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Kost Elisevich and Gary Redekop

✓ A distinct vasomotor and cardioregulatory response first identified experimentally was elicited intraoperatively in a 6-year-old girl by local mechanical stimulation in the vicinity of the fastigial nucleus of the cerebellum. These findings are discussed in the light of current experimental knowledge of the anatomy and physiology of the fastigial pressor response.

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Gary Redekop, Thomas Marotta, and Alain Weill

Object. The authors describe their preliminary clinical experience with the use of endovascular stents in the treatment of traumatic vascular lesions of the skull base region. Because adequate distal exposure and direct surgical repair of these lesions are not often possible, conventional treatment has been deliberate arterial occlusion. The purpose of this report is to demonstrate the safety and efficacy as well as limitations of endovascular stent placement in the management of craniocervical arterial injuries.

Methods. Six patients with vascular injuries were treated using endovascular stents. There were two arteriovenous fistulas and two pseudoaneurysms of the distal extracranial internal carotid or vertebral arteries resulting from penetrating trauma, and two petrous carotid pseudoaneurysms associated with basal skull fractures. In one patient a porous stent placement procedure was undertaken as well as coil occlusion of an aneurysm, whereas in the remaining five patients covered stent grafts were used as definitive treatment.

There were no procedural complications. One patient in whom there was extensive traumatic arterial dissection was found to have asymptomatic stent thrombosis when angiography was repeated 1 week postoperatively. This was the only patient whose associated injuries precluded routine antithrombotic or antiplatelet therapy. Follow-up examinations in the remaining five patients included standard angiography (four patients) or computerized tomography angiography (one patient), which were performed 3 to 6 months postoperatively, and clinical assessments ranging from 3 months to 1 year in duration (mean 9 months). In all five cases the vascular injury was successfully treated and the parent artery remained widely patent. No patient experienced aneurysm recurrence or hemorrhage, and there were no thromboembolic complications.

Conclusions. The authors' experience demonstrates that endovascular treatment of traumatic vascular lesions of the skull base region is both feasible and safe. The advantages of minimally invasive stent placement and parent artery preservation make this procedure for repair of neurovascular injuries a potentially important addition to existing methods.

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Gary J. Redekop and Christian C. G. Naus

✓ Aberrant autocrine control by peptide growth factors is a possible mechanism by which disordered regulation of cell proliferation may occur. The authors used the C6 glioma cell line as a model to study the role of basic fibroblast growth factor (bFGF) in tumor growth by transfection with bFGF complementary deoxyribonucleic acid in both the sense and antisense orientation. Clones with high messenger ribonucleic acid expression of the sense construct have increased proliferation in cell culture and increased levels of intracellular and extracellular bFGF. Clones with high expression of the antisense construct show decreased proliferation in culture and reduced levels of immunologically detectable bFGF.

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Gary Redekop, Kost Elisevich, and Joseph Gilbert

✓ A schwannoma arising from the dorsum of the pontomedullary junction and presenting as an exophytic mass in the fourth ventricle is described. A ventricular schwannoma has not previously been reported in the literature. The presenting clinical and radiographic features and the pathology of this tumor are summarized, and an explanation is sought for its unusual location.

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Gary Redekop, Karel TerBrugge, Walter Montanera, and Robert Willinsky

Object. The goal of this study was to develop a classification system for aneurysms associated with arteriovenous malformations (AVMs) based on their anatomical and pathophysiological relationships and to determine the incidence and bleeding rates for these aneurysms as well as the effects of AVM treatment on their natural history.

Methods. Of 632 patients with AVMs, intranidal aneurysms were found in 35 (5.5%) and flow-related aneurysms in 71 (11.2%). Patients with intranidal aneurysms presented more frequently with hemorrhage (72% compared with 40%, p < 0.001) and had a 9.8% per year risk rate of bleeding during follow-up review. Twelve (17%) of the patients with flow-related aneurysms associated with an AVM presented with hemorrhage from an aneurysm, whereas 15 (21%) bled from their AVM. Seventeen patients underwent angiography after AVM treatment (mean 2.25 years). Of 23 proximal aneurysms, 18 (78.3%) were unchanged, four (17.4%) were smaller, and one (4.3%) had disappeared, whereas four (80%) of five distal aneurysms regressed completely and one was unchanged. Sixteen patients underwent angiography after partial AVM treatment (mean 3.8 years). In cases with less than a 50% reduction in the AVM, no aneurysms regressed, although two enlarged and bled. In cases with greater than a 50% reduction in the AVM, two of three distal aneurysms disappeared and five proximal aneurysms were unchanged.

Conclusions. Arterial aneurysms associated with cerebral AVMs may be classified as intranidal, flow-related, or unrelated to the AVM nidus. Intranidal aneurysms have a high correlation with hemorrhagic clinical presentation and a risk of bleeding during the follow-up period that considerably exceeds that which would be expected in their absence. Patients with flow-related aneurysms in association with an AVM may present with hemorrhage from either lesion. Aneurysms that arise on distal feeding arteries near the nidus have a high probability of regressing with substantial or curative AVM therapy.

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Gary J. Redekop, Felix A. Durity, and W. Barrie Woodhurst

✓ A series of 49 consecutively treated patients with 52 aneurysms of the upper basilar artery (BA) is presented. Thirtynine aneurysms arose at the BA bifurcation, 11 at the origin of the superior cerebellar artery (SCA), and two from the upper BA trunk just below the SCA. The patient population consisted of 36 women and 13 men, with a mean age of 50 years (range 23–74 years). Of the 35 patients presenting with subarachnoid hemorrhage, 10 were Grade I, 10 were Grade II, 11 were Grade III, and four were Grade IV according to the Hunt and Hess scale. Treatment consisted of aneurysm neck clipping in 28, proximal occlusion of the BA in three, and endovascular therapy with coils in four patients. The remaining 14 patients with unruptured aneurysms underwent direct neck clipping. Postoperatively, 38 patients developed diplopia in at least one direction of gaze but this had resolved in 31 of them at the last follow-up evaluation. There were four deaths (8.2%): two as a result of rebleeding following coil compaction at 8 days and 9 months posttreatment, respectively; one as a result of vasospasm; and one as a result of brainstem infarction after proximal occlusion of the BA in a giant bifurcation aneurysm. Of the surviving patients, 33 (67.3%) made an excellent recovery, seven (14.3%) made a good recovery, and five (10.2%) were in poor condition at the last follow-up review. Direct microsurgical clipping of most aneurysms of the BA apex region can be performed with acceptable rates of morbidity. These data from an unselected series of patients in a general hospital provide a basis for comparison with developing alternative techniques.

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Charlotte Dandurand, Lily Zhou, Swetha Prakash, Gary Redekop, Peter Gooderham, and Charles S. Haw

OBJECTIVE

The main goal of preventive treatment of unruptured intracranial aneurysms (UIAs) is to avoid the morbidity and mortality associated with aneurysmal subarachnoid hemorrhage. A comparison between the conservative approach and the surgical approach combining endovascular treatment and microsurgical clipping is currently lacking. This study aimed to conduct an updated evaluation of cost-effectiveness comparing the two approaches in patients with UIA.

METHODS

A decision tree with a Markov model was developed. Quality-adjusted life-years (QALYs) associated with living with UIA before and after treatment were prospectively collected from a cohort of patients with UIA at a tertiary center. Other inputs were obtained from published literature. Using Monte Carlo simulation for patients aged 55, 65, and 75 years, the authors modeled the conservative management in comparison with preventive treatment. Different proportions of endovascular and microsurgical treatment were modeled to reflect existing practice variations between treatment centers. Outcomes were assessed in terms of QALYs. Sensitivity analyses to assess the model’s robustness and completed threshold analyses to examine the influence of input parameters were performed.

RESULTS

Preventive treatment of UIAs consistently led to higher utility. Models using a higher proportion of endovascular therapy were more cost-effective. Models with older cohorts were less cost-effective than those with younger cohorts. Treatment was cost-effective (willingness to pay < 100,000 USD/QALY) if the annual rupture risk exceeded a threshold between 0.8% and 1.9% in various models based on the proportion of endovascular treatment and cohort age. A higher proportion of endovascular treatments and younger age lowered this threshold, making the treatment of aneurysms with a lower risk of rupture more cost-effective.

CONCLUSIONS

Preventive treatment of aneurysms led to higher utility compared with conservative management. Models with a higher proportion of endovascular treatment and younger patient age were most cost-effective.

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William W. G. Jia, Jiren Tan, Gary J. Redekop, and James H. Goldie

✓ Previous studies have shown that genetically engineered thymidine kinase (tk)—defective herpes simplex virus type 1 (HSV-1) can effectively and selectively destroy gliomas in animal models. The consequences of viral infection and tumor regression must be characterized before this therapy can be applied in human trials. To study the potential for long-term toxicity, immunocompetent rats harboring 9L gliosarcomas were injected intratumorally with a tk—defective HSV-1, KOS-SB, at titers that previously have been demonstrated to cause tumor regression. In animals surviving 3 months or longer following viral treatment, there was no evidence of persistent infection or inflammation in peritumoral brain tissue or in remote systemic organs studied with routine histological and immunocytochemical analyses. Polymerase chain reaction using primers specific for HSV-1 detected HSV-1 DNA in peritumoral tissue only in animals sacrificed within 3 months of viral injection. There was no evidence of HSV-1 DNA in systemic tissues at any time after treatment. We conclude that stereotactic intratumoral injection of tk—deficient HSV can be attempted for the treatment of brain tumors without risk of systemic infection or significant toxicity to normal brain or remote proliferating tissues.

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Gary J. Redekop, Kost V. Elisevich, Laurie E. Gaspar, Karen P. Wiese, and Charles G. Drake

✓ Conventional radiation therapy has been used in the treatment of arteriovenous malformations (AVM's) for many years, but there are limited data pertaining to specific treatment parameters, long-term results, and complications. Between 1955 and 1985, 15 patients with AVM's deemed inoperable or incompletely obliterated using surgical or endovascular techniques were treated at the University of Western Ontario. There were nine males and six females, aged 15 to 48 years (mean 29 years). Presenting symptoms included hemorrhage in nine patients, seizures in four, and focal neurological deficits in two. There were three infratentorial and 12 supratentorial AVM's, ranging in size from 1.5 to 6.5 cm. Therapy prior to irradiation consisted of incomplete surgical removal in four cases and subtotal embolization in four. One patient received 2000 cGy of irradiation, while 4000 to 5000 cGy were delivered in the remaining patients to fields ranging in size from 4 × 4 to 14 × 14 cm in 15 to 28 fractions. The 15 patients have been followed for 1½ to 21 years since undergoing radiotherapy (mean 8.1 years). Angiography in 12 patients at 1 to 21 years following irradiation demonstrated no significant change in seven patients, a slight reduction in AVM size in two, near-complete obliteration in one, and complete obliteration in two. One patient with an AVM measuring 6.5 cm refused angiography but underwent magnetic resonance imaging at 5 years which showed no evidence of residual AVM. There were four hemorrhages in 122 patient-years of follow-up study, indicating a hemorrhage rate of 3.3% per year. The authors conclude that conventional irradiation is successful in obliterating AVM's in only about 20% of cases.