Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions.

Convection-enhanced delivery (CED) is a novel drug delivery technique that uses positive infusion pressure to deliver therapeutic agents directly into the interstitial spaces of the brain. Despite the promise of CED, clinical trials have demonstrated that target-tissue anatomy and patient-specific physiology play a major role in drug distribution using this technique. In this study, we retrospectively tested the ability of a software algorithm using MR diffusion tensor imaging to predict patient-specific drug distributions by CED. A tumor-targeted cytotoxin, cintredekin besudotox (interleukin 13-PE38QQR), was coinfused with iodine 123-labeled human serum albumin (123I-HSA), in patients with recurrent malignant gliomas. The spatial distribution of 123I-HSA was then compared to a drug distribution simulation provided by the software algorithm. The algorithm had a high sensitivity (71.4%) and specificity (100%) for identifying the high proportion (7 of 14) of catheter trajectories that failed to deliver drug into the desired anatomical region (p = 0.021). This usually occurred when catheter trajectories crossed deep sulci, resulting in leak of the infusate into the subarachnoid cerebrospinal fluid space. The mean concordance of the volume of distribution at the 50% isodose level between the actual 123I-HSA distribution and simulation was 65.75% (95% confidence interval [CI], 52.0%-79.5%), and the mean maximal inplane deviation was less than 8.5 mm (95% CI, 4.0-13.0 mm). The use of this simulation algorithm was considered clinically useful in 84.6% of catheters. Routine use of this algorithm, and its further developments, should improve prospective selection of catheter trajectories, and thereby improve the efficacy of drugs delivered by this promising technique.

Omovertebral bone associated with Sprengel deformity and Klippel-Feil syndrome leading to cervical myelopathy.

The unusual association of an omovertebral bone with Sprengel deformity and Klippel-Feil syndrome is a complex bone anomaly of unknown incidence and etiology. However, several cases of this rare disease pattern have been reported in the literature. In this paper, the authors present the case of a 34-year-old woman with a 5-month history of progressive gait ataxia and intermittent urinary incontinence, which was found to be caused by aberrant bone growth into the spinal canal from an omovertebral bone that extended from the left scapula pressing into the C-6 vertebral arch and subsequently causing cervical myelopathy. The patient underwent isolated resection of the omovertebral bone and decompression of the spinal canal, and her functional and neurological outcome was favorable.

Magnetically guided neuronavigation of flexible instruments in shunt placement, transsphenoidal procedures, and craniotomies.

OBJECTIVE: Magnetically guided neuronavigation of flexible instruments is a new tool that can be used in the frameless navigation of deep-seated lesions or shunt placements. Disadvantages of optical systems such as the line-of-sight problem, the necessity of rigid pin fixation of the head, and missing tracking of the tip of flexible instruments should be solved by the new tracking system. Until now, the accuracy of magnetically guided systems was mostly estimated in laboratory setups. METHODS: In this study, intraoperative accuracy of the system was tested in 60 patients with either hydrocephalus or cranial base tumors. In daily routine use, different operative setups with a variety of metallic instruments were examined. Accuracy of the neuronavigation system was estimated, comparing microscopically or endoscopically identified anatomic landmarks with neuronavigated data and postoperative computed tomographic scans. RESULTS: The main advantage of the new system is the tracking of a magnetic coil at the tip of a flexible instrument. After an initial learning curve during the developmental phase of the system, the latter showed reliable accuracy values with no operative setups leading to mismatch of more than 2 mm. CONCLUSION: Tracking of flexible instruments was easily accomplished as the tip of the instrument was followed within the patient's head. There were no major interferences with other metallic instruments within the surgical field.

Effects of drug efflux on convection-enhanced paclitaxel delivery to malignant gliomas: technical note.

OBJECTIVE: Convection-enhanced delivery (CED) is an approach in local brain tumor treatment. The spread of infusate in CED can be thought of as involving three phases: backflow, convection, and diffusion. Uncontrolled backflow may lead to efflux of the infusate outside the cranium. METHODS: Based on an interim analysis of a clinical trial, the effects of drug efflux on convection were assessed. In a Phase I/II trial, eight patients with recurrent glioblastomas were treated with CED of paclitaxel. The first group of patients was treated with paclitaxel at a concentration of 0.5 mg/ml according to previously approved protocols. RESULTS: These Group 1 patients developed severe skin necrosis due to an efflux of paclitaxel out of the cranium. The average volume of distribution (Vd) in these patients was 12.8 cm. To prevent paclitaxel efflux, the burr hole was sealed with bone wax during and after CED in Groups 2 and 3. Surprisingly, patients in Group 2 showed a larger Vd (22.9 cm per catheter), exceeding the boundaries of the previous tumor, which led to subsequent neurological deficits. To allow a large Vd without severe side effects, the infusion volume was maintained, but the concentration of paclitaxel was reduced (paclitaxel concentration in Group 3, 0.25 mg/ml). CONCLUSION: Vd remained high and no adverse effects were seen in Group 3. Sealing the burr hole during CED prevented efflux. The simple measure of sealing seems to increase Vd. These data demonstrate that uncontrolled backflow may have an important impact on CED and must be avoided.