{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T22:40:55Z","timestamp":1776724855121,"version":"3.51.2"},"reference-count":25,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1991,8]]},"abstract":"<jats:p content-type=\"fine-print\">\u2713 Recent laboratory studies have demonstrated that intracisternal administration of recombinant tissue plasminogen activator (rt-PA) can facilitate the normal clearing of blood from the subarachnoid space and prevent or ameliorate delayed arterial spasm. The results of a preliminary Phase I trial of intracisternal rt-PA in 10 patients are reported with documented aneurysmal subarachnoid hemorrhage (SAH). All patients enrolled were classified as clinical Grade III or IV (according to Hunt and Hess) with thick clots or layers of blood in the basal cisterns and major cerebral fissures (Fisher Grade 3). Ventriculostomy and surgery for clipping of the aneurysms were performed within 48 hours of hemorrhage. In one patient, 10 mg rt-PA was instilled into the subarachnoid cisterns prior to closing the dura. In the remaining nine patients, a small silicone catheter was left in the subarachnoid space and rt-PA (5 mg in four cases or 1.5 mg (0.5 mg every 8 hours for three infusions) in five cases) was instilled 12 to 24 hours after surgery. Minor local bleeding complications were noted in all patients receiving 5 or 10 mg rt-PA. Oozing was noted at the operative incision site in four of five patients and at the ventriculostomy site in two patients. One patient developed a small epidural hematoma that was treated by delayed drainage. No bleeding complications were noted in the patients receiving the lower regimen of rt-PA (three infusions of 0.5 mg each). Serial coagulation studies demonstrated no evidence of systemic fibrinolysis. Analysis of cisternal cerebrospinal fluid samples revealed thrombolytic tissue plasminogen activator (t-PA) levels for 24 to 48 hours. Follow-up cerebral angiography 7 to 8 days after rupture disclosed mild to moderate spasm in nine patients, while one patient with hemorrhage from a posterior inferior cerebellar artery aneurysm had severe focal spasm of the vertebral arteries that was not symptomatic. These results suggest that postoperative treatment with rt-PA may be effective in reducing the severity of delayed cerebral vasospasm. The results of serial t-PA levels suggest that the lower dosage regimen with divided dosages at 8-hour intervals is well tolerated and that even lower dosages may be effective. Further studies are clearly indicated.<\/jats:p>","DOI":"10.3171\/jns.1991.75.2.0189","type":"journal-article","created":{"date-parts":[[2009,5,19]],"date-time":"2009-05-19T16:21:01Z","timestamp":1242750061000},"page":"189-196","source":"Crossref","is-referenced-by-count":119,"title":["Phase I trial of tissue plasminogen activator for the prevention of vasospasm in patients with aneurysmal subarachnoid hemorrhage"],"prefix":"10.3171","volume":"75","author":[{"given":"Joseph M.","family":"Zabramski","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert F.","family":"Spetzler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. Stuart","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen M.","family":"Papadopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edwin","family":"Bovill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard S.","family":"Zimmerman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua B.","family":"Bederson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1754","reference":[{"key":"b1","series-title":"N Engl J Med","first-page":"619","article-title":"Cerebral arterial spasm \u2014 controlled trial of nimodipine in patients with subarachnoid hemorrhage.","volume":"308","author":"Allen","year":"1983"},{"key":"b2","series-title":"Stroke","first-page":"864","article-title":"Measurements of acute cerebral infarction: a clinical examination scale.","volume":"20","author":"Brott","year":"1989"},{"key":"b3","series-title":"Neurosurgery","first-page":"491","article-title":"Safety and efficacy of intrathecal thrombolytic therapy in a primate model of cerebral vasospasm.","volume":"24","author":"Findlay","year":"1989"},{"key":"b4","series-title":"Neurosurgery","first-page":"201","article-title":"The effect of timing of intrathecal fibrinolytic therapy on cerebral vasospasm in a primate model of subarachnoid hemorrhage.","volume":"26","author":"Findlay","year":"1990"},{"key":"b5","series-title":"J Neurosurg","first-page":"723","article-title":"Effect of intrathecal thrombolytic therapy on subarachnoid clot and chronic vasospasm in a primate model of SAH.","volume":"69","author":"Findlay","year":"1988"},{"key":"b6","series-title":"Neurosurgery","first-page":"1","article-title":"Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning.","volume":"6","author":"Fisher","year":"1980"},{"key":"b7","series-title":"J Neurosurg","first-page":"558","article-title":"The effect of timing of clot removal on chronic vasospasm in a primate model.","volume":"67","author":"Handa","year":"1987"},{"key":"b8","series-title":"Thromb Haemost","first-page":"684","article-title":"Assay of human tissue-type plasminogen activator (t-PA) with an enzyme-linked immunosorbent assay (ELISA) based on three murine monoclonal antibodies to t-PA.","volume":"54","author":"Holvoet","year":"1985"},{"key":"b9","series-title":"J Neurosurg","first-page":"14","article-title":"Surgical risk as related to time of intervention in the repair of intracranial aneurysms.","volume":"28","author":"Hunt","year":"1968"},{"key":"b10","series-title":"Lancet","first-page":"480","article-title":"Assessment of outcome after severe brain damage. A practical scale.","volume":"1","author":"Jennett","year":"1975"},{"key":"b11","series-title":"J Neurol Neurosurg Psychiatry","first-page":"68","article-title":"Arterial spasm in subarachnoid haemorrhage: mechanical considerations.","volume":"21","author":"Johnson","year":"1958"},{"key":"b12","series-title":"Neurology","first-page":"424","article-title":"The relation of cerebral vasospasm to the extent and location of subarachnoid blood visualized by CT scan: a prospective study.","volume":"33","author":"Kistler","year":"1983"},{"key":"b13","series-title":"N Engl J Med","first-page":"1512","article-title":"Thrombolytic therapy: current status.","volume":"318","author":"Marder","year":"1988"},{"key":"b14","series-title":"Brain Nerve","first-page":"861","article-title":"Computed tomography of ruptured intracranial aneurysms in acute stage. Relationship between vasospasm and high density of CT scan.","volume":"30","author":"Mizukami","year":"1978"},{"key":"b15","series-title":"Neurosurgery","first-page":"301","article-title":"Prevention of vasospasm by early operation with removal of subarachnoid blood.","volume":"10","author":"Mizukami","year":"1982"},{"key":"b16","series-title":"J Neurosurg","first-page":"416","article-title":"Effect of clot removal at 24 hours on chronic vasospasm after SAH in the primate model.","volume":"66","author":"Nosko","year":"1987"},{"key":"b17","series-title":"J Neurosurg","first-page":"403","article-title":"Prolonged vasospasm produced by the breakdown products of erythrocytes.","volume":"47","author":"Osaka","year":"1977"},{"key":"b18","series-title":"J Neurosurg","first-page":"505","article-title":"Nimodipine treatment in poor-grade aneurysm patients. Results of a multicenter double-blind placebo-controlled trial.","volume":"68","author":"Petruk","year":"1988"},{"key":"b19","series-title":"Bull NY Acad Med","first-page":"357","article-title":"Early treatment of ruptured intracranial aneurysms of the circle of Willis with special clip technique.","volume":"35","author":"Pool","year":"1959"},{"key":"b20","series-title":"Cerebral Arterial Spasm.","first-page":"294","article-title":"Vasospasm after aneurysm rupture: incidence, onset, and course","author":"Saito","year":"1980"},{"key":"b21","series-title":"Neurosurgery","first-page":"590","article-title":"Efficacy of single intracisternal bolus injection of recombinant tissue plasminogen activator to prevent delayed cerebral vasospasm after experimental subarachnoid hemorrhage.","volume":"25","author":"Seifert","year":"1989"},{"key":"b22","series-title":"Circulation","first-page":"160","article-title":"Thrombolysis, clot selectivity, and kinetics.","volume":"70","author":"Sobel","year":"1984"},{"key":"b23","series-title":"Circulation","first-page":"1222","article-title":"Pharmacodynamics of thrombolysis with recombinant tissue-type plasminogen activator. Correlation with characteristics of and clinical outcomes in patients with acute myocardial infarction.","volume":"80","author":"Stump","year":"1989"},{"key":"b24","series-title":"J Neurosurg","first-page":"622","article-title":"Effect of early operation for ruptured aneurysms on prevention of delayed ischemic symptoms.","volume":"57","author":"Taneda","year":"1982"},{"key":"b25","series-title":"Neurosurgery","first-page":"1","article-title":"Chronic cerebral vasospasm: effect of volume and timing of hemorrhage in a canine model.","volume":"18","author":"Zabramski","year":"1986"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/75\/2\/article-p189.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/75\/2\/article-p189.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/75\/2\/article-p189.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,19]],"date-time":"2023-03-19T22:05:35Z","timestamp":1679263535000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/75\/2\/article-p189.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,8]]},"references-count":25,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3171\/jns.1991.75.2.0189","relation":{},"ISSN":["0022-3085"],"issn-type":[{"value":"0022-3085","type":"print"}],"subject":[],"published":{"date-parts":[[1991,8]]}}}