Correlation of chondroitin sulfate proteoglycan expression on proliferating brain capillary endothelial cells with the malignant phenotype of astroglial cells.

Human glioblastomas (five of five), the most malignant astroglial-derived tumors, specifically express a chondroitin sulfate proteoglycan that is recognized by monoclonal antibody 9.2.27 and localized to the glioma cell surface, proliferating endothelial cells, and the perivascular extracellular matrix within the tumor bed. In contrast, the expression of this proteoglycan in normal adult neocortex and white matter is limited to the smooth muscle of small arteries, while normal glia, endothelial cells, and endothelial cell basement membranes are nonreactive. Moreover, two anaplastic astrocytomas, representing medium-grade astroglial-derived tumors, fail to react with monoclonal antibody 9.2.27. In culture, glioblastoma and capillary brain endothelial cells specifically synthesize a 250-kDa core protein and a high-molecular-mass chondroitin sulfate proteoglycan, recognized by monoclonal antibody 9.2.27. These data suggest a correlation between the expression of this chondroitin sulfate proteoglycan on proliferating brain capillary endothelial cells and the malignant phenotype of astroglial cells. The prominent perivascular localization of chondroitin sulfate proteoglycan makes it a marker for both proliferating brain capillary endothelial cells and the most malignant transformed astroglial cells, thus providing an ideal target for the immunotherapy of glioblastoma.

Absence of methylthioadenosine phosphorylase in human gliomas.

All normal mammalian tissues contain methylthioadenosine phosphorylase, which plays a role in the recycling of purines and methionine consumed during polyamine synthesis. A complete deficiency of methylthioadenosine phosphorylase has been reported in some human leukemias and lymphomas and in a few solid tumors. The exact incidence of the enzyme deficiency among fresh human tumor specimens has been difficult to establish because the measurement of enzyme catalytic activity is laborious and requires carefully preserved specimens. We have generated two antibodies against methylthioadenosine phosphorylase and have used them to develop a simple immunoblot assay for the enzyme. Specifically, studies showed that all cells with catalytically active methylthioadenosine phosphorylase had a 32-kDa band that reacted with the anti-enzyme antibodies. In a reciprocal manner, all malignant cell lines that were naturally deficient in methylthioadenosine phosphorylase activity lacked detectable immunoreactive enzyme protein. The immunoassay was used to analyze human gliomas. Seventy-five % (9 of 12) of the gliomas were completely methylthioadenosine phosphorylase deficient. This common metabolic difference between most gliomas and all normal cells is a potential target for tumor-specific chemotherapy.

Primary intracranial hypotension and bilateral isodense subdural hematomas.

A 39-year-old woman with headache and an organic mental syndrome was found to have primary intracranial hypotension (PIH). Bilateral isodense subdural hematomas were discovered in association with an absence of detectable CSF pressure on two lumbar punctures. This case study emphasizes that PIH is not an entirely benign condition and that intracranial hemorrhage may accompany persistent intracranial hypotension.

Locating the central sulcus: comparison of MR anatomic and magnetoencephalographic functional methods.

PURPOSE: To compare MR anatomic and magnetoencephalographic (MEG) functional methods in locating the central sulcus. METHODS: Eleven healthy subjects and five patients with focal cerebral lesions were studied. The central sulcus was located anatomically with MR by two independent observers using axial vertex and sagittal (midline and lateral) images. Locations via the MEG functional method were based on detecting the somatosensory-evoked magnetic fields elicited by painless tactile stimuli. RESULTS: The axial method yielded the most consistent interrater results, with complete agreement in 76% of sections in both control subjects and patients. The intermethod discordance of the sagittal midline and lateral methods was 32% in control subjects and 33% in patients. The concordance of MR and MEG methods ranged from 55% to 84% in control subjects and 65% to 67% in patients. CONCLUSION: MR anatomic techniques can usually identify the central sulcus, but in the presence of anatomic distortion, the MEG functional method adds significant information.

Percutaneous injection of glycerol for the treatment of trigeminal neuralgia.

There continues a significant debate over the best contemporary method for treating trigeminal neuralgia. Glycerol injection into the trigeminal cistern has been used in a consecutive series of 200 patients. A total of 80% of the patients have had good or excellent pain relief. Side effects have been a mild and usually transient numbness and tingling or mild objective sensory deficit to pin and touch in approximately 1/2 of the patients. Complications have been extremely infrequent and have resolved in time. A recurrence rate of 24% has been the single largest disadvantage of the procedure. Reinjection is usually successful in treatment of recurrence. The combination of efficacy, minimal and temporary neurologic dysfunction, and low complication rate make this procedure, in our opinion, the procedure of choice for the first step, when surgical treatment is required.

Coccidioidal meningitis. Intrathecal treatment with hyperbaric amphotericin B.

The localization of coccidioidal meningitis in the basilar regions, with resultant hydrocephalus and uniformly fatal outcome, has necessitated intrathecal injection of amphotericin B via cisternal puncture or subcutaneous ventricular reservoir for successful therapy. A simpler form of treatment is described here, whereby amphotericin B diluted in 10 percent glucose solution is injected via lumbar puncture, and delivered to the base of the skull by tilting the patient to a head-down position. A simultaneously performed hyperbaric cisternogram with (131)I-serum albumin has demonstrated satisfactory migration of the injected bolus to the occiput. This method of administration resulted in successful suppressive treatment of one patient, including two years of follow-up without serious sequelae or relapse.

The beneficial effect of intracarotid urokinase on acute stroke in a baboon model.

The capacity of intracarotid infusion of urokinase to salvage neurologic function in a baboon model of acute thrombotic stroke has been studied. The model consists of reversible eccentric balloon compression (3 hours) of the right middle cerebral artery (MCA) proximal to the take-off of the lenticulostriate arteries (LSA), resulting in in situ thrombosis of perforating branches supplying the right corpus striatum. Neurologic endpoints included quantitative assessment of neurologic function (NE), estimation of cerebral infarction volume by computerized tomographic (CT) scan, and carotid angiography. In untreated acute stroke control animals (n = 6), a persistent decrease in functional score (from 100 to 36 +/- 11) at 14 days and a defined region of cerebral infarction (volume = 3.2 +/- 1.5) were detected at 10 days. Intracarotid urokinase administered to five animals (1.2 X 10(6) IU over 60 min) following the 3 hour period of MCA occlusion improved neurologic function (NE = 50, 55, 85, 100, 100) and reduced infarction size (0.3, 0.5, 0.8, 0.7, 1.1 cm3, respectively) without evidence of intracranial hemorrhage. Systemic fibrinogenolysis was produced in all five treated animals. We conclude that thrombolytic therapy given within 3 hours of experimental thrombotic occlusion may salvage neurologic function and reduce cerebral infarction volume without CT scan detectable intracranial bleeding.

Experimental acute thrombotic stroke in baboons.

To study the effects of antithrombotic therapy in experimental stroke, we have characterized a baboon model of acute cerebrovascular thrombosis. In this model an inflatable silastic balloon cuff has been implanted by transorbital approach around the right middle cerebral artery (MCA), proximal to the take-off of the lenticulostriate arteries (LSA). Inflation of the balloon for 3 hours in six animals produced a stereotypic sustained stroke syndrome characterized by contralateral hemiparesis. An infarction volume of 3.2 +/- 1.5 cm3 in the ipsilateral corpus striatum was documented by computerized tomographic (CT) scanning at 10 days following stroke induction and 3.9 +/- 1.9 cm3 (n = 4) at 14 days by morphometric neuropathologic determinations of brain specimens fixed in situ by pressure-perfusion with 10% buffered formalin. Immediate pressure-perfusion fixation following deflation of the balloon was performed in 16 additional animals given Evans blue dye intravenously prior to the 3 hour MCA balloon occlusion. Light microscopy and transmission electron microscopy consistently confirmed the presence of thrombotic material occluding microcirculatory branches of the right LSA in the region of Evans blue stain, but not those of the contralateral corpus striatum. When autologous 111In-platelets were infused intravenously in four animals from the above group prior to the transient 3 hour occlusion of the right MCA, gamma scintillation camera imaging of each perfused-fixed whole brain demonstrated the presence of a single residual focus of 111In-platelet activity involving only the Evans blue-stained right corpus striatum. Focal right hemispheric activity was equivalent to 0.55 +/- 0.49 ml of whole blood, and the occlusion score derived from histologic examination of the microcirculation of the Evans blue-stained corpus striatum averaged 34.8 +/- 2.8. Similar 111In-platelet imaging and histologic scoring experiments carried out in four animals pretreated with the antithrombotic combination heparin and ticlopidine showed marked reduction of both 111In-platelet activity (0.01 +/- 0.03 ml vs. 0.55 +/- 0.49 ml; p less than 0.01) and thrombotic occlusion of the microcirculation (10.8 +/- 7.4 units vs. 34.8 +/- 2.8 units; p less than 0.01) in the right corpus striatum following 3 hours of MCA occlusion. In separate control experiments 111In-labeled autologous platelets were infused after the 3 hour period of right MCA occlusion and subsequent balloon deflation in two animals; no focus of 111In-platelet activity was demonstrated in fixed whole brain.(ABSTRACT TRUNCATED AT 400 WORDS)