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Garnette R. Sutherland, Martin E. King, S. J. Peerless, William C. Vezina, G. William Brown and Mike J. Chamberlain

✓ Turbulence within intracranial aneurysms may result in tearing of the aneurysmal wall, exposing the subendothelial matrix to circulating platelets. In this study, platelet interaction in giant intracranial aneurysms was evaluated by a dual-isotope technique employing 111In-labeled platelets and 99mTc-labeled red blood cells. The use of two isotopes allows the subtraction of the blood pool and the calculation of the ratio indium deposited:indium blood pool (In(D)/In(BP)). A ratio greater than zero indicates platelet deposition within the aneurysm.

Thirteen patients were evaluated in this way, with platelet deposition demonstrated in six. In these six patients, the ratio In(D)/In(BP) was found to be significantly elevated, with a mean value of 0.96 ± 0.65. Three of these six patients had symptoms of recurrent transient neurological deficits; one of these three suffered a complete stroke following documentation of platelet deposition. In this case, the aneurysm was obtained at surgery and was found to contain intraluminal platelet aggregation when viewed by scanning electron microscopy. In the remaining seven patients, the ratio In(D)/In(BP) was found not to be significantly elevated (mean −0.03 ± 0.06), indicating the absence of active platelet deposition. Two of these patients had prior symptoms of cerebral ischemia; one of these was found to have an ulcer in the ipsilateral internal carotid artery which was probably responsible for thromboembolic events to the hemisphere.

The authors conclude that platelet aggregation occurs more frequently than previously recognized in giant intracranial aneurysms, and their data substantiate the hypothesis that platelet metabolic products or thrombi originating from a large aneurysm may embolize to distal cerebral vessels.

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Garnette R. Sutherland, Martin E. King, Charles G. Drake, Sidney J. Peerless and William C. Vezina

✓ Turbulence within cerebral arteriovenous malformations (AVM's) may lead to endothelial disruption, platelet aggregation, and thrombus formation. This hypothesis would account for many of the pathological features in AVM's, including intimal hyperplasia and arterial thrombosis with or without organization. In this study, a dual-isotope method employing indium-111-labeled platelets and technetium-99m-labeled red blood cells was used to evaluate in vivo platelet aggregation in 20 patients with AVM's. The use of two isotopes allows subtraction of the blood-pool platelets and calculation of the ratio of the indium deposited:the indium in the blood pool (In(D)/In(BP)).

After a 24-hour incubation period, eight of the 20 patients demonstrated platelet aggregation in their AVM's with a mean In(D)/In(BP) ratio of 0.71 ± 0.36 (± standard deviation). Seven of these AVM's were available for pathological study and all of them demonstrated evidence of arterial thrombosis of variable age. In the remaining 12 patients, the In(D)/In(BP) ratio was not significantly elevated (mean 0.02 ± 0.13), indicating the absence of active platelet aggregation during this short interval of study. Five of these AVM's were pathologically examined, four of which showed evidence of arterial occlusion. It is concluded that platelet aggregation is a common occurrence in cerebral AVM's and may account for the dynamic histopathology often seen in these lesions.

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James Peeling, Garnette Sutherland, Kirk Marat, Edward Tomchuk and Ernst Bock

✓ Plasma from patients with malignant and benign primary intracranial neoplasms and from healthy control subjects has been examined using proton (1H) and carbon-13 nuclear magnetic resonance (NMR) spectroscopy. Some features in the spectra of plasma from patients with malignant tumors differ significantly (p < 0.01) from the corresponding features in the spectra of plasma from control subjects and from patients with benign tumors. The NMR spectral parameters vary consistently with the Kernohan grade of astrocytoma, which may suggest that they give a measure of tumor growth kinetics. The observed spectral differences are shown to be due to elevated levels of monounsaturated and polyunsaturated fatty acid residues in the plasma of cancer patients. It is proposed that these lipid residues arise from cell membranes shed from cells in growing tumors. The ability to follow tumor growth kinetics directly may be of considerable importance in elucidating the effects of primary intracranial neoplasm therapy.

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Kesava K. V. Reddy, Marc R. Del Bigio and Garnette R. Sutherland

✓ Although posttraumatic syringomyelia is a well-established clinicopathological entity, there is a paucity of information on the ultrastructural features of this condition. This study documents the light and electron microscopic features of posttraumatic syringes obtained from two patients who underwent surgical cordectomy. The syringes were lined largely by cell processes of astrocytes. Small regions near the caudal end were lined by flattened ependymal cells that lacked surface specializations. These were thought to represent remnants of the central canal ependyma. The ultrastructural appearance of the syrinx was similar to that of the communicating syringomyelia as well as the periventricular changes that accompany hydrocephalus. The authors conclude that the changes represent the nonspecific sequelae of a distensile force within the syrinx cavity.

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Martin Rohringer, Garnette R. Sutherland, Deon F. Louw and Anders A. F. Sima

✓ The incidence of intracranial meningioma in Manitoba, Canada, was reviewed from 1980 through 1987. During that time, 193 tumors were diagnosed, with a male:female ratio of 1:2. This occurrence corresponded to crude incidence rates of 2.3/100,000 for all meningiomas and 0.17/100,000 for malignant meningiomas. Among malignant meningiomas, the male:female ratio was 1:1. The age-specific annual incidence rate increased with age up to the eighth decade where it peaked at 8.4/100,000. The distribution of histopathological subtypes was: 74 meningotheliomatous (38%), 64 transitional (33%), 14 malignant (7%), 14 fibroblastic (7%), seven psammomatous (4%), four angioblastic (2%), and 16 unknown (8%). The diagnosis of malignant meningioma was based on the World Health Organization criteria, with only Grade III and IV tumors included in this subtype. Clinical features did not allow for differentiation of benign from malignant neoplasms. Individuals with malignant tumors were, however, more likely to suffer paresis (50%) and less likely to be without deficit (14%) than their benign counterparts. The radiographic appearance of “mushrooming” was observed only in patients with malignant meningioma. All malignant tumors showed evidence of peritumoral edema; however, none exhibited calcification. During the 8-year study interval, the tumor recurred in 10 (71%) of the 14 patients with malignant meningioma. Tumor recurrence was accompanied by dedifferentiation from a more benign histology in four patients (2% of the total material).

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Deon Louw, Garnette Sutherland, William Halliday and John Kaufmann

✓ A brain tumor with histological features reminiscent of schwannoma with underlying meningioangiomatosis was subjected to electron microscopic and immunohistochemical analysis, which confirmed the neoplasm as a meningioma. This prompted reexamination of a similar tumor, described in a previous publication as a cerebral schwannoma, with identical immunohistochemical techniques. The results obtained favored alteration of this diagnosis to that of meningioma. This experience has led the authors to recommend the use of immunohistochemistry techniques when evaluating unusual intracranial neoplasms.

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Taro Kaibara, Garnette R. Sutherland, Fred Colbourne and Randy L. Tyson

Object. Hypothermia is used in neurosurgery and other surgical disciplines to reduce tissue injury, but the mechanism of such protection remains elusive. The authors have endeavored to delineate the mechanism of neural protection afforded by hypothermia through a study of glucose metabolism.

Methods. Nuclear magnetic resonance spectroscopy was used to follow the carbon-13 label from [1-13C]glucose as it was metabolized through the glycolytic and tricarboxylic acid pathways. Male Sprague—Dawley rats were maintained at either 37.5°C or 31°C and infused with labeled glucose for 10, 30, 60, 100, or 200 minutes (five rats were used for each time point and for each temperature). At the end of the infusion period, the rats' brains were subjected to rapid freeze-funnel fixation. Water-soluble metabolites were extracted from samples of the neocortex and hippocampus by using perchloric acid extraction. The fractional enrichment of these metabolites was used to calculate the reaction rate constant of formation and steady-state enrichment for a number of metabolites.

Hypothermia resulted in a 30 to 40% depression of metabolism (p < 0.0001) in both the neocortex and hippocampus. Steady-state fractional enrichment of metabolites was also decreased by 20 to 25% with hypothermia (p < 0.0001), implying a loss of label during metabolism.

Conclusions. The results of this study suggest that an increased fraction of glucose metabolism was shunted through the pentose phosphate pathway in the presence of hypothermia.

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Garnette R. Sutherland, Taro Kaibara, Deon Louw and John Saunders

The authors' goal was to place a mobile, 1.5 tesla magnetic resonance (MR) imaging system into a neurosurgical operating room without adversely affecting established neurosurgical management. The system would help to plan accurate surgical corridors, confirm the accomplishment of operative objectives, and detect acute complications such as hemorrhage or ischemia.

The authors used an actively shielded 1.5 tesla magnet, together with 15 m tesla/m gradients, MR console computers, gradient amplifiers, a titanium, hydraulic-controlled operating table, and a radio frequency coil that can be disassembled. The magnet is moved to and from the surgical field by using overhead crane technology. To date, the system has provided unfettered access to 46 neurosurgical patients.

In all patients, high-definition T1- and/or T2-weighted images were rapidly and reproducibly acquired at various stages of the surgical procedures. Eleven patients underwent craniotomy that was optimized after pre-incisional imaging. In four patients who harbored subtotally resected tumor, intraoperative MR imaging allowed removal of remaining tumor. Interestingly, the intraoperative administration of gadolinium in the management of patients with malignant glioma demonstrated a dynamic expansion of enhancement beyond the preoperative contrast contour. These zones of new enhancement proved, on examination of biopsy sample, to be tumor.

The authors have demonstrated that high-quality MR images can be obtained within reasonable time constraints in the operating room. Procedures can be conducted without compromising or altering traditional neurosurgical, nursing, or anesthetic techniques. It is feasible that within the next decade intraoperative MR imaging may become the standard of care in neurosurgery.

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Garnette R. Sutherland, Taro Kaibara, Deon Louw, David I. Hoult, Boguslaw Tomanek and John Saunders

Object. The authors' goal was to place a mobile, 1.5-tesla magnetic resonance (MR) imaging system into a neurosurgical operating room without adversely affecting established neurosurgical management. The system would help to plan accurate surgical corridors, confirm the accomplishment of operative objectives, and detect acute complications such as hemorrhage or ischemia.

Methods. The authors used an actively shielded 1.5-tesla magnet, together with 15 mtesla/m gradients, MR console computers, gradient amplifiers, a titanium, hydraulic-controlled operating table, and a radiofrequency coil that can be disassembled. The magnet is moved to and from the surgical field by using overhead crane technology. To date, the system has provided unfettered access in 46 neurosurgical patients.

In all patients, high-definition T1- and/or T2-weighted images were rapidly and reproducibly acquired at various stages of the surgical procedures. Eleven patients underwent craniotomy that was optimized after preincision imaging. In four patients who harbored subtotally resected tumor, intraoperative MR imaging aided the surgeon in removing the remaining tumor. Interestingly, the intraoperative administration of gadolinium demonstrated a dynamic expansion of enhancement beyond the preoperative contrast contour in patients with malignant glioma. These zones of new enhancement proved, on examination of biopsy samples, to be tumor.

Conclusions. The authors have demonstrated that high-quality MR images can be obtained in the operating room within reasonable time constraints. Procedures can be conducted without compromising or altering traditional neurosurgical, nursing, or anesthetic techniques. It is feasible that within the next decade intraoperative MR imaging may become the standard of care in neurosurgery.

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Aaron S. Dumont, Fina Lovren, John H. McNeill, Garnette R. Sutherland, Christopher R. Triggle, Todd J. Anderson and Subodh Verma

Object. Cerebral revascularization with saphenous vein (SV) conduits is used in the management of hard-to-treat lesions that require deliberate arterial occlusion and in selected patients with occlusive vascular disease. Endothelial dysfunction is thought to contribute to acute perioperative vasospasm and chronic graft atherosclerosis. In the present study the authors examined the contribution of the potent vasoconstrictor endothelin-1 (ET-1) to endothelial dysfunction in human SVs.

Methods. The effects of an ETA/B receptor antagonist (bosentan), an ETA receptor antagonist (BQ-123), and an ETB receptor antagonist (BQ-788) on in vitro endothelium-dependent and -independent responses were studied in human SVs. Vascular segments were obtained in 34 patients who had undergone revascularization procedures, and isometric dose—response curves (DRCs) were constructed using the isolated tissue bath procedure as follows: 1) cumulative DRCs to norepinephrine; and 2) DRCs to acetylcholine (ACh) and sodium nitroprusside in the absence and presence of bosentan, BQ-123, or BQ-788. Maximal vasodilatory responses and sensitivity were compared between groups. In the presence of bosentan (Experiment 1) and BQ-123 or BQ-788 (Experiment 2), ACh responses were significantly augmented (percent maximum relaxation values: 7 ± 2 [control] compared with 17 ± 3 [bosentan], p < 0.002 [Experiment 1]; and 12 ± 2 [control] compared with 29 ± 2 [BQ-123] and 25 ± 2 [BQ-788], p < 0.003 and p < 0.002, respectively [Experiment 2]). The sensitivity of SVs to ACh was unaffected by treatment. These beneficial effects were specific for the endothelium.

Conclusions. Blockade of ET receptors significantly improves endothelial function in SVs. Furthermore, these effects appear to be independently and maximally mediated by antagonism of either ETA or ETB receptors. Interventions aimed at improving endothelial function may serve to counter perioperative vasospasm and impede atherosclerosis in SVs used for revascularization procedures.