Neurological recovery after cranioplasty.

A patient who sustained a gunshot wound to the head was successfully treated with acute neurosurgical intervention. Six months after the injury, cranioplasty was used to repair a large skull defect. After cranioplasty, the patient developed significant improvement in motor function in his left upper extremity, which had been plegic after his injury. Although the mechanism of neurological recovery after cranioplasty is controversial, the occurrence of such improvement may be a sufficient indication for cranioplasty in certain patients.

Hydrocephalus in Apert syndrome: a retrospective review.

A retrospective evaluation was carried out to define the incidence of hydrocephalus and associated factors in 44 patients with Apert syndrome treated at The Hospital for Sick Children in Toronto over a 22-year period. Forty-three of these patients underwent cranioorbital decompressive procedures within 1 year of birth. Fifteen of 25 (60%) patients who had either a computed tomography scan or pneumoencephalogram had ventriculomegaly, and 3 of the 25 (12%) had associated brain anomalies. Ten of the 44 (23%) patients had cerebrospinal fluid (CSF) shunts placed, 7 lumboperitoneal and 3 ventriculoperitoneal. Six of the shunts were placed early after cranioorbital procedures (CSF leaks in 5 cases and a subgaleal fluid collection in 1 case). The average IQ of 15 patients evaluated by the Wechsler Intelligence Scale was 72.5, indicative of significant intellectual impairment. There was no correlation between IQ and ventricular size. Although hydrocephalus characterized by progressive ventricular dilatation is uncommon in Apert syndrome, postoperative problems related to impaired CSF circulation are common and may indicate an underlying CSF absorptive deficit.

Pediatric spinal axis tumors.

Pediatric spinal cord tumors occur in the intramedullary or extramedullary spaces. The extramedullary tumors are further divided into those in intradural-extramedullary or extradural locations. Tumors in the intradural-extramedullary region include nerve sheath tumors, meningiomas, and "embryonal" tumors. In the extradural space are neuroblastomas, sarcomas, and other primary tumors of bone. The radiographic findings, histology, and management of each type of tumor are included in this article, which focuses on extramedullary tumors.

Magnetic resonance imaging in myelocystoceles. Report of two cases.

Two cases of terminal myelocystocele, a rare localized cystic dilatation of the caudal spinal central canal, are reviewed. Magnetic resonance imaging is a useful diagnostic tool for its evaluation. Terminal myelocystocele consists of the following: a myelocystocele which contains a "trumpet-like" flaring of the distal spinal cord central canal and thus is partially lined by ependymal tissue; a meningocele or dilated subarachnoid space located around the myelocystocele, which bulges into the subcutaneous region; and fibrolipomatous tissue surrounding the two cysts. This condition is usually associated with abnormalities of the vertebral column and sacrum as well as compression of the spinal cord and meningocele by a fibrous band. There is a possible relationship of the myelocystocele to teratogens such as loperamide HCl and retinoic acid, although the exact etiology of this entity is not known.

Absence of contrast enhancement on CT brain scans of patients with supratentorial malignant gliomas.

The medical records of 229 consecutive patients with supratentorial malignant gliomas were reviewed with respect to histology, age at diagnosis, tumor location, and enhancement pattern on the CT obtained after the administration of contrast material at the time of operation. Nonenhancing tumors were identified in four (4%) of 93 patients with glioblastoma multiforme (GM), three (30%) of ten with gemistocytic astrocytoma (GA), 23 (31%) of 74 with highly anaplastic astrocytoma (HAA), and 28 (54%) of 52 with moderately anaplastic astrocytoma (MoAA). The age-related incidence of the various glioma histiotypes (both enhancing and nonenhancing) was reflected by the median age at diagnosis: 50 years in GM, 52 years in GA, 40 years in HAA, and 34 years in MoAA. The age and CT contrast enhancement pattern were similar in patients with GM, GA, and MoAA; patients with nonenhancing HAAs tended to be younger at presentation. The tumor location and the frequency of enhancing and nonenhancing lesions were similar for all groups except MoAA, in which nonenhancing tumors were most often frontotemporal and enhancing tumors were usually frontoparietal. Our results demonstrate that it is important to obtain histologic confirmation of the diagnosis in patients with supratentorial gliomas regardless of the presence or absence of contrast enhancement of the tumor on CT, because neither of these characteristics correlates with the tumor histology.

Pediatric central nervous system tumors: a cell kinetic study with bromodeoxyuridine.

Bromodeoxyuridine (BrdU), 150 to 200 mg/m2, was administered at the time of operation to 20 pediatric patients with neuroectodermal tumors to label tumor cells in the S phase. Immunocytochemical techniques were used on excised tumor specimens to detect cells containing BrdU, and the BrdU labeling index (LI) was calculated as the number of BrdU-labeled cells divided by the total number of cells counted. Four medulloblastomas, three glioblastomas multiforme, and two highly anaplastic astrocytomas had average BrdU LIs of 13.0 +/- 3.0% (SE), 12.7 +/- 4.3%, and 14.6 +/- 6.7%, respectively. Three of nine moderately anaplastic astrocytomas had BrdU LIs of greater than 1% (average, 6.5 +/- 2.4%), whereas six had LIs of less than 1%. In two juvenile pilocytic astrocytomas, which are considered slow-growing, the BrdU LIs were unexpectedly high, averaging 6.5 +/- 1.4%. Thus pediatric medulloblastomas, glioblastomas multiforme, highly anaplastic astrocytomas, and a minority of moderately anaplastic astrocytomas had high proliferative potentials, whereas most of the moderately anaplastic astrocytomas had low proliferative potentials. Although the number of cases in this study is still too small to yield statistically significant comparisons, the results indicate that some pediatric tumors have considerably higher LIs than histologically similar adult tumors studied previously.

Computerized tomography in the prognosis of malignant cerebral gliomas.

Ninety-seven patients with supratentorial malignant gliomas who received postoperative radiation therapy and chemotherapy at the University of California, San Francisco, from 1977 through 1984 showed improvement in their follow-up computerized tomography (CT) scans. Twenty-one of these 97 "CT responders" were designated "complete responders" because on serial CT scans they had complete disappearance of the tumor mass and contrast enhancement, which had been present postoperatively. In the remaining 76 patients, CT scans showed reduction in the size, but not disappearance, of the lesions, and these were designated "partial responders." Fifty-eight partial responders had glioblastoma multiforme (GM); their median survival time was 72 weeks. The median survival time for the 11 complete responders with GM has not yet been achieved, but survival at the 53rd percentile is 172 weeks. Among patients with highly anaplastic astrocytoma, the median survival time was 211 weeks for the 10 complete responders and 125 weeks for the 18 partial responders. Eleven of the 21 complete responders are alive at a median postoperative follow-up time of 163 weeks (range 114 to 470 weeks). Eighteen of these patients had subtotal resection of tumor; three patients had gross total tumor resections, but postoperative CT scans showed evidence of residual or possibly recurrent tumor within 1.5 to 4.5 months. Resolution of the tumor mass and contrast enhancement took 9 to 151 weeks; the time to resolution did not depend upon the configuration of the remaining tumor mass and contrast enhancement after surgery. In this study, patients with malignant gliomas whose CT scans eventually showed sustained complete disappearance of the tumor mass and contrast enhancement had a more favorable prognosis than did patients whose CT scans showed improvement, but not complete disappearance, of the tumor. These CT findings may prove useful in determining the prognosis of patients with malignant gliomas.

Gd-DTPA in clinical MR of the brain: 1. Intraaxial lesions.

Over 35 intraaxial lesions in 15 patients suspected of having intracranial tumors were studied with MR before and after injection of Gadolinium-DTPA (Gd-DTPA). Diseases included primary and metastatic brain tumors, plaques of multiple sclerosis, occult arteriovenous malformations, lymphoma, toxoplasmosis, and pituitary adenoma. The precontrast T2-weighted sequence (SE 2000/30, 60) was found to be most sensitive in detecting intraaxial lesions, showing 17 lesions that were not seen on the post-Gd-DTPA T1-weighted sequence (SE 500/30). In one case of multiple sclerosis, several lesions seen on the pre-Gd-DTPA study on T2-weighted images faded after injection of Gd-DTPA (due to T2 shortening). In two patients with large metastatic foci, other small metastatic lesions were seen better after Gd-DTPA on both T1- and T2-weighted sequences. Four other patients with only one focal-enhancing lesion and one patient with multifocal lesions on T1-weighted images actually had a much larger single glioma depicted on pre-Gd-DTPA T2-weighted images. In a patient with AIDS, a ring-enhancing lesion thought to be an abscess proved to be lymphoma. The cryptic arteriovenous malformations enhanced but showed more characteristic findings, such as hemorrhage, on pre-Gd-DTPA studies. Our experience suggests that Gd-DTPA may not improve sensitivity of MR in the detection of intraaxial lesions. However, functional aspects of brain disease, such as the presence of perfusion of a lesion and active breach of the blood-brain barrier, are depicted well with Gd-DTPA and are vital for proper diagnosis in many instances.

Gd-DTPA in clinical MR of the brain: 2. Extraaxial lesions and normal structures.

Fifteen patients with suspected extraaxial tumors were evaluated with MR before and after intravenous injection of Gadolinium-DTPA (Gd-DTPA). Meningiomas (7), neurinomas (4), chordomas (2), a previously irradiated dural metastasis, and a giant aneurysm were studied. All the lesions except the dural metastasis enhanced. In two patients with asymptomatic meningiomas, the use of Gd-DTPA with MR allowed definitive diagnosis of the lesions when the routine MR did not. Gd-DTPA also provided improved definition of intracranial tumor margins, produced differential enhancement of dura and nasopharyngeal mucosa from tumor, and caused enhancement of the choroid plexus, some venous structures, the pituitary gland, and its stalk. The enhancement of the pituitary suggests a role for Gd-DTPA in the diagnosis of microadenomas. Routine T2-weighted images without Gd-DTPA were useful in differentiating neurinomas from meningiomas. Judicious use of Gd-DTPA should improve the ability of MR to detect extraaxial lesions, delineate their extent, and characterize their perfusion.

Prediction of tumor doubling time in recurrent meningiomas. Cell kinetics studies with bromodeoxyuridine labeling.

Eight patients with recurrent meningiomas (four malignant, two hemangiopericytic, and two nonmalignant) were given intravenous bromodeoxyuridine (BUdR), 200 mg/sq m, at the time of surgery to label cells in the deoxyribonucleic acid (DNA) synthesis phase; labeled cells were detected in excised tumor specimens by immunoperoxidase staining using anti-BUdR monoclonal antibody. These tumors showed a wide range of BUdR labeling indices (LI's), calculated as the percentage of BUdR-labeled cells divided by the total number of cells scored, from 0.3% to 5.4%. The tumor doubling times (Td's), estimated from serial computerized tomography scans, ranged from 8 to 440 days and showed a close inverse correlation with the BUdR LI's. A semilogarithmic linear regression analysis of these values yielded a correlation coefficient of 0.99. Tumor doubling time (Td) can be estimated using the formula: Td = 500 X Exp (-0.73 X LI), where Exp signifies the natural log base. By predicting the growth rate of meningiomas, the BUdR LI may supplement histopathological diagnosis and improve both the determination of prognosis and the design of treatment modalities in individual patients.

Phase II study of combined carmustine, 5-fluorouracil, hydroxyurea, and 6-mercaptopurine (BFHM) for the treatment of malignant gliomas.

The Neuro-oncology Service of the University of California Brain Tumor Research Center conducted a nonrandomized phase II study to evaluate, in patients with recurrent malignant glioma, the benefit of a four-drug combination (BFHM) consisting of carmustine (1,3-bis (2-chloroethyl)-1-nitrosourea), 5-fluorouracil, hydroxyurea, and 6-mercaptopurine. There were 29 evaluable glioblastoma multiforme patients and 45 nonglioblastoma anaplastic glioma patients available for analysis. Tumor progression was analyzed as the primary study endpoint. Of the glioblastoma patients, 16 of 29 (55%) responded or stabilized on therapy; of the other anaplastic gliomas, 32 of 45 (71%) responded or stabilized. For patients who stabilized or responded to treatment, BFHM achieved a median time to tumor progression of 46 weeks with a 25th percentile time to tumor progression of 68 weeks for anaplastic gliomas and a median time to tumor progression of 23 weeks with a 25th percentile time to tumor progression of 36 weeks for glioblastoma multiforme patients. A Cox multivariate analysis demonstrated that age and Karnofsky score were important prognostic variables for these patients.

Proliferative potential of human meningiomas of the brain. A cell kinetics study with bromodeoxyuridine.

Twenty patients with intracranial meningiomas were given a 1-hour intravenous infusion of bromodeoxyuridine (BrdU), 200 mg/m2, at the time of surgery to label tumor cells in the DNA synthesis phase (S phase). The excised tumor specimens were fixed with 70% ethanol, embedded in paraffin, sectioned, and stained by an indirect immunoperoxidase method using anti-BrdU monoclonal antibody as the first antibody. The BrdU labeling index (LI), or S-phase fraction, was determined by counting the number of BrdU-labeled cells in the tissue sections. The average LIs for nonmalignant (11 cases) and histologically malignant meningiomas (seven cases) were 0.45% and 3.9% respectively (P less than 0.05). Two hemangiopericytic variants showed average LIs of 0.53% and 4.1%. Four of seven malignant meningiomas and both hemangiopericytomas were recurrent tumors. Nine of 20 meningiomas had an LI greater than 1%, and six of those nine (67%) were recurrent. Thus, meningiomas with an LI greater than 1% appear to grow faster and recur more frequently than those with LIs less than 1%; the higher LI may indicate biological malignancy. The measurement of BrdU LI in meningioma may prove valuable in establishing the diagnosis of "malignant meningioma."

S-phase fraction of human brain tumors in situ measured by uptake of bromodeoxyuridine.

One hundred fifty-four patients with brain tumors of various types were given an intravenous infusion of the thymidine analogue bromodeoxyuridine (BUdR), 200 mg/m2, at the time of surgery but before biopsy of the tumor to label S-phase cells. Excised tumor specimens were fixed, sectioned, and stained by immunoperoxidase methods to detect BUdR. The labelling index (LI), or percentage of BUdR-labelled cells, was calculated for each tumor specimen. The LIs of glioblastomas, medulloblastomas, and most highly anaplastic astrocytomas were 5% to 20%. The majority of moderately anaplastic astrocytomas showed LIs of less than 1%, but 30% of them had LIs similar to those of highly malignant gliomas. Most pituitary adenomas and neurinomas showed LIs of less than 1%. Nonmalignant meningiomas had LIs of less than 1%, whereas malignant meningiomas had LIs higher than 2.7%. This is an important observation, because malignant meningiomas are not well-defined histopathologically and their growth rate and rate of recurrence cannot be predicted by current diagnostic procedures. By estimating the proliferative potential of individual tumors more precisely, the BUdR LI supplements histopathological diagnosis, allowing a more accurate estimate of prognosis and facilitating the design of treatment regimens for individual patients.

Cell kinetics analysis in a case of teratoma of the thoracic spine.

The authors report cell kinetics studies in an infant who had multiple operations for removal of a rare benign thoracic spinal teratoma with retroperitoneal extension. Before the final surgical procedure for recurrent tumor, bromodeoxyuridine (BUdR), 200 mg/sq m, was administered intravenously to label tumor cells in the S (deoxyribonucleic acid (DNA) synthesis) phase of the cell cycle. Histologically, the tumor was a mature teratoma consisting of components derived from all three germ-cell layers. Cells labeled with BUdR were found in the basal layer of stratified squamous epithelia, in respiratory epithelia, in the cartilage and surrounding perichondrial mesenchyme, and in loose mesenchymal tissue throughout the teratoma. In contrast to neuroectodermal tumors, which show widespread BUdR uptake throughout the tissue and which have different average labeling indices according to their histological type (range less than 1% to 15.2%), the teratoma showed BUdR labeling only in certain areas, indicating fairly organized growth patterns; the labeling indices in these areas ranged from 0.39% to 1.9%.

The proliferative potential of human pituitary tumors in situ.

At the start of transsphenoidal microsurgery for removal of various types of pituitary adenomas, 21 patients received a 1-hour intravenous infusion of 5-bromodeoxyuridine (BUdR, 200 mg/sq m) to label tumor cells in the deoxyribonucleic acid (DNA) synthesis phase (S-phase). Excised tumor specimens were fixed in 70% ethanol and stained by the indirect peroxidase method using anti-BUdR monoclonal antibody as the first antibody. The percentage of BUdR-labeled cells, or S-phase fraction, was calculated for each specimen. The S-phase fraction was less than 0.1% in nine cases, 0.1% to 0.5% in seven, and greater than 0.5% in five. Except in two cases of Nelson's syndrome, in which it was greater than 1%, the S-phase fraction did not correlate with any other variable, including patient age, tumor size, or the duration of signs and symptoms. The small S-phase fraction of most of the pituitary adenomas correlates well with the clinical behavior of these tumors, which grow much more slowly than other kinds of brain tumors such as gliomas. However, the S-phase fractions varied by as much as one order of magnitude. The higher S-phase fractions may reflect aggressive and invasive growth. These results indicate that immunohistochemical studies of cell kinetics using BUdR and anti-BUdR monoclonal antibodies may provide information about the biological characteristics of pituitary adenomas which could lead to the design of appropriate treatment regimens (including surgery, radiation therapy, and chemotherapy) for individual patients.

In situ cell kinetics studies on human neuroectodermal tumors with bromodeoxyuridine labeling.

Thirty-eight patients undergoing surgical removal of neuroectodermal tumors of the central nervous system were given a 1-hour intravenous infusion of bromodeoxyuridine (BUdR), 150 to 200 mg/sq m, to label tumor cells in the deoxyribonucleic acid (DNA) synthesis phase (S-phase). The excised tumor specimens were divided into two portions: one was fixed with 70% ethanol and embedded in paraffin and the other was digested with an enzyme cocktail to make a single-cell suspension. The paraffin-embedded tissues were stained by an indirect peroxidase method using anti-BUdR monoclonal antibody (MA) as the first antibody. Single-cell suspensions were reacted with fluorescein isothiocyanate (FITC)-conjugated anti-BUdR MA's for flow cytometric analysis. S-phase cells that had incorporated BUdR into their DNA were well stained by both methods. The percentage of BUdR-labeled cells, or S-phase fraction, was calculated in tissue sections by microscopic examination and in single-cell suspensions by flow cytometric analysis. The biological malignancy of the tumors was reflected in the S-phase fractions, which were 5% to 20% for glioblastoma multiforme, medulloblastoma, and highly anaplastic astrocytoma, but less than 1% in most moderately anaplastic astrocytomas, ependymomas, and mixed gliomas. Two juvenile pilocytic astrocytomas and two low-grade astrocytomas from children had high S-phase fraction despite the fairly benign and slow-growing nature of these tumors. These results indicate that the S-phase fraction obtained immunocytochemically with anti-BUdR MA's may provide useful information in estimating the biological malignancy of human central nervous system tumors in situ.

Cell kinetic studies of in situ human brain tumors with bromodeoxyuridine.

At the time of surgery, 18 patients with various brain tumors were given a 1-h i.v. infusion of bromodeoxyuridine (BrdUrd), 150-200 mg/m2. At an infusion rate of 200 mg/m2/h, serum BrdUrd levels of 8 microM were achieved. After the infusion, tumor tissue was obtained and divided into two portions. One portion was fixed in 70% ethanol, embedded in paraffin, and sectioned; the sections were deparaffinized, denatured with 2 N HCl, and reacted with monoclonal antibodies against BrdUrd (anti-BrdUrd MAb). BrdUrd-labeled nuclei were demonstrated satisfactorily by an indirect peroxidase method. The other portion was dissociated into single cells with a DNase enzyme cocktail and reacted with FITC-conjugated anti-BrdUrd MAb to determine the percentage of BrdUrd-labeled cells or with chromomycin A3 for DNA analysis. The single-cell suspensions were analyzed by flow cytometry. The fraction of S-phase cells in the tissue sections was similar to both the percentage of BrdUrd-labeled nuclei and the S-phase fraction determined by flow cytometric analysis. The results obtained with BrdUrd-labeled nuclei were similar to those obtained from previous autoradiographic studies of various brain tumors exposed to a pulse of 3H-thymidine. Since BrdUrd is not radioactive and is nontoxic at the dosage used, these techniques, together with the histopathological diagnosis, may help to predict the biological malignancy of individual tumors.

Immunocytochemical demonstration of S-phase cells by anti-bromodeoxyuridine monoclonal antibody in human brain tumor tissues.

Five patients with various brain tumors received bromodeoxyuridine (BrdU), 150-200 mg/m2 i.v., at the time of craniotomy. Biopsied materials were fixed in 70% ethanol, sectioned, denatured with hydrochloric acid, and reacted with monoclonal antibodies against BrdU. Immunofluorescence and immunocytochemical methods were used to visualize BrdU-labeled nuclei. Our results showed that both methods demonstrated BrdU-labeled nuclei satisfactorily in tissue sections. Thus, BrdU can be used to measure the proliferative potential of human tumors in situ.

Manifestations and therapeutic considerations in pineal yolk-sac tumors. Case report.

A 20-month-old patient with a paraventricular and parapineal yolk-sac tumor was treated with subtotal excision and total neuraxis irradiation. She has done well in the 3 1/2 years since surgery. A comparative review of similar pineal and gonadal yolk-sac tumors suggests role for surgery combined with radiotherapy and chemotherapy. Additional experience with these unusual germ-cell neoplasms should establish the need for aggressive extirpation, not only to determine the exact diagnosis, but also to provide the basis for subsequent adjunctive therapy. The latter may include specific combination of antineoplastic drugs in addition to radiation.