Researchers at Temple University School of Medicine, Philadelphia, PA tested the hypothesis that human papillomavirus type 16 oncoprotein E6 (HPV16 E6) is present in human focal cortical dysplasia type IIB (FCDIIB) specimens. HPV was assayed by immunohistochemistry in FCDIIB specimens (n=50) and control brain specimens (n=36). HPV DNA was assayed by PCR and in situ hybridization. HPV16 E6 protein was expressed in all FCDIIB specimens in balloon cells (BC), but not in regions without BCs or control tissue including normal brain and cortical tubers. Transfection of E6 into fetal mouse brains caused a focal cortical malformation in association with enhanced mTORC 1 signaling. [1]

COMMENT. HPV16 E6 expression during fetal brain development is a novel etiology for FCDIIB, but the mechanism and relation of the HPV16 to the cause of epilepsy associated with focal cortical dysplasia is unexplained.

TORC1 Activation and Inflammation in Fetal TSC Lesions

A current neuropathological publication from the University of Amsterdam; University of Calgary, Canada; and other centers reports that abnormal cells scattered through the cortex and white matter of fetal brain lesions in tuberous sclerosis complex (TSC) show activation of TORC1, similar to that observed in FCD/HPV. This finding supports the concept of increased TORC1 activity during embryonic brain development as a precursor and precipitant of brain malformations in tuberous sclerosis complex [2]. This study also provides evidence for the immunogenicity of giant cells and the prenatal activation of inflammatory pathways in developing TSC brain lesions, a probable explanation for the epileptogenicity of TSC lesions and focal cortical dysplasias.