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Derek Yecies, Paul Graham Fisher, Samuel Cheshier, Michael Edwards and Gerald Grant

OBJECTIVE

Primarily metastatic juvenile pilocytic astrocytoma (JPA) is rare, likely representing 2%–3% of all cases of JPA. Due to the rarity of primarily metastatic JPA, there is currently no standard treatment paradigm and the long-term outcomes are not fully known. The goal of this case series was to add to the current understanding of this disease process.

METHODS

The authors searched a comprehensive database of pediatric patients with brain and spinal cord tumors treated at Lucile Packard Children’s Hospital from 1997 to 2016 and identified 5 patients with primarily metastatic JPA. A retrospective chart review was performed and details of the patients’ treatment and clinical course were recorded for further analysis.

RESULTS

For the 5 patients with primarily metastatic JPA, the mean follow-up period was 12.3 years. All patients in our series had biopsies or subtotal resections and upfront treatment. Three patients were treated with chemotherapy alone, one was treated with chemotherapy and radiotherapy, and one was treated with radiotherapy alone. Four patients had stable disease after initial treatment, and one patient had multiple episodes of progressive disease but underwent successful salvage therapy and has had stable disease for 19 years. One patient died of an intracerebral hemorrhage 10 years following initial radiation treatment believed to be secondary to radiation vasculopathy.

CONCLUSIONS

Evaluation of the entire neuraxis should be performed in all instances of initial JPA diagnosis to properly assess for primarily metastatic disease. Many patients with primarily metastatic JPA will have stable disease after upfront treatment, although the higher rate of stable disease found in this series relative to other reports is likely secondary to the small sample size.

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Samuel Cheshier, Michael D. Taylor, Olivier Ayrault and Sabine Mueller

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Jun Jae Shin, Sang Hyun Kim, Yong Eun Cho, Samuel H. Cheshier and Jon Park

Object

Several controversial issues arise in the management of unstable hangman's fractures. Some surgeons perform external reduction and immobilize the patient's neck in a halo vest, while others perform surgical reduction and internal fixation. The nonsurgical treatments with rigid collar or halo vest immobilization present problems, including nonunion, pseudarthrosis, skull fracture, and scalp laceration and may also fail to achieve anatomical realignment of the local C2–3 kyphosis. With recent advances in surgical technique and technology, surgical intervention is increasingly performed as the primary treatment in high cervical fractures. The outcomes of such surgeries are often superior to those of conservative treatment. The authors propose that surgical intervention as a primary management for hangman's fracture may avoid risks inherent in conservative management when severe circumferential discoligamentous instability is present and may reduce the risk of catastrophic results at the fracture site.

The purposes of this study were to assess fracture healing following expedient reduction and surgical fixation and to propose a guideline for treatment of unstable hangman's fractures.

Methods

From April 2006 to December 2011, the authors treated 105 patients with high cervical fractures. This study included 23 (21.9%) of these patients (15 men and 8 women; mean age 46.4 years) with Type II, IIa, and III hangman's fractures according to the Levine and Edwards classification. The patient's age, sex, mechanism of injury, associated injuries, neurological status, and complications were ascertained. The authors retrospectively assessed the clinical outcome (Neck Disability Index), radiological findings (disc height, translation, and angulation), and bony healing.

Results

The average follow-up period was 28.9 months (range 12–63.2 months). The overall average Neck Disability Index score at the time of this study was 6.6 ± 2.3. The average duration of hospitalization was 20.3 days, and fusion was achieved in all cases by 14.8 ± 1.6 weeks after surgery, as demonstrated on dynamic radiographs and cervical 3D CT scans.

The mean pretreatment translation was 6.9 ± 3.2 mm, and the mean postoperative translation was 1.6 ± 1.8 mm (mean reduction 5.2 ± 3.1 mm). The initial angulation was 4.7° ± 5.3° and the postoperative angulation was 2.5° ± 1.8° (mean reduction 6.1° ± 5.3°). The preoperative and postoperative values for translation and angulation differed significantly (p < 0.05). The overall C2–3 disc height was 6.7 ± 1.2 mm preoperatively, whereas 3 months after surgery it was 6.4 ± 1.1 mm. These values did not differ significantly (p = 0.0963).

Conclusions

The authors observed effective reduction and bony healing in cases of unstable hangman's fractures after fixation, and all patients experienced favorable clinical outcomes with neck pain improvement. The protocols allowed for physiological reconstruction of the fractured deformities and avoided external fixation. The authors suggest that posterior reduction and screw fixation should be used as a primary treatment to promote stability of hangman's fracture in the presence of discoligamentous instability or combined fractures.

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Katalin A. Szabo, Samuel H. Cheshier, M. Yashar S. Kalani, Jonathan W. Kim and Raphael Guzman

To the authors' knowledge, this is the first report of the use of anterior orbitotomy via the supraorbital eyelid crease to repair a dural tear caused by an orbital roof fracture. When transorbital penetrating injuries occur in children, they are commonly caused by accidental falls onto pointed objects. The authors report on their experience with a 7-year-old girl who fell onto a blunt metal rod hanger that penetrated her left eyelid, traversed superior to the eye globe, and penetrated the orbital roof at a depth of 3–4 cm, lacerating the dura mater and entering the cerebrum. An anterior transpalpebral transorbital approach was used to perform the microsurgical anterior skull base and dural repair. The authors advocate the application of this approach to orbital roof fractures because it provides excellent access to the orbital roof, eliminates the need for more invasive craniotomy, results in a small and well-hidden scar in the eye crease, and overall offers a shorter recovery time with less psychological stress to the patient.

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Jennifer L. Quon, Lily H. Kim, Peter H. Hwang, Zara M. Patel, Gerald A. Grant, Samuel H. Cheshier and Michael S. B. Edwards

OBJECTIVE

Transnasal endoscopic transsphenoidal approaches constitute an essential technique for the resection of skull base tumors in adults. However, in the pediatric population, sellar and suprasellar lesions have historically been treated by craniotomy. Transnasal endoscopic approaches are less invasive and thus may be preferable to craniotomy, especially in children. In this case series, the authors present their institutional experience with transnasal endoscopic transsphenoidal approaches for pediatric skull base tumors.

METHODS

The authors retrospectively reviewed pediatric patients (age ≤ 18 years) who had undergone transnasal endoscopic transsphenoidal approaches for either biopsy or resection of sellar or suprasellar lesions between 2007 and 2016. All operations were performed jointly by a team of pediatric neurosurgeons and skull base otolaryngologists, except for 8 cases performed by one neurosurgeon.

RESULTS

The series included 42 patients between 4 and 18 years old (average 12.5 years) who underwent 51 operations. Headache (45%), visual symptoms (69%), and symptoms related to hormonal abnormalities (71%) were the predominant presenting symptoms. Improvement in preoperative symptoms was seen in 92% of cases. Most patients had craniopharyngiomas (n = 16), followed by pituitary adenomas (n = 12), Rathke cleft cysts (n = 4), germinomas (n = 4), chordomas (n = 2), and other lesion subtypes (n = 4). Lesions ranged from 0.3 to 6.2 cm (median 2.5 cm) in their greatest dimension. Gross-total resection was primarily performed (63% of cases), with 5 subsequent recurrences. Nasoseptal flaps were used in 47% of cases, fat grafts in 37%, and lumbar drains in 47%. CSF space was entered intraoperatively in 15 cases, and postoperative CSF was observed only in lesions with suprasellar extension. There were 8 cases of new hormonal deficits and 3 cases of new cranial nerve deficits. Length of hospital stay ranged from 1 to 61 days (median 5 days). Patients were clinically followed up for a median of 46 months (range 1–120 months), accompanied by a median radiological follow-up period of 45 months (range 3.8–120 months). Most patients (76%) were offered adjuvant therapy.

CONCLUSIONS

In this single-institution report of the transnasal endoscopic transsphenoidal approach, the authors demonstrated that this technique is generally safe and effective for different types of pediatric skull base lesions. Favorable effects of surgery were sustained during a follow-up period of 4 years. Further refinement in technology will allow for more widespread use in the pediatric population.

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Robert M. Lober, Raphael Guzman, Samuel H. Cheshier, Douglas R. Fredrick, Michael S. B. Edwards and Kristen W. Yeom

Object

Magnetic resonance imaging is commonly used in diagnosis and surveillance for optic pathway glioma (OPG). The authors investigated the role of diffusion tensor (DT) tractography in assessing the location of visual pathway fibers in the presence of tumor.

Methods

Data in 10 children with OPG were acquired using a 3T MRI generalized autocalibrating parallel acquisitions DT–echo planar imaging sequence (25 isotropic directions with a b value of 1000 seconds/mm2, slice thickness 3 mm). Fiber tractography was performed, with seed regions placed within the optic chiasm and bilateral nerves on the coronal plane, including the tumor and surrounding normal-appearing tissue. Tracking was performed with a curvature threshold of 30°.

Results

For prechiasmatic lesions, fibers either stopped abruptly at the tumor or traversed abnormally dilated nerve segments. Similar findings were seen with chiasmatic lesions, with an additional arrangement in which fibers diverged around the tumor. For each patient, DT tractography provided additional information about visual fiber arrangement in relation to the tumor that was not evident by using conventional MRI methods. Retrospective reconstruction of visual fibers in 1 patient with new postoperative hemianopia revealed an unexpected superior displacement of the optic tract that might have been helpful information had it been applied to preoperative planning or surgical navigation.

Conclusions

Optic pathway DT tractography is feasible in patients with OPG and provides new information about the arrangement of visual fibers in relation to tumors that could be incorporated into surgical navigation for tumor biopsy or debulking procedures.

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Stephen L. Huhn, Yun Yung, Samuel Cheshier, Griffith Harsh, Laurie Ailles, Irving Weissman, Hannes Vogel and Victor Tse

Object

The goal of this study was to illustrate the findings of a significant subpopulation of cells within a pediatric astroblastoma that have the specific cell surface phenotype found on known human neural stem cells.

Methods

Cells with a cell surface marker profile characteristic of human neural stem cells were isolated using fluorescence-activated cell sorting from a mostly nonmitotic astroblastoma removed from the brain of an 11-year-old girl. An unusually high proportion (24%) of the cells were CD133 positive and CD24, CD34, and CD45 negative (CD133+ CD24CD34CD45 cells), the phenotypic antigenic pattern associated with neural stem cells; very few CD133-positive cells were not also CD24, CD34, and CD45 negative. Some cells (12%) were CD34 positive, indicating the presence within the tumor of hematopoietic stem cells. Cells formed cytospheres that resembled neurospheres when seeded into stem cell media and coexpressed β-tubulin and glial fibrillary acidic protein (GFAP) but did not express the oligodendrocyte marker O4. Cell proliferation was demonstrated by incorporation of bromodeoxyuridine. The cells lost their capacity for self-renewal in vitro after four to six passages, although they continued to coexpress β-tubulin and GFAP. The cells did not differentiate into neurons or astrocytes when placed in differentiation medium.

Conclusions

Although this astroblastoma contained a high proportion of phenotypic neural stemlike cells, the cells had limited proliferative capacity and multipotency. Their role in astroblastoma formation and growth is unknown.

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Alexandra D. Beier, Samuel H. Cheshier, Aabir Chakraborty and Peter Dirks

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is occasionally seen after hypothalamic injury or dysfunction, although it typically occurs in association with other endocrine disturbances. It is has never been described as a presenting feature of a suprasellar arachnoid cyst (SAC) in the pediatric population. The authors describe the case of an enlarging SAC resulting in SIADH as the only presenting feature, with an otherwise normal hypothalamic-pituitary axis.

An SAC was diagnosed in utero in this 5-month-old girl who had a normal functioning hypothalamic-pituitary axis on presentation. Because of cyst enlargement and hydrocephalus, the patient was scheduled for surgery; however, preoperative labs revealed SIADH. After stabilizing the serum sodium concentration with fluid restriction and the administration of 3% sodium chloride, the patient underwent endoscopic cyst fenestration. Postoperatively, she had complete resolution of the SIADH.

Syndrome of inappropriate antidiuretic hormone secretion as the presenting symptom of an SAC has not been previously described. In the aforementioned patient, the proposed mechanism for SIADH was enlargement of the suprasellar arachnoid cyst causing compression of the supraoptic and paraventricular nuclei and thus overstimulating the secretion of arginine vasopressin, which resulted in SIADH.

The association of SIADH with an SAC is reportable, as is the resolution of the SIADH via cyst fenestration. The authors suggest that SIADH is an uncommon presenting feature of SACs and that syndrome resolution is possible with cyst decompression.

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Marco Lee, M. Yashar S. Kalani, Samuel Cheshier, Iris C. Gibbs, John R. Adler Jr. and Steven D. Chang

Object

Many benign intracranial tumors are amenable to radiotherapy treatment including meningiomas, schwannomas, pituitary tumors, and craniopharyngiomas. The authors present their experience in the treatment of craniopharyngiomas in 16 patients using frameless CyberKnife stereotactic radiosurgery (SRS). The authors discuss the role of radiation therapy in the management of these tumors, and more specifically, the role of CyberKnife SRS.

Methods

Sixteen patients were treated for residual or recurrent craniopharyngioma between 2000 and 2007 with CyberKnife SRS at Stanford University Medical Center. All patients underwent magnetic resonance imaging and visual and neuroendocrine evaluations before and at regular intervals after SRS. A multisession treatment regimen and a nonisocentric treatment plan for each patient were used with a mean marginal dose of 21.6 Gy and a mean maximal dose of 29.9 Gy.

Results

There were adequate clinical data to assess outcomes in 11 of 16 patients. Evaluation of patients between 13 and 71 years of age (mean 34.5 years) with a mean follow-up period of 15.4 months revealed no deterioration in visual or neuroendocrine function. Tumor shrinkage was achieved in 7 of these 11 patients, and tumor control in another 3. One patient had cystic enlargement of the residual tumor.

Conclusions

The authors' early experience with the application of CyberKnife SRS to residual or recurrent craniopharyngiomas has been positive; control or shrinkage of the tumor was achieved in 91% of patients, with no visual or neuroendocrine complications. Longer-term follow-up with a larger group of patients is required to fully evaluate the safety and effectiveness of this treatment modality.

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Derek Yecies, Katie Shpanskaya, Rashad Jabarkheel, Maryam Maleki, Lisa Bruckert, Samuel H. Cheshier, David Hong, Michael S. B. Edwards, Gerald A. Grant and Kristen W. Yeom

OBJECTIVE

Posterior fossa syndrome (PFS) is a common complication following the resection of posterior fossa tumors in children. The pathophysiology of PFS remains incompletely elucidated; however, the wide-ranging symptoms of PFS suggest the possibility of widespread cortical dysfunction. In this study, the authors utilized arterial spin labeling (ASL), an MR perfusion modality that provides quantitative measurements of cerebral blood flow without the use of intravenous contrast, to assess cortical blood flow in patients with PFS.

METHODS

A database of medulloblastoma treated at the authors’ institution from 2004 to 2016 was retrospectively reviewed, and 14 patients with PFS were identified. Immediate postoperative ASL for patients with PFS and medulloblastoma patients who did not develop PFS were compared. Additionally, in patients with PFS, ASL following the return of speech was compared with immediate postoperative ASL.

RESULTS

On immediate postoperative ASL, patients who subsequently developed PFS had statistically significant decreases in right frontal lobe perfusion and a trend toward decreased perfusion in the left frontal lobe compared with controls. Patients with PFS had statistically significant increases in bilateral frontal lobe perfusion after the resolution of symptoms compared with their immediate postoperative imaging findings.

CONCLUSIONS

ASL perfusion imaging identifies decreased frontal lobe blood flow as a strong physiological correlate of PFS that is consistent with the symptomatology of PFS. This is the first study to demonstrate that decreases in frontal lobe perfusion are present in the immediate postoperative period and resolve with the resolution of symptoms, suggesting a physiological explanation for the transient symptoms of PFS.