High-Resolution MRI Findings following Trigeminal Rhizotomy.

BACKGROUND AND PURPOSE: Patients with trigeminal neuralgia often undergo trigeminal rhizotomy via radiofrequency thermocoagulation or glycerol injection for treatment of symptoms. To date, radiologic changes in patients with trigeminal neuralgia post-rhizotomy have not been described, to our knowledge. The aim of this study was to evaluate patients after trigeminal rhizotomy to characterize post-rhizotomy changes on 3D high-resolution MR imaging. MATERIALS AND METHODS: A retrospective review of trigeminal neuralgia protocol studies was performed in 26 patients after rhizotomy compared with 54 treatment-naïve subjects with trigeminal neuralgia. Examinations were reviewed independently by 2 neuroradiologists blinded to the side of symptoms and treatment history. The symmetry of Meckel's cave on constructive interference in steady-state and the presence of contrast enhancement within the trigeminal nerves on volumetric interpolated breath-hold examination images were assessed subjectively. The signal intensity of Meckel's cave was measured on coronal noncontrast constructive interference in steady-state imaging on each side. RESULTS: Post-rhizotomy changes included subjective clumping of nerve roots and/or decreased constructive interference in steady-state signal intensity within Meckel's cave, which was identified in 17/26 (65%) patients after rhizotomy and 3/54 (6%) treatment-naïve patients (P < .001). Constructive interference in steady-state signal intensity within Meckel's cave was, on average, 13% lower on the side of the rhizotomy in patients posttreatment compared with a 1% difference in controls (P < .001). Small regions of temporal encephalomalacia were noted in 8/26 (31%) patients after rhizotomy and 0/54 (0%) treatment-naïve patients (P < .001). CONCLUSIONS: Post-trigeminal rhizotomy findings frequently include nerve clumping and decreased constructive interference in steady-state signal intensity in Meckel's cave. Small areas of temporal lobe encephalomalacia are encountered less frequently.

Combination bacteriolytic therapy for the treatment of experimental tumors.

Current chemotherapeutic approaches for cancer are in part limited by the inability of drugs to destroy neoplastic cells within poorly vascularized compartments of tumors. We have here systematically assessed anaerobic bacteria for their capacity to grow expansively within avascular compartments of transplanted tumors. Among 26 different strains tested, one (Clostridium novyi) appeared particularly promising. We created a strain of C. novyi devoid of its lethal toxin (C. novyi-NT) and showed that intravenously injected C. novyi-NT spores germinated within the avascular regions of tumors in mice and destroyed surrounding viable tumor cells. When C. novyi-NT spores were administered together with conventional chemotherapeutic drugs, extensive hemorrhagic necrosis of tumors often developed within 24 h, resulting in significant and prolonged antitumor effects. This strategy, called combination bacteriolytic therapy (COBALT), has the potential to add a new dimension to the treatment of cancer.

AR-R17779, and alpha7 nicotinic agonist, improves learning and memory in rats.

Nicotinic acetylcholine systems have been found to be important for learning and memory function. The prototypic nicotinic agonist nicotine has been shown in a variety of studies to improve aspects of cognitive function. The specific involvement of nicotinic receptor subtypes is now being investigated. The involvement of alpha7 nicotinic receptors was assessed in this project using a novel alpha7 nicotinic agonist, AR-R 17779. Repeated doses (subcutaneous injection 20 min before testing) of the racemic mixture AR-R 13489 and its active isomer AR-R 17779 were assessed in adult female Sprague-Dawley rats using the eight-arm radial maze. AR-R 13489 (2 mg/kg) caused a significant improvement of long-term win-shift acquisition after 3 weeks of training (n = 10 per group). The same dose of AR-R 17779 also caused a significant improvement in repeated acquisition within each daily session in the radial-arm maze. In another study, the active isomer AR-R 17779 significantly improved radial-arm maze working memory function in rats with lesions to the septohippocampal projection. Fimbria-fornix lesions significantly impaired working memory performance and AR-R 17779 significantly reversed that impairment. These studies showed that alpha7 nicotinic agonist treatment improved learning in two radial-arm maze tasks and reversed working memory impairment caused by fimbria-fornix sections, providing evidence for alpha7 involvement in learning and memory, and the potential therapeutic use of AR-R 17779.

Nicotine-dizocilpine interactions and working and reference memory performance of rats in the radial-arm maze.

Both nicotinic cholinergic and NMDA glutaminergic systems are important for memory function. Nicotine has been found repeatedly to significantly improve working memory performance in the radial-arm maze. The NMDA antagonist dizocilpine has been found to impair working memory performance. There is neuropharmacological evidence that these two systems are functionally related. Nicotine is potent at releasing many transmitters including glutamate. The current study was conducted to examine the interaction of nicotinic and NMDA systems with regard to working and reference memory. Rats were trained on a working/reference procedure on a 16-arm radial maze. After acquisition, they were administered nicotine (0, 0.2, and 0.4 mg/kg) and dizocilpine (0, 100, and 200 microg/kg) alone or in combination in a repeated measures, counterbalanced design. As seen previously, nicotine at a dose of 0.2 mg/kg caused a significant improvement in working but not reference memory performance in the radial-arm maze. The 200 microg/kg dose of dizocilpine made the rats nonresponsive on the maze so that choice accuracy could not be assessed. The 100 microg/kg dose of dizocilpine caused significant impairments in both working and reference memory. The 0.4 mg/kg dose of nicotine significantly attenuated the dizocilpine-induced deficit in both working and reference memory. NMDA blockade impairs working and reference memory and blocks the expression of the working memory improvement caused by 0.2 mg/kg of nicotine. However, a higher dose of 0.4 mg/kg of nicotine is effective at attenuating the dizocilpine-induced deficit, even though this dose alone is not effective in improving performance. A second study examined the effects of a lower dose range of dizocilpine. Comensurately smaller memory impairments were seen with lower doses of dizocilpine down to 12.5 microg/kg, which did not produce any significant effects on memory performance or response latency. Nicotine had a more modest effect in attenuating the smaller deficits caused by these lower doses of dizocilpine. These studies provide evidence for important interactions between nicotinic and NMDA systems with regard to memory function.