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Infants afflicted with meningomyelocele are paralyzed as a result of physiologic disconnection of the neural plate from the spinal cord. Intact neural elements within the placode often maintain segmental reflex innervation of paralyzed lower extremity muscles. It was hypothesized that bridging this central peripheral gap with viable intercostal nerves would restore limited voluntary movement to paralyzed muscles. The surgical technique and initial results are the subject of this report.

Within 3 weeks of definitive surgery, 609 patients with histologically demonstrated, supratentorial malignant glioma were randomized to receive, in addition to 6000 rads of radiotherapy, one of four treatment regimens: carmustine (BCNU), high-dose methylprednisolone, procarbazine, or BCNU plus high-dose methylprednisolone. We analyzed the data for the total randomized population and for the 527 patients (87% with glioblastoma multiforme) in whom the initial protocol specifications were met (the valid study group). Significantly longer survival was experienced by patients receiving procarbazine or BCNU alone compared to those receiving only high-dose methylprednisolone. No other pairwise comparisons demonstrated differences significant at the 0.05 level. However, the combination of BCNU plus high-dose methylprednisolone tended to be less effective than BCNU alone in patients with poor prognosis. This study indicates that BCNU and procarbazine are moderately useful agents in conjunction with radiotherapy for patients with malignant glioma. In addition, future protocols may allow use of corticosteroids in conventional dosages for treating cerebral edema and controlling symptoms; conclusions based on survival as the endpoint are unlikely to be affected by administering steroids at somewhat greater than the usual dose. More effective regimens for the treatment of malignant glioma should be sought.

A series of cats were made hydrocephalic by intracisternal injection of kaolin, and four weeks later ventriculography confirmed the presence of hydromyelia. Ten days later, laminectomy in the lower thoracic region was performed. Several days later ventriculography revealed a markedly dilated central canal beneath the entire laminectomy, and pathological examination confirmed the presence of a focal bulge confined to the same region. On sectioning, it was evident that the central canal was massively enlarged to fill the entire spinal cord beneath the bulging region. The conclusion from these findings is that myelomeningocele is the result of progressive intra-uterine disease which begins with pathological hydromyelia and culminates in rupture of the unsupported spinal cord as a result of maldevelopment of associated dermal tissue.

A case is reported of a tumor composed of both oligodendrogliomatous and sarcomatous elements. The interpretation is offered that the sarcoma arose secondarily by neoplastic transformation of the hyperplastic blood vessels formed in response to the presence of the oligodendroglioma. This tumor may be considered analogous to the astrocytoma-sarcoma, which is much more common, and to the metastatic carcinoma with secondary sarcoma, of which one case has been reported.

Computerized axial tomography (CAT) is a new, highly accurate technique for studying the skull and intracranial contents. It is rapid enough to be utilized in acute emergencies and safe enough to be utilized for routine serial followups and evaluation of outpatients with equivocal findings. Because CAT can delineate the ventricular system without need for contrast agent, can distinguish clearly between hematoma and edema and can differentiate cystic from solid tumors, it finds wide application in the evaluation of neurological disease.

Traumatic fistulas were successfully embolized using various transvascular approaches in 33 of 34 lesions. Complete superselective angiographic demonstration of the exact site of the shunt and possible collaterals was necessary to choose the appropriate embolization techniques. Improvement in the signs of orbital congestion was seen in all cases. Embolization, which directly occludes the fistula, precludes recurrences via collateralization and restores the normal arteriovenous gradient to the eye and optic nerve.

The authors have summarized their experience in the application of computerized axial tomography to the overall management of hydrocephalus.

Twelve patients with cerebral vasospasm following subarachnoid hemorrhage were treated with intravenous aminophylline and isoproterenol. After angiographic demonstration of spasm, all patients were begun on a continuous intravenous infusion of isoproterenol, 125 mug/hr, and aminophylline, 125 mg/hr, for a period of up to two weeks. The infusion was continued until there was clinical or angiographic evidence that spasm had diminished. Nine patients improved on this regimen and three remained unchanged. The use of isoproterenol and aminophylline is based on their effect on the enzymes responsible for the formation and degradation of cyclic adenosine monophosphate (cyclic AMP). An increase in cyclic AMP has been noted to produce relaxation of vascular smooth muscle. It is proposed that manipulation of these biochemical pathways may provide a method for influencing blood flow through cerebral vessels.

Desmosterol (5, 24-cholestadien-3beta-ol; delta 24-cholesterol; 24-dehydrocholesterol), an immediate precursor of brain cholesterol, increased in malignant intracranial tumors induced in rats by nitrosourea derivatives. The average increase in desmosterol was higher in intracerebral gliomas than in neurinomas of the trigeminal nerve. Similarly, desmosterol increased only slightly in developing normal trigeminal nerve compared to the high levels observed in developing cerebrum. The differences may have been partly related to the predominantly growing cell type, i.e., glial (central nervous system) or Schwann (peripheral nervous system) cells seen at the time of study.

In patients with acoustic neurinomas protruding less than 2 cm from the porus acusticus and free of the brain stem, hearing can often be preserved. Our neurosurgical/otologic team uses the combined suboccipital/transmeatal approach with the patient in the seated position. This operation has been attempted on 21 patients from 1974 to 1982. Nine had tumors larger than 2 cm that touched the brain stem; one had useful hearing preserved. Of the 12 patients with tumors smaller than 2 cm, hearing at or near the preoperative level was preserved in seven. In one patient, hearing was improved. There have been up to 7 years of follow-up with no recurrences of the neurinomas or diminution of hearing evident on computed tomographic scan. All had preservation of the seventh cranial nerve, while complications were mild and comparable to the remainder of our 101 patients operated on during the same period. We will review the surgical technique and audiologic results in detail.

Previous work has shown that unsaturated fatty acid components of model membrane phospholipids in vitro, damaged via a free radical mechanism, are protected by the presence of cholesterol in these membranes. The participation of these membrane lipids in the pathogenesis of traumatic injury to brain was studied in vivo using the Klatzo method of cryogenic injury in rats. Increased edema 4 hr after cryogenic injury was noted on the lesioned side. Total cerebral cholesterol was decreased significantly in the lesioned hemispheres 10 hr following injury. In lesioned animals pretreated and post-treated with methylprednisolone, there were no significant differences in the cholesterol levels. Arachidonic acid isolated from total membrane phospholipids was significantly reduced on the injured side 24 hr after injury, but not before. Other fatty acids were not significantly affected. Methylprednisolone treatment prevented the decrease in arachidonic acid. Animals that had received a cold injury had significant decreases in ascorbic acid levels after 4 hr on the lesioned side of the brain. This decrease was significantly ameliorated by corticosteroid administration. These results support the hypothesis that the protective effect of corticosteroids in cryogenic cerebral trauma may be due to antioxidant protection of major cell membrane lipid components such as cholesterol and phospholipids.

We report a case of malignant melanoma, metastatic to the brain, in which disease was not detected by magnetic resonance imaging but was detected by contrast enhanced computed tomography. At least in some instances, magnetic resonance imaging fails to detect disease that is apparent by computed tomography.

Two models have been used to study the effects of ethanol on injuries of the central nervous system. The spinal cords of cats were injured by delivering a 200 gm-cm impact to the exposed dura mater. A second group of animals received a similar injury to the exposed dura mater overlying the cerebral hemispheres. The animals were divided into two groups, those that received an infusion of ethanol before injury, and control animals that received no ethanol. The parameters of injury used in this model produced small and insignificant lesions in those animals that received no ethanol; however, when the animals were pretreated with ethanol, a considerable increase in the extent of the injury was noted. These include alterations in membranes-bound enzymes and clotting mechanisms, and alteration of cell membranes through abnormal free radical reactions.

Biochemical analyses of caudate nucleus biopsy samples from patients with Parkinson's disease undergoing autologous adrenal transplantation were performed. Activity of the dopamine biosynthetic enzyme tyrosine hydroxylase, and concentrations of dopamine and its primary metabolite homovanillic acid were significantly greater than anticipated on the basis of previously published postmortem values. These data suggest that postmortem changes in various biochemical parameters of dopamine function are more rapid than has been generally appreciated. Further analysis of striatal biopsy samples may reveal predictive relationships between striatal indices of dopamine function and therapeutic response to adrenal transplantation.

An approach to the treatment of neonatal hydrocephalus is proposed which is intended to reduce or eliminate shunt dependency by increasing the effectiveness of remaining pathways of absorption of cerebrospinal fluid. In suitable cases, intermittent cranial compression by means of an elastic bandage or a helmet with an inflatable inner-lining may be effective. Hydrocephalus was arrested in nine of 14 children treated with this method, eight of whom have developed normally. When cranial compression is contra-indicated or not successful, the preferred method of treatment is an 'on-off' type of valve which is used intermittently to drain a fixed volume of cerebrospinal fluid. Of 18 children who had such shunts inserted, 10 have become totally independent of their shunts and their hydrocephalus has become compensated. All are of normal intelligence. Subtemporal craniectomy was performed on seven shunt-dependent children with recurrent catheter obstruction. Four have been followed for six months and three for two years and in no case has there been further malfunction of the proximal catheter.

In Brain Tumor Cooperative Group Study 77-02, eleven institutions randomized 603 adult patients with supratentorial malignant glioma to one of four treatment groups following surgery: conventional radiotherapy (6000 cGy in 30-35 fractions) + BCNU, conventional radiotherapy + streptozotocin, hyperfractionated (twice daily) radiotherapy (6600 cGy in 60 fractions) + BCNU, and conventional radiotherapy with misonidazole followed by BCNU. Data were analyzed for the total randomized population and for the 557 patients (86% with glioblastoma multiforme) who met protocol eligibility specifications (including confirmed histopathology on central review). Median survival was approximately 10 months following randomization. Overall there was no statistically significant difference in survival among the four groups. Among non-glioblastoma patients, the misonidazole group appeared to have poor survival. Peripheral neuropathy was a dose-limiting toxicity with misonidazole. It is concluded that neither the addition of misonidazole nor hyperfractionated radiotherapy as given in this protocol offered any advantage over conventional radiotherapy plus either BCNU or streptozotocin for treatment of malignant glioma.

Inbred CDF rats (cesarean-delivered F344 rats) were immunized with either a nitrosourea-induced glioma EA-285 or its subline EA-285A and both with and without Corynebacterium parvum. A humoral immune response in syngeneic rats to the immunizing tumor was demonstrated with micromodifications of different rosette assays (immune adherence assay, protein-A assay, and anti-C3-mixed hemadsorption assay). Extensive absorption studies of two immune sera with the highest reactivity revealed two glioma-specific antigens (or two components of one antigen) on the cell surface of the cloned tumor subline. One antigen was present only on the cell surface of the subline of the glioma used for both immunization and absorption analyses. The other antigen appeared on the cell surface of both the cloned subline EA-285A and the parental cell line EA-285. These preliminary studies showed that CDF rats immunized against a syngeneic glioma mounted a humoral immune response that appeared to be individually tumor-specific.

The stereochemical course of the phospho group transfer catalyzed by mutant (S102C) alkaline phosphatase from Escherichia coli was investigated by using 31P nuclear magnetic resonance spectroscopy. Transphosphorylation from 4-nitrophenyl (Rp)-[16O, 17O, 18O]phosphate to (S)-propane-1,2-diol occurs with overall retention of configuration at phosphorus. This result is consistent with the view that the hydrolysis of substrates by this mutant enzyme proceeds by way of a covalent phosphoenzyme intermediate in the same manner as the wild-type alkaline phosphatase.

Within 3 weeks of definitive surgery, 571 adult patients with histologically confirmed, supratentorial malignant gliomas were randomly assigned to receive one of three chemotherapy regimens: BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) alone, alternating courses (every 8 weeks) of BCNU and procarbazine, or BCNU plus hydroxyurea alternating with procarbazine plus VM-26 (epipodophyllotoxin). Patients accrued in 1980 and 1981 were to receive 6020 rads of whole-brain radiotherapy concurrent with the first course of chemotherapy. Patients accrued in 1982 and 1983 were randomly assigned to receive either whole-brain irradiation as above, or 4300 rads of whole-brain radiotherapy plus 1720 rads coned down to to the tumor volume. The data were analyzed for the total randomized population and separately for the 510 patients, termed the "Valid Study Group (VSG)," who met protocol eligibility specifications (including central pathology review), 80% of whom had glioblastoma multiforme. The median survival times from time of randomization for the three chemotherapy groups of the VSG ranged from 11.3 to 13.8 months, and 29% to 37% of the patients survived for 18 months (life-table estimate); the differences between these groups were not statistically significant. Survival differences between the radiotherapy groups were small and not statistically significant. It is concluded that, for malignant glioma, giving part of the radiotherapy by coned-down boost is as effective as full whole-brain irradiation, and that multiple-drug chemotherapy as outlined in this protocol conferred no significant survival advantage over BCNU alone.

Cerebral blood flow was measured by the indicator fractionation technique in normal, acute hydrocephalic, chronic compensated hydrocephalic and craniectomized hydrocephalic cats. In the five normal cats the mean total brain blood flow was 136.1 ml/min/100 g dry weight. The six acute hydrocephalic animals demonstrated a relatively uniform 22% reduction in total blood flow. In eight chronic hydrocephalic cats CBF increased to the point where there was only an overall 7% decrease. In three hydrocephalic and craniectomized cats the CBF was reduced by 30.6%. In the acute phases there was a decrease in the number of blood vessels. Chronic compensated hydrocephalic brains had somewhat more vessels than the normal, whereas the craniectomized, massively hydrocephalic brain had a dramatic increase in both the number and caliber of blood vessels. These results clearly demonstrate that in acute obstructive hydrocephalus in cats, there is a significant decrease in CBF. The blood vessels revert to normal in shunted cats.

We describe a patient with a foot drop attributable to both herniated disk and peripheral neuropathy susceptible to external compression. Early electrodiagnostic studies and sural nerve biopsy indicated a role for myelin dysfunction in this disorder.

During a two-year period, intra-operative ultrasonic explorations were performed in 44 patients for the purpose of localisation of intracranial masses. This facilitated accurate intraoperative assessment of the location and consistency of the mass. We consider operative ultrasound to be an invaluable adjunct to surgery of small intracerebral masses.

Paraplegia has been an unpredictable, devasting complication following operations upon the thoracoabdominal aorta for over 30 years. The frequency ranges from 0.5% with operations for coarctation to as high as 15% following surgery for thoracoabdominal aneurysms. Both uncertainty and controversy exist about the value of different protective methods during aortic crossclamping (AXC): heparinized shunts, partial bypass, and reimplantation of intercostal arteries. This report describes the authors' initial clinical experience with a highly sensitive indicator of spinal cord ischemia, somatosensory evoked potentials (SEP) in an attempt to prevent paraplegia associated with surgical procedures on the thoracoabdominal aorta. Seven consecutive patients (one coarctation, five thoracic aneurysms, one thoracoabdominal aneurysm) underwent continuous operative monitoring of SEP. Cortical response to simultaneous electrical stimulation (20 mAmps, 0.6 mSec., 2.3 cps) of both the right and left posterior tibial nerves was recorded before, during, and after AXC, and following operation. When ischemic changes were detected by SEP, increasing distal circulation by different maneuvers (heparinized shunt, femoral-femoral bypass, reimplantation of intercostal arteries) reversed these changes. In two patients with thoracic aneurysms, ischemic changes appeared within three minutes after AXC and all potentials disappeared in nine minutes. Rapid insertion of a graft (AXC 28 and 37 minutes) resulted in SEP return 40 minutes following restoration of flow. These changes were prevented by a heparinized shunt in two patients, femoral/femoral bypass in one, and T8-T9 intercostal reimplantation in one. No SEP changes occurred in the patient with coarctation. No postoperative neurologic complications occurred. Continuous operative monitoring of SEP has exciting possibilities for preventing paraplegia. It is simple, highly sensitive, and seems to provide a precise measurement of adequacy of circulation to the spinal cord.

Levamisole, a drug that stimulates the immunologic defenses of the host, was tested on the experimental malignant neurinoma grown subcutaneously in young female inbred CDF rats in 3-month trial. The drug resulted in prevention of tumor growth in 80% of the treated animals, whereas tumors grew in 100% of the controls. After discontinuation of the drug, none of the animals in the treated group showed evidence of tumor growth upon clinical and pathologic examination 1 month after drug treatment was terminated. Treated animals failed to show any side effects related to levamisole upon clinical and pathologic examination.

The serial pre- and postoperative computed tomographic (CT) scans of 115 patients entered in the Cooperative Brain Tumor Study between 1975 and 1982 were analyzed in order to define CT prognostic criteria and to test the hypothesis that radical glioma surgery prolongs patient survival. The CT parameters of mass size, associated edema, and intensity of enhancement were quantitated on all scans. Clinical parameters evaluated included gender, age, length of survival, and useful (Karnofsky greater than 30) survival. Data analyses indicated postoperative residual tumor burden was inversely related to length of survival (p less than 0.01). Postoperative associated edema and intensity of image enhancement were also of prognostic value and showed an inverse relation to survival. Younger patients proved more likely than older patients to attain long-term survival. Residual tumor burden of less than 45 mm diameter on postoperative CT scans was associated with 70% chance of long-term survival. These findings support the radical surgical management of glioma.

Eleven patients with inoperable brain tumours were treated with high doses of corticosteroids (methylprednisolone 200-2000 mg/day) for up to 151 days (mean 55 days). Neurological improvement occurred in eight patients on high doses after deterioration on concentional doses (methylprednisolone 80-120 mg/day). In two patients steroids could be completely discontinued for several months. Serious adverse effects included sepsis in three patients and myopathy in tow. All three patients with sepsis also received chemotherapy. There were no deaths that could be attributed to steroids. The most likely effect of high dosage steroids is reduction of cerebral oedema. It is conceivable that in some instances high dose steroids may also result in tumour inhibition or oncolysis or both.

Multimodal treatment of malignant gliomas is routinely used at New York University Medical Center. Overall, our treatment program has resulted in survival rates of 78% at six months, 51% at one year, and 7% at five years for these high-grade brain tumors. However, various subgroups (based on tumor or host factors, or both) fared significantly better or worse than others. Particularly limited survival rates were found in patients who experienced paresis/paralysis or impaired mental function, who had tumors that were markedly anaplastic, who were elderly, or who for a variety of reasons did not receive the multimodal treatment we consider optimal.

Inbred CDF rats received 250 mg N-ethyl-N-nitrosourea (ENU)/kg body weight in monosodium phosphate buffer (pH 5.5) during late pregnancy (18-21 days). Control rats received only buffer. One hour after ENU or buffer administration, the fetuses were delivered and fetal brain cells (FBC) were put in long-term tissue culture. Cell growth consisted of monolayers of glial, fibroblastic, and epithelial-like cells. FBC from buffer-treated rats could not be subcultured for more than 13-15 passages; only one culture was maintained up to the 26th passage. FBC from ENU-treated rats showed in vitro malignant transformation beginning at the 8th passage (100 days). Injection of these cells sc into irradiated or neonatally thymectomized syngeneic rats induced small palpable tumors that regressed completely by 15-28 days. Small nonprogressively growing subcutaneous tumors in normal rats, however, were obtained only after the 19th in vitro passage (200 days). These transformed FBC appeared highly antigenic. Tumor-associated antibody was demonmmune adherence assays. Rats immunized with irradiated malignant FBC showed rising tumor antibody titers. The antibody was absorbed by ENU-exposed FBC but not by normal fetal or adult syngeneic brain cells. We concluded that ENU-exposed cells become malignant when grown in vitro for at least 8 passages (100 days) but grow in vivo in X-irradiated or neonatally thymectomized rats only. These antigenic and tumorigenic clones may be selected in vitro, where they grow readily in the absence of immune resistance.

In a series of four patients with intracranial meningiomas, three-dimensional computed tomographic (CT) reconstructions were a useful diagnostic and surgical adjunct. Three-dimensional images are created from standard CT data by a boundary-detecting computer software program. Three-dimensional images of tumor invading or adjacent to the bony calvarium are projected about the x, y, and z axes. Axial and sagittal sections delineate the lesions. The images created allow a surgical view of the meningiomas in three-dimensional space and demonstrate the relationship of these masses to the skull. The use of three-dimensional reconstructions in craniofacial surgery and in neurosurgery is reviewed.

Nitroglycerin was given intravenously to five anesthetized, hyperventilated (PaCO2 25 to 30 torr) patients during craniotomy, to facilitate surgery by creating a relatively bloodless field, and to decrease the potential need to blood transfusion. A subarachnoid screw and an indwelling radial artery catheter were inserted to monitor intracranial pressure (ICP) and mean arterial pressure (MAP). As MAP decreased from 10.4 +/- 4.0 (SE) to 69.0 +/- 1.8 torr, ICP increased from 14.2 +/- 0.7 (SEM) to 30.8 +/- 1.1 torr. Cerebral perfusion pressure decreased from 90.2 +/- 3.6 (SEM) to 38.2 +/- 2.3 torr (p < 0.0005). We attribute this nitroglycerin-induced ICP increase to capacitance vessel dilation within the relatively noncompliant cranial cavity, with subsequent cerebral blood volume increase.

Open autologous adrenal medullary to caudate nucleus transplantation was performed in 12 patients with advanced Parkinson's disease (PD). Ten of these patients had diurnal response fluctuations including "wearing off" and "on/off" phenomena. All of the patients were no longer satisfactorily responding to levodopa/carbidopa and dopamine agonists. The mean age of the patients was 55.1 years (range 37-65 yrs); mean duration of PD was 11.7 years (range 4-40 yrs); mean stage "on" was 3.3 (range 2-4); mean stage "off" was 4.8 (range 4-5). Mean duration of follow up from surgery was 10.4 months (range 2-17 months). Three patients improved dramatically with major changes in their lifestyle. The course of improvement in these 3 patients was different in each, implying that different mechanisms were responsible for the improvement. One of the patients died unexpectedly. In this patient, there were no surviving adrenal cells. Three patients improved moderately. Patients reported that they were "on" longer and had to take medication less often and were less dependent on individual doses of levodopa/carbidopa. The improvement has been sustained in two patients. However, in one of these patients there had to be frequent changes in scheduling to maintain the improvement. Two patients after technically successful implants did not improve. One of these patients subsequently died. In this patient there were a few surviving adrenal medullary cells. Four patients suffered major complications. One patient had a cerebral infarction and two had cerebral hemorrhages. One of these patients has shown a good recovery. One patient with autonomic insufficiency had a cardiac arrest with cerebral anoxia one week after surgery. This patient has shown a partial recovery.(ABSTRACT TRUNCATED AT 250 WORDS)