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Peng Roc Chen, Kai Frerichs and Robert Spetzler

After an aneurysmal subarachnoid hemorrhage, nearly half of the patients die and the half who survive suffer from irreversible cerebral damage. With increasing use of noninvasive neuroimaging techniques (for example, magnetic resonance and computerized tomography angiography), more unruptured cerebral aneurysms are found. To understand the prevalence of unruptured aneurysms in the general population, along with the risks of aneurysm formation, data on growth and rupture rates are crucial. The risk of rupture in aneurysms smaller than 10 mm is still not quite clear without a population-based prospective study. Nevertheless, a 0.5 to 2% annual risk may be a reasonable estimate. Growing aneurysms and those larger than 10 mm carry a higher rate of rupture. The management of an unruptured intracranial aneurysm should be based on a thorough understanding of the natural history of these lesions and careful evaluation of the morbidity and mortality levels associated with each treatment option.

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John Mealey Jr., Tsu T. Chen and Robert Shupe

✓Individual and combined effects of ionizing radiation and chemotherapy with 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) on glial tumor cells were assessed in cultures derived from human glioblastomas. Drug and radiation exposures were performed on cell monolayers in 0.02 ml wells of microtest plates. Response to treatment was determined from serial observations on surviving populations in the original wells and comparisons with matched control cultures. Chemosensitivity was more variable than radiosensitivity in cell lines derived from five different glioblastomas: BCNU caused growth inhibition of 4% to 85% in doses of 8 µg/ml for 3 days compared to a 40% to 73% reduction after 400 rads of radiation. These findings were all significant statistically. Single doses above 600 to 800 rads appeared lethal, causing widespread loss of cells or transformation into giant forms that did not multiply. The doseresponse curves after BCNU and radiation treatment of cultured glial tumor cells were exponential, demonstrating that both modalities affected a constant fraction of the exposed cell populations according to dose. The observations on radiosensitivity of human glial tumor cells conformed to the generally known responses of cultured normal and neoplastic mammalian cells to ionizing radiation. BCNU in the higher doses tested acted as a possible radiosensitizing agent to potentiate the lethal effects of radiation since an increased rate of cell loss was demonstrated in glioma cultures exposed to this drug and radiation compared to those treated only by irradiation. These results in a controlled experimental environment support the concept that a combination of BCNU and radiation therapy should increase the time of survival of patients with malignant gliomas.

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Peng Roc Chen, Kai Frerichs and Robert Spetzler

A patient with an unruptured intracranial aneurysm has three options: surgical clip placement, endovascular coil occlusion, and observation. The decision making about management of these lesions should be based on the risk of aneurysm rupture and the risks associated with surgical or endovascular intervention. For patients who require interventions, factors such as aneurysm recurrence rate, its location, surgical or endovascular accessibility, the patient's general medical condition, and the individual's treatment preference should be taken into account to determine the choice of therapies. Currently, a team approach by neurosurgeons and endovascular interventionists is recommended to evaluate each patient and to tailor the best treatment plan.

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Matthew Burry, Adam S. Reig, Elizabeth A. Beierle, Mike K. Chen and Robert A. Mericle

✓ The authors describe a novel approach to the management of high-output heart failure secondary to an intracranial high-flow dural arteriovenous fistula (DAVF) by using extracorporeal membrane oxygenation (ECMO). To the best of the authors' knowledge, this represents the first report of an embolization performed in conjunction with the use of an ECMO circuit and the first report in which an ECMO cannula was used for intraarterial access for cerebral angiography.

A 2-day-old girl presented with severe, high-output heart failure secondary to a high-flow intracranial DAVF. The patient was neurologically intact and no brain parenchymal abnormalities were revealed on computerized tomography scanning of the head, but she suffered severe heart failure, pulmonary hypertension, and liver and renal dysfunction. The patient underwent three endovascular embolization procedures involving coils and liquid embolic agents. Despite a decrease in the DAVF flow, the patient had only transient improvement in her pulmonary hypertension, and venoarterial ECMO therapy was instituted. Another embolization was performed while the patient was receiving ECMO therapy. Her cardiovascular status improved, she was weaned from ECMO, and she was eventually discharged home to her family.

Extracorporeal membrane oxygenation can be used to sustain severely ill neonates with high-output heart failure secondary to intracranial AVFs. Embolization can be performed while the patient is receiving ECMO therapy.

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Gene H. Barnett, Clark C. Chen, Robert E. Gross and Andrew E. Sloan

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Chen Guang Yu, Omar Jimenez, Alexander E. Marcillo, Brian Weider, Kurt Bangerter, W. Dalton Dietrich, Santiago Castro and Robert P. Yezierski

Object. Local spinal cord cooling (LSCC) is associated with beneficial effects when applied following ischemic or traumatic spinal cord injury (SCI). However, the clinical application of LSCC is associated with many technical difficulties such as the requirement of special cooling devices, emergency surgery, and complicated postoperative management. If hypothermia is to be considered for future application in the treatment of SCI, alternative approaches must be developed. The objectives of the present study were to evaluate 1) the relationship between systemic and epidural temperature after SCI; 2) the effects of modest systemic hypothermia on histopathological damage at 7 and 44 days post-SCI; and 3) the effects of modest systemic hypothermia on locomotor outcome at 44 days post-SCI.

Methods. A spinal cord contusion (12.5 mm at T-10) was produced in adult rats that had been randomly divided into two groups. Group 1 rats (seven in Experiment 1; 12 in Experiment 2) received hypothermic treatment (epidural temperature 32–33°C) 30 minutes postinjury for 4 hours; Group 2 rats (nine in Experiment 1; eight in Experiment 2) received normothermic treatment (epidural temperature 37°C) 30 minutes postinjury for 4 hours. Blood pressure, blood gas levels, and temperatures (epidural and rectal) were monitored throughout the 4-hour treatment period. Twice weekly assessment of locomotor function was performed over a 6-week survival period by using the Basso-Beattie-Bresnahan locomotor rating scale. Seven (Experiment 1) and 44 (Experiment 2) days after injury, animals were killed, perfused, and their spinal cords were serially sectioned. The area of tissue damage was quantitatively analyzed from 16 longitudinal sections selected from the central core of the spinal cord.

Conclusions. The results showed that 1) modest changes in the epidural temperature of the spinal cord can be produced using systemic hypothermia; 2) modest systemic hypothermia (32–33°C) significantly protects against locomotor deficits following traumatic SCI; and 3) modest systemic hypothermia (32–33°C) reduces the area of tissue damage at both 7 and 44 days postinjury. Although additional research is needed to study the therapeutic window and long-term benefits of systemic hypothermia, these data support the possible use of modest systemic hypothermia in the treatment of acute SCI.

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Robert Chen, David R. Macdonald and David A. Ramsay

✓ The authors describe a case of a diffuse primary leptomeningeal oligodendroglioma in a 17-year-old girl who presented with raised intracranial pressure and hydrocephalus. She underwent imaging studies and a left frontotemporal craniotomy that revealed a cystic oligodendroglioma in the suprasellar cistern and spread of neoplastic cells to the spinal leptomeninges. The tumor showed little response to maximum radiotherapy and chemotherapy, and the patient died from complications of high-dose chemotherapy 2 years after diagnosis. Postmortem examination of the brain and spinal cord revealed diffuse meningeal infiltration by neoplastic cells and no evidence of an intraparenchymal origin. Glial heterotopias were noted at several sites along the brain base, adding circumstantial support to the theory that leptomeningeal gliomas are derived from ectopic glial tissue in the subarachnoid space.

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Robert C. Rennert, Kate T. Carroll, Mir Amaan Ali, Thomas Hamelin, Leon Chang, Brian P. Lemkuil and Clark C. Chen

OBJECTIVE

Stereotactic laser ablation (SLA) is typically performed in the setting of intraoperative MRI or in a staged manner in which probe insertion is performed in the operating room and thermal ablation takes place in an MRI suite.

METHODS

The authors describe their experience, in which SLA for glioblastoma (GBM) treatment was performed entirely within a conventional MRI suite using the SmartFrame stereotactic device.

RESULTS

All 10 patients with GBM (2 with isocitrate dehydrogenase 1 mutation [mIDH1] and 8 with wild-type IDH1 [wtIDH1]) were followed for > 6 months. One of these patients underwent 2 independent SLAs approximately 12 months apart. Biopsies were performed prior to SLA for all patients. There were no perioperative morbidities, wound infections, or unplanned 30-day readmissions. The average time for a 3-trajectory SLA (n = 3) was 436 ± 102 minutes; for a 2-trajectory SLA (n = 4) was 321 ± 85 minutes; and for a single-trajectory SLA (n = 4) was 254 ± 28 minutes. No tumor recurrence occurred within the blue isotherm line ablation zone, although 2 patients experienced recurrence immediately adjacent to the blue isotherm ablation line. Overall survival for the patient cohort averaged 356 days, with the 2 patients who had mIDH1 GBMs exhibiting the longest survival (811 and 654 days).

CONCLUSIONS

Multitrajectory SLA for treatment of GBM can be safely performed using the SmartFrame stereotactic device in a conventional MRI suite.

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H. Isaac Chen, Mark G. Burnett, Jason T. Huse, Robert A. Lustig, Linda J. Bagley and Eric L. Zager

✓Late cerebral radiation necrosis usually occurs within 3 years of stereotactic radiosurgery. The authors report on a case of recurrent radiation necrosis with rapid clinical deterioration and imaging findings resembling those of a malignant glioma. This 68-year-old man, who had a history of a left posterior temporal and thalamic arteriovenous malformation (AVM) treated with linear accelerator radiosurgery 13 years before presentation and complicated by radiation necrosis 11 years before presentation, exhibited new-onset mixed aphasia, right hemiparesis, and right hemineglect. Imaging studies demonstrated hemorrhage and an enlarging, heterogeneously enhancing mass in the region of the previously treated AVM. The patient was treated medically with corticosteroid agents, and stabilized temporarily. Unfortunately, his condition worsened precipitously soon thereafter, requiring the placement of a shunt for relief of obstructive hydrocephalus. Further surgical intervention was offered, but the patient’s family opted for hospice care instead. The patient died 10 weeks after initially presenting to the authors’ institution, and the results of an autopsy demonstrated radiation necrosis.

Symptomatic radiation necrosis can occur more than a decade after stereotactic radiosurgery, necessitating patient follow up during a longer period of time than currently practiced. Furthermore, there is a need for more careful reporting on the natural history of such cases to clarify the pathogenesis of very late and recurrent radiation necrosis after radiosurgery and to define patient groups with a higher risk for these entities.

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Patrick D. S. Chan, J. Max Findlay, Bozena Vollrath, David A. Cook, Michael Grace, Ming H. Chen and Robert A. Ashforth

✓ Despite growing clinical use of transluminal balloon angioplasty (TBA) to treat cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH), the precise mechanism of action of balloon dilation on the cerebral arterial wall is unknown. In this experiment the authors examined the pharmacological and morphological changes in 10 normal and 12 vasospastic canine basilar arteries following in vitro silicone microballoon TBA. For the SAH group in which the double-hemorrhage model was used, vasospasm was confirmed by angiography and the animals were killed on Day 7 after the first SAH. In vitro TBA was performed on basilar arteries from normal and SAH dogs immediately after sacrifice and removal of the brain. The procedure was performed while the arteries were maintained in oxygenated Krebs buffer. In the pharmacological studies, potassium chloride, prostaglandin F, serotonin, and noradrenaline were used as vasoconstrictors, and bradykinin and calcium ionophore A23187 were used to produce an endothelium-dependent dilation. In both normal and vasospastic groups, the pharmacological responses of dilated segments of basilar arteries were compared to those of nondilated segments of the same arteries.

Vessels from all groups were examined using scanning electron microscopy (EM) and transmission EM. Scanning EM was used to study the intact vessel wall, the smooth-muscle cell layer obtained after digestion with hydrochloric acid, and the extracellular matrix obtained after digestion with bleach. Cross-sections of the vessel wall were examined using transmission EM.

The most striking finding was that immediately after in vitro TBA of both normal and vasospastic canine basilar arteries, there was a significant reduction (p < 0.05) of responses to both vasoconstrictors and vasorelaxants. As revealed by scanning EM and transmission EM, both normal and vasospastic vessels dilated with TBA showed flattening and patchy denudation of the endothelium, and straightening and occasional rupturing of the internal elastic lamina. In addition, vasospastic vessels dilated with TBA showed decreased surface rippling and mild stretching and straightening of smooth-muscle cells, and mild thinning of the tunica media. There was no gross vascular disruption or obvious change in the extracellular matrix of the vessel walls of either normal or vasospastic arteries after TBA. These results suggest that functional impairment of vasoreactivity in the vessel wall as a result of mechanical stretching of the smooth-muscle layer plays a more important role than structural alteration, at least in the immediate dilation produced in vasospastic arteries byTBA.