The role of deregulated E2F1 expression in brain tumors

Mutations disabling the retinoblastoma (Rb) pathway are among the most common in human cancers, including brain cancer. These mutations promote tumor development through deregulated control of the E2F family of transcription factors. E2F1 belongs to a class of E2F's identified as transcriptional activators and involved in the G1/S phase transition of the cell. However, E2F-1 presents with a paradox as it is considered to have membership in two gene classes, functioning as both an oncogene and a tumor suppressor. This unusual trait generates a degree of uncertainty on the role that E2F1 plays in the development or maintenance of any given tumor. Here we show that E2F1 functions as an oncogene in brain tumors through the generation of mice engineered to overexpress E2F1 specifically within glial cells and neuronal progenitors as directed by the GFAP promoter. Mice carrying the transgene develop with high penetrance a phenotype characterized by neurological deficits including paresia, ataxia, head tilt and seizures. MRI imagining of the tgE2F1 mice reveals a low incidence of mild hydrocephalus, and most notably, histological analysis demonstrates that 25% of tgE2F1 mice present with the spontaneous formation of malignant brain tumors. Overall these neoplasms show histological features from a wide range of aggressive brain cancers including medulloblastoma, choroid plexus carcinoma, primary neuroectodermic tumor and malignant gliomas. Isolation and characterization of astrocytes from the tgE2F1 animal reveals a highly proliferative population of cells with 55% ± 2.5 of the tgE2F1astrocytes, 35% ± 3.4 normal mouse astrocytes in S-phase and the acquired capacity to grow in anchorage independent conditions. Additionally tgE2F1 astrocytes show an aberrant phenotype with random chromosomal fusions and nearly all cells demonstrating polyploidy. Taken together, this model forces a comparison to human brain tumor formation. Mouse age as related to tumoral mimics the human scenario with juvenile tgE2F1 mice presenting embryonal tumors typically identified in children, and older tgE2F1 mice demonstrating gliomas. In this regard, this study suggests a global role for E2F1 in the formation and maintenance of multilineage brain tumors, irrefutably establishing E2F1 as an oncogene in the brain. ^

Atividade eletroencefalográfica de pacientes com acidente vascular cerebral na aprendizagem motora de um jogo baseado em realidade virtual

Stroke is the leading cause of long-term disability among adults and motor relearning is essential in motor sequelae recovery. Therefore, various techniques have been proposed to achieve this end, among them Virtual Reality. The aim of the study was to evaluate electroencephalographic activity of stroke patients in motor learning of a virtual reality-based game. The study included 10 patients with chronic stroke, right-hande; 5 with left brain injury (LP), mean age 48.8 years (± 4.76) and 5 with injury to the right (RP), mean age 52 years (± 10.93). Participants were evaluated for electroencephalographic (EEG) activity and performance while performing 15 repetitions of darts game in XBOX Kinect and also through the NIHSS, MMSE, Fugl-Meyer and the modified Ashworth scale. Patients underwent a trainning with 45 repetitions of virtual darts game, 12 sessions in four weeks. After training, patients underwent reassessment of EEG activity and performance in virtual game of darts (retention). Data were analyzed using ANOVA for repeated measures. According to the results, there were differences between the groups (PD and PE) in frequencies Low Alpha (p = 0.0001), High Alpha (p = 0.0001) and Beta (p = 0.0001). There was an increase in alpha activation powers and a decrease in beta in the phase retention of RP group. In LP group was observed increased alpha activation potency, but without decrease in beta activation. Considering the asymmetry score, RP group increased brain activation in the left hemisphere with the practice in the frontal areas, however, LP group had increased activation of the right hemisphere in fronto-central areas, temporal and parietal. As for performance, it was observed a decrease in absolute error in the game for RP group between assessment and retention (p = 0.015), but this difference was not observed for LP group (p = 0.135). It follows then that the right brain injury patients benefited more from darts game training in the virtual environment with respect to the motor learning process, reducing neural effort in ipsilesionais areas and errors with the practice of the task. In contrast, patients with lesions in left hemisphere decrease neural effort in contralesionais areas important for motor learning and showed no performance improvements with practice of 12 sessions of virtual dart game. Thus, the RV can be used in rehabilitation of stroke patients upper limb, but the laterality of the injury should be considered in programming the motor learning protocol.

Síndrome del nervio interóseo posterior: presentación de 3 casos.

La neuropatía compresiva del nervio interóseo posterior es poco frecuente. Clínicamente se expresa por una paresia (o plejia) de los músculos extensores del puño, los dedos y abductores del pulgar. El estudio eléctrico es fundamental para determinar la topografía de la lesión, y la ecografía o imagen por resonancia magnética ayudan a descartar causas secundarias de compresión, pero el diagnóstico sigue reposando en un correcto examen clínico. En los casos que no mejoran o que tienen un déficit severo, se debe indicar el tratamiento quirúrgico dado que tiene hasta un 95% de buenos resultados cuando se acompaña de una buena rehabilitación posterior. Se presentan tres casos de parálisis del nervio interóseo posterior por compresión en su recorrido por debajo del músculo supinador corto. De los mismos, uno tuvo mejoría espontánea y dos requirieron cirugía descompresiva.

Neuropatía oftalmoplejica dolorosa recurrente (migraña oftalmoplejica): Caso clínico

La Neuropatía oftalmopléjica dolorosa recurrente o migraña oftalmopléjica es una variante infrecuente de cefalea primaria. Se define como al menos dos episodios de cefalea unilateral que se acompaña de paresia ipsilateral de uno, dos o los tres nervios oculomotores. Se debe excluir una lesión orbitaria, paraselar o de la fosa posterior, y no debe ser mejor explicada por otro diagnóstico. Se describe el caso de un pre-escolar de 3 años, sin antecedentes a destacar, que presenta 3 episodios de oftalmoparesia caracterizada por ptosis palpebral y estrabismo divergente con descenso ocular del ojo izquierdo, de hasta 10 días de duración, precedido por irritabilidad, cefalea, vómitos y somnolencia posterior. Se realizó estudios de laboratorio, los cuales fueron normales. La resonancia magnética craneal mostró captación de contraste a nivel de la emergencia del III par craneano izquierdodurante uno de los episodios. Destacamos la importancia de considerar este cuadro como causa recurrente de parálisis óculo-motora. Consideramos importante el valor de la resonancia, no solo para descartar diagnósticos diferenciales, sino como herramienta de confirmación diagnóstica. Se reporta la reducción de los días de compromiso oculomotor tras la administración de corticoides.