Comparative Effectiveness of Stereo-EEG versus Subdural Grids in Epilepsy Surgery

OBJECTIVE: To compare the outcomes of subdural electrode (SDE) implantations versus stereo-electroencephalography (SEEG), the two predominant methods of intracranial EEG (iEEG) performed in difficult to localize drug-resistant focal epilepsy. METHODS: The Surgical Therapies Commission of the International League Against Epilepsy created an international registry of iEEG patients implanted between 2005-2019 with ≥ 1 year follow-up. We used propensity score matching to control exposure selection bias and generate comparable cohorts. Study endpoints: 1) likelihood of resection after iEEG; 2) seizure-freedom at last follow-up; and 3) complications (composite of either post-operative infection, symptomatic intracranial hemorrhage, or permanent neurologic deficit). RESULTS: Ten study sites from seven countries and three continents contributed 2,012 patients, including 1,468 (73%) eligible for analysis (526 SDE, 942 SEEG) of whom 988 (67%) underwent subsequent resection. Propensity score matching improved covariate balance between exposure groups for all analyses. Propensity-matched patients who underwent SDE had higher odds of subsequent resective surgery (odds ratio OR = 1.4, 95% CI 1.05 - 1.84), and higher odds of complications (OR=2.24, 95% CI 1.34-3.74; unadjusted: 9.6% after SDE vs. 3.3% after SEEG). Odds of seizure-freedom in propensity-matched resected patients were 1.66 times higher (95% CI 1.21, 2.26) for SEEG compared to SDE (unadjusted: 55% seizure-free after SEEG-guided resections vs. 41% after SDE) INTERPRETATION: Compared to SEEG, SDE evaluations are more likely to lead to brain surgery in patients with drug-resistant epilepsy, but have more surgical complications and lower probability of seizure-freedom. This comparative-effectiveness study provides the highest feasible evidence level to guide decisions on iEEG. This article is protected by copyright. All rights reserved

Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells

<p>Abstract</p> <p>Background</p> <p>Effective transvascular delivery of nanoparticle-based chemotherapeutics across the blood-brain tumor barrier of malignant gliomas remains a challenge. This is due to our limited understanding of nanoparticle properties in relation to the physiologic size of pores within the blood-brain tumor barrier. Polyamidoamine dendrimers are particularly small multigenerational nanoparticles with uniform sizes within each generation. Dendrimer sizes increase by only 1 to 2 nm with each successive generation. Using functionalized polyamidoamine dendrimer generations 1 through 8, we investigated how nanoparticle size influences particle accumulation within malignant glioma cells.</p> <p>Methods</p> <p>Magnetic resonance and fluorescence imaging probes were conjugated to the dendrimer terminal amines. Functionalized dendrimers were administered intravenously to rodents with orthotopically grown malignant gliomas. Transvascular transport and accumulation of the nanoparticles in brain tumor tissue was measured <it>in vivo </it>with dynamic contrast-enhanced magnetic resonance imaging. Localization of the nanoparticles within glioma cells was confirmed <it>ex vivo </it>with fluorescence imaging.</p> <p>Results</p> <p>We found that the intravenously administered functionalized dendrimers less than approximately 11.7 to 11.9 nm in diameter were able to traverse pores of the blood-brain tumor barrier of RG-2 malignant gliomas, while larger ones could not. Of the permeable functionalized dendrimer generations, those that possessed long blood half-lives could accumulate within glioma cells.</p> <p>Conclusion</p> <p>The therapeutically relevant upper limit of blood-brain tumor barrier pore size is approximately 11.7 to 11.9 nm. Therefore, effective transvascular drug delivery into malignant glioma cells can be accomplished by using nanoparticles that are smaller than 11.7 to 11.9 nm in diameter and possess long blood half-lives.</p

Laser interstitial thermal therapy for epileptogenic periventricular nodular heterotopia.

OBJECTIVE: Epilepsy with periventricular nodular heterotopia (PVNH) lacks a conclusive surgical treatment strategy as eloquent cortex and important white matter tracts frequently overlay the deep periventricular nodules. Our goal was to evaluate the safety and efficacy of laser interstitial thermal therapy (LITT) for the treatment of epilepsy in PVNH. METHODS: Data on demographic characteristics, complications, visual outcomes, Engel classification at last follow up, anti-epileptic drug use, morbidity, and mortality among patients who underwent this procedure were retrospectively reviewed. RESULTS: Between May 2015 and January 2019, five patients underwent six LITT procedures for epilepsy with PVNH. One patient had residual nodules after their first procedure and underwent a second ablation. The average follow up time was 12 months. Three patients were Engel class Ia, one patient was Engel class II, and one patient was Engel class III at last follow up. Two patients were able to reduce their anti-epileptic drugs post-operatively. Three patients had no changes in vision, one patient experienced a quadrantanopsia, and one patient had subjective blurry vision after their procedures. No patients experienced motor deficits, dysphasia, infection, or mortality. CONCLUSION: LITT appears to be a safe and promising option to provide seizure relief for patients with refractory epilepsy and PVNH that otherwise may not be surgical candidates. Some appropriately determined patients with refractory epilepsy may benefit from LITT before proceeding with an invasive intracranial evaluation. A larger sample size and long-term follow-up is necessary to further elucidate safety and efficacy

Routine High-Resolution Forecasts/Analyses for the Pacific Disaster Center: User Manual

Enclosed herein is our HWCMO user manual. This manual constitutes the final report for our NASA/PDC grant, NASA NAG5-8730, "Routine High Resolution Forecasts/Analysis for the Pacific Disaster Center". Since the beginning of the grant, we have routinely provided experimental high resolution forecasts from the RSM/MSM for the Hawaii Islands, while working to upgrade the system to include: (1) a more robust input of NCEP analyses directly from NCEP; (2) higher vertical resolution, with increased forecast accuracy; (3) faster delivery of forecast products and extension of initial 1-day forecasts to 2 days; (4) augmentation of our basic meteorological and simplified fireweather forecasts to firedanger and drought forecasts; (5) additional meteorological forecasts with an alternate mesoscale model (MM5); and (6) the feasibility of using our modeling system to work in higher-resolution domains and other regions. In this user manual, we provide a general overview of the operational system and the mesoscale models as well as more detailed descriptions of the models. A detailed description of daily operations and a cost analysis is also provided. Evaluations of the models are included although it should be noted that model evaluation is a continuing process and as potential problems are identified, these can be used as the basis for making model improvements. Finally, we include our previously submitted answers to particular PDC questions (Appendix V). All of our initially proposed objectives have basically been met. In fact, a number of useful applications (VOG, air pollution transport) are already utilizing our experimental output and we believe there are a number of other applications that could make use of our routine forecast/analysis products. Still, work still remains to be done to further develop this experimental weather, climate, fire danger and drought prediction system. In short, we would like to be a part of a future PDC team, if at all possible, to further develop and apply the system for the Hawaiian and other Pacific Islands as well as the entire Pacific Basin