Systemic administration of the iron chelator deferiprone attenuates subarachnoid hemorrhage-induced cerebral vasospasm in the rabbit.

OBJECTIVE: Iron catalyzed generation of injurious free radicals has been implicated in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). The present study assessed the effects of the iron chelator deferiprone on cerebral vasospasm in an in vivo rabbit model of SAH. METHODS: Twenty-four rabbits were assigned to three groups as follows: SAH plus placebo (n = 8), SAH plus deferiprone (n = 8), or control plus placebo (n = 8). Deferiprone was administered to an additional group of three rabbits that were not subjected to SAH. Drug administration was initiated 8 hours after SAH was induced and was repeated at 8-hour intervals. The animals were killed using perfusion-fixation 48 hours after SAH. Cross-sectional areas of basilar artery histological sections were measured by an investigator blinded to the treatment groups. RESULTS: In placebo-treated animals, the average luminal cross-sectional area of the basilar artery was reduced by 54% after SAH compared to controls (i.e., from 0.272 to 0.125 mm2). The vasospastic response after SAH was attenuated significantly in animals treated with deferiprone (0.208 mm2, representing a 24% reduction). CONCLUSION: Previous experimental studies suggested that iron chelation can be effective in attenuating cerebral vasospasm after SAH. Deferiprone is a recently developed iron chelator that has been extensively evaluated for the treatment of patients requiring chronic blood transfusions. The present study demonstrates that deferiprone is effective in attenuating experimental cerebral vasospasm. Because of its stability, lipophilicity, and ability to penetrate the blood-brain barrier, deferiprone represents an attractive candidate for the treatment of cerebral vasospasm.

Long-term outcome after surgical excision of parenchymal arteriovenous malformations in patients over 60 years of age.

BACKGROUND: Age is considered an important limiting factor for surgical excision of parenchymal arteriovenous malformations (AVMs) and a more conservative therapeutic approach has been advocated in the elderly. There are no studies available investigating the long-term outcome after surgical excision of parenchymal AVMs in patients over 60 years of age. METHODS: We report the surgical outcome after excision of an AVM in a series of 13 consecutive patients older than 60 years. Medical records were analyzed retrospectively. RESULTS: Hemorrhage was the mode of presentation in all patients. Three patients were admitted in a comatose state. Surgery was performed within 1 week from the initial bleeding in seven cases and within 2 weeks in five cases. There were no deaths directly related to surgery in this series. However, one patient died as a result of an intracranial hemorrhage complicating preoperative embolization and another patient died 3 months after surgery from intervening medical complications. During the follow-up period (mean 46 months), three more patients had died 8, 19, and 48 months after surgery, respectively. Of the remaining eight patients, six are doing well and are independent in the activities of daily living. One patient is independent but requires supervision, and the remaining one was lost to follow-up. CONCLUSIONS: Age alone should no longer be considered a contraindication to treatment. In selected cases, surgery can be performed safely even in the elderly patient with an AVM. After surgical excision, elderly patients have the potential for several years of active life.

Molecular methods of enhancing lumbar spine fusion.

OBJECTIVE: An optimal method for spinal fusion would induce rapid growth of bone via an osteoconductive and osteoinductive implant. This study examines the spinal fusion enhancement potential of some osteoconductive and osteoinductive biomaterials. METHODS: Four similar canines received unilateral posterolateral fusions on the left side at T13-L1 and L4-L5 and on the right side at L2-L3 and L6-L7. The experiments were grouped as follows: Group A, autogenous bone harvested from the iliac crest; Group B, autogenous bone and collagen; Group C, no implant; and Group D, autogenous bone, collagen, and recombinant human bone morphogenetic protein-2. Radiographic assessment, three-dimensional computed tomographic volumetric analysis, and biomechanical testing were performed at each level. RESULTS: For Groups A and B, the fusions demonstrated moderate bone formation at 6 and 12 weeks postoperatively. Group D fusions exhibited earlier and more dramatic increases in volume and radiodensity and eventually were comparable in size to the vertebral bodies. Average fusion volumes computed from three-dimensional computed tomographic analysis were: Group A = 1.243 cc, Group B = 0.900 cc, Group C = 0.000 cc, and Group D = 6.668 cc (P = 0.003 compared to Group A). Group D exhibited flexion and extension biomechanical properties much greater than controls. The addition of recombinant human bone morphogenetic protein-2 consistently yielded the strongest fused segments and, on average, enhanced extension stiffness by 626% and flexion stiffness by 1120% over controls. CONCLUSION: The most advantageous spinal fusion implant matrix consisted of recombinant human bone morphogenetic protein-2, autogenous bone, and collagen. Future investigators, however, need to examine the appropriate quantities of the individual components and clarify the efficacy of the matrix for the various types of spinal fusion approaches.