Summary: Direct neuroaxis drug delivery has expanded the physician's armamentarium to provide treatment options to those who have failed more conservative interventions. Starting from Bier's 'cocainization of the spinal cord' in 1898, direct nervous system pharmacy delivery has long been recognized as an effective means to treat pain. Intrathecal pump systems are now commonplace in the management of numerous pain states, as well as of neuromuscular sequelae of central nervous system injury. There has been much advancement in the physiologic and pharmacologic understanding of direct neuromodulation, providing a growing number of treatment options depending on the specific disease state. As well, surgical techniques and catheter systems have undergone refinements providing improved long-term safety and efficacy. We present a review of the historical evolution to current intrathecal therapies, as well as a dialog regarding patient selection, drug options, and side effects. Also, included is a discussion of surgical techniques, current delivery options and complications concerning pump placement.

Object Medulloblastomas are the most common malignant brain tumors in children. These tumors are highly invasive, and patients harboring these lesions are frequently diagnosed with distant spread. In this study, the authors investigated the role of Rac1, a member of the Rho family of small guanosine triphosphatases, in medulloblastoma invasion. Methods Three established medulloblastoma cell lines were used: DAOY, UW-228, and ONS-76. Specific depletion of Rac1 protein was accomplished by transient transfection of small interfering RNA. Cell invasion through extracellular matrix (Matrigel) was quantified using a transwell migration assay. Mitogen activated protein kinase activation was determined using phospho-MAP kinase–specific antibodies, and inhibition of MAP kinase pathways was achieved by specific small molecule inhibitors. Localization of Rac1 and its expression levels were determined by immunohistochemical analysis using a Rac1-specific antibody, and Rac1 activation was qualitatively assessed by Rac1 plasma membrane association. Results Small interfering RNA–mediated depletion of Rac1 strongly inhibited medulloblastoma cell invasion. Although depletion of Rac1 inhibited the proliferation of UW-228 cells, and of ONS-76 cells to a lesser extent, it stimulated the proliferation of DAOY cells. Depletion of Rac1 also inhibited the activation of the ERK and JNK MAP kinase pathways, and inhibition of either pathway diminished invasion and proliferation. Immunohistochemical analysis demonstrated that the Rac1 protein was overexpressed in all medulloblastoma tumors examined, and indicated that Rac1 was hyperactive in 6 of 25 tumors. Conclusions The authors' data show that Rac1 is necessary for the invasive behavior of medulloblastoma cells in vitro, and plays a variable role in medulloblastoma cell proliferation. In addition, these results indicate that Rac1 stimulates medulloblastoma invasion by activating the ERK and JNK pathways. The authors suggest that Rac1 and signaling elements controlled by this guanosine triphosphatase may serve as novel targets for therapeutic intervention in malignant medulloblastomas.

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Modern imaging techniques, when applied in the appropriate clinical setting, may serve as a valuable tool for diagnosis and management of patients with mTBI. An understanding of modern neuroanatomical imaging will enhance our ability to analyse injury and recognize the manifestations of mTBI.