OBJECTIVE Complications of laser interstitial thermal therapy (LITT) are underreported. The authors discuss how they have modified their technique in the context of technical and treatment-related adverse events. METHODS The Medtronic Visualase system was used in 49 procedures in 46 patients. Between 1 and 3 cooling catheters/laser fiber assemblies were placed, for a total of 62 implanted devices. Devices were placed using frameless stereotaxy (n = 3), frameless stereotaxy with intraoperative MRI (iMRI) (n = 9), iMRI under direct vision (n = 2), MRI alone (n = 1), or frame-based (n = 47) techniques. LITT was performed while monitoring MRI thermometry. Indications included brain tumors (n = 12), radiation necrosis (n = 2), filum terminale ependymoma (n = 1), mesial temporal lobe epilepsy (n = 21), corpus callosotomy for bifrontal epilepsy (n = 3), cavernoma (n = 1), and hypothalamic hamartomas (n = 6). RESULTS Some form of adverse event occurred in 11 (22.4%) of 49 procedures. These included 4 catheter malpositions, 3 intracranial hemorrhages, 3 cases of neurological deficit related to thermal injury, and 1 technical malfunction resulting in an aborted procedure. Of these, direct thermal injury was the only cause of prolonged neurological morbidity and occurred in 3 of 49 procedures. Use of frameless stereotaxy and increased numbers of devices were associated with significantly increased complication rates (p < 0.05). A number of procedural modifications were made to avoid complications, including the use of 1) frame-based catheter placement, a 1.8-mm alignment rod to create a track and titanium skull anchors for long trajectories to improve accuracy; 2) a narrow-gauge instrument for dural puncture and coregistration of contrast MRI with CT angiography to reduce intracranial hemorrhage; 3) general endotracheal anesthesia for posterior-placed skull anchors to reduce the likelihood of damage to the cooling catheter; 4) use of as few probes as possible to reduce complications overall; and 5) dose modification of thermal treatment and use of short (3-mm) diffusing tips to limit treatment when structures to be spared do not have intervening CSF spaces to act as heat sinks. CONCLUSIONS Laser ablation treatment may be used for a variety of neurosurgical procedures for patients with tumors and epilepsy. While catheter placement and thermal treatment may be associated with a range of suboptimal operative and postoperative courses, permanent neurological morbidity is less common. The authors' institutional experience illustrates a number of measures that may be taken to improve outcomes using this important new tool in the neurosurgical arsenal.
The microtubule inhibitor vincristine is currently used to treat a variety of brain tumors, including low-grade glioma and anaplastic oligodendroglioma. Vincristine, however, does not penetrate well into brain tumor tissue, and moreover, it displays dose-limiting toxicities, including peripheral neuropathy. Mebendazole, a Food and Drug Administration-approved anthelmintic drug with a favorable safety profile, has recently been shown to display strong therapeutic efficacy in animal models of both glioma and medulloblastoma. Importantly, appropriate formulations of mebendazole yield therapeutically effective concentrations in the brain. Mebendazole has been shown to inhibit microtubule formation, but it is not known whether its potency against tumor cells is mediated by this inhibitory effect. To investigate this, we examined the effects of mebendazole on GL261 glioblastoma cell viability, microtubule polymerization and metaphase arrest, and found that the effective concentrations to inhibit these functions are very similar. In addition, using mebendazole as a seed for the National Cancer Institute (NCI) COMPARE program revealed that the top-scoring drugs were highly enriched in microtubule-targeting drugs. Taken together, these results indicate that the cell toxicity of mebendazole is indeed caused by inhibiting microtubule formation. We also compared the therapeutic efficacy of mebendazole and vincristine against GL261 orthotopic tumors. We found that mebendazole showed a significant increase in animal survival time, whereas vincristine, even at a dose close to its maximum tolerated dose, failed to show any efficacy. In conclusion, our results strongly support the clinical use of mebendazole as a replacement for vincristine for the treatment of brain tumors.
stroke risk and complication rate likely reflects 4 important factors: careful patient selection, excellent surgical technique, meticulous intraoperative and perioperative management, and attentive patient follow-up. Moreover, although this study does not prove that a combined indirect and direct revascularization procedure is superior to other approaches, the low rate of recurrent stroke and hemorrhage is compelling. Moving forward, prospective cohort and randomized trials are needed to further define best evidence-based practice. Future studies should also assess cognitive function and quality of life in greater depth. Adult moyamoya disease is an important cause of stroke and cognitive decline and a critical area for continued research.
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