Posts tagged #MRI

Rise and Shine: A Review of the WAKE-UP Trial

Written by: Gabrielle Bunney, MD (NUEM PGY-2) Edited by: Alex Ireland, (NUEM PGY-4) Expert commentary by: Chris Richards, MD, MS

Introduction

Wake up strokes have always been a clinical conundrum. Current practice guidelines from the American Stroke Association on the treatment of acute ischemic strokes specify a maximum of 4.5 hours from time of symptom onset to the delivery of alteplase therapy. [1] However, patients often awaken with these symptoms or are unable to give a clear history of symptom onset and thus are not eligible for alteplase therapy. Initial non-contrast computed tomography can identify whether or not an acute hemorrhage is present, but confirmatory imaging for ischemic stroke involves magnetic resonance imaging (MRI). Studies are now looking at the utility of early MRI in the diagnostic and therapeutic pathways of acute ischemic stroke. These studies are specifically looking at a positive signal on diffusion-weighted imaging (DWI) and a negative signal on FLAIR imaging to identify recent cerebral infarction. Multiple studies have found that there is adequate sensitivity and specificity of DWI-FLAIR mismatch to suggest stroke onset within 4.5 hours. [2-4] Armed with these new data, this paper’s goal was to determine whether patients with an unknown time of symptom onset, but with a mismatch on DWI and FLAIR MRI imaging, would benefit from thrombolysis with intravenous alteplase.

Study

Thomalla G, Simonsen CZ, et. al “MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset | NEJM.” New England Journal of Medicine, Oxford University Press, www.nejm.org/doi/full/10.1056/NEJMoa1804355. [5]

Study Design

This study was a multi-center, randomized, double blind, and placebo controlled clinical trial. It involved 70 experienced stroke research centers in eight European countries. There was a central image-reading committee that reviewed all images for patient enrollment to evaluate inclusion and exclusion, and to arbitrate disagreements.

Population

Patients between the ages of 18 and 80 were eligible for the study if they clinically had an acute stroke and were able to perform their activities of daily living prior to this event. The patient had to awaken with these symptoms, be unsure about the time of onset secondary to confusion or aphasia, or have a timeline of symptoms greater than 4.5 hours, without an upper limit. 1,362 patients underwent screening. 859 were excluded, leaving 503 that were randomized. 254 of those were given alteplase and 249 received placebo.

Intervention Protocol

Selected patients underwent DWI and FLAIR MRI imaging. Those who had a mismatch, defined as an abnormal signal on DWI, but no signal on FLAIR, were then randomized. Excluded were those with intracranial hemorrhage, lesions larger than one third of the middle cerebral artery territory, those who were to undergo thrombectomy, those with severe stroke, defined as greater than 25 on the National Institute of Health Stroke Scale (NIHSS), and those that had any other contraindication to alteplase aside from time from last known normal. Those that were randomized into the alteplase group were given 0.9mg/kg of alteplase with 10% administered as a bolus and the rest given as an infusion over 60 minutes. Assessments were then conducted between 22 and 36 hours after randomization, between 5 and 9 days, and finally at 90 days.

Outcome Measures

This study had two end point measurements: efficacy and safety. The primary efficacy outcome measurement was favorable clinical outcome defined as a score of 0 to 1 on the modified Rankin scale 90 days after randomization. Secondary efficacy outcome measurements ranged from depression scores to activities of daily living measurements.

The primary safety outcome was death and a composite outcome of death or dependence (4-6 on the modified Rankin scale) at 90 days. Secondary safety endpoints were symptomatic intracranial hemorrhage and the incidence of parenchymal hematoma type 2 on MRI 22 to 36 hours after randomization.

Results

The demographics between the alteplase and placebo groups were similar for age, sex, and medical history. However, in the alteplase group there was a higher rate of intracranial occlusion of the internal carotid artery. The average time for treatment of the alteplase and placebo groups was 3.1 and 3.2 hours after symptom recognition, respectively.

Alteplase was found to be associated with favorable outcome at 90 days, with 53.3% in the alteplase group and only 41.8% in the placebo group having a modified Rankin score between 0 and 1 at 90 days, p=0.02. The secondary efficacy endpoints lacked power due to the fact that the study was terminated early because of a loss of funding. Table 2 from the original article describes the efficacy findings.

The safety groups were sized 251 in the alteplase group due to 5 patients not receiving alteplase and 244 in the placebo group due to 4 patients not receiving placebo. Death or dependency was found in 13.5% of the alteplase group and 18.3% of the placebo group, p=0.17. However, death at 90 days was higher in the alteplase group at 4.1%, while in the placebo group it was 1.2%, p=0.07. There were numerically more parenchymal hemorrhages in the alteplase group than in the placebo group, with 10 in the alteplase group and 1 in the placebo group. Table 3 from the original article describes the safety outcomes.

Interpretation

The primary efficacy outcome of this study, favorable functional outcome at 90 days, was higher in the group that received alteplase than in the group that received placebo and was statistically significant. Additionally, the primary safety outcome of death or disability was higher in the placebo group than in the alteplase group, though this was not found to be statistically significant. Death at 90 days was found to be numerically higher in the alteplase group than the placebo group, although not statistically significant. In extrapolating the data from the paper, the number needed to treat is 9.4 and the number needed to harm is 36.3. The ratio of these numbers suggests that treatment provides a greater benefit than risk.

There are several limitations to this study. The trial was stopped early due to lack of funding, and so we may be overestimating the benefit or underestimating the risk. The authors estimated that they needed approximately 800 patients to have sufficient power, yet enrolled only 503. Bleeding complications and death at 90 days were numerically higher in the alteplase group, though this was not statistically significant. Trials such as ATLANTIS A and B, and ASK, were all stopped early due to harm because of increased bleeding in the alteplase groups. [6-8] It is unknown whether the addition of 297 patients to meet the pre-specified enrollment target of 800 in the WAKE-UP trial would have resulted in statistical significance.

The population of this study had a median NIHSS of 6 out of 42, a relatively low stroke severity. The DAWN, DEFUSE, NINDS, and SITS-MOST trials, all significant studies in the progression of stroke research, had NIHSS medians of 17, 16, 14, and 12, respectively. [9-12] It is unclear if MRI-guided alteplase therapy would benefit patients with more severe strokes. Additionally, this paper excluded patients who were selected for thrombectomy. Patients selected for thrombectomy have large clot burdens in the internal carotid artery or middle cerebral artery that often have a modified Rankin score greater than 6. [13] By not including these patients, the WAKE-UP trial does not show the benefit of medical treatment in these sicker patients with a larger clot burden.

Lastly, the study was only performed in experienced research stroke centers with readily available diagnostic pathways and MRI. Of the 1,362 patients imaged and screened, only 37% met intervention criteria. Many did not have DWI-FLAIR mismatch, and some did not have any DWI lesion, suggesting a transient ischemic attack or a stroke mimic. A smaller hospital is unlikely to have the experience or equipment to be able to screen these more difficult patients for the few that can actually proceed to intervention.

Future Areas of Research

A replication of this study with additional subjects and sufficient power to confirm the beneficial effect of alteplase in MRI-guided thrombolysis would be the next step. Inclusion of alteplase plus thrombectomy in appropriate patients presenting after 4.5 hours with mismatch on DWI-FLAIR is another possible study. For example, TWIST (ClinicalTrials.gov Identifier: NCT03181360) and TIMELESS (ClinicalTrials.gov Identifier: NCT03785678) are two large clinical trials that will hopefully give more information about expanding the time window for thrombolysis. [14,15]

Review

MRI DWI-FLAIR mismatch may be able to allow more patients to receive alteplase therapy after an acute ischemic stroke
Alteplase still shows benefit for treating stroke even with an unknown timeline when used in conjunction with MRI DWI-FLAIR mismatch
Similar to prior studies, alteplase is associated with numerically higher instances of intracranial hemorrhage
Further research needs to be done to increase the power of this study

Expert Commentary

Really nice summary of the recent WAKE-UP* trial, and you bring up important considerations about both the pros and the cons of this study. WAKE-UP addressed an important clinical question: is it safe and effective for patients who have no other disqualifying reasons aside from their last known normal time to receive thrombolysis, if imaging shows a small area of infarction but a large area of ischemia? As you mention, intervention patients in the study: a) received intravenous tissue plasminogen activator (IV tPA) when otherwise they would not have, b) had increased odds of having a favorable outcome compared to standard of care, c) though with numerically greater instances of hemorrhage.

WAKE-UP fits into a narrative with two other important recent trials, DAWN* and DEFUSE-3*that studied the outcomes of patients with last known normal (LKN) times greater than conventional LKN time cut-offs (4.5 hours for IV tPA and 6 hours for endovascular therapy) and have found efficacy of reperfusion in these extended windows for select patients. A third trial, EXTEND,* has been presented in abstract form and has demonstrated clinical improvement in select AIS patients receiving IV tPA up to 9 hours from LKN time (https://abstractsonline.com/pp8/#!/4715/presentation/13367). Importantly, these trials that expand the time window for reperfusion used imaging-based criteria for inclusion: WAKE-UP used MR, DAWN used a non-contrast CT scan compared to severity of clinical syndrome, DEFUSE-3 used CT perfusion along with a computer software program to identify the infarcted “core” and the ischemic penumbra, and EXTEND required a penumbral mismatch on CT perfusion or MRI.

From a pathophysiological perspective, this makes sense. If imaging can identify a large area of ischemia and small area of infarction, reperfusion should potentially result in the salvage of at least some of those reversibly damaged cells. It should also result in less pronounced hemorrhagic side effects because the area of known infarction is less – remember, not only neurons die in infarcted brain, so do blood vessel endothelium cells, a contributing factor in post-reperfusion hemorrhage. [16]

Looking into the future of acute stroke care, these clinical trials give promise for individualized acute stroke treatment. Rather than being beholden to a rigid time cut-off (that evidence is showing is not one-size-fits-all), we can look to imaging to inform acute treatment decision. We have learned from subgroup analysis from DEFUSE-3 that some patients slowly progress in their stroke pathophysiology, meaning that even beyond 24 hours, some patients have a favorable core to penumbra ratio. [17] Other patients quickly progress in their stroke pathophysiology and may match their ischemic core to their salvageable penumbra well before traditional time-cut offs. [18]

It is possible that image-based selection criteria could be integral to the screening of all candidates for acute reperfusion therapy in the future. As WAKE-UP, EXTEND, DAWN, and DEFUSE-3 have shown us, there are some patients that can be reasonably considered for treatment beyond traditional time cut-offs. The same imaging criteria that extended the window for patients in these studies may be the same criteria that, in the future, could identify patients within the traditional time window who are likely to not benefit from treatment and who may have an increased risk of hemorrhagic conversion. One can image a patient without evidence of a salvageable penumbra presenting at 3 hours, for example, for whom the risks of IV tPA may, in fact, outweigh the potential benefits.

Lastly, I would hazard readers from interpreting the results of WAKE-UP, EXTEND, DAWN, and DEFUSE-3 as providing comfort in delaying thrombolysis or endovascular therapy for patients in extended time windows who would otherwise have indications for reperfusion. For IV tPA, longer delay is associated with increased risk of symptomatic intracranial hemorrhage and more timely treatment is associated with better outcomes. In the 2015 endovascular therapy trials, [19-23] even for patients within 6 hours of LKN, more timely treatment was associated with better outcomes. Even if the imaging protocols used in WAKE-UP, EXTEND, DAWN, and DEFUSE-3 can identify “slow progressors” that can be treated outside current treatment windows, these patients’ stroke are still progressing as time goes by. [18] Systems that promote timely evaluation of patients with stroke systems should be expected to help patients in extended time window, as they do patients within traditional time windows. {24,25]

Studies like WAKE-UP that test traditional inclusion and exclusion criteria for reperfusion give promise for safer and more effective stroke treatment. We look forward to future clinical trials, like TIMELESS* and TWIST*, that hopefully will give further clarity on this clinical question.

WAKE-UP [5]: Efficacy and Safety of MRI-based Thrombolysis in Wake-up Stroke Trial

DAWN [10]: Diffusion Weighted Imaging (DWI) or Computerized Tomography Perfusion (CTP) Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention Trial

DEFUSE-3 [9]: Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 Trial

EXTEND [26]: EXtending the time for Thrombolysis in Emergency Neurological Deficits Trial

TIMELESS: Tenecteplase in Stroke Patients Between 4 and 24 Hours Trial (https://clinicaltrials.gov/ct2/show/NCT03785678)

TWIST: Tenecteplase in Wake-up Ischaemic Stroke Trial (https://clinicaltrials.gov/ct2/show/NCT03181360)

Chris Richards, MD, MS

Assistant Professor

Department of Emergency Medicine

Northwestern University

How to Cite this Post

[Peer-Reviewed, Web Publication] Bunney G, Ireland A. (2019, Sept 9). Rise and Shine: A Review of the WAKE-UP Trial. [NUEM Blog. Expert Commentary by Richards C]. Retrieved from http://www.nuemblog.com/blog/wake-up-trial.

C-spine Clearance with Negative CT: Are We There Yet?

Screen Shot 2019-05-07 at 10.46.34 AM.png

Written by: M. Terese Whipple, MD (NUEM PGY-3) Edited by: Quentin Reuter, MD (NUEM ‘18) Expert commentary by: Matthew Levine, MD

We have excellent decision rules for clinically clearing cervical spine injury in low risk patients without imaging. However, a frustrating situation arises when a CT of their c-spine is obtained and negative, but they are having persistent midline pain. What do we do then? Are we forced to order an MR of the c-spine even when they have no neurological deficits and our gestalt tells us there is no clinically significant injury? MR often means admission, worsening of already overwhelming ED crowding, and unhappy patients when they cannot remove the c-collar for at least several more hours. Recent data and recommendations suggest that this may not be the case; a negative CT may be enough to rule out clinically significant injury. This blog post will explore some of the historical and recent data on the subject of cervical spine clearance after CT scan alone.

There has been great historical debate over the best management for patients with persistent midline pain after negative CT, however that evidence is beyond the scope of this post. Current common practice and the recommendation of the American College of Radiology leads down the path of cervical spine MR when this situation arises [1]. Due to the cumbersome logistics of MR, much work has been done to determine if MR truly adds value to the patient’s workup. Is MR catching clinically significant injury missed by CT that changes clinical management? The majority of studies have concluded that the answer to that question is no.

In 2015 the Eastern Association for the Surgery of Trauma (EAST) sought to tackle this question by reviewing all studies to date examining C-spine evaluation in obtunded patients [2]. They evaluated 11 studies with a total of 1718 obtunded patients who underwent C-Spine imaging with CT. None were ultimately found to have unstable fractures or unstable ligamentous injury missed by CT. There was a 9% incidence of stable injuries missed on CT and found on follow up MR, flex-x, upright XR, or clinical follow up. They found a cumulative 100% NPV for unstable C-Spine injury with CT and 91% NPV for stable injury. They did rate the quality of evidence as low for various reasons, including non-comparable imaging protocols, inconsistently reported and variable outcomes, publication bias, and an overall inability to perform a meta-analysis with the data. However, they rated the data from which they derived the NPV as moderate quality as the NPV was consistently 100% throughout all of the trials. Based on their analysis they provided the following recommendation for obtunded blunt trauma patients:

“We conditionally recommend cervical collar removal after negative high-quality c-spine CT scan results alone.”

They went on to further clarify,

“It should be acknowledged that cervical collar removal can result in neurological change and even paralysis, although this may be underreported in the literature. However we cannot continue indiscriminate two-stage sequential screening for C-spine injuries if the injury rate is near 0% for the first test and the second adjunctive test results in false positives and inconsistent treatment plans.”

But the real question that is more pertinent to us as EM physicians (obtunded MR’s are usually dealt with upstairs), is: if we can remove the c-collars of obtunded patients after negative CT, why couldn’t that be extrapolated to awake patients? Well, they commented on that too:

“Therefore, if collars are to be removed in a high risk obtunded population […] cervical collar removal can be logically argued for any population-obtunded or not.” [2]

They finally call for multicenter prospective research on the subject, again citing the low quality of evidence that they used for their recommendation. That call was answered in 2017 by the Western Trauma Association. The group completed a multi institution trial with 10,000 patients who were getting a CT for evaluation of cervical spine injury prospectively enrolled at 17 centers [3]. They found only 3 CT scans that missed clinically significant injury (.03%). All of those patients had focal neurological abnormalities on exam. There was no clinically significant injury missed by CT and exam combined. CT scan alone had an NPV of 99.97%, and an NPV of 100% when combined with clinical exam. Therefore, they proposed this diagnostic algorithm:

Most trials have found similar results, with a few exceptions. Two trials prior to the publication of the Western Trauma Association (WTA) paper found that CT missed a few clinically significant injuries in patients with no neurological symptoms. Both trials enrolled significantly fewer patients than the WTA paper, and only enrolled patients with negative CT who would be evaluated with MR, meaning they couldn’t comment on the overall sensitivity of CT in unstable c-spine injury. The ReConect trial in 2016 found 5 of 767 patients (.6%) with injuries requiring surgical intervention that were missed on CT [4]. Another study with similar methods published in Annals of Emergency Medicine in 2011 evaluated those who had a negative CT but were MR’ed for persistent midline C-Spine tenderness [5]. They found that out of 178 patients, 5 had injury requiring operative management that was missed on CT but found on subsequent MR (2.8%) [5]. The Annals paper is certainly an outlier, with a considerably higher rate of missed clinically significant injury than the remainder of the literature, with rates usually between 0-1% [6-18]. The authors believe this may be due to more stringent methodology. For instance, they required MR to be performed within 48 hours when it is the most sensitive for edema, and only enrolled patients with midline tenderness rather than subjective pain [5]. While this may be true, the results have not been replicated in subsequent studies.

With the publication of the WTA paper, evidence certainly seems to be tipping in favor of CT clearance of cervical spine in neurologically intact patients. However, a few questions remain. In every study discussed here, MR resulted in discharge with hard collar in a portion of patients. Indications ranged from stable injury to persistent pain with no evidence of injury on MR. It is unclear whether hard collar placement makes a difference in the clinical course of these patients, if their stable injuries would have become unstable without it, or if it has any long term impact on outcomes such as chronic pain. This is an important question not yet adequately addressed in the literature. The majority of these trials were also completed at trauma centers with radiologists well trained in reading c-spine imaging and high quality CT scanners. It could be difficult to generalize this data to centers with older scanners or whose radiology departments are not as expert in trauma radiology.

Incredibly high quality and reproducible evidence is required to change practice when high stakes, such as potentially missed cervical spine injury, are involved. So far we have multiple trials showing an NPV of close to 100% when CT and good neurological exam are combined, and the conditional recommendation by the EAST group. Time will tell if recommendations in the future remove the “conditional” portion as CT technology continues to improve, further studies with stringent methodologies are conducted, and the results of the WTA paper are hopefully replicated.

Expert Commentary

Thank you Dr Whipple for that really practical review of a real-life common clinical question we face all the time: Can we remove the collar? Some important takeaways are:

There is a robust and growing body of evidence that removing the collar after a negative high-quality CT is safe if the patient is neurologically intact.
This practice is endorsed by two major trauma organizations, EAST and WTA.

The endorsement by respected major trauma societies is important in translating evidence into practice. It seems like all that is left at this point for widespread implementation is overcoming culture. This would likely require addressing the outlier studies listed by Dr Whipple to win over those still skeptical. Part of overcoming culture would involve buy-in from neurosurgical societies. What do neurosurgical societies say regarding clearing these patients? There are many instances in which a patient is discharged with recommendations from the neurosurgeon to wear a hard collar despite a negative CT and MRI. On the surface this seems like defensive medicine and impractical for the patient. Is the patient really going to comply with this until follow up? Is this collar really protecting them and preventing further injury which, after negative CT and MRI and with a normal neuro exam, seems exceedingly unlikely? Does evidence support this practice?

In the end, decision rules should be used when you want evidence to support your clinical decisions, such as removing the C collar after negative imaging in a neurologically intact patient. Do not use decision rules, however, to overturn or replace sound clinical judgement. If there is something about a case that makes you still feel like you could be missing an outlier injury by removing the collar, listen to that voice inside of you. It is that sound clinical judgement that will guide you through your career, not decision rules.

Matthew Levine, MD

Northwestern Medicine, Assistant Professor of Emergency Medicine

How To Cite This Post

[Peer-Reviewed, Web Publication] Whipple T, Reuter Q. (2019, May 13). C-spine clearance with negative CT: Are we there yet? [NUEM Blog. Expert Commentary by Levine M]. Retrieved from http://www.nuemblog.com/blog/cspine-clearance-ct

References:

American College of Radiology. ACR appropriateness criteria on suspected spine trauma. Available at: http://www.acr.org.
Patel MB, et al. Cervical spine collar clearance in the obtunded adult blunt trauma patient: A systematic review and practice management guideline from the Eastern Association for the Surgery of Trauma. J Acute Care Trauma Surgery. 789(2): 432-441.
Inaba, K et al. Cervical Spine Clearance: A Prospective Western Trauma Association Multi-Institutional Trial. J Trauma Acute Care Surg. 2016 Dec: 81(6): 1122-1130.doi: 10.1097/TA.0000000000001194
Maung A, et al. Cervical spine MRI in patients with negative CT: A prospective, multicenter study of the Research Consortium of New England Centers for Trauma (ReCONECT). J Trauma Acute Care Surg. 82 (2): 263-269.
Ackland HM, et al. Cervical Spine Magnetic Resonance Imaging in Alert, Neurologically Intact Trauma Patients With Persistent Midline Tenderness and Negative Computed Tomography Results. Ann of Em Med. 2011 Dec. 58 (6): 521-530.
Chew B, et al. Cervical spine clearance in the traumatically injured patient: is multidector CT scanning sufficient alone? J Neurosurg Spine. 2013. 19: 576-581
Bush L, et al. Evaluation of cervical spine clearance by computed tomographic scan alone in intoxicated patients with blunt trauma. JAMA Surg. 2016; 151 (9): 807-813
D’Alise et al. Magnetic resonance imaging for the evaluation of the cervical spine in the comatose or obtunded trauma patient. J Neurosurgery (Spine 1) 1999; 91:54-59.
Resnick S, et al. Clinical relevance of magnetic resonance imaging in cervical spine clearance: a prospective study. JAMA Surg. 2014; 149 (9): 934-9.
Menaker J, Philp A, Boswell S, Scalea TM. Computed tomography alone for cervical spine clearance in the unreliable patient--are we there yet? J Trauma. 2008; 64(4):898–903.
Chew BG, Swartz C, Quigley MR, Altman DT, Daffner RH, Wilberger JE. Cervical spine clearance in the traumatically injured patient: is multidetector CT scanning sufficient alone? Clinical article. J Neurosurg Spine. 2013; 19(5):576–81.
Como JJ, Leukhardt WH, Anderson JS, Wilczewski PA, Samia H, Claridge JA. Computed tomography alone may clear the cervical spine in obtunded blunt trauma patients: a prospective evaluation of a revised protocol. J Trauma. 2011; 70(2):345–9. discussion 9-51.
Khanna P, Chau C, Dublin A, Kim K, Wisner D. The value of cervical magnetic resonance imaging in the evaluation of the obtunded or comatose patient with cervical trauma, no other abnormal neurological findings, and a normal cervical computed tomography. J Trauma Acute Care Surg. 2012; 72(3):699–702.
Schuster R, Waxman K, Sanchez B, Becerra S, Chung R, Conner S, Jones T. Magnetic resonance imaging is not needed to clear cervical spines in blunt trauma patients with normal computed tomographic results and no motor deficits. Arch Surg. 2005; 140(8):762–6.
Anekstein Y, Jeroukhimov I, Bar-Ziv Y, Shalmon E, Cohen N, Mirovsky Y, Masharawi Y. The use of dynamic CT surview for cervical spine clearance in comatose trauma patients: a pilot prospective study. Injury. 2008; 39(3):339–46.
Brohi K, Healy M, Fotheringham T, Chan O, Aylwin C, Whitley S, Walsh M. Helical computed tomographic scanning for the evaluation of the cervical spine in the unconscious, intubated trauma patient. J Trauma. 2005; 58(5):897–901.
Harris TJ, Blackmore CC, Mirza SK, Jurkovich GJ. Clearing the cervical spine in obtunded patients. Spine (Phila Pa 1976). 2008; 33(14):1547–1553.
Steigelman M, Lopez P, Dent D, Myers J, Corneille M, Stewart R, Cohn S. Screening cervical spine MRI after normal cervical spine CT scans in patients in whom cervical spine injury cannot be excluded by physical examination. Am J Surg. 2008; 196(6):857–862.

Posted on May 13, 2019 by NUEM Blog and filed under Trauma and tagged c-spine clearance MRI c-collar cervical fracture.

Expert Commentary

How to Cite this Post

Other Posts You May Enjoy

Expert Commentary

How To Cite This Post

Other Posts You May Enjoy

References:

Posts by Topic Category

Creative Commons

Quick Links

Stay in Touch