Prolongation of survival for high-grade malignant gliomas with adjuvant high-dose BCNU and autologous bone marrow transplantation.

Employment of postoperative brain irradiation in the initial management of high-grade malignant glial tumors has now become standard. The addition of conventional chemotherapy to irradiation has not significantly improved median survival beyond 1 year. We treated 25 consecutive patients (13 pilot patients and 12 protocol patients) with histologically confirmed unresectable grade 3 or 4 malignant gliomas with high-dose BCNU (carmustine) followed by autologous bone marrow transplantation and whole brain irradiation. Within 3 weeks of initial surgery, each patient had autologous bone marrow stored (median 2 X 10(8) nucleated cells/kg), and then received BCNU 1,050 mg/m2 intravenously (IV). Peripheral granulocytes recovered (greater than 500/microL) at a median of 19 days (range, 10 to 37 days), and platelets recovered (greater than 20,000/microL) at a median of 18 days (range, 13 to 40 days), following bone marrow infusion. Patients received 60 Gy whole brain irradiation when granulocytes were greater than 1,500/microL. Toxicity was well tolerated. Nausea occurred in 19 patients (76%); however, only eight patients (32%) experienced vomiting (mild in three, moderate in five). Eleven patients (44%) did not require empiric antibiotics, six of whom never developed an absolute granulocyte count less than 500/microL. Three patients with a poor performance status died early (one seizure with vomiting and asphyxiation; one, klebsiella urinary tract infection (UTI) with bacteremia; one, candidal pneumonia), and one additional patient who was performing well died of pulmonary hemorrhage. The 13 pilot patients have now been followed for a median of 23 months, with a significant survival advantage compared with the 52 consecutive historical control patients who received similar surgery and radiotherapy without high-dose BCNU (P = .037). The overall study group of 25 patients also has a significant survival advantage when compared with the same historical control group, with a projected median survival of 26 months (P = .007). This new approach using early postoperative intensive therapy consisting of high-dose BCNU, autologous bone marrow transplantation, and whole brain irradiation appears to significantly improve survival.

Direct endarterectomy of the middle cerebral artery for treatment of symptomatic stenosis: case report.

The authors report the clinical course and surgical technique used to treat a patient with a high-grade stenosis of the proximal middle cerebral artery that had caused a previous infarction and threatened the remaining dominant hemisphere. Trapping of the involved middle cerebral artery segment allowed direct exposure for excision of the atheromatous plaque and subsequent closure of the arteriotomy. Intraoperative angiography confirmed the reestablishment of flow. The patient made an uneventful postoperative recovery. Direct middle cerebral artery endarterectomy has the advantage of potentially reestablishing flow to lenticulostriate branches. The technique may also avoid the problem of occlusion at the site of maximum stenosis that can be caused by the use of an extra/intracranial bypass graft. Middle cerebral artery endarterectomy is a potentially valuable technique that deserves further investigation.

Transcallosal, transventricular approach to a basilar apex aneurysm.

A new approach to the basilar apex in a patient with a megadolichobasilar anomaly and an abnormally rostral basilar apex aneurysm is described. The details of the surgical approach and the advantages and limitations of this transcallosal, interseptal approach are described.

Direct repair of an extracranial vertebral artery pseudoaneurysm: case report and review of the literature.

A case of a 47-year-old man with weakness secondary to ossification of the posterior longitudinal ligament is presented. During removal of the ossified ligament, the patient's dominant right vertebral artery was injured. Although the bleeding from this artery was controlled intraoperatively, the patient developed an expanding cervical hematoma on the 3rd postoperative day. An angiogram demonstrated a large pseudoaneurysm of the right vertebral artery. The patient was taken back to the operating room where the cervical hematoma was removed, and direct repair of the pseudoaneurysm of the vertebral artery was performed. The previously reported cases of pseudoaneurysms of the extracranial vertebral artery are reviewed. We advocate the use of direct vascular repair as the treatment of choice in these lesions.

Combined reconstruction of the vertebral and carotid artery in one single procedure.

Patients suffering from vertebrobasilar insufficiency frequently have multiple areas of involvement in the extracranial circulation. Eight patients admitted to Henry Ford Hospital had symptoms suggestive of vertebrobasilar insufficiency and angiograms showing multiple abnormalities. A combined operation that reconstructed the carotid and vertebral circulations in one single procedure was completed in all patients with minimal morbidity and no mortality. The surgical procedure is described in detail.

Temporalis myofascial repair of traumatic defects of the anterior fossa. Technical note.

Bilateral temporalis myofascial flaps in continuity with frontal periosteum can be used in repairing extensive dural and bone defects of the anterior cranial fossa floor. The technique of preserving and using this flap is described and offers an alternative to the use of frontal pericranial tissue for repair of anterior dural defects.

Posterior circulation revascularization. Superficial temporal artery to superior cerebellar artery anastomosis.

Eight patients were evaluated for severe vertebrobasilar insufficiency (VBI). There were five males and three females, with an average age of 60.2 years (range 42 to 67 years). Three were diabetic and five hypertensive, including two patients who had both diseases. Seven of the eight had ongoing episodes of VBI refractory to anticoagulant and/or antiplatelet agents. Symptoms included two or more of the following in all patients: dizziness, diplopia, hemiparesis, hemihypesthesia, perioral numbness, bilateral visual blurring, dysarthria, and ataxia. Angiography revealed severe atherosclerotic stenosis of the proximal or midsection of the basilar artery in all patients. A 10-cm segment of the anterior or posterior division of the superficial temporal artery (STA) was anastomosed to a proximal segment of the superior cerebellar artery (SCA) through a right subtemporal approach. Seven of eight (87%) postoperative angiograms demonstrated patency as evidenced by filling of the SCA and, in most cases, of the basilar artery. Six of the eight patients were improved or asymptomatic after the operation, one was unchanged, and one died. The average follow-up period was 14 months, with a range of 4 to 23 months. Transient morbidity included temporal lobe swelling in four patients and a subdural hematoma in one. Anastomosis of the STA to the SCA is a feasible therapeutic option in the patient with VBI secondary to stenosis of the proximal or midsection of the basilar artery.

Surgical reconstruction of the proximal vertebral artery.

The authors have reviewed their experience in the management of 55 patients admitted to Henry Ford Hospital with symptoms of vertebrobasilar insufficiency and associated proximal vertebral artery stenosis or occlusion. In 48 patients, the symptoms occurred as multiple repeated events, five of which resulted in permanent deficits. The remaining seven patients had single events, four of which caused permanent deficit. These patients had been treated unsuccessfully with antiplatelet agents (37 cases) and with anticoagulant drugs (15 cases) before surgery. Most patients had multiple angiographic abnormalities, including bilateral vertebral stenosis in 19 cases, unilateral vertebral stenosis and contralateral occlusion in 18, unilateral vertebral hypoplasia and contralateral stenosis in 10, subclavian artery stenosis with steal in seven, and bilateral vertebral artery occlusion in one case. Posterior communicating arteries could not be demonstrated angiographically in 18 patients. Thirty-four patients had associated stenotic or occlusive lesions of the internal carotid artery. Forty-eight underwent a vertebral-to-carotid artery transposition. Of these, 18 had an associated carotid endarterectomy and seven had a vertebral artery endarterectomy immediately before the transposition. Two patients had saphenous vein grafts, one from the subclavian and one from the common carotid artery to the vertebral artery. Other surgical procedures included vertebral artery ligation in one case, transposition of the vertebral artery to the thyrocervical trunk in two cases and to the subclavian artery in one case, and endarterectomy of the origin of the vertebral artery in one case. All but two patients had complete resolution of their symptoms: one had persistent dizziness and the other had syncopal episodes. Complications included transient Horner's syndrome (30 cases) which became permanent in four cases, vocal cord paralysis (three cases), elevated hemidiaphragm without respiratory difficulty (two cases), and superficial would infection (one case). There were no deaths. Although the presentation of patients with vertebrobasilar insufficiency is generally characteristic, we believe that a specific diagnosis can be established only by angiographic means. Anticoagulants have been used to alleviate symptoms in some cases but are ineffective in solving the primary hemodynamic problem. Surgical reconstruction of the affected area deserves further evaluation in the management of these patients.

Acute cerebral revascularization.

Fifteen patients evaluated for acute cerebral ischemia underwent acute cerebral revascularization between March, 1979, and May, 1983. Clinical presentation included crescendo transient ischemic attacks (TIA's) in eight cases, progressing neurological dysfunction in three cases, and completed nonfluctuating deficits in four cases. Nine patients received intravenous heparin but did not improve neurologically. The patients with crescendo TIA's were operated on within 4 hours of their last event; those with progressing deficits were operated on while the deficit was developing, and those with established deficits were operated on 4, 6, 9, and 12 hours, respectively, after the event began. The clinical picture for 10 patients had resolved within 10 hours after surgery. One patient with crescendo TIA's, two with progressing deficits, and two with established deficits had postoperative residual deficits, of which three were mild and two severe. One patient, who had a saphenous vein graft to the middle cerebral artery, developed an intracerebral hematoma. In this prospective noncontrolled nonrandomized study, acute cerebral revascularization was performed safely, had limited risks, and offered the potential to help some patients. Further controlled randomized studies are indicated.

Transoral-transclival clipping of a giant lower basilar artery aneurysm.

The authors discuss the choice of the transoral-transclival approach for the repair of a lower basilar artery aneurysm in a 32-year-old sickle-cell patient. Efficiency of approach and minimization of damage to vital structures support the use of this technique. The risks of cerebrospinal fluid fistula and meningitis are considered. One year after operation, the patient is neurologically intact.

Endarterectomy of the vertebral artery from C2 to posterior inferior cerebellar artery intracranially.

A new technical approach to endarterectomy of the vertebral artery at the cranial cervical junction is discussed. A patient had symptoms of vertebrobasilar insufficiency on clinical examination. Angiography demonstrated a stenotic plaque in the vertebral artery at the level of C1, and an additional tandem lesion at the origin of the posterior inferior cerebellar artery. He underwent vertebral endarterectomy and was symptomatically improved postoperatively. The surgical approach used and possible alternatives will be discussed in detail.

Anastomosis of occipital artery to anterior inferior cerebellar artery for vertebrobasilar junction stenosis.

A new approach to revascularization of the posterior fossa for vertebrobasilar insufficiency due to vertebrobasilar junction stenosis is reported. The procedure involves anastomosing the occipital artery to a branch of the anterior inferior cerebellar artery. Rationale for the procedure and surgical technique are discussed.

Direct angioplasty of the basilar artery in baboons.

The lower portion of the basilar artery is a site of significant disease, both aneurysmal and stenotic, but has been considered inaccessible via traditional surgical approaches. A baboon model was used to evaluate the feasibility of a direct surgical reconstruction via a transoral-transclival approach, utilizing temporary occlusion of the basilar artery. An arteriotomy was performed and either repaired primarily or a venous patch graft was sutured in place. All animals survived the surgery; one suffered fatal postoperative upper airway obstruction, but the other four were neurologically intact at the time of death. Patency at the site of repair was confirmed both angiographically and histologically. We conclude that temporary clamping in conjunction with direct reconstruction of the basilar artery is feasible in this primate model. Future studies will focus on further applications of this technique.

Agents for cerebral edema.

Hyperventilation, ventricular drainage, and mannitol remain the mainstays of the treatment of cerebral edema not amenable to or following surgical therapy. There appears to be good therapeutic rationale for the use of "low-dose" mannitol in more prolonged treatment of intracranial hypertension (Table 5.1). The beneficial effects of steroids, either in "standard" or "high" doses, is less clear but, pending evidence to the contrary, we favor the use of "high-dose" corticosteroid therapy. Barbiturates appear to hold promise, but pending controlled, randomized trials to confirm or refute their efficacy, the logistics of their use, as well as their potential complications, precludes their widespread use outside of major centers. Certainly, the "ideal" agent for the treatment of cerebral edema, one that would selectively mobilize and/or prevent the formation of edema fluid with a rapid onset and prolonged duration of action, and with minimal side effects, remains to be discovered. In the meantime, research to refine the use of the older agents and determine the usefulness of the newer ones should be encouraged.

Observation of pulsed gamma-rays above 25 GeV from the Crab pulsar with MAGIC.

One fundamental question about pulsars concerns the mechanism of their pulsed electromagnetic emission. Measuring the high-end region of a pulsar's spectrum would shed light on this question. By developing a new electronic trigger, we lowered the threshold of the Major Atmospheric gamma-ray Imaging Cherenkov (MAGIC) telescope to 25 giga-electron volts. In this configuration, we detected pulsed gamma-rays from the Crab pulsar that were greater than 25 giga-electron volts, revealing a relatively high cutoff energy in the phase-averaged spectrum. This indicates that the emission occurs far out in the magnetosphere, hence excluding the polar-cap scenario as a possible explanation of our measurement. The high cutoff energy also challenges the slot-gap scenario.

Very-high-energy gamma rays from a distant quasar: how transparent is the universe?

The atmospheric Cherenkov gamma-ray telescope MAGIC, designed for a low-energy threshold, has detected very-high-energy gamma rays from a giant flare of the distant Quasi-Stellar Radio Source (in short: radio quasar) 3C 279, at a distance of more than 5 billion light-years (a redshift of 0.536). No quasar has been observed previously in very-high-energy gamma radiation, and this is also the most distant object detected emitting gamma rays above 50 gigaelectron volts. Because high-energy gamma rays may be stopped by interacting with the diffuse background light in the universe, the observations by MAGIC imply a low amount for such light, consistent with that known from galaxy counts.

Variable very-high-energy gamma-ray emission from the microquasar LS I +61 303.

Microquasars are binary star systems with relativistic radio-emitting jets. They are potential sources of cosmic rays and can be used to elucidate the physics of relativistic jets. We report the detection of variable gamma-ray emission above 100 gigaelectron volts from the microquasar LS I 61 + 303. Six orbital cycles were recorded. Several detections occur at a similar orbital phase, which suggests that the emission is periodic. The strongest gamma-ray emission is not observed when the two stars are closest to one another, implying a strong orbital modulation of the emission or absorption processes.