The putative mechanism of vagus nerve stimulation (VNS) for medically refractory epilepsy is desynchronization of hippocampal and thalamocortical circuitry; however, the nature of the dose-response relationship and temporal dynamics is poorly understood. For greater elucidation, a study in a nonepileptic rat model was previously conducted and showed that rapid-cycle (RC) VNS achieved superior desynchrony compared to standard-cycle (SC) VNS. Here, the authors report on the first in-human analysis of the neuromodulatory dose-response effects of VNS in a patient with posttraumatic, independent, bilateral mesial temporal lobe epilepsy refractory to medications and SC-VNS who was referred as a potential candidate for a responsive neurostimulation device. During stereotactic electroencephalography (SEEG) recordings, the VNS device was initially turned off, then changed to SC-VNS and then RC-VNS settings. Spectral analysis revealed a global reduction of power in the theta (4–8 Hz) and alpha (8–15 Hz) bands with both SC- and RC-VNS compared to the stimulation off setting (p < 0.001). Furthermore, in the alpha band, both SC- and RC-VNS were associated with greater global desynchrony compared to the off setting (p < 0.001); and, specifically, in the bilateral epileptogenic hippocampi, RC-VNS further reduced spectral power compared to SC-VNS (p < 0.001). The dose-response and temporal effects suggest that VNS modulates regional and global dynamics differently.
Adeel Ilyas, Emilia Toth, Diana Pizarro, Kristen O. Riley and Sandipan Pati
Adeel Ilyas, Ching-Jen Chen, Dale Ding, Davis G. Taylor, Shayan Moosa, Cheng-Chia Lee, Or Cohen-Inbar and Jason P. Sheehan
Several recent studies have improved our understanding of the outcomes of volume-staged (VS) and dose-staged (DS) stereotactic radiosurgery (SRS) for the treatment of large (volume > 10 cm3) brain arteriovenous malformations (AVMs). In light of these recent additions to the literature, the aim of this systematic review is to provide an updated comparison of VS-SRS and DS-SRS for large AVMs.
A systematic review of the literature was performed using PubMed to identify cohorts of 5 or more patients with large AVMs who had been treated with VS-SRS or DS-SRS. Baseline data and post-SRS outcomes were extracted for analysis.
A total of 11 VS-SRS and 10 DS-SRS studies comprising 299 and 219 eligible patients, respectively, were included for analysis. The mean obliteration rates for VS-SRS and DS-SRS were 41.2% (95% CI 31.4%–50.9%) and 32.3% (95% CI 15.9%–48.8%), respectively. Based on pooled individual patient data, the outcomes for patients treated with VS-SRS were obliteration in 40.3% (110/273), symptomatic radiation-induced changes (RICs) in 13.7% (44/322), post-SRS hemorrhage in 19.5% (50/256), and death in 7.4% (24/323); whereas the outcomes for patients treated with DS-SRS were obliteration in 32.7% (72/220), symptomatic RICs in 12.2% (31/254), post-SRS hemorrhage in 10.6% (30/282), and death in 4.6% (13/281).
Volume-staged SRS appears to afford higher obliteration rates than those achieved with DS-SRS, although with a less favorable complication profile. Therefore, VS-SRS or DS-SRS may be a reasonable treatment approach for large AVMs, either as stand-alone therapy or as a component of a multimodality management strategy.
Adeel Ilyas, Ching-Jen Chen, Dale Ding, Andrew Romeo, Thomas J. Buell, Tony R. Wang, M. Yashar S. Kalani and Min S. Park
Stroke is one of the leading causes of death worldwide and a significant source of long-term morbidity. Unfortunately, a substantial number of stroke patients either are ineligible or do not significantly benefit from contemporary medical and interventional therapies. To address this void, investigators recently made technological advances to render transcranial MR-guided, high-intensity focused ultrasound (MRg-HIFU) sonolysis a potential therapeutic option for both acute ischemic stroke (AIS)—as an alternative for patients with emergent large-vessel occlusion (ELVO) who are ineligible for endovascular mechanical thrombectomy (EMT) or as salvage therapy for patients in whom EMT fails—and intracerebral hemorrhage (ICH)—as a neoadjuvant means of clot lysis prior to surgical evacuation. Herein, the authors review the technological principles behind MRg-HIFU sonolysis, its results in in vitro and in vivo stroke models, and its potential clinical applications. As a noninvasive transcranial technique that affords rapid clot lysis, MRg-HIFU thrombolysis may develop into a therapeutic option for patients with AIS or ICH. However, additional studies of transcranial MRg-HIFU are necessary to ascertain the merit of this treatment approach for thrombolysis in both AIS and ICH, as well as its technical limitations and risks.
Adeel Ilyas, Ching-Jen Chen, Dale Ding, Panagiotis Mastorakos, Davis G. Taylor, I. Jonathan Pomeraniec, Cheng-Chia Lee and Jason Sheehan
Cyst formation can occasionally occur after stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVMs). Given the limited data regarding post-SRS cyst formation in patients with AVM, the time course, natural history, and management of this delayed complication are poorly defined. The aim of this systematic review was to determine the incidence, time course, and optimal management of cyst formation after SRS for AVMs.
A literature review was performed using PubMed to identify studies reporting cyst formation in AVM patients treated with SRS. Baseline and outcomes data, including the incidence and management of post-SRS cysts, were extracted from each study that reported follow-up duration. The mean time to cyst formation was calculated from the subset of studies that reported individual patient data.
Based on pooled data from 22 studies comprising the incidence analysis, the overall rate of post-SRS cyst formation was 3.0% (78/2619 patients). Among the 26 post-SRS cyst patients with available AVM obliteration data, nidal obliteration was achieved in 20 (76.9%). Of the 64 cyst patients with available symptomatology and management data, 21 (32.8%) were symptomatic; 21 cysts (32.8%) were treated with surgical intervention, whereas the remaining 43 (67.2%) were managed conservatively. Based on a subset of 19 studies reporting individual time-to-cyst-formation data from 63 patients, the mean latency period to post-SRS cyst formation was 78 months (6.5 years).
Cyst formation is an uncommon complication after SRS for AVMs, with a relatively long latency period. The majority of post-SRS cysts are asymptomatic and can be managed conservatively, although enlarging or symptomatic cysts may require surgical intervention. Long-term follow-up of AVM patients is crucial to the appropriate diagnosis and management of post-SRS cysts.
Joshua D. Bernstock, James H. Mooney, Adeel Ilyas, Gustavo Chagoya, Dagoberto Estevez-Ordonez, Ahmed Ibrahim and Ichiro Nakano
Glioblastoma (GBM), the most common primary malignant brain tumor in adults, is associated with significant morbidity and mortality despite maximal safe resection followed by chemo- and radiotherapy. GBMs contain self-renewing, tumorigenic glioma stem cells that contribute to tumor initiation, heterogeneity, therapeutic resistance, and recurrence. Intratumoral heterogeneity (ITH) of GBMs is also a major contributing factor to poor clinical outcomes associated with these high-grade glial tumors. Herein, the authors summarize recent discoveries and advances in the molecular and phenotypic characterization of GBMs with particular focus on ITH. In so doing, they attempt to highlight recent advances in molecular signatures/properties and metabolic alterations in an effort to clarify translational implications that may ultimately improve clinical outcomes.