In this review paper the authors analyze new therapeutic options for the embolization of meningiomas, as well as the future of meningioma treatment through recent relevant cohorts and articles. They investigate various embolic materials, types of meningiomas amenable to embolization, imaging techniques, and potential imaging biomarkers that could aid in the delivery of embolic materials. They also analyze perfusion status, complications, and new technical aspects of endovascular preoperative embolization of meningiomas. A literature search was performed in PubMed using the terms “meningioma” and “embolization” to investigate recent therapeutic options involving embolization in the treatment of meningioma. The authors looked at various cohorts, complications, materials, and timings of meningioma treatment. Liquid embolic materials are preferable to particle agents because particle embolization carries a higher risk of hemorrhage. Liquid agents maximize the effect of devascularization because of deeper penetration into the trunk and distal tumor vessels. The 3 main imaging techniques, MRI, CT, and angiography, can all be used in a complementary fashion to aid in analyzing and treating meningiomas. Intraarterial perfusion MRI and a new imaging modality for identifying biomarkers, susceptibility-weighted principles of echo shifting with a train of observations (SW-PRESTO), can relay information about perfusion status and degrees of ischemia in embolized meningiomas, and they could be very useful in the realm of therapeutics with embolic material delivery. Direct puncture is yet another therapeutic technique that would allow for more accurate embolization and less blood loss during resection.
Aatman Shah, Omar Choudhri, Henry Jung, and Gordon Li
Gordon Li, Steven Chang, John R. Adler Jr., and Michael Lim
✓ Glomus jugulare tumors are rare, slow-growing vascular lesions that arise from the chief cells of the paraganglia within the jugular bulb. They can be associated with the tympanic branch of the glossopharyngeal nerve (Jacobsen nerve) or the auricular branch of the vagus nerve (Arnold nerve) and are also referred to as chemodectomas or nonchromaffin paragangliomas. Optimal treatment of these histologically benign tumors remains controversial. Surgery remains the treatment of choice, but can carry high morbidity rates. External-beam radiation was originally used for subtotal resections and in patients who were poor surgical candidates; however, radiosurgery has recently been introduced as an effective and safe treatment option for patients with these tumors. In this article the authors discuss the history of radiation therapy for glomus jugulare tumors, focusing on recent radiosurgical results.
Adrian J. Rodrigues, Michael C. Jin, Adela Wu, Hriday P. Bhambhvani, Gordon Li, and Gerald A. Grant
Although past studies have associated external-beam radiation therapy (EBRT) with higher incidences of secondary neoplasms (SNs), its effect on SN development from pediatric low-grade gliomas (LGGs), defined as WHO grade I and II gliomas of astrocytic or oligodendrocytic origin, is not well understood. Utilizing a national cancer registry, the authors sought to characterize the risk of SN development after EBRT treatment of pediatric LGG.
A total of 1245 pediatric patient (aged 0–17 years) records from 1973 to 2015 were assembled from the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable subdistribution hazard regression models were used to evaluate the prognostic impact of demographic, tumor, and treatment-related covariates. Propensity score matching was used to balance baseline characteristics. Cumulative incidence analyses measured the time to, and rate of, SN development, stratified by receipt of EBRT and controlled for competing mortality risk. The Fine and Gray semiparametric model was used to estimate future SN risk in EBRT- and non–EBRT-treated pediatric patients.
In this study, 366 patients received EBRT and 879 did not. Forty-six patients developed SNs after an LGG diagnosis, and 27 of these patients received EBRT (OR 3.61, 95% CI 1.90–6.95; p < 0.001). For patients alive 30 years from the initial LGG diagnosis, the absolute risk of SN development in the EBRT-treated cohort was 12.61% (95% CI 8.31–13.00) compared with 4.99% (95% CI 4.38–12.23) in the non–EBRT-treated cohort (p = 0.013). Cumulative incidence curves that were adjusted for competing events still demonstrated higher rates of SN development in the EBRT-treated patients with LGGs. After matching across available covariates and again adjusting for the competing risk of mortality, a clear association between EBRT and SN development remained (subhazard ratio 2.26, 95% CI 1.21–4.20; p = 0.010).
Radiation therapy was associated with an increased risk of future SNs for pediatric patients surviving LGGs. These data suggest that the long-term implications of EBRT should be considered when making treatment decisions for this patient population
Shivanand P. Lad, Raphael Guzman, Michael E. Kelly, Gordon Li, Michael Lim, Karl Lovbald, and Gary K. Steinberg
✓Vasospasm following cerebral aneurysm rupture is one of the most devastating sequelae and the most common cause of delayed ischemic neurological deficit (DIND). Because vasospasm also is the most common cause of morbidity and mortality in patients who survive the initial bleeding episode, it is imperative not only to diagnose the condition but also to predict which patients are likely to become symptomatic. The exact pathophysiology of vasospasm is complex and incompletely elucidated. Early recognition of vasospasm is essential because the timely use of several therapeutic interventions can counteract this disease and prevent the occurrence of DIND. However, the prompt implementation of these therapies depends on the ability to predict impending vasospasm or to diagnose it at its early stages.
A number of techniques have been developed during the past several decades to evaluate cerebral perfusion, including positron emission tomography, xenon-enhanced computed tomography, single-photon emission computed tomography, perfusion- and diffusion-weighted magnetic resonance imaging, and perfusion computed tomography. In this article, the authors provide a general overview of the currently available perfusion imaging techniques and their applications in treating vasospasm after a patient has suffered a subarachnoid hemorrhage. The use of cerebral perfusion imaging techniques for the early detection of vasospasm is becoming more common and may provide opportunities for early therapeutic intervention to counteract vasospasm in its earliest stages and prevent the occurrence of DINDs.
Chirag G. Patil, Anand Veeravagu, Regina S. Bower, Gordon Li, Steven D. Chang, Michael Lim, and John R. Adler Jr.
Patients with atypical trigeminal neuralgia (TN) have unilateral pain in the trigeminal distribution that is dull, aching, or burning in nature and is constant or nearly constant. Studies of most radiosurgical and surgical series have shown lower response rates in patients with atypical TN. This study represents the first report of the treatment of atypical TN with frameless CyberKnife stereotactic radiosurgery (SRS).
Between 2002 and 2007, 7 patients that satisfied the criteria for atypical TN and underwent SRS were included in our study. A 6–8-mm segment of the trigeminal nerve was targeted, excluding the proximal 3 mm at the brainstem. All patients were treated in a single session with a median maximum dose of 78 Gy and a median marginal dose of 64 Gy.
Outcomes in 7 patients with a mean age of 61.6 years and a median follow-up of 20 months are reported. Following SRS, 4 patients had complete pain relief, 2 had minimal pain relief with some decrease in the intensity of their pain, and 1 patient experienced no pain relief. Pain relief was reported within 1 week of SRS in 4 patients and at 4 months in 2 patients. After a median follow-up of 28 months, pain did not recur in any of the 4 patients who had reported complete pain relief. Complications after SRS included bothersome numbness in 3 patients and significant dysesthesias in 1 patient.
The authors have previously reported a 90% rate of excellent pain relief in patients with classic TN treated with CyberKnife SRS. Compared with patients with classic TN, patients with atypical TN have a lower rate of pain relief. Nevertheless, the nearly 60% rate of success after SRS achieved in this study is still comparable to or better than results achieved with any other treatment modality for atypical TN.
Allen L. Ho, John G. D. Cannon, Jyodi Mohole, Arjun V. Pendharkar, Eric S. Sussman, Gordon Li, Michael S. B. Edwards, Samuel H. Cheshier, and Gerald A. Grant
Topical antimicrobial compounds are safe and can reduce cost and complications associated with surgical site infections (SSIs). Topical vancomycin has been an effective tool for reducing SSIs following routine neurosurgical procedures in the spine and following adult craniotomies. However, widespread adoption within the pediatric neurosurgical community has not yet occurred, and there are no studies to report on the safety and efficacy of this intervention. The authors present the first institution-wide study of topical vancomycin following open craniotomy in the pediatric population.
In this retrospective study the authors reviewed all open craniotomies performed over a period from 05/2014 to 12/2016 for topical vancomycin use, SSIs, and clinical variables associated with SSI. Topical vancomycin was utilized as an infection prophylaxis and was applied as a liquid solution following replacement of a bone flap or after dural closure when no bone flap was reapplied.
Overall, 466 consecutive open craniotomies were completed between 05/2014 and 12/2016, of which 43% utilized topical vancomycin. There was a 1.5% SSI rate in the nontopical cohort versus 0% in the topical vancomycin cohort (p = 0.045). The number needed to treat was 66. There were no significant differences in risk factors for SSI between cohorts. There were no complications associated with topical vancomycin use.
Routine topical vancomycin administration during closure of open craniotomies can be a safe and effective tool for reducing SSIs in the pediatric neurosurgical population.
Gordon Li, Chirag Patil, John R. Adler, Shivanand P. Lad, Scott G. Soltys, Iris C. Gibbs, Laurie Tupper, and Maxwell Boakye
By targeting the medial branches of the dorsal rami, radiofrequency ablation and facet joint injections can provide temporary amelioration of facet joint–producing (or facetogenic) back pain. The authors used CyberKnife radiosurgery to denervate affected facet joints with the goal of obtaining a less invasive yet more thorough and durable antinociceptive rhizotomy.
Patients with refractory low-back pain, in whom symptoms are temporarily resolved by facet joint injections, were eligible. The patients were required to exhibit positron emission tomography–positive findings at the affected levels. Radiosurgical rhizotomy, targeting the facet joint, was performed in a single session with a marginal prescription dose of 40 Gy and a maximal dose of 60 Gy.
Seven facet joints in 5 patients with presumptive facetogenic back pain underwent CyberKnife lesioning. The median follow-up was 9.8 months (range 3–16 months). The mean planning target volume was 1.7 cm3 (range 0.9–2.7 cm3). A dose of 40 Gy was prescribed to a mean isodose line of 79% (range 75–80%). Within 1 month of radiosurgery, improvement in pain was observed in 3 of the 5 patients with durable responses at 16, 12, and 6 months, respectively, of follow-up. Two patients, after 12 and 3 months of follow-up, have neither improved nor worsened. No patient has experienced acute or late-onset toxicity.
These preliminary results suggest that CyberKnife radiosurgery could be a safe, effective, and non-invasive alternative to radiofrequency ablation for managing facetogenic back pain. No patient suffered recurrent symptoms after radiosurgery. It is not yet known whether pain relief due to such lesions will be more durable than that produced by alternative procedures. A larger series of patients with long-term follow-up is ongoing.
Zachary D. Guss, Sachin Batra, Gordon Li, Steven D. Chang, Andrew T. Parsa, Daniele Rigamonti, Lawrence Kleinberg, and Michael Lim
In this article the authors review the literature for recent studies of radiosurgical treatment for glomus jugulare. These studies demonstrate that radiosurgery results in similar glomus jugulare tumor control and a superior morbidity profile compared with surgical treatment. In addition, patients treated with radiosurgery usually remain stable clinically or improve. Given the indolent nature of these tumors, however, more follow-up is required to ensure that the immediate benefits are lasting. These preliminary reports demonstrate that the use of radiosurgery as a primary treatment for glomus jugulare should be extended to encompass more of the patients who are currently assigned to microsurgical treatment.
Michael C. Jin, Jonathon J. Parker, Michael Zhang, Zack A. Medress, Casey H. Halpern, Gordon Li, John K. Ratliff, Gerald A. Grant, Robert S. Fisher, and Stephen Skirboll
Status epilepticus (SE) is associated with significant mortality, cost, and risk of future seizures. In one of the first studies of SE after neurosurgery, the authors assess the incidence, risk factors, and outcome of postneurosurgical SE (PNSE).
Neurosurgical admissions from the MarketScan Claims and Encounters database (2007 through 2015) were assessed in a longitudinal cross-sectional sample of privately insured patients who underwent qualifying cranial procedures in the US and were older than 18 years of age. The incidence of early (in-hospital) and late (postdischarge readmission) SE and associated mortality was assessed. Procedural, pathological, demographic, and anatomical covariates parameterized multivariable logistic regression and Cox models. Multivariable logistic regression and Cox proportional hazards models were used to study the incidence of early and late PNSE. A risk-stratification simulation was performed, combining individual predictors into singular risk estimates.
A total of 197,218 admissions (218,217 procedures) were identified. Early PNSE occurred during 637 (0.32%) of 197,218 admissions for cranial neurosurgical procedures. A total of 1045 (0.56%) cases of late PNSE were identified after 187,771 procedure admissions with nonhospice postdischarge follow-up. After correction for comorbidities, craniotomy for trauma, hematoma, or elevated intracranial pressure was associated with increased risk of early PNSE (adjusted OR [aOR] 1.538, 95% CI 1.183–1.999). Craniotomy for meningioma resection was associated with an increased risk of early PNSE compared with resection of metastases and parenchymal primary brain tumors (aOR 2.701, 95% CI 1.388–5.255). Craniotomies for infection or abscess (aHR 1.447, 95% CI 1.016–2.061) and CSF diversion (aHR 1.307, 95% CI 1.076–1.587) were associated with highest risk of late PNSE. Use of continuous electroencephalography in patients with early (p < 0.005) and late (p < 0.001) PNSE rose significantly over the study time period. The simulation regression model predicted that patients at high risk for early PNSE experienced a 1.10% event rate compared with those at low risk (0.07%). Similarly, patients predicted to be at highest risk for late PNSE were significantly more likely to eventually develop late PNSE than those at lowest risk (HR 54.16, 95% CI 24.99–104.80).
Occurrence of early and late PNSE was associated with discrete neurosurgical pathologies and increased mortality. These data provide a framework for prospective validation of clinical and perioperative risk factors and indicate patients for heightened diagnostic suspicion of PNSE.
Navjot Sandhu, Kathryn R. K. Benson, Kiran A. Kumar, Rie V. Eyben, Daniel T. Chang, Iris C. Gibbs, Steven L. Hancock, Antonio Meola, Steven D. Chang, Gordon Li, Melanie Hayden-Gephart, Scott G. Soltys, and Erqi L. Pollom
Colorectal cancer (CRC) and other gastrointestinal (GI) cancers are believed to have greater radioresistance than other histologies. The authors report local control and toxicity outcomes of stereotactic radiosurgery (SRS) to spinal metastases from GI primary cancers.
A retrospective single-center review was conducted of patients with spinal metastases from GI primary cancers treated with SRS from 2004 to 2017. Patient demographics and lesion characteristics were summarized using medians, interquartile ranges (IQRs), and proportions. Local failure (LF) was estimated using the cumulative incidence function adjusted for the competing risk of death and compared using Gray’s test for equality. Multivariable analyses were conducted using Cox proportional hazard models, adjusting for death as a competing risk, on a per-lesion basis. Patients were stratified in the Cox model to account for repeated measures for clustered outcomes. Median survival was calculated using the Kaplan-Meier method.
A total of 74 patients with 114 spine lesions were included in our analysis. The median age of the cohort was 62 years (IQR 53–70 years). Histologies included CRC (46%), hepatocellular carcinoma (19%), neuroendocrine carcinoma (13%), pancreatic carcinoma (12%), and other (10%). The 1- and 2-year cumulative incidence rates of LF were 24% (95% confidence interval [CI] 16%–33%) and 32% (95% CI 23%–42%), respectively. Univariable analysis revealed that older age (p = 0.015), right-sided primary CRCs (p = 0.038), and single fraction equivalent dose (SFED; α/β = 10) < 20 Gy (p = 0.004) were associated with higher rates of LF. The 1-year cumulative incidence rates of LF for SFED < 20 Gy10 versus SFED ≥ 20 Gy10 were 35% and 7%, respectively. After controlling for gross tumor volume and prior radiation therapy to the lesion, SFED < 20 Gy10 remained independently associated with worse LF (hazard ratio 2.92, 95% CI 1.24–6.89, p = 0.014). Toxicities were minimal, with pain flare observed in 6 patients (8%) and 15 vertebral compression fractures (13%).
Spinal metastases from GI primary cancers have high rates of LF with SRS at a lower dose. This study found that SRS dose is a significant predictor of failure and that prescribed SFED ≥ 20 Gy10 (biological equivalent dose ≥ 60 Gy10) is associated with superior local control.