We have previously demonstrated safety of G207, a doubly mutated (deletion of both gamma(1)34.5 loci, insertional inactivation of U(L)39) herpes simplex virus (HSV) for patients stereotactically inoculated in enhancing portions of recurrent malignant gliomas. We have now determined safety of two inoculations of G207, before and after tumor resection. Inclusion criteria were histologically proven recurrent malignant glioma, Karnofsky score >or=70, and ability to resect the tumor without ventricular system breach. Patients received two doses of G207 totaling 1.15 x 10(9) plaque-forming units with 13% of this total injected via a catheter placed stereotactically in the tumor. Two or five days later, tumor was resected en bloc with catheter in place. The balance of G207 dose was injected into brain surrounding the resection cavity. Six patients with recurrent glioblastoma multiforme were enrolled. Two days after the second G207 inoculation, one patient experienced transient fever, delirium, and hemiparesis, which entirely resolved on high-dose dexamethasone. No patient developed HSV encephalitis or required treatment with acyclovir. Radiographic and neuropathologic evidence suggestive of antitumor activity is reported. Evidence of viral replication was demonstrated. G207 appears safe for multiple dose delivery, including direct inoculation into the brain surrounding tumor resection cavity.
The LAO is a constant anatomical structure of the craniocervical junction that might be of concern to the clinician. This ligament inhibits lateral flexion of the atlantooccipital joint and its disruption appears to add to instability at this articulation.
Signs and symptoms indicative of a tethered spinal cord appear to correspond to increases in the LSA. Although the authors do not advocate the use of LSA measurement as the sole indicator of a tethered spinal cord, this imaging finding may prove useful to the clinician as an indication of the tethered spinal cord or as an adjunct in verifying symptomatology in patients harboring a lipomyelomeningocele.
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