Report of two cases
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.
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.
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.
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.
Neurosurgical “pearls” and neurosurgical evidence
E. Antonio Chiocca
Rajesh K. Bindal, Raymond Sawaya, Milam E. Leavens and J. Jack Lee
✓ The authors conducted a retrospective review of the charts of 56 patients who underwent resection for multiple brain metastases. Of these, 30 had one or more lesions left unresected (Group A) and 26 underwent resection of all lesions (Group B). Twenty-six other patients with a single metastasis who underwent resection (Group C) were selected to match Group B by type of primary tumor, time from first diagnosis of cancer to diagnosis of brain metastases, and presence or absence of systemic cancer at the time of surgery. Statistical analysis indicated that Groups A and B were also homogeneous for these prognostic indicators. Median survival duration was 6 months for Group A, 14 months for Group B, and 14 months for Group C. There was a statistically significant difference in survival time between Groups A and B (p = 0.003) and Groups A and C (p = 0.012) but not between Groups B and C (p > 0.5). Brain metastasis recurred in 31% of patients in Group B and in 35% of those in Group C; this difference was not significant (p > 0.5). Symptoms improved after surgery in 65% of patients in Group A, 83% in Group B, and 84% in Group C. Symptoms worsened in 13% of patients in Group A, 6% in Group B, and 0% in Group C. Groups A, B, and C had complication rates per craniotomy of 8%, 9%, and 8%, and 30-day mortality rates of 3%, 4%, and 0%, respectively. Guidelines for management of patients with multiple brain metastases are discussed. The authors conclude that surgical removal of all lesions in selected patients with multiple brain metastases results in significantly increased survival time and gives a prognosis similar to that of patients undergoing surgery for a single metastasis.
Yan Michael Li, Dima Suki, Kenneth Hess and Raymond Sawaya
Glioblastoma multiforme (GBM) is the most common and deadliest primary brain tumor. The value of extent of resection (EOR) in improving survival in patients with GBM has been repeatedly confirmed, with more extensive resections providing added advantages. The authors reviewed the survival of patients with significant EORs and assessed the relative benefit/risk of resecting 100% of the MRI region showing contrast-enhancement with or without additional resection of the surrounding FLAIR abnormality region, and they assessed the relative benefit/risk of performing this additional resection.
The study cohort included 1229 patients with histologically verified GBM in whom ≥ 78% resection was achieved at The University of Texas MD Anderson Cancer Center between June 1993 and December 2012. Patients with > 1 tumor and those 80 years old or older were excluded. The survival of patients having 100% removal of the contrast-enhancing tumor, with or without additional resection of the surrounding FLAIR abnormality region, was compared with that of patients undergoing 78% to < 100% EOR of the enhancing mass. Within the first subgroup, the survival durations of patients with and without resection of the surrounding FLAIR abnormality were subsequently compared. The data on patients and their tumor characteristics were collected prospectively. The incidence of 30-day postoperative complications (overall and neurological) was noted.
Complete resection of the T1 contrast-enhancing tumor volume was achieved in 876 patients (71%). The median survival time for these patients (15.2 months) was significantly longer than that for patients undergoing less than complete resection (9.8 months; p < 0.001). This survival advantage was achieved without an increase in the risk of overall or neurological postoperative deficits and after correcting for established prognostic factors including age, Karnofsky Performance Scale score, preoperative contrast-enhancing tumor volume, presence of cyst, and prior treatment status (HR 1.53, 95% CI 1.33–1.77, p < 0.001). The effect remained essentially unchanged when data from previously treated and previously untreated groups of patients were analyzed separately. Additional analyses showed that the resection of ≥ 53.21% of the surrounding FLAIR abnormality beyond the 100% contrast-enhancing resection was associated with a significant prolongation of survival compared with that following less extensive resections (median survival times 20.7 and 15.5 months, respectively; p < 0.001). In the multivariate analysis, the previously treated group with < 53.21% resection had significantly shorter survival than the 3 other groups (that is, previously treated patients who underwent FLAIR resection ≥ 53.21%, previously untreated patients who underwent FLAIR resection < 53.21%, and previously untreated patients who underwent FLAIR resection ≥ 53.21%); the previously untreated group with ≥ 53.21% resection had the longest survival.
What is believed to be the largest single-center series of GBM patients with extensive tumor resections, this study supports the established association between EOR and survival and presents additional data that pushing the boundary of a conventional 100% resection by the additional removal of a significant portion of the FLAIR abnormality region, when safely feasible, may result in the prolongation of survival without significant increases in overall or neurological postoperative morbidity. Additional supportive evidence is warranted.