Purpose: Recent data suggest that methylation of the DNA repair gene O 6 -methylguanine DNA methyltransferase (MGMT), by increasing the chemosensitivity of glioblastoma multiforme, is significantly associated with improved prognosis. Results in contradiction with these findings, however, are present in the literature and the clinical and genetic context framing MGMT methylation is poorly characterized. Experimental Design: To address these issues, we have investigated the MGMT methylation status, clinical and magnetic resonance imaging characteristics, and relevant genetic features (loss of heterozygosity on17p and19q, EGFR amplification, and p53 mutations) in a retrospective study on 86 patients affected by glioblastoma multiforme: 72 patients had a clinical history indicating de novo insurgence of the tumor and the remaining 14 were secondary glioblastoma multiforme. Results: MGMT methylation was detected by methylation-specific PCR in 41 of 86 cases (47.7%; Meth+). Progression-free survival and overall survival were significantly longer in Meth+ than in Meth-patients [10 versus 7 months (P = 0.003, log-rank test) and 18 versus 14 months (P = 0.0003, log-rank test), respectively]. Mixed-nodular enhancement at magnetic resonance imaging was significantly more frequent in Meth+ and secondary glioblastoma multiforme and ring enhancement in Meth-and primary glioblastoma multiforme (P < 0.005). MGMT methylation was more present in secondary glioblastoma multiforme (P = 0.006) and associated with loss of heterozygosity on 17p and/or 19q (P = 0.005). Conclusions: These observations suggest that MGMT methylation is part of a genetic signature of glioblastomas that developed from lower-grade gliomas.
Spontaneous intracranial hypotension (SIH) is caused by leakage of CSF, and characterized on MRI by brain sagging, dilatation of veins and dural sinuses, subdural fluid collections and post-contrast enhancement of the thickened dura. A few cases may present a very severe brain sagging through the tentorial notch and swelling of the diencephalic-mesencephalic structures, with absent or scarce subdural collections and post-contrast enhancement. These patients may have surprisingly few neurological signs or may become drowsy and even lapse into coma due to central herniation. We retrospectively examined the diffusion studies obtained in five patients with these MRI findings, in seven patients with SIH without brain swellings and in ten controls. Mean diffusivity was increased in SIH patients with brain swelling in areas draining into the deep venous system, collected by the vein of Galen (vG) and straight sinus (SS). In the hypothesis that central herniation might be responsible for venous stagnation because of impaired flow of the vG into the SS, the vG/SS angle was measured. The angle formed by the vG entering the SS was not altered in patients without brain swelling (group E, 67.8 degrees +/- 10.3 degrees, mean +/- SD, range 49-80 degrees) when compared to controls (group C, 73.3 degrees +/- 12.3 degrees, mean +/- SD, range 56-95 degrees). It was, however, grossly decreased in patients with brain swelling (group D, 40.7 degrees +/- 12.8 degrees, mean +/- SD, range 22-61 degrees), P < 0.001 for comparison with groups E and C. As suggested by previous studies, downward stretching of the vG and narrowing of the vG/SS angle may cause a functional stenosis at the vG-SS junction. We suggest that in the application of the Monro-Kellie doctrine to SIH, the brain volume should not be considered as always invariable.
BACKGROUND AND PURPOSE:Structural MR imaging does not enable reliable differentiation of spinocerebellar ataxia (SCA) types 1 and 2 (SCA1 and SCA2), and imaging may be normal during the first years after the onset of symptoms. We aimed at determining whether measurements of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) may enable their differentiation.
Dural sinus thrombosis (DST) is rarely associated with spontaneous intracranial hypotension (SIH). Engorgement of the venous system, caused by the CSF loss that occurs in SIH, is considered to favour the thrombosis, although signs of both SIH and DST are usually seen simultaneously at the first diagnostic MRI. We observed two patients with SIH and DST. Changes in pattern of headaches and MRI findings demonstrated that DST followed SIH. In SIH, the velocity of the blood flow in the dural sinuses may be reduced because of dilatation of the venous system which compensates the CSF loss. Other possible mechanisms seem unlikely on the grounds of both clinical presentation and MRI studies.
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