Subcortical pathways serving cortical language sites: initial experience with diffusion tensor imaging fiber tracking combined with intraoperative language mapping

The combination of mapping functional cortical neurons by intraoperative cortical stimulation and axonal architecture by diffusion tensor MRI fiber tracking can be used to delineate the pathways between functional regions. In this study the authors investigated the feasibility of combining these techniques to yield connectivity associated with motor speech and naming. Diffusion tensor MRI fiber tracking provides maps of axonal bundles and was combined with intraoperative mapping of eloquent cortex for a patient undergoing brain tumor surgery. Tracks from eight stimulated sites in the inferior frontal cortex including mouth motor, speech arrest, and anomia were generated from the diffusion tensor MRI data. The regions connected by the fiber tracking were compared to foci from previous functional imaging reports on language tasks. Connections were found between speech arrest, mouth motor, and anomia sites and the SMA proper and cerebral peduncle. The speech arrest and a mouth motor site were also seen to connect to the putamen via the external capsule. This is the first demonstration of delineation of subcortical pathways using diffusion tensor MRI fiber tracking with intraoperative cortical stimulation. The combined techniques may provide improved preservation of eloquent regions during neurological surgery, and may provide access to direct connectivity information between functional regions of the brain.     

Subchondral cysts of the atlantoaxial joint: a risk factor for odontoid fractures in the elderly

Background contextScholars have postulated that cervical degeneration can predispose the upper cervical spine to injury after minor trauma. Subchondral cysts have previously been recognized as potentiators of fracture in the hip and knee but no cases of cervical degenerative cysts contributing to fracture have been reported.PurposeThis report documents a case series in which patients sustained significant injury to the upper cervical spine in the setting of subchondral cervical cysts.Study design/settingCase series/academic level I trauma center.MethodsBetween 2004 and 2008, six patients (ages 73–91 years) with cervical pathology were admitted to the trauma service at our Level I trauma center. The most common mechanism of injury was a low velocity fall, which occurred in 5 out of 6 patients. All patients suffered an odontoid fracture. In all cases, there was radiographic evidence of cyst formation, and computed tomographic imaging demonstrated fracture communication with the subchondral cyst.ResultsOf the six cases, four were treated definitively with immobilization in a cervical orthosis and two required surgery. One patient was treated with an occipital-cervical fusion, whereas the other underwent Brooks wiring. All patients ultimately went on to heal their fractures.ConclusionsDegenerative changes in the cervical spine have previously been recognized to potentiate injury. This report raises the question of whether degenerative processes at the C1–C2 articulation predispose elderly patients to injury at this level. The presence of cystic degeneration at the atlantoaxial joint should be recognized as a potential risk factor for cervical injury after relatively minor trauma.     

Contribution of Notch signaling activation to human glioblastoma multiforme

OBJECT: Because activation of Notch receptors has been suggested to be critical for Ras-mediated transformation, and because many gliomas exhibit deregulated Ras signaling, the authors measured Notch levels and activation in primary samples and cell lines derived from glioblastoma multiforme (GBM) as well as the contribution of Notch pathway activation to astrocytic transformation and growth. METHODS: Western blot analysis of Notch 1 expression and activation showed that Notch 1 protein was overexpressed and/or activated in Ras-transformed astrocytes, in three of four GBM cell lines, and in four of five primary GBM samples. Expansion of these studies to assess mRNA expression of components of the Notch signaling pathway by cDNA expression array showed that cDNAs encoding components of the Notch signaling pathway, including the Notch ligand Jagged-1, Notch 3, and the downstream targets of Notch (HES1 and HES2), were also overexpressed relative to non-neoplastic brain controls in 23, 71, and 51% of 35 primary GBMs, respectively. Furthermore, inhibition of Notch signaling by genetic or pharmacological means led to selective suppression of the growth and expression of markers of differentiation in cells exhibiting Notch pathway deregulation. CONCLUSIONS: Notch activation contributes to Ras-induced transformation of glial cells and to glioma growth, survival, or both and as such may represent a new target for GBM therapy.