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David G. Brachman, Emad Youssef, Christopher J. Dardis, Nader Sanai, Joseph M. Zabramski, Kris A. Smith, Andrew S. Little, Andrew G. Shetter, Theresa Thomas, Heyoung L. McBride, Stephen Sorensen, Robert F. Spetzler and Peter Nakaji

OBJECTIVE

Effective treatments for recurrent, previously irradiated intracranial meningiomas are limited, and resection alone is not usually curative. Thus, the authors studied the combination of maximum safe resection and adjuvant radiation using permanent intracranial brachytherapy (R+BT) in patients with recurrent, previously irradiated aggressive meningiomas.

METHODS

Patients with recurrent, previously irradiated meningiomas were treated between June 2013 and October 2016 in a prospective single-arm trial of R+BT. Cesium-131 (Cs-131) radiation sources were embedded in modular collagen carriers positioned in the operative bed on completion of resection. The Cox proportional hazards model with this treatment as a predictive term was used to model its effect on time to local tumor progression.

RESULTS

Nineteen patients (median age 64.5 years, range 50–78 years) with 20 recurrent, previously irradiated tumors were treated. The WHO grade at R+BT was I in 4 (20%), II in 14 (70%), and III in 2 (10%) cases. The median number of prior same-site radiation courses and same-site surgeries were 1 (range 1–3) and 2 (range 1–4), respectively; the median preoperative tumor volume was 11.3 cm3 (range 0.9–92.0 cm3). The median radiation dose from BT was 63 Gy (range 54–80 Gy). At a median radiographic follow-up of 15.4 months (range 0.03–47.5 months), local failure (within 1.5 cm of the implant bed) occurred in 2 cases (10%). The median treatment-site time to progression after R+BT has not been reached; that after the most recent prior therapy was 18.3 months (range 3.9–321.9 months; HR 0.17, p = 0.02, log-rank test). The median overall survival after R+BT was 26 months, with 9 patient deaths (47% of patients). Treatment was well tolerated; 2 patients required surgery for complications, and 2 experienced radiation necrosis, which was managed medically.

CONCLUSIONS

R+BT utilizing Cs-131 sources in modular carriers represents a potentially safe and effective treatment option for recurrent, previously irradiated aggressive meningiomas.

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Time is spine: a review of translational advances in spinal cord injury

JNSPG 75th Anniversary Invited Review Article

Jetan H. Badhiwala, Christopher S. Ahuja and Michael G. Fehlings

Acute traumatic spinal cord injury (SCI) is a devastating event with far-reaching physical, emotional, and economic consequences for patients, families, and society at large. Timely delivery of specialized care has reduced mortality; however, long-term neurological recovery continues to be limited. In recent years, a number of exciting neuroprotective and regenerative strategies have emerged and have come under active investigation in clinical trials, and several more are coming down the translational pipeline. Among ongoing trials are RISCIS (riluzole), INSPIRE (Neuro-Spinal Scaffold), MASC (minocycline), and SPRING (VX-210). Microstructural MRI techniques have improved our ability to image the injured spinal cord at high resolution. This innovation, combined with serum and cerebrospinal fluid (CSF) analysis, holds the promise of providing a quantitative biomarker readout of spinal cord neural tissue injury, which may improve prognostication and facilitate stratification of patients for enrollment into clinical trials. Given evidence of the effectiveness of early surgical decompression and growing recognition of the concept that “time is spine,” infrastructural changes at a systems level are being implemented in many regions around the world to provide a streamlined process for transfer of patients with acute SCI to a specialized unit. With the continued aging of the population, central cord syndrome is soon expected to become the most common form of acute traumatic SCI; characterization of the pathophysiology, natural history, and optimal treatment of these injuries is hence a key public health priority. Collaborative international efforts have led to the development of clinical practice guidelines for traumatic SCI based on robust evaluation of current evidence. The current article provides an in-depth review of progress in SCI, covering the above areas.

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Arnaud Dagain, Olivier Aoun, Aurore Sellier, Nicolas Desse, Christophe Joubert, Nathan Beucler, Cédric Bernard, Mathilde Fouet, Jean-Marc Delmas and Renaud Dulou

This article aims to describe the French concept regarding combat casualty neurosurgical care from the theater of operations to a homeland hospital. French military neurosurgeons are not routinely deployed to all combat zones. As a consequence, general surgeons initially treat neurosurgical wounds. The principle of this medical support is based on damage control. It is aimed at controlling intracranial hypertension spikes when neuromonitoring is lacking in resource-limited settings. Neurosurgical damage control permits a medevac that is as safe as can be expected from a conflict zone to a homeland medical treatment facility. French military neurosurgeons can occasionally be deployed within an airborne team to treat a military casualty or to complete a neurosurgical procedure performed by a general surgeon in theaters of operation. All surgeons regardless of their specialty must know neurosurgical damage control. General surgeons must undergo the required training in order for them to perform this neurosurgical technique.

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Arthur Carminucci, Ke Nie, Joseph Weiner, Eric Hargreaves and Shabbar F. Danish

OBJECTIVE

The Leksell Gamma Knife Icon (GK Icon) radiosurgery system can utilize cone-beam computed tomography (CBCT) to evaluate motion error. This study compares the accuracy of frame-based and frameless mask-based fixation using the Icon system.

METHODS

A retrospective cohort study was conducted to evaluate patients who had undergone radiosurgery with the GK Icon system between June and December 2017. Patients were immobilized in either a stereotactic head frame or a noninvasive thermoplastic mask with stereotactic infrared (IR) camera monitoring. Setup error was defined as displacement of the skull in the stereotactic space upon setup as noted on pretreatment CBCT compared to its position in the stereotactic space defined by planning MRI for frame patients and defined as skull displacement on planning CBCT compared to its position on pretreatment CBCT for mask patients. For frame patients, the intrafractionation motion was measured by comparing pretreatment and posttreatment CBCT. For mask patients, the intrafractionation motion was evaluated by comparing pretreatment CBCT and additional CBCT obtained during the treatment. The translational and rotational errors were recorded.

RESULTS

Data were collected from 77 patients undergoing SRS with the GK Icon. Sixty-four patients underwent frame fixation, with pre- and posttreatment CBCT studies obtained. Thirteen patients were treated using mask fixation to deliver a total of 33 treatment fractions. Mean setup and intrafraction translational and rotation errors were small for both fixation systems, within 1 mm and 1° in all axes. Yet mask fixation demonstrated significantly larger intrafraction errors than frame fixation. Also, there was greater variability in both setup and intrafraction errors for mask fixation than for frame fixation in all translational and rotational directions. Whether the GK treatment was for metastasis or nonmetastasis did not influence motion uncertainties between the two fixation types. Additionally, monitoring IR-based intrafraction motion for mask fixation—i.e., the number of treatment stoppages due to reaching the IR displacement threshold—correlated with increasing treatment time.

CONCLUSIONS

Compared to frame-based fixation, mask-based fixation demonstrated larger motion variations. The variability in motion error associated with mask fixation must be taken into account when planning for small lesions or lesions near critical structures.

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Veronika Paštyková, Josef Novotný Jr., Tomáš Veselský, Dušan Urgošík, Roman Liščák and Josef Vymazal

OBJECTIVE

The aim of this study was to compare 3 different methods to assess the geometrical distortion of two 1.5-T and one 3-T magnetic resonance (MR) scanners and to evaluate co-registration accuracy. The overall uncertainty of each particular method was also evaluated.

METHODS

Three different MR phantoms were used: 2 commercial CIRS skull phantoms and PTGR known target phantom and 1 custom cylindrical Perspex phantom made in-house. All phantoms were fixed in the Leksell stereotactic frame and examined by a Siemens Somatom CT unit, two 1.5-T Siemens (Avanto and Symphony) MRI systems, and one 3-T Siemens (Skyra) MRI system. The images were evaluated using Leksell GammaPlan software, and geometrical deviation of the selected points from the reference values were determined. The deviations were further investigated for both definitions including fiducial-based and co-registration–based in the case of the CIRS phantom images. The same co-registration accuracy assessment was also performed for a clinical case. Patient stereotactic imaging was done on 3-T Skyra, 1.5-T Avanto, and CT scanners.

RESULTS

The accuracy of the CT scanner was determined as 0.10, 0.30, and 0.30 mm for X, Y, and Z coordinates, respectively. The total estimated uncertainty in distortion measurement in one coordinate was determined to be 0.32 mm and 0.14 mm, respectively, for methods using and not using CT as reference imaging. Slightly more significant distortions were observed when using the 3-T than either 1.5-T MR units. However, all scanners were comparable within the estimated measurement error. Observed deviation/distortion for individual X, Y, and Z stereotactic coordinates was typically within 0.50 mm for all 3 scanners and all 3 measurement methods employed. The total radial deviation/distortion was typically within 1.00 mm. Maximum total radial distortion was observed when the CIRS phantom was used; 1.08 ± 0.49 mm, 1.15 ± 0.48 mm, and 1.35 ± 0.49 mm for Symphony, Avanto, and Skyra, respectively. The co-registration process improved image stereotactic definition in a clinical case in which fiducial-based stereotactic definition was not accurate; this was demonstrated for 3-T stereotactic imaging in this study. The best results were shown for 3-T MR image co-registration with CT images improving image stereotactic definition by about 0.50 mm. The results obtained with patient data provided a similar trend of improvement in stereotactic definition by co-registration.

CONCLUSIONS

All 3 methods/phantoms used were evaluated as satisfactory for the image distortion measurement. The method using the PTGR phantom had the lowest uncertainty as no reference CT imaging was needed. Image co-registration can improve stereotactic image definition when fiducial-based definition is not accurate.

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Stacy A. Shackelford, Deborah J. del Junco, Michael C. Reade, Randy Bell, Tyson Becker, Jennifer Gurney, Randall McCafferty and Donald W. Marion

OBJECTIVE

In combat and austere environments, evacuation to a location with neurosurgery capability is challenging. A planning target in terms of time to neurosurgery is paramount to inform prepositioning of neurosurgical and transport resources to support a population at risk. This study sought to examine the association of wait time to craniectomy with mortality in patients with severe combat-related brain injury who received decompressive craniectomy.

METHODS

Patients with combat-related brain injury sustained between 2005 and 2015 who underwent craniectomy at deployed surgical facilities were identified from the Department of Defense Trauma Registry and Joint Trauma System Role 2 Registry. Eligible patients survived transport to a hospital capable of diagnosing the need for craniectomy and performing surgery. Statistical analyses included unadjusted comparisons of postoperative mortality by elapsed time from injury to start of craniectomy, and Cox proportional hazards modeling adjusting for potential confounders. Time from injury to craniectomy was divided into quintiles, and explored in Cox models as a binary variable comparing early versus delayed craniectomy with cutoffs determined by the maximum value of each quintile (quintile 1 vs 2–5, quintiles 1–2 vs 3–5, etc.). Covariates included location of the facility at which the craniectomy was performed (limited-resource role 2 facility vs neurosurgically capable role 3 facility), use of head CT scan, US military status, age, head Abbreviated Injury Scale score, Injury Severity Score, and injury year. To reduce immortal time bias, time from injury to hospital arrival was included as a covariate, entry into the survival analysis cohort was defined as hospital arrival time, and early versus delayed craniectomy was modeled as a time-dependent covariate. Follow-up for survival ended at death, hospital discharge, or hospital day 16, whichever occurred first.

RESULTS

Of 486 patients identified as having undergone craniectomy, 213 (44%) had complete date/time values. Unadjusted postoperative mortality was 23% for quintile 1 (n = 43, time from injury to start of craniectomy 30–152 minutes); 7% for quintile 2 (n = 42, 154–210 minutes); 7% for quintile 3 (n = 43, 212–320 minutes); 19% for quintile 4 (n = 42, 325–639 minutes); and 14% for quintile 5 (n = 43, 665–3885 minutes). In Cox models adjusted for potential confounders and immortal time bias, postoperative mortality was significantly lower when time to craniectomy was within 5.33 hours of injury (quintiles 1–3) relative to longer delays (quintiles 4–5), with an adjusted hazard ratio of 0.28, 95% CI 0.10–0.76 (p = 0.012).

CONCLUSIONS

Postoperative mortality was significantly lower when craniectomy was initiated within 5.33 hours of injury. Further research to optimize craniectomy timing and mitigate delays is needed. Functional outcomes should also be evaluated.

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Thara Tunthanathip, Kanutpon Khocharoen and Nakornchai Phuenpathom

OBJECTIVE

In the ongoing conflict in southern Thailand, the improvised explosive device (IED) has been a common cause of blast-induced traumatic brain injury (bTBI). The authors investigated the particular characteristics of bTBI and the factors associated with its clinical outcome.

METHODS

A retrospective cohort study was conducted on all patients who had sustained bTBI between 2009 and 2017. Collected data included clinical characteristics, intracranial injuries, and outcomes. Factors analysis was conducted using a forest plot.

RESULTS

During the study period, 70 patients met the inclusion criteria. Fifty individuals (71.4%) were military personnel. One-third of the patients (32.9%) suffered moderate to severe bTBI, and the rate of intracerebral injuries on brain CT was 65.7%. Coup contusion was the most common finding, and primary blast injury was the most common mechanism of blast injury. Seventeen individuals had an unfavorable outcome (Glasgow Outcome Scale score 1–3), and the overall mortality rate for bTBI was 11.4%. In the univariate analysis, factors associated with an unfavorable outcome were preoperative coagulopathy, midline shift of the brain ≥ 5 mm, basal cistern effacement, moderate to severe TBI, hypotension, fixed and dilated pupils, surgical site infection, hematocrit < 30% on admission, coup contusion, and subdural hematoma. In the multivariable analysis, midline shift ≥ 5 mm (OR 29.1, 95% CI 2.5–328.1) and coagulopathy (OR 28.7, 95% CI 4.5–180.3) were the only factors predicting a poor outcome of bTBI.

CONCLUSIONS

bTBIs range from mild to severe. Midline shift and coagulopathy are treatable factors associated with an unfavorable outcome. Hence, in cases of bTBI, reversing an abnormal coagulogram is required as soon as possible to improve clinical outcomes. The management of brain shift needs further study.

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Hitoshi Aiyama, Masaaki Yamamoto, Takuya Kawabe, Shinya Watanabe, Takao Koiso, Yasunori Sato, Yoshinori Higuchi, Eiichi Ishikawa, Tetsuya Yamamoto, Akira Matsumura and Hidetoshi Kasuya

OBJECTIVE

Although the conformity index (CI) and the gradient index (GI), which were proposed by Paddick and colleagues, are both logically considered to correlate with good posttreatment results after stereotactic radiosurgery (SRS), this hypothesis has not been confirmed clinically. The authors’ aim was to reappraise whether high CI values correlate with reduced tumor progression rates, and whether low GI values correlate with reduced complication incidences.

METHODS

This was an institutional review board–approved, retrospective cohort study conducted using a prospectively accumulated database including 3271 patients who underwent Gamma Knife SRS for brain metastases (BMs) during the 1998–2016 period. Among the 3271 patients, 925 with a single BM at the time of SRS (335 women and 590 men, mean age 66 [range 24–93] years) were studied. The mean/median CIs were 0.62/0.66 (interquartile range [IQR] 0.53–0.74, range 0.08–0.88) and the mean/median GIs were 3.20/3.09 (IQR 2.83–3.39, range 2.27–11.4).

RESULTS

SRS-related complications occurred in 38 patients (4.1%), with a median post-SRS interval of 11.5 (IQR 6.0–25.8, maximum 118.0) months. Cumulative incidences of post-SRS complications determined by a competing risk analysis were 2.2%, 3.2%, 3.6%, 3.8%, and 3.9% at the 12th, 24th, 36th, 48th, and 60th post-SRS month, respectively. Multivariable analyses showed that only two clinical factors (i.e., peripheral doses and brain volume receiving ≥ 12 Gy) correlated with complication rates. However, neither CIs nor GIs impacted the incidences of complications. Among the 925 patients, post-SRS MRI was performed at least once in 716 of them, who were thus eligible for local progression evaluation. Among these 716 patients, local progression was confirmed in 96 (13.4%), with a median post-SRS interval of 10.8 (IQR 6.7–19.5, maximum 59.8) months. Cumulative incidences of local progression determined by a competing risk analysis were 7.7%, 12.6%, 14.2%, 14.8%, and 15.3% at the 12th, 24th, 36th, 48th, and 60th post-SRS month, respectively. Multivariable analyses showed neurological symptoms, extracerebral metastases, repeat SRS, and CIs to correlate with incidences of local progression, whereas GIs had no impact on local tumor progression. Particularly, cumulative incidences of local progression were significantly lower in patients with CIs < 0.65 than in those with CIs ≥ 0.65 (adjusted hazard ratio 1.870, 95% confidence interval 1.299–2.843; p = 0.0034).

CONCLUSIONS

To the authors’ knowledge, this is the first analysis to focus on the clinical significance of CI and GI based on a large series of patients with BM. Contrary to the majority opinion that dose planning with higher CI and lower GI results in good post-SRS outcomes (i.e., low local progression rates and minimal complications), this study clearly showed that the lower the CIs were, the lower the local progression rates were, and that the GI did not impact complication rates.

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Rachel Lazarus, Katherine Helmick, Saafan Malik, Emma Gregory, Yll Agimi and Donald Marion

Over the past 8 years, advances in the US Military Health System (MHS) have led to extensive changes in the way combat casualty care is provided to deployed service members with a traumatic brain injury (TBI). Changes include the application of cutting-edge Clinical Practice Guidelines, use of pioneering technologies, and advances in evacuation procedures. Compared with previous engagements, current operations occur on a much smaller scale, and more frequently in austere environments, such that effective medical support is increasingly challenging. In this paper, the authors describe key aspects of the current continuum of TBI care in the US military, from the point of injury through rehabilitation, with an emphasis on how emerging technologies and evidence-based Clinical Practice Guidelines assist MHS clinicians with providing the best clinical care possible in the changing battlefield.