A prospective, observational clinical trial was conducted by the International Cooperative Study on the Timing of Aneurysm Surgery to determine the best time in relation to the hemorrhage for surgical treatment of ruptured intracranial aneurysms. Sixty-eight centers contributed 3521 patients in a 2 1/2-year period beginning in December, 1980. Analysis by a prespecified "planned" surgery interval demonstrated that there was no difference in early (0 to 3 days after the bleed) or late surgery (11 to 14 days). Outcome was worse if surgery was performed in the 7 to 10-day post-bleed interval. Surgical results were better for patients operated on after 10 days. Patients alert on admission fared best; however, alert patients had a mortality rate of 10% to 12% when undergoing surgery prior to Day 11 compared with 3% to 5% when surgery was performed after Day 10. Patients drowsy on admission had a 21% to 25% mortality rate when operated on up to Day 11 and 7% to 10% with surgery thereafter. Overall, early surgery was neither more hazardous nor beneficial than delayed surgery. The postoperative risk following early surgery is equivalent to the risk of rebleeding and vasospasm in patients waiting for delayed surgery.

In this prospective multicenter study, the authors have examined data derived from the initial computerized tomography (CT) scans of 753 patients with severe head injury. When the CT findings were related to abnormal intracranial pressure and to death, the most important characteristics of the scans were: midline shift: compression or obliteration of the mesencephalic cisterns: and the presence of subarachnoid blood. Diffuse hemispheric swelling was also found to be associated with an early episode of either hypoxia or hypotension.

Preoperative neoadjuvant therapy provides a valuable complement to radical craniofacial resection, leading to reduction in tumor burden. Patients experiencing reduction in tumor volume by neoadjuvant therapy demonstrate an improved prognosis.

A small number of patients with an apparently minor head injury will develop a life-threatening intracranial hematoma that must be rapidly detected and removed. To assess the risk of a significant intracranial neurosurgical complication after apparently minor head injury, the authors collected data prospectively on 610 patients who had sustained a transient posttraumatic loss of consciousness or other neurological function and who had a Glasgow Coma Scale (GCS) score of 13, 14, or 15 in the emergency room. Skull x-ray films were obtained in 583 patients, 66 of whom (10.8% of the study population) had cranial fractures. Eighteen of the 610 patients (3.0%) required a neurosurgical procedure. Three acute subdural hematomas, one epidural hematoma, and one traumatic intracerebral hematoma required craniotomy. Of the 66 patients who had skull fracture, 7.6% required a craniotomy for intracranial hematoma. Thirteen (19.7%) of the 66 patients with skull fracture required an operative procedure as compared to five (1.0%) of the 517 patients without skull fracture. Two patients with a normal GCS score of 15 and normal skull x-ray films subsequently underwent operative treatment. The cost of three alternative management schemes for these patients was estimated. A 50% reduction in cost of management could be effected by the use of computerized tomography (CT) scans (or possibly skull x-ray films) in determining which of the patients who are alert at the time of presentation should be admitted for observation. Several other conclusions can be drawn from this study. First, an initial GCS score between 13 and 15 does not necessarily indicate that a patient has sustained a trivial head injury, since 3% of such patients will require an operative procedure despite an initially normal level of alertness. Second, an abnormal skull x-ray film increases by a factor of 20 the probability that a patient will need neurosurgical treatment. Third, it is very unusual for patients who have a GCS score of 15 and a normal skull x-ray film to have a significant neurosurgical complication. Fourth, the alternative management schemes that depend on selective use of skull films and CT scans may significantly reduce the cost of caring for patients with minor head injury.

Malignant gliomas are thought to be highly dependent on the mevalonate pathway for cell growth. Lovastatin, a cholesterol-lowering drug, inhibits not only the rate-limiting step in the mevalonate pathway (hepatic hydroxymethyl glutaryl coenzyme A reductase), but also the prenylation of several key regulatory proteins including ras and the small guanosine triphosphate binding proteins. Therefore, from August 1994 through March 1996, 18 patients with either anaplastic glioma or glioblastoma multiforme were entered into a trial testing the safety of high-dose lovastatin with or without radiation. Although the response data is too premature to evaluate activity, the fact that high doses of lovastatin are well tolerated with concurrent radiation suggests that central nervous system toxicity will not be a significant limiting toxicity as more selective farnesyltransferase inhibitors are brought into the clinic as radiation sensitizers.