RESUMO
The phenotypic heterogeneity of low-grade gliomas (LGGs) is still inconsistently explained by known molecular abnormalities in patients treated according to the present standards of care. IDH1 codon 132 and IDH2 codon 172 sequencing was performed in a series of 47 LGGs and correlated with clinical presentation, MR imaging characteristics, genomic profile and outcome. A total of 38 IDH1 mutations at codon 132 and 2 IDH2 mutations at codon 172 were found, including 35 R132H (87.5%), 2 R132C (5.0%), 1 R132S (2.5%) and 2 R172 M (5%). The IDH mutations were significantly associated with 1p19q deleted genotype (P = 0.031) and p53 expression (P = 0.014). The presence (vs. absence) of IDH mutations was associated with a better outcome (5-year survival rate, 93% vs. 51%, respectively, P = 0.000001). After adjustment for age, tumor location and size, radiologic infiltration pattern and extent of surgery, multivariate analysis confirmed that IDH mutations was an independent favorable prognostic factor (hazard ratio = 40.9; 95% CI, 2.89-578.49, P = 0.006). Furthermore, we showed that patients with IDH-nonmutated tumors were significantly older (P = 0.020) and that these tumors involved significantly more frequently the insula (P = 0.004), were larger in size (>6 cm, P = 0.047), displayed an infiltrative pattern on MRI (P = 0.007) and were all p53 negative with no 1p19q deletion (P < 10â»6). The absence of IDH mutations in LGGs identifies a novel entity of LGGs with distinctive location, infiltrative behavior, specific molecular alterations, and dismal outcome. These findings could significantly modify the LGG classification and may represent a new tool to guide patient-tailored therapy.
Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioma/genética , Glioma/patologia , Isocitrato Desidrogenase/deficiência , Mutação/genética , Organização Mundial da Saúde , Adulto , Idoso , Neoplasias Encefálicas/enzimologia , Movimento Celular/genética , Feminino , Predisposição Genética para Doença/genética , Glioma/enzimologia , Humanos , Isocitrato Desidrogenase/genética , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
We report a SPECT and PET voxel-based analysis of cerebral blood flow and metabolic rate for glucose in a 23-year-old woman with familial hemiplegic migraine (FHM) caused by ATP1A2 gene mutation. In comparison with healthy subjects, a PET scan showed brain glucose hypometabolism, controlaterally to the hemiplegia, in the perisylvian area early in the attack (Day 1), without any SPECT perfusion abnormalities. Decrease in metabolic rate was only partially reversible at Day 78, concordant at this time with a remaining hemisensory loss. These findings provide further evidence for a primary cortical metabolic dysfunction in FHM.
Assuntos
Encefalopatias Metabólicas/genética , Encefalopatias Metabólicas/metabolismo , Córtex Cerebral/metabolismo , Enxaqueca com Aura/genética , Enxaqueca com Aura/metabolismo , Encefalopatias Metabólicas/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Feminino , Humanos , Enxaqueca com Aura/fisiopatologia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada de Emissão de Fóton Único , Adulto JovemRESUMO
During the last decade, increasing interest in magnetic resonance imaging has emerged for the evaluation of fetal abnormalities detected on ultrasound. The advent of single-shot rapid acquisition sequences has greatly facilitated our ability to obtain detailed imaging information of the fetal brain. To date, fetal magnetic resonance imaging has shown to have an important role in the investigation of cerebral abnormalities suspected by sonography, and in the detection of subtle brain anomalies associated with high-risk pregnancies. Magnetic resonance imaging has proved to be a useful adjunct to sonography during the prenatal period of development, especially for the detection of acquired disorders.
Assuntos
Encefalopatias/diagnóstico , Encéfalo/anormalidades , Imageamento por Ressonância Magnética , Diagnóstico Pré-Natal , Encefalopatias/congênito , Lesões Encefálicas/diagnóstico , Feminino , Humanos , GravidezRESUMO
Vigabatrin is an antiepileptic drug that produces intramyelinic edema in several animal models. This study investigates the effect of vigabatrin on the developing human brain. The authors retrospectively blindly review 34 brain magnetic resonance imaging of 22 epileptic infants (age: 9 +/- 1 months) that received vigabatrin, focusing on the presence of hyperintensity on T2- and diffusion-weighted images. Patients treated with vigabatrin displayed significant magnetic resonance imaging hyperintensity of basal ganglia and brain stem (P < .001, Wilcoxon test). This hyperintensity was transient and maximal 3 to 6 months after the beginning of vigabatrin. Hyperintensity was independent from duration and type of epilepsy, and from the presence or absence of seizures. The authors conclude that vigabatrin treatment is associated with transient hypersignal of the basal ganglia and brain stem in epileptic infants. Such transient hyperintensity is likely to be age-dependent and time-dependent because it has never been observed in adult patients.