Peter E. Fecci, Ranjith Babu, D. Cory Adamson and John H. Sampson
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
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.
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.
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.
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.
Christian Schneider, Vijay Ramaswamy, Abhaya V. Kulkarni, James T. Rutka, Marc Remke, Uri Tabori, Cynthia Hawkins, Eric Bouffet and Michael D. Taylor
While medulloblastoma was initially thought to comprise a single homogeneous entity, it is now accepted that it in fact comprises 4 discrete subgroups, each with its own distinct demographics, clinical presentation, transcriptomics, genetics, and outcome. Hydrocephalus is a common complication of medulloblastoma and not infrequently requires CSF diversion. The authors report the incidence of CSF diversion surgery in each of the subgroups of medulloblastoma (Wnt, Shh, Group 3, and Group 4).
The medical and imaging records for patients who underwent surgery for medulloblastoma at The Hospital for Sick Children were retrospectively reviewed. The primary outcome was the requirement for CSF diversion surgery either before or within 60 days of tumor resection. The modified Canadian Preoperative Prediction Rule for Hydrocephalus (mCPPRH) was compared among subgroups.
Of 143 medulloblastoma patients, treated from 1991 to 2013, sufficient data were available for 130 patients (15 with Wnt, 30 with Shh, 30 with Group 3, and 55 with Group 4 medulloblastomas). Of these, 28 patients (22%) ultimately underwent CSF diversion surgery: 0% with Wnt, 29% with Shh, 29% with Group 3, and 43% with Group 4 tumors. Patients in the Wnt subgroup had a lower incidence of CSF diversion than all other patients combined (p = 0.04). Wnt patients had a lower mCPPRH score (lower risk of CSF diversion, p = 0.045), were older, had smaller ventricles at diagnosis, and had no leptomeningeal metastases.
The overall rate of CSF diversion surgery for Shh, Group 3, and Group 4 medulloblastomas is around 30%, but no patients in the present series with a Wnt medulloblastoma required shunting. The low incidence of hydrocephalus in patients with Wnt medulloblastoma likely reflects both host factors (age) and disease factors (lack of metastases). The absence of hydrocephalus in patients with Wnt medulloblastomas likely contributes to their excellent rate of survival and may also contribute to a higher quality of life than for patients in other subgroups.
Mark Calayag, Christian Cantillano Malone, Brian Drake, Govind Chavhan and James T. Rutka
Fetal ovarian cysts are common congenital lesions encountered in the neonatal population. These cysts are typically benign and rarely require any invasive intervention. Abdominal pseudocyst formation as a result of a ventriculoperitoneal shunt is a relatively infrequent occurrence and is similarly an uncommon cause of shunt failure. The authors present the case of a 4-month-old girl with shunted hydrocephalus who presented with shunt failure from a suspected abdominal pseudocyst that was found to be a fetal ovarian cyst.
Gregory W. Albert, George M. Ibrahim, Hiroshi Otsubo, Ayako Ochi, Cristina Y. Go, O. Carter Snead III, James M. Drake and James T. Rutka
Resective surgery is increasingly used in the management of pediatric epilepsy. Frequently, invasive monitoring with subdural electrodes is required to adequately map the epileptogenic focus. The risks of invasive monitoring include the need for 2 operations, infection, and CSF leak. The aim of this study was to evaluate the feasibility and outcomes of resective epilepsy surgery guided by magnetoencephalography (MEG) in children who would have otherwise been candidates for electrode implantation.
The authors reviewed the records of patients undergoing resective epilepsy surgery at the Hospital for Sick Children between 2001 and 2010. They identified cases in which resections were based on MEG data and no intracranial recordings were performed. Each patient's chart was reviewed for presentation, MRI findings, MEG findings, surgical procedure, pathology, and surgical outcome.
Sixteen patients qualified for the study. All patients had localized spike clusters on MEG and most had abnormal findings on MRI. Resection was carried out in each case based on the MEG data linked to neuronavigation and supplemented with intraoperative neuromonitoring. Overall, 62.5% of patients were seizure free following surgery, and 20% of patients experienced an improvement in seizures without attaining seizure freedom. In 2 cases, additional surgery was performed subsequently with intracranial monitoring in attempts to obtain seizure control.
MEG is a viable alternative to invasive monitoring with intracranial electrodes for planning of resective surgery in carefully selected pediatric patients with localization-related epilepsy. Good candidates for this approach include patients who have a well-delineated, localized spike cluster on MEG that is concordant with findings of other preoperative evaluations and patients with prior brain pathologies that make the implantation of subdural and depth electrodes somewhat problematic.
Odeya Bennett-Back, Ayako Ochi, Elysa Widjaja, Shohei Nambu, Akio Kamiya, Cristina Go, Sylvester Chuang, James T. Rutka, James Drake, O. Carter Snead III and Hiroshi Otsubo
Porencephalic cyst/encephalomalacia (PC/E) is a brain lesion caused by ischemic insult or hemorrhage. The authors evaluated magnetoencephalography (MEG) spike sources (MEGSS) to localize the epileptogenic zone in children with intractable epilepsy secondary to PC/E.
The authors retrospectively studied 13 children with intractable epilepsy secondary to PC/E (5 girls and 8 boys, age range 1.8–15 years), who underwent prolonged scalp video-electroencephalography (EEG), MRI, and MEG. Interictal MEGSS locations were compared with the ictal and interictal zones as determined from scalp video-EEG.
Magnetic resonance imaging showed PC/E in extratemporal lobes in 3 patients, within the temporal lobe in 2 patients, and in both temporal and extratemporal lobes in 8 patients. Magnetoencephalographic spike sources were asymmetrically clustered at the margin of PC/E in all 13 patients. One cluster of MEGSS was observed in 11 patients, 2 clusters in 1 patient, and 3 clusters in 1 patient. Ictal EEG discharges were lateralized and concordant with MEGSS in 8 patients (62%). Interictal EEG discharges were lateralized and concordant with MEGSS hemisphere in 9 patients (69%). Seven patients underwent lesionectomy in addition to MEGSS clusterectomy with (2 patients) and without (5 patients) intracranial video-EEG. Temporal lobectomy was performed in 1 patient and hemispherectomy in another. Eight of 9 patients achieved seizure freedom following surgery.
Magnetoencephalography delineated the extent of the epileptogenic zone adjacent to PC/E in patients with intractable epilepsy. Complete resection of the MEGSS cluster along with PC/E can provide favorable seizure outcomes.
Mustafa Nadi, Navid Khezri, Tahani Ahmad, Michael Ellis, Eric Bouffet, James T. Rutka and Michael D. Taylor
Medulloblastoma is a highly malignant brain tumor of childhood. Although craniospinal dissemination within the subarachnoid space is common, invasion of the dural sinuses is rare. Here, the authors report on a 15-year-old girl who presented with a right cerebellar mass, obstructive hydrocephalus, and radiographic evidence of tumor invasion into the right transverse–sigmoid sinus junction. The patient underwent posterior fossa craniotomy, gross-total resection of the intraparenchymal component of the right cerebellar tumor, and coagulation of the tumor invading the transverse sinus. After pathological confirmation of anaplastic medulloblastoma, the patient underwent craniospinal radiation therapy and high-dose chemotherapy. At 2 years posttreatment, the child was neurologically intact with no radiographic evidence of residual disease or recurrence. The implications for disease prognosis and management are discussed.