Effects of posterior fossa decompression with and without duraplasty on Chiari malformation-associated hydromyelia.

OBJECTIVE: The optimal surgical treatment of Chiari malformation is unclear, especially in patients with hydromyelia. Various surgical approaches have included suboccipital craniectomy, syringostomy, obex plugging, syringosubarachnoid shunting, and fourth ventriculosubarachnoid shunting. The purpose of this study is to differentiate extradural and intradural approaches in the treatment of Chiari I malformation. METHODS: We reviewed the medical records and magnetic resonance imaging (MRI) scans of 34 surgical corrections' of Chiari malformation performed at our institution from 1988 to 1998. The age and sex of the patient, the presence of hydromyelia, the type of surgery (duraplasty or nonduraplasty), and the clinical outcome were determined. RESULTS: Eleven patients underwent posterior fossa decompression (PFD) and C1 laminectomy without duraplasty. Eight (73%) of these patients had an improvement in symptoms. Seven of the 11 patients had hydromyelia. Of the six patients who underwent follow-up MRI, three (50%) had a decrease in the size of the hydromyelia, and all three had clinical improvement. We also noted a morphometric increase in posterior fossa volume on postoperative MRI scans in these three patients, which was not observed in those without improvement. Two of the three patients whose hydromyelia did not decrease on follow-up MRI scans worsened clinically, and one underwent a reoperation with duraplasty. Twenty-three patients underwent combined PFD, C1 laminectomy, and duraplasty. Twenty (87%) of these patients had improvement. Twelve of the patients who underwent duraplasty had hydromyelia; nine underwent follow-up MRI. All nine of these patients (100%) had a decrease in the cavity size, including eight with clinical improvement. There were 10 minor complications (seroma, 4; superficial infection, 3; cerebrospinal fluid leak, 2; aseptic meningitis and occipital nerve pain, 1) when the dura was opened, compared with one superficial wound infection that resolved in patients who underwent PFD only. CONCLUSION: PFD, C1 laminectomy, and duraplasty for the treatment of Chiari I malformation may lead to a more reliable reduction in the volume of concomitant hydromyelia, compared with PFD and C1 laminectomy alone. However, there seems to be a subset of patients whose symptoms will resolve and whose hydromyelic cavity will decrease with the removal of bone only. These patients seem to undergo a volumetric increase in the posterior fossa. Further studies are needed to better characterize these patients, to determine which patients with Chiari I malformation are better served with bony decompression only, and which will require duraplasty to resolve their hydromyelia.

Low grade gliomas treated with adjuvant radiation therapy in the modern imaging era.

The purpose of this study is to evaluate tumor control and failure patterns in patients with low grade gliomas treated with surgery and conventional adjuvant radiation therapy. Twenty-eight patients with low grade gliomas (7 grade I, 21 grade II) were retrospectively evaluated. Extent of resection was gross total (3), subtotal (17), and biopsy alone (8). All grade I tumors underwent subtotal resection. Median radiation therapy dose was 54 Gy delivered to localized fields. Tumor control and patterns of failure were determined from follow-up computed tomography and/or magnetic resonance scans. Median follow-up was 86 months (range, 2.4-177 months). Thirteen patients (46%) (four grade I, nine grade II) developed tumor progression. The 5-year actuarial progression-free survival rates for grade I and grade II patients were 86% and 51%, respectively. Corresponding 5-year actuarial survival rates were 100% and 70%. All recurrences were within the treated volume. Our results reveal that conventional adjuvant radiation therapy is associated with high rates of local tumor progression in both grade II and incompletely resected grade I low grade gliomas. Alternative strategies need to be explored in these patients in an effort to improve tumor control and outcome.

Safety of perioperative subcutaneous heparin for prophylaxis of venous thromboembolism in patients undergoing craniotomy.

OBJECTIVE: To determine whether perioperative subcutaneous heparin is safe to use for patients undergoing craniotomy and to determine the incidence of venous thromboembolism in patients undergoing craniotomy. METHODS: Perioperative prophylaxis with subcutaneous heparin, 5000 U every 12 hours, was begun at induction of anesthesia for craniotomy and continued for 7 days postoperatively or until the patient was ambulating. Entry criteria to the study included patient age over 18 years and no evidence of deep vein thrombosis (DVT) preoperatively as judged by lower limb duplex ultrasound. Patients were excluded if they had duplex evidence of DVT or clinical evidence of pulmonary embolus (PE) preoperatively, had hypersensitivity to heparin or related products, had sustained a penetrating head injury, or refused informed consent. Any patient undergoing craniotomy was eligible, including patients with a ruptured aneurysm or arteriovenous malformation and those with spontaneous intracranial hemorrhage. Patients underwent duplex study 1 week after surgery and 1 month of clinical follow-up. Records were also kept on 68 nonstudy patients who refused consent. All patients were treated with lower limb pneumatic compression devices. RESULTS: One hundred six patients were treated. No differences were noted between study and nonstudy patients in some individual risk factors for DVT or PE, such as obesity, smoking, paralysis, infection, pregnancy or postpartum state, varicose veins, heart failure, or previous DVT or PE. Significantly more (43 of 106) patients in the study group had a history of risk factors for DVT or PE, particularly malignancy, however, compared with nonstudy patients (20 of 68 patients; chi2, P < 0.01). There were no differences between groups in intraoperative blood loss, transfusion requirements, or postoperative platelet counts. Four clinically significant hemorrhages occurred during surgery in patients receiving heparin. Three resulted from intraoperative aneurysm rupture and one from intraventricular bleeding during resection of an arteriovenous malformation. These events were believed to be related to known complications of these operations, not to heparin. Of the study patients, two developed symptomatic DVT and one developed a nonfatal PE during the 1-month postoperative period. One additional study patient developed DVT below the popliteal veins, which was not treated. Four study patients developed DVT 1 to 2 months after surgery. In nonstudy patients, three developed DVT and two developed PE (one fatal, one nonfatal). CONCLUSION: Perioperative heparin may be safe to administer to patients undergoing craniotomy, but a larger study is needed to demonstrate efficacy.

Quantitative imaging study of extent of surgical resection and prognosis of malignant astrocytomas.

OBJECTIVE: This study used quantitative radiological imaging to determine the effect of surgical resection on postoperative survival of patients with malignant astrocytomas. Previous studies relied on the surgeons' impressions of the amount of tumor removed, which is a less reliable measure of the extent of resection. METHODS: Information concerning possible prognostic factors was collected for 75 patients undergoing magnetic resonance imaging or computed tomography preoperatively and within 10 days postoperatively. Image analysis of the neuroradiological studies was conducted to quantify pre- and postoperative total tumor volumes and enhancing volumes. Univariate and multivariate proportional hazards models were used to analyze the regression of survival regarding 22 covariates that might affect survival. The covariates that were entered included age, gender, tumor grade, cumulative radiation dose, chemotherapy, seizures as a first symptom, Karnofsky performance status at presentation, pre- and postoperative total and enhancing tumor volumes, ratio of pre- to postoperative total and enhancing tumor volumes, tumor location, surgeon's impression of the degree of resection, and subsequent surgery. RESULTS: There were 23 patients with anaplastic astrocytomas and 52 with glioblastomas multiforme. The estimated mean survival time was 27 months for patients undergoing gross total resection, 33 months for subtotal resection, and 13 months for open or stereotactic biopsy. Five factors that were significant predictors of survival in multivariate analysis were tumor grade, age, Karnofsky performance status, radiation dose, and postoperative complications (P < 0.05). In univariate analysis, tumor grade, radiation dose, age, Karnofsky status, complications, presence of enhancing tumor in postoperative imaging, and postoperative volume of enhancing tumor were significantly associated with survival (P < 0.05). CONCLUSION: We conclude that the most important prognostic factors affecting survival of patients with anaplastic astrocytomas and glioblastomas multiforme are tumor grade, age, preoperative performance status, and radiation therapy. Postoperative complications adversely affect survival. Aggressive surgical resection did not impart a significant increase in survival time. Surgical resection may improve survival, but its importance is less than that of other factors and may be demonstrable only by larger studies.

Concomitant chemoradiotherapy, neutron boost, and adjuvant chemotherapy for anaplastic astrocytoma and glioblastoma multiforme.

The survival rate for patients with malignant gliomas is poor. We describe the results of a prospective study using concomitant chemoradiotherapy, neutron boost, and adjuvant chemotherapy for patients with malignant gliomas. Forty-two patients with anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) were treated with postoperative photon radiation 45 Gy/25 fraction (fxs) with concomitant continuous intravenous infusion of 5-fluorouracil at 300 mg/m2/day x 5 days and hydroxyurea 0.5 g orally every 12 hr for 6 days for 5 consecutive weeks, followed by a neutron boost of 450 N cGy/6 fxs delivered twice weekly. Adjuvant chemotherapy with procarbazine, CCNU, and vincristine (PCV) was given up to 1 year or until tumor progression. Thirty-four patients (81%) had GBM and 8 patients (19%) had AA. Sixteen patients (38%) were ineligible for the neutron boost because of large tumors or poor performance status and instead received a photon boost with concomitant chemotherapy for a total dose of 60-65 Gy to the tumor. The overall median survival is 68 weeks at a median follow-up of 203 weeks (range 166-302 weeks for the 11 patients remaining alive); 7/8 patients with AA are alive, 2 of these with progressive disease. For AA the median survival is not reached at a median follow-up of 203 weeks (range 166-302 weeks for the 7 patients alive with AA). Time to tumor progression for the 1 dead patient with AA was 35 weeks and the other 2 patients failed at 171 weeks and 179 weeks following treatment. The median survival for the 34 patients with GBM was 62 weeks; 4/34 patients with GBM are alive at 285, 238, 216, and 206 weeks. Multivariate survival analysis in the 34 patients with GBM revealed age and Karnofsky performance status as important prognostic factors. Extent of surgery and neutrons did not affect survival. Concomitant chemoradiotherapy was well tolerated by all patients. The only toxicities observed were mucositis < or = grade II in 3 patients (7%) and mild myelosuppression in 1 patient (2.4%). Adjuvant PCV was well tolerated. Continuous concomitant chemoradiotherapy was well tolerated by all patients with acceptable side effects. The survival rate for the patients with GBM suggests no significant impact on the prognosis for these patients. Patients with AA did well; however, the patient numbers are small.

Alcohol consumption by nursing rats and its effect on the cerebellum of the offspring.

To study the effect of alcohol on Purkinje cells and on myelination of the cerebellum of neonate rats, female Sprague-Dawley rats were fed alcohol (ethanol) during their nursing period. The alcohol was given in amounts of 5% or 10% per volume of drinking water. Food and liquids, equal in calories, were distributed among dams receiving alcohol. One group of control rats received similar diet but no alcohol. The results were then compared with those of a second group of controls, receiving no alcohol but having access to unlimited supplies of food and water. Histological examination of pups revealed degenerative changes in Purkinje cells and delayed myelination of the cerebellum.

"Instant-mix" whole brain photon with neutron boost radiotherapy for malignant gliomas.

From July 1985 through March 1987, 44 consecutive patients with supratentorial, nonmetastatic anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) were treated with whole brain photon irradiation with concomitant neutron boost at the University of Chicago. All patients had biopsy proven disease and surgery ranged from biopsy to total gross excision. Whole brain photon radiation was given at 1.5 Gy per fraction, 5 days weekly for a total dose of 45 Gy in 6 weeks. Neutron boost radiation was prescribed to a target minimum dose that included the pre-surgical CT tumor volume plus 1 cm margin. Neutrons were administered 5-20 minutes prior to photon radiation twice weekly and a total dose of 5.2 Gyn gamma was administered over 6 weeks. Median follow-up was 36 months. The median survival was 40.3 months for anaplastic astrocytoma (10 patients) and 11 months for glioblastoma multiforme (34 patients) and 12 months for the overall group. Variables that predicted longer median survival included histology (AA vs. GBM), age (less than or equal to 39 years vs. older), and extent of surgery (total gross or partial excision vs. biopsy) whereas tumor size and Karnofsky performance status did not have a significant influence. The median survival of the anaplastic astrocytoma group was better than expected compared to the RTOG 80-07 study (a dose-finding study of similar design to this study) and historical data. Reasons for this are discussed.

Three-dimensional magnetic resonance images of the brain: application to neurosurgical planning.

Data from single 10-minute magnetic resonance scans were used to create three-dimensional (3-D) views of the surfaces of the brain and skin of 12 patients. In each case, these views were used to make a preoperative assessment of the relationship of lesions to brain surface structures associated with movement, sensation, hearing, and speech. Interactive software was written so that the user could "slice" through the 3-D computer model and inspect cross-sectional images at any level. A surgery simulation program was written so that surgeons were able to "rehearse" craniotomies on 3-D computer models before performing the actual operations. In each case, the qualitative accuracy of the 3-D views was confirmed by intraoperative inspection of the brain surface and by intraoperative electrophysiological mapping, when available.

Reconstruction of large cranial defects in the presence of heavy radiation damage and infection utilizing tissue transferred by microvascular anastomoses.

Six cases of large defects of the scalp, skull, and dura following tumor ablation and radiation are presented. Each was accompanied by chronic infection in the irradiated defect. Efforts to reconstruct the resulting defects with local flaps were not successful. One-stage reconstruction was then accomplished in each case utilizing a latissimus dorsi musculocutaneous or myo-osteocutaneous free flap transferred by microvascular anastomoses. The versatility of the latissimus dorsi musculocutaneous and/or osseous flap allows single-stage reconstruction of these complex defects.

Microvascular alterations following cerebral contusion in rats. Light, scanning, and electron microscope study.

Cerebral contusion was caused in 18 rats by dropping various weights on an exposed dura of one hemisphere. One or 3 hours after the injury the animals were sacrificed by perfusion with paraformaldehyde-glutaraldehyde solution. The traumatic microvascular and neural tissue alterations were studied with light, scanning, and electron microscopic techniques. The microvascular obstructions and damage were revealed in this study as major histological alterations, causing secondary neural damage. The obstruction of the vessels appeared to have been caused 1) by extravascular pressure from destroyed and swollen tissue, petechial hemorrhage, and dissecting extraluminal clots; and 2) by intravascular clots. Besides the tearing and shearing effects causing petechial hemorrhages, the capillary walls were often thinned and irregular.

Brain-tumor imaging using radiopaque perfluorocarbon. A preliminary report.

Perfluorocarbon, a new tumor-seeking x-ray contrast agent, was injected into three rats with experimental brain tumors. After 1 to 3 days the rats were sacrificed, and the brains were removed and subjected to x-ray study. All showed dense radiopaque areas which correlated with the size and shape of the corresponding brain tumors. Conversely, none of the radiograms taken of the brain tumor in five rats receiving no perfluorocarbon (control animals) showed similar increased density. These findings suggest that perfluorocarbon may serve a useful role as a contrast medium for computerized tomography studies of brain tumors in man.

Treatment of grade III and IV astrocytomas with BCNU alone and in combination with VM-26 following surgery and radiation therapy.

Twenty-one patients with grade III or IV astrocytomas were assigned randomly to receive either BCNU alone or BCNU and VM-26 after surgery and radiation therapy. Patients surviving radiation therapy and receiving single-agent chemotherapy had a median survival of 14 months while those receiving combination chemotherapy had a median survival of 22 months (P greater than 0.05). None of the patients who failed BCNU-only therapy responded to VM-26. Performance status was not affected by either regimen. Computerized tomographic scanning of the brain was useful only in confirming tumor progression. Two patients died from BCNU-related interstitial pulmonary fibrosis.