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Michael R. Chicoine and Daniel L. Silbergeld

✓ Brain tumor dispersal far from bulk tumor contributes to and, in some instances, dominates disease progression. Three methods were used to characterize brain tumor cell motility in vivo and in vitro: 1) 2 weeks after implantation in rat cerebral cortex, single C6 cells labeled with a fluorescent tag had migrated to brain sites greater than 16 mm distant from bulk tumor; 2) time-lapse videomicroscopy of human brain tumor cells revealed motility of 12.5 µm/hr. Ruffling leading edges and pseudopod formation were most elaborate in more malignant cells; 3) an in vitro assay was devised to quantitatively evaluate motility from a region of high cell density to one of lower cell density.

Human brain tumor cells were plated in the center of a petri dish, washed, and refed, establishing a 2-cm circular zone of cells in the dish center. Motility was determined by counting cells daily at predetermined distances from the central zone perimeter. Cells were found 1 cm from the perimeter by 24 hours and 3 cm from the perimeter by 4 days. Increasing serum concentration increased motility; however, neither fibronectin nor arrest of cells in the G0 phase by hydroxyurea altered motility. The addition of cytochalasin B to block cytoskeletal assembly prevented cell motility. Motility increased with increased malignancy. Subpopulations of cells were created by clonal amplification of cells that had migrated most rapidly to the dish periphery. Although morphologically indistinguishable when compared to the original cell line from which they were derived, these subpopulations demonstrated significantly increased motility.

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Michael R. Chicoine and Daniel L. Silbergeld

✓ To characterize rat glioma cell invasion, 2 × 106 fluorophore-labeled or transfection-labeled C6 rat glioma cells were implanted in the rat frontal lobe. Eighty percent of the rats implanted formed bulk tumors (3–4 mm in diameter). Two weeks after implantation, fluorescence microscopy revealed single tumor cells in sites over 16 mm from the bulk brain tumor. Tumor cells distant from the bulk tumor remained single without mass formation and invaded primarily along white matter tracts. Two weeks after tumor implantation, three cell lines were created from each brain by disaggregation and initiation in culture of 1) bulk tumor, 2) contralateral hemisphere, and 3) cerebellum; all disaggregated specimens generated viable cultures. Cells cultured from the contralateral hemisphere were morphologically indistinguishable from cells from the bulk tumor and from the original C6 cell line. Cells cultured from the cerebellum were morphologically quite distinct from the C6 cell line. Cells from disaggregated specimens obtained from the tumor, contralateral hemisphere, and cerebellum were implanted in the frontal lobe of naive rats to test tumorgenicity. Bulk tumor formed in 58% of the rats implanted with specimens from tumor, in 75% of the rats implanted with specimens from contralateral hemisphere, and in only 12.5% of the rats implanted with specimens from the cerebellar hemispheres. Experiments using C6 cells labeled by transfection with the p3′ss DNA vector prior to implantation confirmed that the cells cultured from the contralateral hemisphere were derived from the implanted C6 cells. Experiments with C6 cells anchored in agar served to verify that movement to the contralateral hemisphere was secondary to parenchymal invasion rather than dispersion in the cerebrospinal fluid.

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Daniel L. Silbergeld and Michael R. Chicoine

✓ Brain invasion prevents complete surgical extirpation of malignant gliomas; however, invasive cells from distant, histologically normal brain previously have not been isolated, cultured, and characterized. To evaluate invasive human malignant glioma cells, the authors established cultures from gross tumor and histologically normal brain. Three men and one woman, with a mean age of 67 years, underwent two frontal and two temporal lobectomies for tumors, which yielded specimens of both gross tumor and histologically normal brain. Each specimen was acquired a minimum of 4 cm from the gross tumor. The specimens were split: a portion was sent for neuropathological evaluation (three glioblastomas multiforme and one oligodendroglioma) and a portion was used to establish cell lines. Morphologically, the specimens of gross tumor and histologically normal brain were identical in three of the four cell culture pairs. Histochemical staining characteristics were consistent both within each pair and when compared with the specimens sent for neuropathological evaluation. Cultures demonstrated anchorage-independent growth in soft agarose and neoplastic karyotypes. Growth rates in culture were greater for histologically normal brain than for gross tumor in three of the four culture pairs. Although the observed increases in growth rates of histologically normal brain cultures do not correlate with in vivo behavior, these findings corroborate the previously reported stem cell potential of invasive glioma cells. Using the radial dish assay, no significant differences in motility between cultures of gross tumor and histologically normal brain were found.

In summary, tumor cells were cultured from histologically normal brain acquired from a distance greater than 4 cm from the gross tumor, indicating the relative insensitivity of standard histopathological identification of invasive glioma cells (and hence the inadequacy of frozen-section evaluation of resection margins). Cell lines derived from gross tumor and histologically normal brain were usually histologically identical and demonstrated equivalent motility, but had different growth rates.

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Michael R. Chicoine, T. S. Park and Bruce A. Kaufman

✓ If the spasticity of cerebral palsy (CP) is reduced in children at a young age by selective dorsal rhizotomy, the incidence of lower-extremity deformities requiring orthopedic surgery may be reduced; however, this has never been investigated in detail. The authors examined the effects of selective dorsal rhizotomy on rates of lower-extremity orthopedic surgery in 178 children with CP. Age at selective dorsal rhizotomy ranged from 2 to 19.3 years (mean 5.5 years) with follow-up intervals ranging from 24 to 70 months (mean 44 months). Spastic CP was classified as quadriplegia (33%), diplegia (65%), and hemiplegia (2%). To assess the effects of early versus late rhizotomy on rates of orthopedic surgery, patients were grouped as follows: Group I underwent rhizotomy between 2 and 4 years of age (54 patients), and Group II underwent rhizotomy between 5 and 19 years of age (124 patients). Comparison of Kaplan—Meier plots of lifetime orthopedic surgery rates revealed that Group II underwent orthopedic surgery at a higher rate than Group I (p = 0.037). Analysis by procedure type revealed higher orthopedic surgery rates in Group II than Group I for heel cord releases (p = 0.0025), adductor releases (p = 0.018), and hamstring releases (p = 0.02). Orthopedic surgery rates were no higher for Group II compared to Group I for ankle/foot operations (p = 0.023), femoral osteotomy (p = 0.25), iliopsoas releases (p = 0.35), and “other” operations (p = 0.013). The data indicate that early rhizotomy reduces the need for orthopedic surgery for heel cord, hamstring, and adductor releases.

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William W. Ashley Jr. and Michael R. Chicoine

✓ Various anatomical courses of the vertebral artery (VA) and posterior inferior cerebellar artery (PICA) have been described. The authors present a unique case of a subarachnoid hemorrhage resulting from an aneurysm in a patient with an anatomical variation of the extracranial portion of the VA and cervical origin of the PICA. The surgical implications of this variant are discussed, and the pertinent literature reviewed. Subarachnoid hemorrhage caused by rupture of a PICA aneurysm is reported for the first time in association with a rare variation of the course of the VA.

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Sam Q. Sun, Ammar H. Hawasli, Jiayi Huang, Michael R. Chicoine and Albert H. Kim

The management of WHO Grade II “atypical” meningiomas (AMs) and Grade III “malignant” meningiomas (MMs) remains controversial and under-investigated in prospective studies. The roles of surgery, radiation therapy, radiosurgery, and chemotherapy have been incompletely delineated. This has left physicians to decipher how they should treat patients on a case-by-case basis. In this study, the authors review the English-language literature on the management and clinical outcomes associated with AMs and MMs diagnosed using the WHO 2000/2007 grading criteria. Twenty-two studies for AMs and 7 studies for MMs were examined in detail. The authors examined clinical decision points using the literature and concepts from evidence-based medicine. Acknowledging the retrospective nature of the studies concerning AM and MM, the authors did find evidence for the following clinical strategies: 1) maximal safe resection of AM and MM; 2) active surveillance after gross-total resection of AM; 3) adjuvant radiation therapy after subtotal resection of AM, especially in the absence of putative radioresistant features; and 4) adjuvant radiation therapy after resection of MM.

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Amar S. Shah, Alexander T. Yahanda, Umeshkumar Athiraman, Rene Tempelhoff and Michael R. Chicoine

Paraplegia after posterior fossa surgery is a rare and devastating complication. The authors reviewed a case of paraplegia following Chiari decompression and surveyed the literature to identify strategies to reduce the occurrence of such events.

An obese 44-year-old woman had progressive left arm pain, weakness, and numbness and tussive headaches. MRI studies revealed a Chiari I malformation and a cervicothoracic syrinx. Immediately postoperatively after Chiari decompression the patient was paraplegic, with a T6 sensory level bilaterally. MRI studies revealed equivocal findings of epidural hematoma at the site of the Chiari decompression and in the upper thoracic region. Surgical exploration of the Chiari decompression site and upper thoracic laminectomies identified possible venous engorgement, but no hematoma. Subsequent imaging suggested a thoracic spinal cord infarction. Possible explanations for the spinal cord deficit included spinal cord ischemia related to venous engorgement from prolonged prone positioning in an obese patient in the chin-tucked position. At 6.5 years after surgery the patient had unchanged fixed motor and sensory deficits.

Spinal cord infarction is rare after Chiari decompression, but the risk for this complication may be increased for obese patients positioned prone for extended periods of time. Standard precautions may be insufficient and intraoperative electrophysiological monitoring may need to be considered in these patients.

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Ralph G. Dacey Jr., Gregory J. Zipfel, William W. Ashley, Michael R. Chicoine and Michael Reinert

The authors describe the use of the Cardica C-Port xA Distal Anastomosis System to perform an automated, high-flow extracranial–intracranial bypass. The C-Port system has been developed and tested in coronary artery bypass surgery for rapid distal coronary artery anastomoses. Air-powered, it performs an automated end-to-side anastomosis within seconds by nearly simultaneously making an arteriotomy and inserting 13 microclips into the graft and recipient vessel. Intracranial use of the device was first simulated in a cadaver prepared for microsurgical anatomical dissection.

The authors used this system in a 43-year-old man who sustained a subarachnoid hemorrhage after being assaulted and was found to have a traumatic pseudoaneurysm of the proximal intracranial internal carotid artery. The aneurysm appeared to be enlarging on serial imaging studies and it was anticipated that a bypass would probably be needed to treat the lesion. An end-to-side bypass was performed with the C-Port system using a saphenous vein conduit extending from the common carotid artery to the middle cerebral artery. The bypass was demonstrated to be patent on intraoperative and postoperative arteriography. The patient had a temporary hyperperfusion syndrome and subsequently made a good neurological recovery.

The C-Port system facilitates the performance of a high-flow extracranial–intracranial bypass with short periods of temporary arterial occlusion. Because of the size and configuration of the device, its use is not feasible in all anatomical situations that require a high-flow bypass; however it is a useful addition to the armamentarium of the neurovascular surgeon.

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Richard A. Chole, Chris Lim, Brian Dunham, Michael R. Chicoine and Ralph G. Dacey Jr.

Over the last several years minimally invasive surgical approaches to the sella turcica and parasellar regions have undergone significant change. The transsphenoidal approach to this region has evolved from a sublabial transnasal, to transnasal, to pure endonasal approaches with the increasing popularity of endoscopic over microscopic techniques. Endoscopic and microscopic techniques individually or in combination have their own unique advantages, and the preference of one over the other awaits further technological refinements and surgical experience.

In parallel with this evolution in techniques for transsphenoidal surgery, the authors designed an adaptable versatile speculum for the endonasal/transnasal transsphenoidal approach to the sella turcica and parasellar regions that can be used equally effectively with a microscope or an endoscope. The development of this instrument and its unique features are described, and its initial clinical use is summarized.

This transnasal transsphenoidal speculum has interchangeable blades, unique blade angulations, and independent blade opening mechanisms and allows safe, optimal exposure in all patients regardless of the size and anatomical aberrations of individual nasal and endonasal regions. An attached endoscope carrier further allows it to be used interchangeably with microscopic or endoscopic techniques without having to remove the speculum; likewise, a single surgeon can use both hands without need of an assistant. A forehead headrest component adds further stabilization. This device has been used successfully in 90 transsphenoidal procedures.