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Surgical treatment of intractable epilepsy associated with focal cortical dysplasia

Roberto Jose Diaz, Elisabeth M. S. Sherman, and Walter J. Hader

Focal cortical dysplasias (FCDs) are congenital malformations of cortical development that are a frequent cause of refractory epilepsy in both children and adults. With advances in structural and functional neuroimaging, these lesions are increasingly being identified as a cause of intractable epilepsy in patients undergoing surgical management for intractable epilepsy. Comprehensive histological classification of FCDs with the establishment of uniform terminology and reproducible pathological features has aided in our understanding of FCDs as an epilepsy substrate. Complete resection of FCDs and the associated epileptogenic zone can result in a good surgical outcome in the majority of patients.

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Determinants of quality of life in patients with skull base chordoma

Clinical article

Roberto Jose Diaz, Nicole Maggacis, Shudong Zhang, and Michael D. Cusimano

Object

Skull base chordomas can be managed by surgical intervention and adjuvant radiotherapy. As survival for this disease increases, identification of determinants of quality of life becomes an important focus for guiding comprehensive patient care. In this study the authors sought to measure functional outcome and quality of life in patients with skull base chordomas and to identify determinants of quality of life in these patients.

Methods

The authors carried out an internet-based cross-sectional survey, collecting detailed data for 83 individual patients. Demographic and clinical variables were evaluated. Functional outcomes were determined by Karnofsky Performance Scale (KPS) and Glasgow Outcome Scale Extended (GOSE), quality of life was measured using the 36-Item Short Form Health Survey (SF-36), and depression was assessed using Patient Health Questions–9 (PHQ-9) instrument. Caregiver burden was assessed using the Zarit Burden Interview (ZBI). Univariate and multivariate analysis was performed to identify determinants of the physical and mental components of the SF-36.

Results

Patients with skull base chordomas who have undergone surgery and/or radiation treatment had a median KPS score of 90 (range 10–100, IQR 10) and a median GOSE score of 8 (range 2–8, IQR 3). The mean SF-36 Physical Component Summary score (± SD) was 43.6 ± 11.8, the mean Mental Component Summary score was 44.2 ±12.6, and both were significantly lower than norms for the general US population (p < 0.001). The median PHQ-9 score was 5 (range 0–27, IQR 8). A PHQ-9 score of 10 or greater, indicating moderate to severe depression, was observed in 29% of patients. The median ZBI score was 12 (range 0–27, IQR 11), indicating a low burden. Neurological deficit, use of pain medication, and requirement for corticosteroids were found to be associated with worse SF-36 Physical Component Summary score, while higher levels of depression (higher PHQ-9 score) correlated with worse SF-36 Mental Component Summary score.

Conclusions

Patients with skull base chordomas have a lower quality of life than the general US population. The most significant determinants of quality of life in the posttreatment phase in this patient population were neurological deficits (sensory deficit and bowel/bladder dysfunction), pain medication use, corticosteroid use, and levels of depression as scored by PHQ-9.

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Study of the biodistribution of fluorescein in glioma-infiltrated mouse brain and histopathological correlation of intraoperative findings in high-grade gliomas resected under fluorescein fluorescence guidance

Roberto Jose Diaz, Roberto Rey Dios, Eyas M. Hattab, Kelly Burrell, Patricia Rakopoulos, Nesrin Sabha, Cynthia Hawkins, Gelareh Zadeh, James T. Rutka, and Aaron A. Cohen-Gadol

OBJECT

Intravenous fluorescein sodium has been used during resection of high-grade gliomas to help the surgeon visualize tumor margins. Several studies have reported improved rates of gross-total resection (GTR) using high doses of fluorescein sodium under white light. The recent introduction of a fluorescein-specific camera that allows for high-quality intraoperative imaging and use of very low dose fluorescein has drawn new attention to this fluorophore. However, the ability of fluorescein to specifically stain glioma cells is not yet well understood.

METHODS

The authors designed an in vitro model to assess fluorescein uptake in normal human astrocytes and U251 malignant glioma cells. An in vivo experiment was also subsequently designed to study fluorescein uptake by intracranial U87 malignant glioma xenografts in male nonobese diabetic/severe combined immunodeficient mice. A genetically induced mouse glioma model was used to adjust for the possible confounding effect of an inflammatory response in the xenograft model. To assess the intraoperative application of this technology, the authors prospectively enrolled 12 patients who underwent fluorescein-guided resection of their high-grade gliomas using low-dose intravenous fluorescein and a microscope-integrated fluorescence module. Intraoperative fluorescent and nonfluorescent specimens at the tumor margins were randomly analyzed for histopathological correlation.

RESULTS

The in vitro and in vivo models suggest that fluorescein demarcation of glioma-invaded brain is the result of distribution of fluorescein into the extracellular space, most likely as a result of an abnormal blood-brain barrier. Glioblastoma tumor cell–specific uptake of fluorescein was not observed, and tumor cells appeared to mostly exclude fluorescein. For the 12 patients who underwent resection of their high-grade gliomas, the histopathological analysis of the resected specimens at the tumor margin confirmed the intraoperative fluorescent findings. Fluorescein fluorescence was highly specific (up to 90.9%) while its sensitivity was 82.2%. False negatives occurred due to lack of fluorescence in areas of diffuse, low-density cellular infiltration. Margins of contrast enhancement based on intraoperative MRI–guided StealthStation neuronavigation correlated well with fluorescent tumor margins. GTR of the contrast-enhancing area as guided by the fluorescent signal was achieved in 100% of cases based on postoperative MRI.

CONCLUSIONS

Fluorescein sodium does not appear to selectively accumulate in astrocytoma cells but in extracellular tumor cell-rich locations, suggesting that fluorescein is a marker for areas of compromised blood-brain barrier within high-grade astrocytoma. Fluorescein fluorescence appears to correlate intraoperatively with the areas of MR enhancement, thus representing a practical tool to help the surgeon achieve GTR of the enhancing tumor regions.

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Editorial: Turning fluorescence into black and white

Peter E. Fecci, Ranjith Babu, D. Cory Adamson, and John H. Sampson

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Abstracts of the 2011 Meeting of the AANS/CNS Section on Disorders of the Spine and Peripheral Nerves March 2011

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Abstracts for the 2013 Annual Meeting of The American Society of Pediatric Neurosurgeons

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Oral Presentations

2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010

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Oral Presentations 2016 AANS Annual Scientific Meeting Chicago, IL • April 30–May 4, 2016

Published online April 1, 2016; DOI: 10.3171/2016.4.JNS.AANS2016abstracts