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J. Stuart Crutchfield, Raymond Sawaya, Christina A. Meyers and Bartlett D. Moore III

✓ Mutism is defined as a state in which a patient is conscious but unwilling or unable to speak. It has been reported to occur in association with a multitude of conditions, including trauma, epilepsy, tumors, stroke, psychoses, and brain surgery. The cases of two patients who became mute in the immediate postoperative period are presented. The first patient developed mutism following removal of a parasagittal meningioma, and the second following removal of a posterior fossa medulloblastoma. It is believed that transient injury may have occurred to the supplementary motor cortex in the first case and to the dentate nuclei in the second case. It is interesting that these two areas are connected via pathways involving the ventrolateral nucleus of the thalamus, and that lesions of this thalamic nucleus can also lead to mutism. It therefore appears plausible that interruption of these pathways may be involved in the pathogenesis of mutism. Although mutism is an infrequent complication of brain surgery, neurosurgeons should be aware that it may occur following removal of lesions in these areas and that it is generally a transient condition.

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Dan S. Heffez, Raymond Sawaya, George B. Udvarhelyi and Risa Mann

✓ Spinal cord compression by epidural extramedullary hematopoiesis (EMH) is a rare phenomenon. A case of acute compressive myelopathy is reported in a 72-year-old man with EMH secondary to sideroblastic anemia. Technetium colloid scanning was used to document extensive ectopic marrow formation. The patient improved following surgery and radiotherapy. A review of the literature revealed 23 other cases of symptomatic spinal epidural EMH. The underlying hematological disorder varied but was always of long duration. Eighty-eight percent of the patients were males. Symptoms lasted longer than 1 week in 90% of cases, and 91% demonstrated incomplete neurological deficits. Plain x-ray films were rarely helpful in establishing the diagnosis. Technetium sulfur colloid bone marrow scanning has been used successfully to detect EMH and has led to preoperative diagnosis in one case. Decompressive laminectomy with or without postoperative irradiation is the suggested therapy, although there is evidence that radiotherapy alone may be adequate in some cases. Good recovery is the rule despite long-standing neurological deficits.

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Raymond Sawaya, Thaddeus Mandybur, Illona Ormsby and John M. Tew Jr.

✓ This study was designed to evaluate the effect of an inhibitor of plasminogen activation on the growth of a human glioblastoma line grown in nude mice up to the seventh passage. The tumors produced plasminogen activators and showed histological characteristics similar to those of the original tumor. Three groups of mice were studied. Group A received 5% epsilon aminocaproic acid (EACA); Group B received 2.5% EACA; and Group C served as a control. There was no statistical difference among the three groups with regard to: 1) age at time of tumor transplantation; 2) the interval between implant and treatment; or 3) tumor volume at time of treatment. Blood measurements of EACA, performed in a limited number of animals, have shown that the drug at 5% concentration had reached toxic levels. Statistically significant differences between the three groups were noted in the following categories: 1) rate of tumor growth; 2) tumor volume at time of death, where Group A had smaller tumors than Group C; and 3) mean survival times of Groups A and B as compared to Group C.

A statistically significant negative correlation was found between the rate of tumor growth and the length of survival of animals in Group C, while no correlation could be found for either Group A or B, indicating that the antifibrinolytic therapy modified this important biological variable. This study supports the hypothesis that the fibrinolytic system plays a role in the growth and development of malignant gliomas and that interference with the fibrinolytic system may retard the growth of these tumors grown in nude mice.

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Mario Zuccarello, Raymond Sawaya, Robert Lukin and Gabrielle deCourten-Myers

✓ A 24-year-old man developed a spontaneous cerebellar hematoma 5 years after the implantation of cerebellar electrodes. No vascular malformations were found either intraoperatively or radiographically. The histopathological findings of the cerebellar tissue obtained at biopsy from the region surrounding the electrodes support the hypothesis of a causal relationship between the spontaneous cerebellar hemorrhage and chronic cerebellar stimulation.

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Raymond Sawaya, O. Juhani Rämö, Mei Lin Shi and George Mandybur

✓ Fresh brain-tumor samples were obtained at operation and analyzed for their content of tissue type plasminogen activator (tPA) using an activity assay (gel chromatography zymogram) and an enzyme-linked immunospecific assay. The specimens were taken from 23 glioblastomas, 35 metastatic tumors, 42 meningiomas, 16 low-grade gliomas, and seven acoustic neurinomas; seven specimens were from normal brain.

A strong correlation was found between the results of the two assays (r = 0.77, p < 0.0001). There was a threefold difference in the tPA content of the benign tumors as compared to malignant tumors (p = 0.0006), the latter having less tPA. Histologically benign meningiomas contained higher tPA than malignant meningiomas (p = 0.01); however, the difference between low-grade gliomas and high-grade gliomas was less evident. Overall regression analysis data have shown an inverse relationship between the tissue content in tPA and the presence and degree of tumor necrosis and peritumoral brain edema (p = 0.004 and p = 0.0004, respectively). This finding was most consistent in the glioblastoma group where the correlation coefficient values were r = 0.53 and r = −0.55, respectively. There was no significant correlation between the tissue tPA content and the age and sex, steroid use, or plasma tPA of the patients or the duration of symptoms.

In summary, this is the first demonstration of tPA in a large series of human brain tumors and in normal brain. The differences observed have clear biological significance and, although the source of tPA in tumor tissue is still unknown, a relative reduction in tPA in tumor tissue may play an integral role in the development of tissue necrosis and tissue edema. The lack of tPA in tumor necrosis was not due to tissue destruction and cell death since urokinase was readily detectable in that tissue.

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Ajay K. Bindal, Rajesh K. Bindal, Harry van Loveren and Raymond Sawaya

✓ The authors report on a study of eight cases of intracranial plasmacytoma to identify the risk of progression to multiple myeloma and suggest the treatment required for cure of solitary lesions. The diagnosis of multiple myeloma or myelomatous changes was made in the immediate postoperative period in four patients (50%), two of whom had skull base lesions. Of the four remaining patients, three were treated with complete surgical resection and radiation therapy and had no recurrence of plasmacytoma or progression to multiple myeloma during mean follow up of 12 years (range 2–25 years); one patient underwent subtotal surgical resection and had recurrence of the tumor despite radiation therapy.

It is concluded that multiple myeloma is unlikely to develop during the long term in patients with intracranial plasmacytoma who do not develop multiple myeloma or myelomatous changes in the early postoperative period. However, lesions that infiltrate the skull base are not likely to be solitary, and patients who harbor these neoplasms should undergo complete evaluation and close follow-up review to exclude multiple myeloma. A recurrence of solitary intracranial plasmacytoma is possible with subtotal surgical resection despite radiation therapy. Definitive treatment should consist of complete surgical resection with adjuvant radiation therapy.

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Editorial

Neurosurgical “pearls” and neurosurgical evidence

E. Antonio Chiocca