Ian R. Whittle

A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma multiforme. A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers. Because of the small number of patients in that trial, a larger phase 3 trial was performed to confirm these results. Two hundred forty patients were randomized to receive either BCNU or placebo wafers at the time of primary surgical resection; both groups were treated with external beam radiation postoperatively. The two groups were similar for age, sex, Karnofsky performance status (KPS), and tumor histology. Median survival in the intent-to-treat group was 13.9 months for the BCNU wafer-treated group and 11.6 months for the placebo-treated group (log-rank P -value stratified by country = 0.03), with a 29% reduction in the risk of death in the treatment group. When adjusted for factors affecting survival, the treatment effect remained positive with a risk reduction of 28% ( P = 0.03). Time to decline in KPS and in 10/11 neuroperformance measures was statistically significantly prolonged in the BCNU wafer-treated group ( P </= 0.05). Adverse events were comparable for the 2 groups, except for CSF leak (5% in the BCNU wafer-treated group vs. 0.8% in the placebo-treated group) and intracranial hypertension (9.1% in the BCNU wafer-treated group vs. 1.7% in the placebo group). This study confirms that local chemotherapy with BCNU wafers is well tolerated and offers a survival benefit to patients with newly diagnosed malignant glioma.

This study identifies proteins from the postsynaptic density (PSD) of human neocortex and finds that the PSD shows enrichment of genes involved in cognitive and affective phenotypes and that PSD mutations are associated with neurological and psychiatric disease. We isolated the postsynaptic density from human neocortex (hPSD) and identified 1,461 proteins. hPSD mutations cause 133 neurological and psychiatric diseases and were enriched in cognitive, affective and motor phenotypes underpinned by sets of genes. Strong protein sequence conservation in mammalian lineages, particularly in hub proteins, indicates conserved function and organization in primate and rodent models. The hPSD is an important structure for nervous system disease and behavior.

BACKGROUND AND PURPOSE: Optimizing high-grade glioma treatment requires the delineation of edematous and normal brain from tumor, perhaps by using potential differences in the absolute diffusion parameters of water. Our purpose was to determine whether mean diffusivity <D> and diffusion anisotropic MR imaging data help in this differentiation. METHODS: Nine patients with high-grade cerebral glioblastoma underwent contrast-enhanced structural and diffusion tensor MR imaging before therapy. Tumor, edematous brain, and apparently normal white matter regions were determined on T2-weighted and contrast-enhanced T1-weighted structural images. Fractional anisotropy (FA) and <D> were measured in each tissue type. Differences in these values among the tissue types were assessed with a standard analysis of variance. RESULTS: <D> was highest in the necrotic tumor core (1825.38 +/-404.06) x 10(-6) mm(2)/s, followed by edematous brain (1411.23 +/- 322.31) x 10(-6) mm(2)/s, enhancing tumor core (1308.67 +/- 292.50) x 10(-6) mm(2)/s, enhancing tumor margin (1229.80 +/- 206.80) x 10(-6) mm(2)/s, and normal brain (731.53 +/- 35.21) x 10(-6) mm(2)/s. FA was highest in normal brain (0.47 +/- 0.08) and lowest in the necrotic core (0.09 +/- 0.03). <D> was significantly different in enhancing tumor margins and edematous brain in all patients; FA was significantly different in only seven. These values were significantly different from those of normal brain in all cases in which they were measurable. CONCLUSION: <D> values can be used to differentiate normal white matter, edematous brain, and enhancing tumor margins. Diffusion anisotropic data added no benefit to tissue differentiation. Further studies are required to determine if a <D> value that corresponds to the limit of tumor invasion can be identified.

The vein of Galen malformation is a midline arteriovenous fistula with aneurysmal dilatation of the vein of Galen. The clinical details of diagnosis and treatment in 13 patients with such lesions together with a review of 232 cases collected from the literature are presented in this report. There were 132 males, 77 females, and 36 cases in which the sex was not stated. Eighty patients presented as neonates, 82 were 1 to 12 months old, 39 were 1 to 5 years old, 22 were 6 to 20 years old, and 22 were over the age of 20. The most common presenting symptoms were congestive cardiac failure (110 cases), raised intracranial pressure secondary to hydrocephalus (94 cases), cranial bruit (57 cases), focal neurological deficit (37), seizures (26 cases), and hemorrhage (25 cases). The most characteristic vascular supply to the midline fistula involved multiple bilateral vessels, although bilateral posterior cerebral and unilateral posterior cerebral supply was relatively common. The overall figures for treatment and outcome showed that 91 patients (37.1%) were treated by direct operation and 29 patients (11.3%) were treated by other forms of operation, predominantly shunting or remote vessel ligation. Forty-six patients (18.8%) were treated by medical means (digoxin, diuretics, and ventilatory support). In 79 patients (22.2%), there was no treatment or no details of treatment were available. There was an overall series mortality of 55.6% (no details were available in 33 cases) and a 37.4% mortality for surgically treated cases. After operation, there was a 46.3% incidence of significant morbidity in surviving patients. Neonatal patients fared worst, with an overall mortality of 64 of 70 cases (91.4%) where details were available. The outcome was equally bad for surgically and conservatively treated cases. Operation in the 1- to 12-month age group was more successful, but still carried a mortality of 31.7%, with a significant morbidity in approximately half of the surviving patients. Over the age of 1 year, the surgically treated patients had a 25.6% mortality and a 42.3% major morbidity in survivors. Consideration is given to some of the ways in which these figures may be improved, in particular a staged approach during the neonatal period, with the use of selective embolization or occlusion of vessels to reduce the volume of the arteriovenous shunt until the patient is older and better able to tolerate major operation.