Prognostic factors for stereotactic radiosurgery-treated patients with cerebral metastasis: implications on randomised control trial design and inter-institutional collaboration.

INTRODUCTION: Defining key prognostic factors for patients with cerebral metastases who underwent stereotactic radiosurgery (SRS) treatment will greatly facilitate future clinical trial designs. METHODS: We adopted a two-phase study design where results from one cohort were validated in a second independent cohort. The exploratory analysis reviewed the survival outcomes of 1017 consecutive patients (with 3610 metastases) who underwent Gamma radiosurgery at the University of California, San Diego (UCSD)/San Diego Gamma Knife Center (SDGKC). Multivariate analysis was performed to identify prognostic factors. Results were validated using data derived from 2519 consecutive patients (with 17,498 metastases) treated with SRS at the Katsuta Hospital. RESULTS: For the SDGKC cohort, the median overall survival of patients following SRS was 7 months. Two year follow-up data were available for 85% of the patients. Multivariate analysis found that patient age, Karnofsky Performance Status, systemic cancer status, tumour histology, number of metastasis and cumulative tumour volume independently associated with overall survival (p<0.001). All statistical associations were validated by multivariate analysis of data derived from the Katsuta Hospital cohort. CONCLUSIONS: This is the first integrated study that defined prognostic factors for SRS-treated patients with cerebral metastases using an inter-institutional validation study design. The work establishes a model for collaborative interactions between large volume centers and provides prognostic variables that should be incorporated into future clinical trial design.

Pilocytic astrocytoma presenting as an extra-axial tumor in the cerebellopontine angle: case report.

Glial tumors in the cerebellopontine angle (CPA) are rare. Four histologically distinct types of glial tumors of the CPA have been described in the literature as ependymoma, medulloblastoma, mixed glial tumor, and fibrillary astrocytoma. This case report describes a pilocytic astrocytoma of the CPA. A 58-year-old man with a hearing loss had an extra-axial tumor in the left CPA that extended into the internal auditory canal. The characteristics of the tumor on magnetic resonance imaging scans differed from those of typical CPA tumors. It adhered avidly to the cochlear and vestibular nerves, which had to be sacrificed for gross total resection. Microscopic examination showed the typical features of an adult-type pilocytic astrocytoma.

Intraoperative assessment of aneurysm clip placement by intravenous fluorescein angiography.

Clip occlusion of intracranial aneurysms can be difficult, and intraoperative misadventures are still fairly frequent. Many complications are caused by improper clip placement. Intraoperative conventional arteriography is time consuming and requires expensive image-intensifying equipment. As an alternative, we have found that the bolus intravenous administration of fluorescein produces the necessary intra-arterial dye concentration for the direct visualization of the perforating medium and large arteries in proximity to a clipped aneurysm. The technique is straightforward, requiring little additional operating time and an inexpensive set of disposable optical filters. No adverse reactions to fluorescein have been observed.

A comparison of the effects on neuronal Golgi morphology, assessed with electron microscopy, of cardiopulmonary bypass, low-flow bypass, and circulatory arrest during profound hypothermia.

Adult swine (n = 18) were studied to compare the effects on neuronal morphology of hypothermic circulatory arrest with hypothermic very-low-flow cardiopulmonary bypass. Animals were anesthetized with halothane and prepared in a standard manner for nonpulsatile cardiopulmonary bypass. Monitored variables included mean arterial pressure, arterial blood gases, the processed electroencephalogram, and subdural brain temperature. Bypass was initiated with pump flows of 100 ml.kg-1.min-1, and mean arterial pressure was kept above 50 mm Hg at all times. Animals were cooled to 18 degrees C, using a heat exchanger, and were randomly assigned to one of three groups. Group 1 animals were control animals who underwent 1 hour of hypothermic cardiopulmonary bypass. Group 2 animals underwent 1 hour of circulatory arrest. Group 3 animals underwent 1 hour of very-low-flow cardiopulmonary bypass (10% of normal). At the end of the 1 hour of hypothermic bypass, very-low-flow bypass, or arrest period, animals were rewarmed to 37 degrees C with normal bypass flows, and normothermic perfusion continued for 1 additional hour. Animals were then perfusion fixed with formalin and the brains were removed for electron microscopic analysis. Electron microscopic analysis was used to determine the effects of treatment and was limited to 20 neurons of the CA1 sector of the hippocampus in each animal. Golgi bodies were identified and classified as normal, mildly affected, or severely affected. Animals subjected to either very-low-flow bypass or circulatory arrest had significantly more severely affected and significantly fewer normal Golgi bodies than control animals (p < 0.001). Animals maintained with very-low-flow bypass, however, had significantly more severely affected and fewer normal Golgi bodies than animals subjected to circulatory arrest (p < 0.001). We conclude that under the conditions of this experiment very-low-flow hypothermic cardiopulmonary bypass is associated with significantly greater neuronal Golgi abnormalities than total circulatory arrest.

Retromastoid cisternal Ommaya reservoir for intrathecal therapy of coccidioidomycosis meningitis. Technical note.

A method is described that simplifies placement of an Ommaya reservoir for chronic access to the basilar cisterns. This technique is useful in treating coccidioidomycosis and other fungal meningitides.

Effect of uridine 5'-diphosphate on cryogenic brain edema in rabbits.

This study was undertaken to examine the effect of uridine 5'-diphosphate, administered intravenously or intraperitoneally, on cold injury-induced brain edema in rabbits. Bolus injection or continuous intravenous infusion of uridine 5'-diphosphate 26 hours after a lesion was established had adverse effects, such as increased intracranial pressure and lowered systolic arterial blood pressure and cerebral perfusion pressure for approximately 10-29 minutes, but these parameters did not change appreciably from 29 minutes to 3 hours after administration. Intraperitoneally administered uridine 5'-diphosphate did not affect these parameters appreciably during 3 hours. Thus, the intravenous administration of uridine 5'-diphosphate is harmful under neurosurgical conditions. In contrast, 10 mg/kg/day i.p. uridine 5'-diphosphate pretreatment and posttreatment, beginning 24 hours before and continuing until 24 hours after the insult, significantly reduced neurologic abnormalities, Evans blue extravasation, water content in the injured gray matter, and intracranial pressure without affecting water content in the white matter. Intravenous dexamethasone pretreatment and posttreatment in this setting significantly reduced only neurologic abnormalities. However, there were no significant differences between intraperitoneal uridine 5'-diphosphate and intravenous dexamethasone effects on cold-injured brain.

Diagnosis and treatment of an odontoid fracture in a patient with polyostotic fibrous dysplasia: case report.

Fibrous dysplasia of the cervical spine is rare. No prior reports have discussed odontoid fractures in the setting of fibrous dysplasia. We describe a 26-year-old man who suffered a traumatic odontoid fracture in an area of preexisting fibrous dysplasia. The patient was treated conservatively in a sterno-occipito-mandibular immobilizer brace with a good result. A review of fibrous dysplasia is presented. Alternative methods of diagnosis and treatment options in our patient are discussed.

The transoropalatal approach to the atlantoaxial-clival region: considerations for the head and neck surgeon.

The transoropalatal approach to the atlantoaxial-clival area provides excellent exposure for neurosurgical decompression and fusion procedures. The technique has been effectively applied in the treatment of bony and soft tissue abnormalities of the anterior spinal region. Although this approach is safe and reliable, it is not part of the otolaryngologist's usual surgical armamentarium. In the present study, we describe the case histories of five patients who underwent resection of the odontoid process for cervicomedullary compression. Neurological compromise was manifested by progressive upper and/or lower extremity paresis in all patients. In each patient, a transoropalatal approach was used. The surgical technique is discussed, and the prevention of possible sequelae, including velopharyngeal incompetence and palatal or pharyngeal wound dehiscence, is addressed.

Experimental model of symptomatic vasospasm in rabbits.

The common carotid arteries were ligated bilaterally 2 weeks before induction of subarachnoid hemorrhage in rabbits. The rabbits were observed closely for clinical symptoms, and angiographic and pathologic investigations were performed. Thirteen experimental rabbits showed a progressing neurologic deficit that was worst on the fourth or fifth day after the subarachnoid hemorrhage. This symptomatic change did not occur in five rabbits without previous carotid ligation. Presumably, the rabbits with carotid ligation became symptomatic because they no longer had a collateral blood flow to compensate for the reduced blood flow in the basilar artery after subarachnoid hemorrhage. Our model of symptomatic vasospasm after subarachnoid hemorrhage may be beneficial for future studies.

Modification of experimental post-subarachnoid hemorrhage vasculopathy with intracisternal plasmin.

This study using pigs was designed to determine the efficacy of delayed subarachnoid plasmin injection in preventing the vasculopathy secondary to experimental subarachnoid hemorrhage. Animals received cisterna magna injections of either plasmin or saline 2, 4, or 6 days after double subarachnoid blood injection. The cerebral blood vessels of all animals were examined histologically for evidence of intimal proliferation and medial necrosis. Angiography was not done. The results indicate a progressive increase in the extent and severity of intimal proliferation the longer plasmin injection is delayed. In contrast, the severity of medial necrosis did not correlate with the delay. We conclude that subarachnoid clot lysis is an effective way to prevent vascular injury from subarachnoid blood and that, the sooner it is done after hemorrhage, the more effective it will be.

Demonstration by magnetic resonance of symptomatic spinal epidural lipomatosis.

In patients with Cushing's syndrome or morbid obesity, excessive accumulation of fat in the hips, upper back, abdomen, and mediastinum is well known (1, 3, 7). Excessive deposition of fat in the epidural space is less common, but must be recognized as a potential cause of neurological deficit (1-8). We report a patient with iatrogenic Cushing's syndrome, in whom magnetic resonance imaging (MRI) established the specific diagnosis of spinal cord compression secondary to excess epidural fat.

Intranasal schwannoma with extension into the intracranial compartment: case report.

The authors present a case of intranasal schwannoma with extension into the intracranial compartment. Computed tomographic findings are presented, and a combined intranasal and subfrontal operative approach is described. The pathology, origin, and clinical characteristics of intranasal schwannomas are reviewed.

Modification of experimental post-subarachnoid hemorrhage vasculopathy with intracisternal plasmin.

Utilizing a double subarachnoid blood injection model in pigs, we have evaluated the protective effect of the intracisternal injection of the thrombolytic agent, plasmin, in preventing the secondary intracranial arteriopathy seen after artificial subarachnoid hemorrhage in untreated animals. Twelve animals injected with plasmin revealed markedly less intimal proliferation and medial necrosis than were seen in control animals. These observations support the hypothesis that the persistence of clotted blood around the intracranial arteries is the cause of the vasculopathy.

Intimal proliferation of cerebral arteries after subarachnoid blood injection in pigs.

A model of experimental subarachnoid hemorrhage in young pigs has been created using two subarachnoid blood injections. Cerebral arteries of the pig demonstrate intimal proliferation and medial necrosis 10 days after experimental blood injection; this appears to be a reaction to arterial injury. The similarity between the arterial reaction to subarachnoid blood and the general process of atherosclerosis is noted, and steps have been taken to insure that the vasculopathy described is truly a response to the injected blood. The authors conclude that the intimal proliferation observed between 1 and 2 weeks after experimental subarachnoid blood injection is an indicator of arterial injury and is, therefore, a good end point for further studies.

Success of microvascular decompression with and without prior surgical therapy for trigeminal neuralgia.

Clinical records and patient interviews in 37 cases of trigeminal neuralgia treated by microvascular decompression by a single surgeon were studied retrospectively. Outcomes were determined with an average follow-up period of 43 months. Abnormalities in the region of the trigeminal nerve were identified in each case. Patients undergoing microvascular decompression as a primary procedure were cured (total pain relief without further therapy) at a rate of 91%, versus 43% in patients treated with destructive procedures (rhizotomies) prior to microvascular decompression (p less than 0.005). Analysis also suggests that trigeminal neuralgia of greater than 9 years' duration was cured at a rate of only 42%, versus 88% in cases of less lengthy duration (p less than 0.005). Sex and age at time of surgery were not significant predictors of outcome. There were no deaths in this group of patients aged from 32 to 90 years. A horizontal surgical approach is described.

Iotrol, a new myelographic agent: 2. Comparative electroencephalographic evaluation by spectrum analysis.

Iotrol, a nonionic dimer isotonic with cerebrospinal fluid at 300 mg l/ml, was evaluated against metrizamide, iopamidol, and iohexol by electroencephalography (EEG) in nonanesthetized cynomolgus monkeys. Each of four monkeys was injected intrathecally with 0.5 ml/kg of 300 mg l/ml of each contrast medium. EEG was obtained before, 45 min, and 3 hr postinjection. EEG spikes, motor disturbances, convulsions, and behavior changes were observed. The EEG from C3 channel was also computer-analyzed. Average percentage differences between control and test energy content of the entire EEG and of the EEG spectrum subdivided into five frequency bands were calculated. With metrizamide, three animals suffered seizures, and all were lethargic and irritable. With iopamidol, two animals convulsed; all animals were lethargic. Transient apathy and motor disturbances were observed in the iohexol animals. No motor or behavior changes were produced by iotrol. Metrizamide and iopamidol increased the spectrum energy in all bands. Neither iohexol nor iotrol affected the EEG significantly. On the basis of these findings, iotrol holds promise as a clinical contrast material for the subarachnoid space.

Timing of periarterial blood removal for the prevention of vasonecrosis.

In an attempt to provide some data on the time interval during which surgical removal of subarachnoid blood would be beneficial for the prevention of the vasospasm-vasonecrosis syndrome, we have performed experiments on the femoral arteries of rabbits. Blood was allowed to clot around the exposed femoral artery and then removed at 24, 36, 48, and 72 hours. These experiments reveal that after 24 hours of blood contact the arteries appear normal, whereas after 36 hours or more of blood contact a definite pathologic reaction is present. On the basis of these animal experiments, we recommend that if an attempt is to be made at the prevention of delayed neurologic deterioration by surgical removal of clotted blood from around the cerebral arteries, the surgery should be performed within 36 hours or as soon thereafter as possible.

Mechanisms of whole blood-induced cerebral arterial contraction.

Using rabbit cerebral arteries in an in vitro chamber, we examined the cerebral arterial contraction initiated by clotting whole blood. By using methysergide maleate and a novel thromboxane synthetase inhibitor, 1-carboxyheptylimidazole (1-CHI), we studied the contributions of both serotonin and the prostaglandin metabolite thromboxane A2. Nontreated platelet-rich plasma (PRP) in the presence of methysergide produced a reliable contraction, whereas platelet-poor plasma did not. PRP from a rabbit pretreated with 1-CHI (50 mg/kg) compared to nontreated PRP caused a significantly smaller contraction. Blockade of this cerebral arterial contraction occurred without the disruption of platelet aggregation. Whole blood (1 ml) plus thrombin produced a consistent contraction over the 1 hour that was monitored. Whole blood drawn from a rabbit pretreated with 1-CHI (50 mg/kg) produced a smaller contraction, which began to dissipate in 5 minutes. When nontreated whole blood was added to the chamber in the presence of methysergide maleate (1.3 X 10(-5) g/ml), a contraction less than control was produced, and it persisted at 30 minutes. When whole blood pretreated with 1-CHI (50 mg/kg) was added to the chamber containing methysergide, there was a transient contraction that dissipated to nearly zero at 30 minutes. From our results, it is apparent that the thromboxane synthetase inhibitor has a profound effect on the later phase of blood-induced vasoconstriction. In contrast, the serotonin antagonist affected primarily the initial vasoconstriction and left the later phase largely unaltered. The role of thrombin, used to initiate coagulation, was also examined, and it was found to have a minimal direct constrictive effect when in a plasma solution.