Volker A. Coenen and Cameron C. McIntyre
Elizabeth Tong, Qinghua Hou, Jochen B. Fiebach, and Max Wintermark
Neuroimaging has expanded beyond its traditional diagnostic role and become a critical tool in the evaluation and management of stroke. The objectives of imaging include prompt accurate diagnosis, treatment triage, prognosis prediction, and secondary preventative precautions. While capitalizing on the latest treatment options and expanding upon the “time is brain” doctrine, the ultimate goal of imaging is to maximize the number of treated patients and improve the outcome of one the most costly and morbid disease. A broad overview of comprehensive multimodal stroke imaging is presented here to affirm its utilization.
Layton Lamsam, Eli Johnson, Ian D. Connolly, Max Wintermark, and Melanie Hayden Gephart
Magnetic resonance–guided focused ultrasound (MRgFUS) has been used extensively to ablate brain tissue in movement disorders, such as essential tremor. At a lower energy, MRgFUS can disrupt the blood-brain barrier (BBB) to allow passage of drugs. This focal disruption of the BBB can target systemic medications to specific portions of the brain, such as for brain tumors. Current methods to bypass the BBB are invasive, as the BBB is relatively impermeable to systemically delivered antineoplastic agents. Multiple healthy and brain tumor animal models have suggested that MRgFUS disrupts the BBB and focally increases the concentration of systemically delivered antitumor chemotherapy, immunotherapy, and gene therapy. In animal tumor models, combining MRgFUS with systemic drug delivery increases median survival times and delays tumor progression. Liposomes, modified microbubbles, and magnetic nanoparticles, combined with MRgFUS, more effectively deliver chemotherapy to brain tumors. MRgFUS has great potential to enhance brain tumor drug delivery, while limiting treatment toxicity to the healthy brain.
Yuval Grober, Hagit Grober, Max Wintermark, John A. Jane Jr., and Edward H. Oldfield
Many centers use conventional and dynamic contrast-enhanced MRI (DMRI) sequences in patients with Cushing's disease. The authors assessed the utility of the 3D volumetric interpolated breath-hold examination, a spoiled-gradient echo 3D T1 sequence (SGE) characterized by superior soft tissue contrast and improved resolution, compared with DMRI and conventional MRI (CMRI) for detecting microadenomas in patients with Cushing's disease.
This study was a blinded assessment of pituitary MRI in patients with proven Cushing's disease. Fifty-seven patients who had undergone surgery for Cushing's disease (10 male, 47 female; age range 13–69 years), whose surgical findings were considered to represent a microadenoma, and who had been examined with all 3 imaging techniques were included. Thus, selection emphasized patients with prior negative or equivocal MRI on referral. The MRI annotations were anonymized and 4 separate imaging sets were independently read by 3 blinded, experienced clinicians: a neuroradiologist and 2 pituitary surgeons.
Forty-eight surgical specimens contained an adenoma (46 ACTH-staining adenomas, 1 prolactinoma, and 1 nonfunctioning microadenoma). DMRI detected 5 adenomas that were not evident on CMRI, SGE detected 8 adenomas not evident on CMRI, including 3 that were not evident on DMRI. One adenoma was detected on DMRI that was not detected on SGE. McNemar's test for efficacy between the different MRI sets for tumor detection showed that the addition of SGE to CMRI increased the number of tumors detected from 18 to 26 (p = 0.02) based on agreement of at least 2 of 3 readers.
SGE shows higher sensitivity than DMRI for detecting and localizing pituitary microadenomas, although rarely an adenoma is detected exclusively by DMRI. SGE should be part of the standard MRI protocol for patients with Cushing's disease.
Meng Law, Max Wintermark, Charles Liu, and John Darrell Van Horn
Shirley I. Stiver, Max Wintermark, and Geoffrey T. Manley
The “syndrome of the trephined” is an uncommon and poorly understood disorder of delayed neurological deficit following craniectomy. From the authors' extensive experience with decompressive hemicraniectomy for traumatic brain injury (TBI), they have encountered a number of patients who developed delayed motor deficits, also called “motor trephine syndrome,” and reversal of the weakness following cranioplasty repair. The authors set out to study motor function systematically in this patient population to define the incidence, contributing factors, and outcome of patients with motor trephine syndrome.
The authors evaluated patient demographics, injury characteristics, detailed motor examinations, and CT scans in 38 patients with long-term follow-up after decompressive hemicraniectomy for TBI.
Ten patients (26%) experienced delayed contralateral upper-extremity weakness, beginning 4.9 ± 0.4 months (mean ± standard error) after decompressive hemicraniectomy. Motor deficits improved markedly within 72 hours of cranioplasty repair, and all patients recovered full motor function. The CT perfusion scans, performed in 2 patients, demonstrated improvements in cerebral blood flow commensurate with resolution of cerebrospinal fluid flow disturbances on CT scanning and return of motor strength. Comparisons between 10 patients with and 20 patients (53%) without delayed motor deficits identified 3 factors—ipsilateral contusions, abnormal cerebrospinal fluid circulation, and longer intervals to cranioplasty repair—to be strongly associated with delayed, reversible monoparesis following decompressive hemicraniectomy.
Delayed, reversible monoparesis, also called motor trephine syndrome, is common following decompressive hemicraniectomy for TBI. The results of this study suggest that close follow-up of motor strength with early cranioplasty repair may prevent delayed motor complications of decompressive hemicraniectomy.
Bryson B. Reynolds, James Patrie, Erich J. Henry, Howard P. Goodkin, Donna K. Broshek, Max Wintermark, and T. Jason Druzgal
This study directly compares the number and severity of subconcussive head impacts sustained during helmet-only practices, shell practices, full-pad practices, and competitive games in a National Collegiate Athletic Association (NCAA) Division I-A football team. The goal of the study was to determine whether subconcussive head impact in collegiate athletes varies with practice type, which is currently unregulated by the NCAA.
Over an entire season, a cohort of 20 collegiate football players wore impact-sensing mastoid patches that measured the linear and rotational acceleration of all head impacts during a total of 890 athletic exposures. Data were analyzed to compare the number of head impacts, head impact burden, and average impact severity during helmet-only, shell, and full-pad practices, and games.
Helmet-only, shell, and full-pad practices and games all significantly differed from each other (p ≤ 0.05) in the mean number of impacts for each event, with the number of impacts being greatest for games, then full-pad practices, then shell practices, and then helmet-only practices. The cumulative distributions for both linear and rotational acceleration differed between all event types (p < 0.01), with the acceleration distribution being similarly greatest for games, then full-pad practices, then shell practices, and then helmet-only practices. For both linear and rotational acceleration, helmet-only practices had a lower average impact severity when compared with other event types (p < 0.001). However, the average impact severity did not differ between any comparisons of shell and full-pad practices, and games.
Helmet-only, shell, and full-pad practices, and games result in distinct head impact profiles per event, with each succeeding event type receiving more impacts than the one before. Both the number of head impacts and cumulative impact burden during practice are categorically less than in games. In practice events, the number and cumulative burden of head impacts per event increases with the amount of equipment worn. The average severity of individual impacts is relatively consistent across event types, with the exception of helmet-only practices. The number of hits experienced during each event type is the main driver of event type differences in impact burden per athletic exposure, rather than the average severity of impacts that occur during the event. These findings suggest that regulation of practice equipment could be a fair and effective way to substantially reduce subconcussive head impact in thousands of collegiate football players.
Chun-Po Yen, Julie A. Matsumoto, Max Wintermark, Lucia Schwyzer, Avery J. Evans, Mary E. Jensen, Mark E. Shaffrey, and Jason P. Sheehan
The objective of this study was to evaluate the incidence, severity, clinical manifestations, and risk factors of radiation-induced imaging changes (RIICs) following Gamma Knife surgery (GKS) for cerebral arteriovenous malformations (AVMs).
A total of 1426 GKS procedures performed for AVMs with imaging follow-up available were analyzed. Radiation-induced imaging changes were defined as newly developed increased T2 signal surrounding the treated AVM nidi. A grading system was developed to categorize the severity of RIICs. Grade I RIICs were mild imaging changes imposing no mass effect on the surrounding brain. Grade II RIICs were moderate changes causing effacement of the sulci or compression of the ventricles. Grade III RIICs were severe changes causing midline shift of the brain. Univariate and multivariate logistic regression analyses were applied to test factors potentially affecting the occurrence, severity, and associated symptoms of RIICs.
A total of 482 nidi (33.8%) developed RIICs following GKS, with 281 classified as Grade I, 164 as Grade II, and 37 as Grade III. The median duration from GKS to the development of RIICs was 13 months (range 2–124 months). The imaging changes disappeared completely within 2–128 months (median 22 months) following the development of RIICs. The RIICs were symptomatic in 122 patients, yielding an overall incidence of symptomatic RIICs of 8.6%. Twenty-six patients (1.8%) with RIICs had permanent deficits. A negative history of prior surgery, no prior hemorrhage, large nidus, and a single draining vein were associated with a higher risk of RIICs.
Radiation-induced imaging changes are the most common adverse effects following GKS. Fortunately, few of the RIICs are symptomatic and most of the symptoms are reversible. Patients with a relatively healthy brain and nidi that are large, or with a single draining vein, are more likely to develop RIICs.
Stephen Monteith, Jason Sheehan, Ricky Medel, Max Wintermark, Matthew Eames, John Snell, Neal F. Kassell, and W. Jeff Elias
Magnetic resonance–guided focused ultrasound surgery (MRgFUS) has the potential to create a shift in the treatment paradigm of several intracranial disorders. High-resolution MRI guidance combined with an accurate method of delivering high doses of transcranial ultrasound energy to a discrete focal point has led to the exploration of noninvasive treatments for diseases traditionally treated by invasive surgical procedures. In this review, the authors examine the current intracranial applications under investigation and explore other potential uses for MRgFUS in the intracranial space based on their initial cadaveric studies.
Xiao Wu, Sam Payabvash, Charles C. Matouk, Michael H. Lev, Max Wintermark, Pina Sanelli, Dheeraj Gandhi, and Ajay Malhotra
The utility of endovascular thrombectomy (EVT) in patients with acute ischemic stroke, large vessel occlusion (LVO), and low Alberta Stroke Program Early CT Scores (ASPECTS) remains uncertain. The objective of this study was to determine the health outcomes and cost-effectiveness of EVT versus medical management in patients with ASPECTS < 6.
A decision-analytical study was performed with Markov modeling to estimate the lifetime quality-adjusted life-years (QALYs) and associated costs of EVT-treated patients compared to medical management. The study was performed over a lifetime horizon with a societal perspective in the US setting.
The incremental cost-effectiveness ratios were $412,411/QALY and $1,022,985/QALY for 55- and 65-year-old groups in the short-term model. EVT was the long-term cost-effective strategy in 96.16% of the iterations and resulted in differences in health benefit of 2.21 QALYs and 0.79 QALYs in the 55- and 65-year-old age groups, respectively, equivalent to 807 days and 288 days in perfect health. EVT remained the more cost-effective strategy when the probability of good outcome with EVT was above 16.8% or as long as the good outcome associated with the procedure was at least 1.6% higher in absolute value than that of medical management. EVT remained cost-effective even when its cost exceeded $100,000 (threshold was $108,036). Although the cost-effectiveness decreased with age, EVT was cost-effective for 75-year-old patients as well.
This study suggests that EVT is the more cost-effective approach compared to medical management in patients with ASPECTS < 6 in the long term (lifetime horizon), considering the poor outcomes and significant disability associated with nonreperfusion.