographics, and surgical history were retrospectively examined. Differences in the presence and onset of brainstem symptoms by NHS result were assessed.

Results

Failure of NHS was more common among newborns with MMC who developed brainstem symptoms (31%, 4 of 13 patients) than among newborns without MMC (0%, 0 of 50 patients; p = 0.001). Among the 40 newborns with MMC, brainstem symptoms were more common in those who failed NHS (80%, 4 of 5 patients) than in those who passed (26%, 9 of 35 patients; p = 0.031). Respiratory symptom onset occurred later in patients who failed NHS (median 16 months) than among those who passed (median 0 months; p = 0.022). The positive and negative predictive values of NHS for brainstem dysfunction in MMC were 0.80 and 0.74, respectively.

Conclusions

Results of NHS may help predict future brainstem dysfunction in patients with MMC and may be useful to incorporate into prognostic assessment and surgical decision making.

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Retroclival hematoma in the pediatric population

Report of two cases and review of the literature

Daniel Guillaume and Arnold H. Menezes

✓ Case reports of retroclival hematoma are infrequent, and little is known about the mechanism of formation of the lesion, its management strategy, and the outcome in affected patients. The authors report two cases of posttraumatic retroclival hematoma in children and discuss the available literature. Both patients were treated with cervical immobilization and had good outcomes.

Retroclival hematomas are rare. Most reported cases involve pediatric patients in whom the hematomas developed in association with trauma. Spinal trauma in children mainly occurs at the craniovertebral junction due to a high fulcrum of cervical motion and results in ligamentous injuries more often than fractures. The formation of epidural hematomas posterior to the clivus is likely to be due to either clivus fracture or ligament disruption. A high index of suspicion is essential in making the diagnosis. Magnetic resonance imaging is superior to computed tomography in demonstrating retroclival hematomas because of its superiority in delineating the extradural spaces and the integrity of the ligaments. The authors conclude that in most cases retroclival hematomas can be treated conservatively and good outcomes can be expected.

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Daniel J. Guillaume and Su-Chun Zhang

✓ The primary therapeutic goal of embryonic stem cell (ESC) research is cell replacement therapy. During the last decade, great strides have been made in developing in vitro protocols for differentiating human ESCs into neuroepithelial progenitors. More recent progress has been made in further directing them into becoming cells with specialized regional and neurotransmitter identities, such as midbrain dopaminergic and spinal motor neurons. Along with directed differentiation, other current efforts are aimed at efficient enrichment, avoidance of immune rejection, demonstration of functional integration, genetic modification to regulate neurotransmitter and factor release, directed axon growth, in vivo cell tracking, and measures to ensure safety. This review will focus on the potential of ESCs as a source of transplantable cells for use in cell replacement therapy.

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Catherine Miller, Daniel Guillaume, Kathryn Dusenbery, H. Brent Clark, and Christopher Moertel

Brain tumors are the most common solid tumor in childhood, and astrocytomas account for the largest proportion of these tumors. Increasing sophistication in genetic testing has allowed for the detection of specific mutations within tumor subtypes that may represent targets for individualized tumor treatment. The mitogen-activating protein kinase (MAPK) pathway and, more specifically, BRAF mutations have been shown to be prevalent in pediatric pilocytic astrocytomas and may represent one such area to target. Herein, the authors describe 2 cases of inoperable, chemotherapy-resistant pediatric pilocytic astrocytomas with a documented response to trametinib, an MAPK pathway inhibitor. While these cases were not treated in the setting of a clinical trial, their data support further ongoing clinical trial investigation to evaluate the safety and efficacy of this agent in pediatric low-grade gliomas.

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Daniel J. Guillaume, Kristin Knight, Carol Marquez, Dale F. Kraemer, Dianna M. E. Bardo, and Edward A. Neuwelt

Object

Cerebrospinal fluid shunting has previously been associated with hearing loss. Although the mechanism for this is unclear, it is thought that changes in CSF pressure can affect cochlear physiology via endolymph expansion in the setting of a patent cochlear aqueduct. Patients undergoing radiation and cisplatin chemotherapy are at risk for hearing loss. The authors hypothesized that the incidence and severity of hearing loss in patients undergoing radiation and chemotherapy for medulloblastoma would be greater in those with shunts than in those without shunts.

Methods

Baseline and longitudinal audiology data were collected in 33 patients with medulloblastoma who were receiving radiation and cisplatin chemotherapy. Additional data included age, sex, details of shunt placement and revision, and details of chemotherapy and radiation. Hearing sensitivity and peripheral auditory function measures included pure tone audiometry, immittance audiometry, and distortion product evoked otoacoustic emissions. Ototoxicity was determined according to the American Speech-Language-Hearing Association criteria. Severity of hearing loss was determined using the Brock hearing loss grades. Incidence of hearing loss and association with shunting was determined.

Results

Thirteen (39.4%) of the 33 patients evaluated had undergone shunt placement. Hearing loss occurred in 14 (70%) of 20 patients without shunts and in 13 (100%) of 13 patients with shunts. The difference between the rates of hearing loss in patients with shunts versus those without the devices was highly significant (p = 0.0008). The odds ratio for hearing loss in patients with a CSF shunt compared with those without a shunt was 23.49 (95% CI 4.21–131.15). Age, side of shunt, evidence of dissemination, diameter of cochlear aqueduct, and treatment protocol did not have a significant effect on shunt-related ototoxicity.

Conclusions

This study suggests an independent association between CSF shunting and hearing loss in children undergoing treatment for medulloblastoma, laying the foundation for a prospective study evaluating hearing loss in children with shunts who are not treated with ototoxic therapy.

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Mark P. Piedra, Eric M. Thompson, Nathan R. Selden, Brian T. Ragel, and Daniel J. Guillaume

Object

The object of this study was to determine if early cranioplasty after decompressive craniectomy for elevated intracranial pressure in children reduces complications.

Methods

Sixty-one consecutive cases involving pediatric patients who underwent autologous cranioplasty after decompressive craniectomy for raised intracranial pressure at a single academic children's hospital over 15 years were studied retrospectively.

Results

Sixty-one patients were divided into early (< 6 weeks; 28 patients) and late (≥ 6 weeks; 33 patients) cranioplasty cohorts. The cohorts were similar except for slightly lower age in the early (8.03 years) than the late (10.8 years) cranioplasty cohort (p < 0.05). Bone resorption after cranioplasty was significantly more common in the late (42%) than the early (14%) cranioplasty cohort (p < 0.05; OR 5.4). No other complication differed in incidence between the cohorts.

Conclusions

After decompressive craniectomy for raised intracranial pressure in children, early (< 6 weeks) cranioplasty reduces the occurrence of reoperation for bone resorption, without altering the incidence of other complications.

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Nathan R. Selden, Daniel J. Guillaume, Robert D. Steiner, and Stephen L. Huhn

✓ Cellular replacement therapy attempts to improve functioning of the diseased human central nervous system (CNS). In this second installment of a 2-part review, the authors discuss the major challenges to the translation of in vitro and animal studies of neural stem cell (NSC) therapy in the clinical setting. This analysis details the problems unique to the design of clinical trials using human NSCs, outlines patient selection practices, describes surgical techniques for cellular transplantation, and reviews the regulatory issues and ethical concerns in trials involving neurologically impaired children.

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Bharathi D. Jagadeesan, Haralabos Zacharatos, David R. Nascene, Andrew W. Grande, Daniel J. Guillaume, and Ramachandra P. Tummala

A 5-month-old infant was to be treated with elective transarterial embolization for a vein of Galen aneurysmal malformation (VGAM). A team of endovascular surgical neuroradiologists, pediatric interventional radiologists, and pediatric cardiologists attempted conventional femoral arterial access, which was unsuccessful given the small caliber of the femoral arteries and superimposed severe vasospasm. Thereafter, eventual arterial access was achieved by navigating from the venous to the arterial system across the patent foramen ovale following a right femoral venous access. Embolization was then successfully performed. At a later date, the child underwent successful transvenous balloon-assisted embolization and eventual arterial embolization with cure of the VGAM.

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Daniel J. Guillaume, Stephen L. Huhn, Nathan R. Selden, and Robert D. Steiner

✓ Successful cellular replacement in the diseased human central nervous system (CNS) faces numerous hurdles. In this first installment of a 2-part review, the authors report on the preclinical challenges involved in preparing for a major Phase I trial investigating the safety of human neural stem cell transplantation in a lysosomal storage disorder. Specifically, they discuss choice of the ideal disease for treatment, best donor cell type and source for implantation, the in vitro and in vivo methods used to estimate safety and efficacy, the challenges to noninvasive tracking of cells after transplantation, and the unique issues related to the immunology of CNS cellular transplantation.