RESUMEN
BACKGROUND: Migraine may be a factor of increased cerebral sensitivity to ischemia. Previous studies were conducted within 6 to 72 after stroke onset. We aimed to determine if an accelerated infarct growth exists in migraine patients within the first 4.5â¯h. METHOD: A retrospective case-control study was conducted where all patients admitted for acute stroke started <4.5â¯h before and who underwent perfusion CT were assessed. The hypoperfusion and necrosis volumes on initial CT perfusion were analyzed, as well as the final infarct volume on MRI performed within 72â¯h after admission. A no-mismatch pattern was defined as a ratio necrosis/hypoperfusion volumeâ¯>â¯83%. RESULTS: 24 patients with personal history of migraine were identified, 8 of them with aura. The control cohort included 51 patients. No difference was found between groups in terms of demographics, initial severity or outcome or presumed cause of stroke. Mean time to CT scan was 125â¯min in migraine patients and 127â¯min in the control group. A no-mismatch pattern was equally found in migraine patients and controls, even after adjustment for age, sex and presence of proximal occlusion (pâ¯=â¯.22). The final infarct volume was also similar in both groups. CONCLUSIONS: Migraine patients did not display more no-mismatch pattern than controls within the 4.5â¯h of stroke onset. This deviates from previous studies and may be due to our earlier time from stroke onset to CT scan. A history of migraine may lead to malignant progression of ischemia but occurring only after several hours.
Asunto(s)
Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/epidemiología , Trastornos Migrañosos/diagnóstico por imagen , Trastornos Migrañosos/epidemiología , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/terapia , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/terapia , Estudios Retrospectivos , Factores de Tiempo , Tiempo de Tratamiento/tendencias , Tomografía Computarizada por Rayos X/tendenciasRESUMEN
Insulin-like growth factor 2 (IGF2) overexpression is an important molecular marker of adrenocortical carcinoma (ACC), which is a rare but devastating endocrine cancer. It is not clear whether IGF2 overexpression modifies the biology and growth of this cancer, thus more studies are required before IGF2 can be considered as a major therapeutic target. We compared the phenotypical, clinical, biological, and molecular characteristics of ACC with or without the overexpression of IGF2, to address these issues. We also carried out a similar analysis in an ACC cell line (H295R) in which IGF2 expression was knocked down with si- or shRNA. We found no significant differences in the clinical, biological and molecular (transcriptomic) traits between IGF2-high and IGF2-low ACC. The absence of IGF2 overexpression had little influence on the activation of tyrosine kinase pathways both in tumors and in H295 cells that express low levels of IGF2. In IGF2-low tumors, other growth factors (FGF9, PDGFA) are more expressed than in IGF2-high tumors, suggesting that they play a compensatory role in tumor progression. In addition, IGF2 knock-down in H295R cells substantially impaired growth (>50% inhibition), blocked cells in G1 phase, and promoted apoptosis (>2-fold). Finally, analysis of the 11p15 locus showed a paternal uniparental disomy in both IGF2-high and IGF2-low tumors, but low IGF2 expression could be explained in most IGF2-low ACC by an additional epigenetic modification at the 11p15 locus. Altogether, these observations confirm the active role of IGF2 in adrenocortical tumor growth, but also suggest that other growth promoting pathways may be involved in a subset of ACC with low IGF2 expression, which creates opportunities for the use of other targeted therapies.