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Dandy-Walker syndrome

Clinical analysis of 23 cases

Raymond Sawaya and Robert L. McLaurin

✓ A clinical analysis of 23 patients with Dandy-Walker malformation indicates that more than 85% of them were diagnosed at or before 1 year of age, and that the incidence of associated anomalies is approximately 50%, with a 17% incidence for agenesis of the corpus callosum. The significance of the presence of these anomalies is substantiated by the fact that of the seven deaths recorded, six were related to this disease and five were affected by associated anomalies. The high mortality rate (26%) is comparable to that of other series. The differential diagnosis with posterior fossa extra-axial cysts is discussed.

Ten patients were primarily treated with excision of the cyst membrane; all of them required subsequent shunting to control the intracranial pressure, demonstrating the futility of this approach. None of the patients treated with lateral ventricle shunting suffered an upward herniation of the posterior fossa contents, suggesting that combined shunting of the lateral and fourth ventricles is rarely necessary. The technical advantages of posterior fossa shunting alone are outlined. Of the 16 survivors, 14 were assessed for their mental development by means of standard psychometric testing. The results of the intelligence quotient (IQ) scoring have indicated that 71% of the patients have subnormal mental development (IQ < 83). There was no significant relationship between retardation and associated anomalies, although agenesis of the corpus callosum was related to poor intellectual development in the two patients so affected (IQ's of 50 and 73).

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Raymond Sawaya and Robert Highsmith

✓ Fresh human brain-tumor samples were assayed for their plasminogen activator (PA) content. Specific molecular weight patterns were identified for each of five common brain tumors and for normal brain, suggesting a cell-specific origin of the various PA forms. Malignant tumors contained higher PA activity and a larger number of molecular weight patterns than benign tumors, with the exception of acoustic neurinomas. Irradiated tumors contained lower PA activity than nonirradiated tumors. Finally, a slight but definite correlation between brain edema and PA activity was detected. The future role of brain-tumor PA's for diagnostic and therapeutic purposes is discussed.

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Raymond Sawaya, Mario Zuccarello and Robert Highsmith

✓ This study was undertaken to confirm the presence of alpha-1-antitrypsin (α1-AT) in human brain tumors and to attempt to elucidate its significance. Seventy-seven consecutive unselected patients with various brain tumors were entered in this study. The α1-AT and α2-macroglobulin contents of the tumor extracts were qualitatively assessed by Ouchterlony immunodiffusion techniques. Plasminogen activator (PA) activity was assayed electrophoretically on sodium dodecyl sulfate gels. The patients were divided into two groups according to the positivity of their tumors to α1-AT. Sixty-eight percent of the tumors were positive for α1-AT, and all specimens were negative for α2-macroglobulin. Clinical and biological parameters obtained in all study patients failed to show statistically significant differences between the two groups with the exception of PA activity (p = 0.001), the peritumoral edema as seen on computerized tomography, and the preoperative serum fibrinogen level. These three parameters were higher in the group with specimens positive to α1-AT.

This study supports the hypothesis that α1-AT is produced primarily by tumor cells in proportion to the regional proteolytic and inflammatory activity, and may protect the tumor cells.

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Christopher S. Rumana, Kenneth R. Hess, Wei Ming Shi and Raymond Sawaya

Object. Twenty-two patients who had solitary metastatic brain tumors with dural extension were treated surgically over a 3-year period. Their cases were reviewed to characterize these lesions and to compare the patients with a similar cohort in which there was no dural involvement.

Methods. The median age of the patients was 58 years (range 11–68 years) and the male/female ratio was 12:10. The median preoperative Karnofsky Performance Scale (KPS) score in the group was 90 (range 70–100). The most common histological diagnoses seen in these patients included breast cancer, adenocarcinoma and squamous cell carcinoma of the lung, and renal cell carcinoma. All patients underwent gross-total resection of the tumor and 86% received radiation therapy. The median patient survival time was 11 months, with a median time to recurrent intracranial disease of 19 months. Survival was related to the histological diagnosis. Recurrent disease occurred in 41% of cases. Leptomeningeal disease occurred in three patients (14%). The frequency and time course of development of recurrent disease was not affected by dural resection nor was survival.

These results for patients having metastatic brain tumors with dural extension were compared with those for a cohort of 26 patients in which there were similar histological diagnosis, age, gender, and preoperative KPS score were distributed similarly but in which each patient had a single subcortical metastatic lesion. Those patients had a median survival of 10 months and the median time to recurrence was not reached. Leptomeningeal disease occurred in one patient (4%).

Conclusions. To the authors' knowledge, this is the first reported series of patients with metastatic brain tumors with dural extension. Patients with this disease may be more likely to develop recurrences along the dura and leptomeningeal disease, but the overall survival time in these patients is not different from those patients with intraparenchymal lesions.

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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.