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OBJECTIVE: Although the chemotherapy drug hydroxyurea (HU) and the antiprogesterone mifepristone (RU486) have been used to treat meningiomas for which surgical and radiation therapies have failed, results have been disappointing. The addition of calcium channel antagonists (CCAs) to chemotherapeutic drugs enhances tumor growth inhibition in other tumor types, and the authors demonstrated that CCAs can block meningioma growth in vitro and in vivo. The purpose of this study was to test the effects of the addition of a CCA to HU or RU486 on meningioma growth. METHODS: Primary and malignant (IOMM-Lee) meningioma cell lines were treated with HU, RU486, or either of these plus diltiazem or verapamil. Assays for cell growth, apoptosis, and fluorescent-activated cell sorting were performed on in vitro cultures. Similar cell lines were implanted into nude mice and were treated with HU or RU486, in combination with a CCA. Tumors were analyzed by light microscopy, MIB-1, and factor VIII immunohistochemical staining studies. RESULTS: The addition of diltiazem or verapamil to HU or RU486 augmented meningioma growth inhibition by 20 to 60% in vitro. In vivo, tumors treated with combination drugs were smaller; and immunohistochemical analysis of the IOMM-Lee tumors showed a 10% decrease in the MIB-1 ratio (from 0.41 to 0.30) and an approximate 75% decrease in microvascular density. CONCLUSION: The addition of diltiazem or verapamil to HU or RU486 augments meningioma growth inhibition in vitro by inducing apoptosis and G1 cell-cycle arrest. The combination of HU and diltiazem inhibited the growth of meningiomas in vivo by decreasing proliferation and microvascular density. These results suggest a possible role for these drugs as an additional adjuvant therapy for recurrent or unresectable meningiomas.

OBJECTIVE : We report a group of eight patients with a distinctive histological variant of meningioma that is associated with severe peritumoral edema. The clinical presentation, radiographic findings, and histology of this type of tumor may lead to misdiagnosis as an aggressive or malignant process. METHODS : We reviewed the histology from patients who had removal of meningiomas performed in our institution between 1978 and 1992. Tumors having abnormal proliferation of cells in the intramural vascular spaces were selected for study ; case histories and radiographs were reviewed. Tumor material was subjected to special stains, immunocytochemical examination, and electron microscopy. RESULTS : Several lesions were misread radiographically as being malignant. Patients underwent craniotomy with complete excision of the tumor. All lesions were small (≤3 cm), and no brain invasion, unusual tumor vascularity, or dural sinus involvement was noted in any case. Histologically, the meningioma pattern in each case was meningothelial and benign in appearance. The immunocytochemical and electron microscopic features of the unusual cells in the blood vessel walls are most consistent with their being of pericytic origin. All patients have remained asymptomatic and without evidence of tumor recurrence with follow-up from 3 to 12 years. CONCLUSION : These tumors showed proliferation of pericytes in blood vessel walls and represent a new subtype of meningothelial meningioma. The apparently benign nature of these lesions necessitates their recognition. Characteristic findings of pericytic proliferation associated with edema generation have led us to descriptively term this the PEG variant of meningioma.

We physicians are the drivers, the people who select the patients, the people who do the operations, and the people who encourage the instrument companies; it is our responsibility to oversee both the effectiveness of treatment and its cost. The resources available to neurosurgery for improving care, controlling cost, and promoting research include the following. 1. The outstanding spinal neurosurgeons actively participating in excellent clinical care and research, neurosurgeons in training, and neurosurgeons committed to excellence. 2. A commitment by neurosurgery to improve the plight of the patients with spinal disorders. 3. Support from instrument and drug companies and national funding. 4. A medical wave of support for outcome studies and clinical trials. 5. A proven track record in doing clinical trials and a clear indication that others are in process. 6. The knowledge, abilities, and energies of neurosurgeons. Our liabilities include the following. 1. Irresponsible behavior by a few professionals. 2. The negative effects of competition with non-neurosurgical spinal surgeons. We must obtain their support in many of these clinical trials. 3. Inertia. It is much easier to take the path of least resistance, much easier to choose the course of economic incentive. Perhaps, out of all of this, spinal neurosurgery will lead the way to developing a better understanding of the natural history of degenerative diseases of the spine and the way to selecting patients properly on the basis of studies of the efficacy of appropriate surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral edema is usually a complication of the later growth stages of intracranial neoplasms. Three patients with small meningiomas presented with unusually several cerebral edema out of proportion to the size of tumors. All three tumors exhibited benign meningothelial components, the formation of pseudopsammoma bodies, and striking vascular mural proliferation of small dark cells. In two tumors ultrastructural examination of these cells showed features of pericytes. The vascular pericytic component in these tumors may grow more actively than the meningothelial component and thus may cause the production of severe cerebral edema. The clinical, radiological, operative, and light and electron microscopic findings are presented, and the relationship to angioblastic meningiomas is discussed.

Intracranial atypical teratomas are midline brain tumors with both germinomatous and teratomatous elements. When they occur in the suprasellar region, they usually present with a classic triad of visual disturbances, diabetes insipidus, and hypopituitarism. We report the case of a suprasellar atypical teratoma that presented as an intrasellar lesion and caused secondary amenorrhea in a 15-year-old girl.

The natural history of intracranial arteriovenous malformations (AVMs) was studied in 131 patients. The 83 patients managed nonsurgically and the 48 patients treated surgically were followed for an average of 8 years. Hemorrhage occurred in 61.8% of all patients. A second hemorrhage occurred in 67.4% of the survivors of the first hemorrhage. The mortality associated with recurrent hemorrhage did not increase significantly with successive episodes of hemorrhage. The rate of rebleeding was 17.9%/year initially, but declined to 3%/year after 5 years and then to 2%/year after 10 years. Among patients treated nonsurgically, the prognosis was more favorable for patients presenting with seizures than for patients presenting with hemorrhage. Patients in the seizure group had a 26.9% incidence of hemorrhage causing an 11.6% mortality; 40.5% of the patients in the hemorrhage group died. The prognosis was poor for patients with posterior fossa A V Ms; the mortality was 66.7% with the first hemorrhage. Recurrent posterior fossa hemorrhage was the rule in survivors, and most of those hemorrhages were fatal. The prognosis for children with AVMs was no different from that for adults.

Infarction of the central nervous system secondary to embolism from left atrial myxoma is a recognized phenomenon. However, myxoma as the source of an embolus may be overlooked if an index of suspicion is not present during the evaluation of the patient with a stroke without a known cause. We present a case report that illustrates some of the pitfalls and characteristic findings present in the evaluation of these patients. The magnetic resonance image of multiple cerebral aneurysms and infarction associated with this condition is presented along with a unique, arteriographically proven resolution of a fusiform cerebral aneurysm after the removal of the cardiac tumor. A review of published case reports suggests that, if the cardiac tumor is recognized and treated quickly, the ultimate prognosis, while uncertain, is usually good. However, because the potential exists for recurrence of the cardiac tumor, for enlargement of the cerebral lesions, or for late development of cerebral lesions, long term follow-up is mandatory and a vigorous work-up must be pursued if the patient again becomes symptomatic or develops central nervous system manifestations for the first time.

Symptomatic Arnold-Chiari malformation (Chiari II) is a recently described clinical entity, the natural history and surgical management of which remain controversial. The brain stem auditory evoked potentials (BAEPs) have been described as abnormal in 50 to 86% of children with myelomeningocele. We present the case of a full-term infant with myelomeningocele, shunted hydrocephalus, and Chiari II malformation who was surgically treated by decompression when she was 3 weeks old. BAEPs recorded immediately after decompression showed dramatic improvement over BAEPs recorded immediately before decompression, an improvement that could not be attributed to maturation of the central nervous system. It is postulated that in further large series the degree of abnormality in BAEPs may be of value in predicting the clinical course of these patients. The current status of BAEPs as they apply to the evaluation of posterior fossa anomalies is reviewed. (Neurosurgery 16:48–53, 1985)

Although meningiomas are known to cause varying degrees of cerebral edema, the relative importance of their location, size, histological subtype, and other histological features in the production of cerebral edema has not been studied adequately. Therefore, we undertook a retrospective analysis of 43 meningiomas excised between 1975 and 1980. The results indicate that histological subtype has no relationship to the production of cerebral edema, with one exception. Meningiomas containing partly or completely a hemangiopericytic component were the only histological subtype associated consistently with cerebral edema. The location of a meningioma per se may not determine the production of cerebral edema. A relationship between size, aggressive histological features, vascular proliferative changes, and the production of cerebral edema was seen. The need for and the nature of further studies required to explain the cerebral edema that may be associated with small meningiomas are discussed.

Meningiomas have a wide range of biological potential and clinical behavior. Histological findings are helpful in recognizing the malignant potential of a given tumor, but often fail to correlate with gross features, liability of recurrence, and extent of associated cerebral edema. To find alternate approaches to improve the correlation between biological and clinical behavior, 20 meningiomas were studied by flow cytometry (FC), an assessment that has been applied to meningiomas previously. Such FC features as DNA index (DI) and proliferative index (PI, %G2 † %S) were correlated with size, location, brain invasion, associated edema, and recurrence. Tumors with severe edema had significantly higher PIs (19.5 ± 4.1) than those with moderate (12.6 ± 4.5) or minimal (8 ± 0) edema (P < 0.05). The PI was greater than 16 in those tumors that recurred (n = 3) or invaded the brain (n = 3). Six tumors were aneuploid (DI, 1.33 ± 0.17; PI, 17.1 ± 5.3). These were uniformly large when compared with the diploid tumors, which were more variable in size. All of the aneuploid tumors were associated with moderate to severe cerebral edema. Two partly psammomatous tumors with high PIs and foci of high cellularity suggesting recent growth were associated with severe edema. One of these exhibited brain invasion. These preliminary data indicate that FC may have a potential use in the clinical management of meningiomas.

Post-traumatic acalculous cholecystitis is a potentially lethal complication that may develop in patients during hospitalization for trauma. Three case reports illustrate that obscuration of many early diagnostic symptoms and signs may make this complication particularly treacherous in the neurosurgical patient. Suspicion should be aroused by unexplained fever, leukocytosis, elevated serum bilirubin and alkaline phosphatase values, and developing intolerance to oral or tube feedings. There may be a rapid progression to signs of an acute abdominal condition. Symptoms are most likely to occur 1 week to 1 month after the episode of trauma. Patients of all ages are susceptible. Diagnosis is best confirmed by noninvasive iminodiacetic acid hepatobiliary scanning accompanied by ultrasound or abdominal computed tomographic scanning. The treatment of choice is emergency cholecystectomy. The cause is most likely multifactorial and is probably related to hypotension, sepsis, or biliary stasis with subsequent cystic duct obstruction. Although this disease is rare, its incidence is apparently increasing, and a high index of suspicion is warranted in the neurosurgeon involved in the care of the biliary tract disorder.

Although the advent of computerized cranial tomography (CT) has decreased the number of pneumoencephalograms performed for the diagnosis of hydrocephalus and lesions of the posterior fossa, brain stem, and ventricles, there are some patients in whom pneumoencephalography should still be done because it adds valuable information to that obtained with CT. When the temporal horn becomes obstructed, the choroid plexus and ependymal surface “upstream” from the obstructing mass continue to produce cerebrospinal fluid (CSF). The temporal horn can thus enlarge enough to appear as a mass on CT because of its reduced x-ray attenuation coefficient. Pneumoencephalography is effective in this situation because air will flow past a mass that obstructs CSF and because the ventricular system dilates during pneumoencephalography. When pneumoencephalography is used in a patient with a trapped temporal horn, the partially trapped horn may enlarge approximately 24 hours later. With that precaution in mind, the neurosurgeon should find pneumoencephalography to be a useful adjunct to CT in delineating the cause of a trapped temporal horn. In the three patients reported here CT had indicated a unilateral trapped temporal horn; pneumoencephalography confirmed that finding and demonstrated both the location and the nature of the lesion. One patient had a Grade II astrocytoma fungating into the atrium of the right lateral ventricle, one had a mass extending into the right ventricle from the medial and superior ventricular wall with nodular encroachment on the ventricle, and one had a meningioma in the atrium of the right lateral ventricle.

Upward projection of the cerebellar vermis through the tentorial hiatus is called upward vermal herniation (UVH). UVH is less common in clinical practice than uncal herniation. Even more uncommon is chronic vermal herniation and impaction in the tentorial hiatus. To illustrate this phenomenon, we present the clinical, radiological, and morphological features of vermal impaction in a patient with a postradiation osteosarcoma of the occipital bone. In spite of nearly total excision of the tumor pushing the cerebellum upward, his postoperative course was complicated by respiratory problems and an altered level of consciousness, finally resulting in death. His clinical status paralleled the computed tomographic (CT) demonstration of persistent obliteration of the supramesencephalic cistern. CT makes more reliable the detection and management of UVH, but a high index of suspicion is necessary for prevention of this complication.

Six cases of traumatic dissection of the extracranial carotid artery that were all treated conservatively are reported. The initial trauma was believed to be an intimal tear caused by severe stretching of the artery over the process of a cervical vertebra due to sudden hyperextension and lateral flexion of the neck to the opposite side. No clinical evidence of neck trauma was present, but one patient had roentgenographic evidence of cervical spine fracture. Four-vessel angiography was diagnostic in all six patients and was useful during follow-up in the four in whom it was done.

Lhermitte-Duclos disease is a rare, benign cerebellar condition that mimics a posterior fossa mass and has never been diagnosed preoperatively. Grossly, the diseased cerebellar tissue is tough and poorly demarcated; microscopically, the cortex has a thick outer layer of nerve fibers, an inner layer of abnormal ganglion cells, and the absence of normal Purkinje cells. The prognosis, based on cases treated surgically since 1955, is good. A case is reported in which cranial computerized tomography performed 5 years after the partial removal of abnormal tissue showed neither enhancement nor radiolucency.

Computed tomography in a 3 1/2-year-old boy with ataxia, lethargy, fever, vomiting, and increasing irritability revealed moderate hydrocephalus and a blood density mass lesion lying superior and posterior to the 3rd ventricle. On several of the sections, the blood density was greater in the dependent than in the superior portion of the mass. The average attenuation number within the mass was 40 EMI units. The infusion of contrast agent demonstrated capsular enhancement (a target sign), which was also demonstrated by angiography. The diagnosis, which was confirmed at operation, was thrombosis of an aneurysm of the vein of Galen. The massive thrombus was resected, but the aneurysm was not excised. The patient's recovery was uneventful.

A male newborn with a large scalp and skull defect and a cervical meningocele was transferred to the neonatal intensive care unit of the North Carolina Baptist Hospital. The scalp defect measured 8.5 x 9.5 cm, and the sagittal sinus was exposed. Because the defect was considered too large to be covered with a rotation skin flap, it was treated thrice daily with the topical application of bacitracin ointment and circumferential dressings. By the end of 3 months, the skull defect was covered with skin. The cervical meningocele was then removed without incident. At the 9-month follow-up examination, the scalp defect was well healed and the skull defect was closing slowly; the neurological findings were still normal for the patient's age.

Infection of cerebrospinal fluid shunts with Candida albicans is reported in two patients. Scanning electron microscopy in one case demonstrates the relationship of the Candida hyphae to the white blood cells and to silicone plastic. A review of 10 previously reported cases of Candida shunt infection indicates that the infection usually follows a major bacterial infection or direct contamination or occurs spontaneously, Previous therapy has usually involved removal of the shunt, and the role of parenteral antifungal therapy is still unclear. Overall mortality to date is 25%.

A technique for fixation of C-1, C-2, and C-3 for odontoid fractures is described. Fixation wires between the laminae of the atlas and the spinous process of the axis maintain the atlantoaxial alignment. Kirschner wire pins through the spinous processes of C-2 and C-3 act as reinforcing bars for a methyl methacrylate fusion. (Neurosurgery 8:374-377, 1981)

It has been suggested that concentrations of fibrin degradation products (FDPs) after head injury reflect the extent of brain tissue destruction. In addition, elevated FDP concentrations have been associated with the development of the adult respiratory distress syndrome (ARDS). Coagulation variables, including a FDP screen, were measured on the admission of 33 patients with severe closed head injury (Glasgow coma score 8 or less) to define the prognostic value of FDP concentrations. A Glasgow outcome score was assigned to each patient 6 months after injury, and those patients with higher FDP concentrations had poorer functional outcomes. This correlation of outcome with admission FDP concentration was statistically significant, as was the correlation between outcome and the admission Glasgow coma score. Of 22 patients with FDP concentrations of less than 64 micrograms/ml, only 1 developed early respiratory failure, whereas 9 of 11 patients with FDP concentrations of 64 micrograms/ml or more developed ARDS. These findings were not affected by the presence of multiple system trauma. FDP concentrations seem to have prognostic value similar to the Glasgow coma score and seem to identify those patients with head injury who are at high risk for ARDS.

A 42-year-old man with severe testicular failure (testosterone 24 ng/dl, normal 300-1100) was found to have a nonfunctioning chromophobe pituitary adenoma. Resection of the pituitary tumor resulted in recovery of gonadal function (testosterone 359 ng/dl). Hypogonadism caused by pituitary adenomas is usually attributed to either hyperprolactinemia or irreversible destruction of normal pituitary tissue, neither of which is applicable to this patient. The recovery of our patient's gonadal function after operation suggests that a reversible compression of viable tissue or impairment of hypothalamic-pituitary communications was responsible for his endocrine deficiency. (Neurosurgery 22:386-387, 1988)

Surgical stabilization of traumatic fracture-dislocations of the lower cervical spine with wire and methylmethacrylate remains a controversial procedure. Yet, the resultant immediate fixation with minimal patient morbidity seems to indicate that this method provides an ideal stabilization construct. We describe and report the outcome of a technique of posterior cervical fixation with methylmethacrylate and wire for stabilization of traumatic fractures of the lower cervical spine. Over a 12-year period, 124 fracture-dislocations of the lower cervical spine in 99 patients (mean age, 32 years; range, 15-76 years) were treated at this institution using a posterior methylmethacrylate and wire technique. Eighty-two patients had a posterior element fracture; 28 had a vertebral compression with posterior ligamentous injury; and 14 had a ligamentous injury alone. Thirty-six patients were neurologically intact upon admission, while the rest had radiculopathy or partial or complete myelopathy. Ninety-one patients were available for follow-up [mean, 18.6 months; range, 1-100 months (8.33 years)]. Eighty-eight patients (97%) had a stable fixation and 77 (85%) had resumed preoperative activity or were working but with a residual deficit. Complications included fixation failure requiring a second operation in 3 patients, nonlethal pulmonary embolism in 2 patients, lethal pulmonary embolism in 1 patient, and a superficial wound infection in 3 patients (none affected the underlying fixation construct). These results indicate that this technique is a safe, simple, and effective method for stabilizing the lower cervical spine that allows rapid patient mobility with minimal morbidity.