December 2007 An Evidence-Based Approach Volume 9, Number 12 Authors To Imaging Of Acute Joshua Broder, MD, FACEP Assistant Professor, Associate Residency Director, Division of Emergency , Duke University Neurological Conditions Medical Center, Durham, NC Robert Preston, MD Division of , Duke University It’s Monday afternoon, the ED is full, and neuroimaging seems to be the Medical Center, Durham, NC “theme” for the day. You realize how your clinical skills are merged with Peer Reviewers Yu-Feng Yvonne Chan, MD, FACEP technology and how dependent your clinical decision-making is on Assistant Professor, Department of Emergency Medicine, . Mount Sinai School of Medicine, New York, NY A 75-year-old male presents with two hours of right-sided hemiplegia. Andrew Perron, MD Residency Program Director, Department of Emergency The on-call neurologist recommends TPA if the head CT does not show Medicine, Maine Medical Center, Portland, ME hemorrhage. The radiologist tells you there is no but there are early CME Objectives ischemic changes…. Upon completion of this article, you should be able to: A 55-year-old male presents after a syncopal episode. He has a normal 1. Describe indications for neuroimaging for a variety of neurological exam and no evidence of head trauma. His wife asks if a head clinical presentations. 2. Describe a systematic approach to the interpretation CT should be done to rule out …. of non-contrast head CT. A 19-year-old female presents with four days of severe headache. She 3. Select the most appropriate imaging modality for a describes a thunderclap onset, with some improvement over the past several variety of acute neurological complaints. 4. Compare and contrast CT and MR in terms of sensi- days. You initially suspect ; however, her non- tivity and specificity for the evaluation of neurological contrast head CT is normal. After prochlorpromazine and fluids, she is . 5. Identify areas of overuse or misuse of imaging tech- eager to leave…. niques in the assessment of neurological complaints. A 20-year-old male presents with a new onset tonic clonic seizure wit- 6. Select a diagnostic algorithm that improves patient nessed by his roommate. He has no past medical history and takes no medi- care by facilitating rapid and accurate diagnosis while minimizing radiation exposure and cost. cations or drugs. He is back to his baseline and his neurological exam is Date of original release: December 1, 2007 completely normal. The CT scanner is backed up for at least two hours and Date of most recent review: November 8, 2007 you wonder if it would be OK to send him home for an outpatient workup… Termination date: December 1, 2010 A 52-year-old male is involved in a motor vehicle collision. He does not Time to complete activity: 4 hours Medium: Print & online recall the moment of impact and appears to have had a brief loss of con- Method of participation: Print or online answer form sciousness. He is now neurologically intact with no other complaints and a and evaluation Prior to beginning this activity, please see “ CME normal exam. You wonder whether CT is necessary… Information” on the back page. A lot of patients, a lot of decisions; not enough CT scanners!

Editor-in-Chief LSU Health Science Center, New Gregory L. Henry, MD, FACEP, EM/IM Program, University of Beth Wicklund, MD, Regions Orleans, LA. CEO, Medical Practice Risk Maryland, Baltimore, MD. Hospital Emergency Medicine Andy Jagoda, MD, FACEP, Assessment, Inc; Clinical Residency, EMRA Representative. Wyatt W. Decker, MD, Alfred Sacchetti, MD, FACEP, Professor and Vice-Chair of Chair and Professor of Emergency Academic Affairs, Department of Associate Professor of Medicine, University of Michigan, Assistant Clinical Professor, International Editors Emergency Medicine; Mount Sinai Emergency Medicine, Mayo Clinic Ann Arbor. Department of Emergency School of Medicine; Medical College of Medicine, Rochester, Medicine, Thomas Jefferson Valerio Gai, MD, Senior Editor, Director, Mount Sinai Hospital, MN. Keith A. Marill, MD, Instructor, University, Philadelphia, PA. Professor and Chair, Dept of EM, Department of Emergency New York, NY. Francis M. Fesmire, MD, FACEP, Corey M. Slovis, MD, FACP, University of Turin, Italy. Medicine, Massachusetts General Director, Heart-Stroke Center, FACEP, Professor and Chair, Associate Editor Hospital, Harvard , Peter Cameron, MD, Chair, Erlanger Medical Center; Boston, MA. Department of Emergency Emergency Medicine, Monash Assistant Professor, UT College of Medicine, Vanderbilt University John M. Howell, MD, FACEP, University; Alfred Hospital, Medicine, Chattanooga, TN. Charles V. Pollack, Jr, MA, MD, Medical Center, Nashville, TN. Clinical Professor of Emergency Melbourne, Australia. FACEP, Professor and Chair, Medicine, George Washington Michael J. Gerardi, MD, FAAP, Jenny Walker, MD, MPH, MSW, Department of Emergency Amin Antoine Kazzi, MD, FAAEM, University, Washington, DC; FACEP, Director, Pediatric Medicine, Pennsylvania Hospital, Assistant Professor; Division Associate Professor and Vice Director of Academic Affairs, Best Emergency Medicine, Children’s University of Pennsylvania Health Chief, , Chair, Department of Emergency Practices, Inc, Inova Fairfax Medical Center, Atlantic Health System, Philadelphia, PA. Department of Community and Medicine, University of California, Hospital, Falls Church, VA. System; Department of Preventive Medicine, Mount Sinai Irvine; American University, Beirut, Emergency Medicine, Morristown Michael S. Radeos, MD, MPH, Medical Center, New York, NY. Lebanon. Editorial Board Memorial Hospital, NJ. Research Director, Department of Ron M. Walls, MD, Emergency Medicine, New York Professor and Hugo Peralta, MD, Chair of Michael A. Gibbs, MD, FACEP, William J. Brady, MD, Associate Hospital Queens, Flushing, NY; Chair, Department of Emergency Emergency Services, Hospital Professor and Vice Chair, Chief, Department of Emergency Assistant Professor of Emergency Medicine, Brigham & Women’s Italiano, Buenos Aires, Argentina. Department of Emergency Medicine, Maine Medical Center, Hospital, Boston, MA. Medicine, Weill Medical College Maarten Simons, MD, PhD, Medicine, University of Virginia, Portland, ME. of Cornell University, New York, Charlottesville, VA. Research Editors Emergency Medicine Residency Steven A. Godwin, MD, FACEP, NY. Director, OLVG Hospital, Peter DeBlieux, MD Assistant Professor and Robert L. Rogers, MD, FAAEM, Nicholas Genes, MD, PhD, Mount Amsterdam, The Netherlands. Professor of Clinical Medicine, Emergency Medicine Residency Assistant Professor and Sinai Emergency Medicine Director, University of Florida Residency Director, Combined Residency. HSC/Jacksonville, FL.

Accreditation: This activity has been planned and implemented in accordance with the Essentials and Standards of the Accreditation Council for Continuing (ACCME) through the joint sponsorship of Mount Sinai School of Medicine and Emergency Medicine Practice. The Mount Sinai School of Medicine is accredited by the ACCME to provide continuing medical education for . Faculty Disclosure: Dr. Broder, Dr. Preston, Dr. Chan, and Dr. Perron report no significant financial interest or other relationship with the manufacturer(s) of any commercial product(s) discussed in this educational presentation. Commercial Support: Emergency Medicine Practice does not accept any commercial support. mergency physicians are frequently confronted however, strong evidence is lacking for many of the Ewith patients with neurological complaints clinical questions addressed. requiring emergent imaging for diagnosis and treat- Principles Of Evidence-Based Medicine ment. The diversity and variations of imaging modalities may appear confusing, resulting in physi- Imaging studies for neurological emergencies share a cian uncertainty about the most appropriate modality common problem in that the gold-standard for to evaluate the presenting complaint. An evidence- diagnosis is often another imaging study, and there is based approach, with the modality and technique no clear, independent means of settling discrepancies. selected based on patient characteristics and differen- It is unclear what strategy should be used when two tial diagnosis, is essential. In this review, the evidence imaging studies yield divergent results. For example, supporting the use of computed tomography (CT) and if CT is compared to MR for evaluation of acute magnetic resonance imaging (MRI) for the diagnosis intracranial hemorrhage, which test should serve as and treatment of emergency brain disorders will be the gold standard? Given a negative CT in the context reviewed. Adjunctive imaging techniques will also be of a positive MR, is the CT a false negative or the MR considered, including conventional angiography, plain a false positive? Alternative gold standards may films, and ultrasound. Clinical decision rules include clinical follow-up for mortality, readmission, intended to target imaging utilization to high-risk neurosurgical intervention, or neurological outcome. patients will also be discussed. When evaluating a study’s relevance to clinical practice, the strength of the gold standard must be Abbreviations Used In This Article considered. Another important concept when interpreting the CASL: Continuous Arterial Spin Labeling (an MRI results of a study is “point estimate” versus “95% technique for magnetic labeling of blood) confidence interval.” Take the example of a study CCHR: Canadian CT Head Rule with a point estimate sensitivity of 99% and a confi- CT: Computed Tomography dence interval of 66-100%. The 95% confidence CTA: Computed Tomographic Arteriography interval indicates that the sensitivity of the test has a (Angiography) 95% chance of lying between the extreme values of CTPS: CT Perfusion Studies 66% and 100%. While the likelihood of the test having DAI: Diffuse Axonal Injury either of these extreme values is low, it cannot be DWI: Diffusion Weighted Imaging (an MRI sequence) ruled out on the basis of the data. Small studies will GCS: Glasgow Coma Score often have broad 95% confidence intervals for their GEPS: Gradient Echo Pulse Sequencing results, while larger studies usually have narrower ICP: confidence intervals. For a test to be reliable for IV: Intravenous ruling out a disease process, it must have both high LP: Lumbar Puncture sensitivity and a narrow confidence interval. To rule LR: Likelihood Ratio in pathology, the specificity must be high and the MCA: Middle Cerebral Artery confidence interval narrow. The lower boundary of MR: Magnetic Resonance the confidence interval can be considered a “worst MRA: Magnetic Resonance Arteriography case scenario” for the test characteristic. (Angiography) Another means of reporting a test’s ability to “rule MRI: Magnetic Resonance Imaging in” or “rule out” pathology is the likelihood ratio NIH: National Institutes of Health (LR). The likelihood ratio positive (LR+) is the factor NINDS: National Institute Of Neurological Disorders by which the likelihood of disease increases when the And Stroke test result is positive. The likelihood ratio negative PWI: Perfusion Weighted Imaging (an MRI sequence) (LR-) is the factor by which the likelihood of disease SAH: Subarachnoid Hemorrhage decreases when the test result is negative. The pretest TEE: Transesophageal Echocardiography probability multiplied by the LR (positive or negative) TIA: Transient Ischemic Attack yields the post-test probability. TPA: Tissue Plasminogen Activator Positive and negative predictive values are not TTE: Transthoracic Echocardiography emphasized in this review because they are heavily influenced by disease prevalence and must be used Critical Appraisal Of The Literature cautiously in clinical practice.

A large number of studies have examined indications Neuroimaging Modalities for neuroimaging as well as the test characteristics (including sensitivity, specificity, and positive and Indications for neuroimaging are diverse and include negative likelihood ratios) of the available imaging traumatic and non-traumatic conditions. The major modalities. This article focuses on large, multicenter, brain neuroimaging modalities are CT and MRI, with prospective trials whenever possible; unfortunately, adjunctive roles for conventional angiography and ultrasound. Plain films of the calvarium have an

Emergency Medicine Practice® 2 December 2007 • EBMedicine.net extremely limited role, as they can detect bony injury structures (such as the eye or brain). However, there but cannot detect underlying brain injury that may be are now over 230 published prospective cases of present even in the absence of a skull fracture. patients with pacemakers having safely undergone low-field MRI, making MRI a possible imaging option CT in these patients.8 Magnetic effects on tattoos, includ- CT has been in general clinical use in the emergency ing first-degree burns and burning sensation, have department (ED) in the United States since the early been reported, although these appear rare and more 1980s. The modality was simultaneously and inde- likely to interfere with completion of MRI than to pendently described by the British physicist Godfrey cause significant harm.9-11 N. Hounsfield and the American Allan M. Cormack in 1973, and the two were co-recipients of the Nobel Interpretation Of Non-Contrast Head CT Prize for Medicine in 1979.1,2 Advances in computers and the introduction of multi-slice helical technology Several systematic methods for interpretation of non- have dramatically enhanced the resolution, sensitivity, contrast head CT have been described. The and specificity of CT since its introduction. CT relies mnemonic “Blood Can Be Very Bad” has been shown on the differential attenuation of x-ray by body tissues to assist in the sustained improvement of interpreta- of differing density. The image acquisition occurs by tion by emergency medicine residents.12 The rapid movement of the patient through a circular mnemonic reminds the interpreter to look for blood gantry opening equipped with multiple x-ray sources (“blood”), abnormalities of cisterns and ventricles and detectors. A three-dimensional volume of image (“can,” “very”), abnormalities of the brain data is acquired; this volume can be displayed as parenchyma (“be”) and fractures of (“bad”). axial, sagittal, or coronal slices or as a three-dimen- Another mnemonic uses the familiar ABC para- sional image. When performed without intravenous digm to drive the assessment of the head CT. The (IV) contrast, CT is considered to be excellent for mnemonic is reviewed in Table 1, with images detection of bony abnormalities, acute hemorrhage, illustrating each finding in the figures that follow. cerebral edema, hydrocephalus, or mass effect. It is The full mnemonic is freely available from the non- less sensitive for acute ischemic stroke but becomes profit organization EMPACS more sensitive with the passage of time, as will be (http://www.empacs.org/library/headCT/news1001 discussed later. Adding IV contrast improves the 06.htm). Additional images for concepts discussed in sensitivity of CT for neoplastic, infectious, and vascu- this article as well as larger copies of the images lar abnormalities. IV contrast can be used to generate presented here can also be found on this website. CT arteriograms, CT venograms, and CT perfusion maps. These will be described in more detail later in Principles Of Interpretation Of Non-Contrast Head CT this paper. CT does raise some safety concerns with Non-contrast head CT is the most commonly ordered regard to long-term biological effects of the ionizing neuroimaging test in the ED, utilized in up to 12% of radiation and carcinogenesis. The radiation exposure all adult ED visits.13,14 On CT, the density of a tissue to the fetus in a shielded patient undergoing head CT is minimal.3 Most commercially available CT scan- Table 1. A Mnemonic For Systematic Interpretation Of Non- ners have a weight capacity of approximately 450 Contrast Head CT: ABBBC pounds, although some manufacturers now offer units • Air-filled spaces with capacities up to 650 pounds, and a portable head o Sinuses CT scanner with a manufacturer-reported unlimited o Mastoid air-cells weight capacity is also now available.4  Infections  Fractures MRI • • Blood MRI has been in wide clinical use in the U.S. since the o Subarachnoid late 1980s. The modality was co-invented by the o Epidural American Paul C. Lauterbur and the British physicist o Subdural Sir Peter Mansfield, who shared the 2003 Nobel Prize o Intraparenchymal in Medicine for their work.5 MRI allows imaging of • Brain o Infarction the brain by creating variations in the gradient of a o Edema magnetic field and analyzing the radio waves emitted o Masses in response to objects within the field. Advantages of o Midline shift MRI include its noninvasive nature and its apparent • CSF spaces safety in pregnancy.6 It also has no known permanent o Sulci o Ventricles 7 harmful biological effects. Traditionally, contraindica- o Cisterns tions have included the presence of ferromagnetic  ICP material within the body, including electronic devices  Atrophy (such as pacemakers) or metallic debris (such as  Hydrocephalus  shrapnel), especially when they are located in sensitive Edema

EBMedicine.net • December 2007 3 Emergency Medicine Practice® is represented using the Hounsfield scale, with as deviation often indicates pathology (Figure 3). having a value of zero, tissues denser than water However, if the patient’s head is not centered sym- having positive values, and tissues less dense than metrically in the CT gantry, the resulting images can water having negative values (Figure 1). By conven- create a false sense of asymmetry. tion, low density tissues are assigned darker (blacker) The compression or displacement of normal brain colors and high density structures are assigned structures by adjacent masses is called “mass effect.” brighter (whiter) colors. Because the human eye can When this effect becomes extreme, shift of brain perceive only a limited number of gray shades, the structures across the midline of the skull can occur, a full range of density values is typically not displayed finding referred to as “midline shift.” Midline shift for a given image. Instead, the tissues of interest are can indicate significant pathology, including threat- highlighted by devoting the visible gray shades to a ened subfalcine herniation (Figure 6). This finding narrow portion of the full density range, a process should be carefully sought after, as it may be more called “windowing” (Figures 1 and 2). The same important than the underlying etiology of the shift in image data can be displayed in different window determining management. A brain CT should also be settings to allow evaluation of injury to different examined for artifacts which may limit interpretation, tissues. In general, head CT images are viewed on including motion and “streak artifact” from high “brain” or “bone” windows to allow the most emer- density structures such as metal (Figure 7 on page 6). gent pathology to be assessed (Figure 2). Although artifact may degrade the overall quality of The brain, air, CSF spaces, and surrounding bone the study, useful diagnostic information can often still are normally symmetrical structures (Figures 3, 4, 5). be gleaned from an imperfect scan. A head CT should be inspected for normal symmetry, The Mnemonic: ABBBC Figure 1. The CT Hounsfield Scale A systematic approach to the interpretation of the head CT is necessary to avoid missing important abnormalities. An approach will be reviewed here with a discussion of the normal appearance of the brain. A Is For Air The normal brain contains air-filled spaces: the maxillary, frontal, ethmoid, and sphenoid sinuses and the mastoid air-cells (Figure 4). On both “bone” and “brain” window settings, a normal air-filled space appears black. Opacification of an air-space may occur due to fluids (such as pus, mucous, or blood) or The CT Hounsfield scale places water density at a value of zero with air and bone at opposite extreme values of -1000 and +1000. due to tumor invasion of the space. In the setting of The colors associated with these density values can be reassigned trauma, opacification of an air-space may indicate to highlight particular tissues, a process called “windowing.” © 2007 Joshua Broder. Figure 3. Normal Brain Symmetry Figure 2. Hounsfield Units And Windows

This is a single CT slice, shown in brain windows (A) and bone windows (B). • Brain windows allow evaluation of the brain parenchyma, A normal brain is symmetrical. Abnormal masses or hemorrhage hemorrhage, CSF spaces, and soft tissue at the expense of may deviate brain structures across an imaginary line dividing the bony detail. Gross fractures may be seen. brain, creating “midline shift.” The degree of midline shift is more • Bone windows allow detailed examination for fractures (arrow) important acutely than the exact etiology of the shift, since shift is but obscure all soft tissue detail. an indication of threatened subfalcine herniation and may require © 2007 Joshua Broder. surgical intervention. © 2007 Joshua Broder.

Emergency Medicine Practice® 4 December 2007 • EBMedicine.net bleeding into that space, raising suspicion of a fracture Figure 5. Normal CSF Spaces of the surrounding bone (Figure 8 on page 6). In the absence of trauma, opacification may indicate sinus infection, although this is a nonspecific finding. B Is For Bone Bone abnormalities (including acute fractures) are best identified using “bone” windows. Defects in the cortex of bone indicate fracture, but these must be distinguished from normal suture lines (Figure 9 on page 6). Comparing the contralateral side to the side in question may help to distinguish fractures from In a normal brain, the basilar cisterns (A, arrow) are patent (sometimes referred to as the “smile sign”). The lateral ventricles normal sutures. Secondary signs of fracture, such as are open but not enlarged (B). Sulci are visible but not excessive opacification of adjacent air-spaces, may assist in (C). © 2007 Joshua Broder. recognition of fractures (Figures 8 and 9 on page 6). Pneumocephalus (air within the calvarium) may also Figure 6. be present and may provide an additional clue to open fractures (Figure 10 on page 6). B Is For Blood A brain CT should be carefully inspected for the presence of subarachnoid, epidural, subdural, and intraparenchymal blood. On non-contrast head CT, acute hemorrhage appears hyperdense (brighter/ whiter) compared with brain tissue. Multiple hemor- rhage types may co-exist on CT. Blood in the subarachnoid space can diffuse into the sulci, fissures, cisterns, and ventricles (Figure 11 on page 7). Common locations for subarachnoid hemorrhage include the basilar cisterns surrounding the brainstem. Diffuse subarachnoid hemorrhage can Subdural hematomas are most often the result of shearing of dural be symmetrical, so symmetry alone is not enough to veins from blunt trauma. They usually have a crescent shape and rule out this process. Familiarity with the normal may cross suture lines as they lie within the dura and are thus free black appearance of normal CSF spaces (Figure 5) can to extend along the brain surface, rather than being restricted by the tethering of the dura to the calvarium at sutures. help to avoid confusion. This subdural hematoma (arrowheads) demonstrates several Blood in the epidural space classically assumes a classic features: biconvex disc shape (Figure 12 on page 7). Epidural • Crescent shape hematomas most often do not cross suture lines • Crosses suture lines (A) because the dura mater is tightly adherent to the • Mass effect with midline shift (B) • Elevated ICP, with small ventricles (C) calvarium at these locations and restricts extension of • No visible sulci (D) the hematoma. An expanding © 2007 Joshua Broder. Figure 4. Air-filled Spaces

These are the normal locations and appearances of air-filled spaces when viewed on “brain windows.” Air-filled spaces are normally black on both “brain” and “bone windows.” A. Maxillary sinuses B. Mastoid air cells C. Ethmoid sinuses D. Sphenoid sinus E. Frontal sinus © 2007 Joshua Broder. EBMedicine.net • December 2007 5 Emergency Medicine Practice® may exert mass effect, leading to midline shift and injury to the middle meningeal artery. Active bleed- herniation. Epidural hematomas are classically found ing from this vessel may result in the “swirl sign,” a in a temporal location and are due to bleeding from heterogeneous appearance of the epidural hematoma. Subdural hematomas (Figure 6 on page 5) typi- Figure 7. Streak Artifact cally assume a concave or crescent shape and can cross suture lines, as they lie between dura and brain and are not restricted by attachment sites between dura and calvarium. Like epidural hematomas, subdural hematomas may result in mass effect and midline shift. Subdural hematomas are typically caused by injury to dural veins. They frequently have a heterogenous appearance, indicating blood of varying ages. Intraparenchymal hemorrhage (Figure 13 on page 7) may also result in mass effect and midline shift. Streak artifact may result from extremely high density structures, Hemorrhage should be distinguished from such as dental fillings, or in this case, metal objects outside of the patient. The streak artifact is most evident on brain windows (A). Figure 9. Fractures, Viewed On Bone Windows The fact that the source of the artifact is a very high density material is evident on bone windows (B) – the objects (C) are more dense (whiter) than the patient’s calvarium. Although streak artifact may obscure some important details, relevant clinical information may be obtained from an imperfect scan. For example, in this scan, no midline shift is visible. © 2007 Joshua Broder.

Figure 8. Fluid In Normally Air-filled Spaces

Fractures (A) are evident as discontinuities in the bony cortex. It is important to compare the contralateral side to ensure that a normal suture is not misidentified as a fracture. Air in soft tissues (B) and air-fluid levels or opacification of air-spaces (C) are additional clues. © 2007 Joshua Broder.

Figure 10. Pneumocephalus

Fractures of the bony walls of normally air-filled structures, including the sinuses and mastoid air cells, can result in hemor- rhage. Blood pooling in the dependent portion of these air-filled chambers results in an air-fluid level or, occasionally, complete opacification. This may be the only evidence of fracture. If no history of trauma is present, fluid in an air-space may indicate infection, such as or mastoiditis. In this patient with a temporal bone fracture (A) and associated Viewed here on bone windows, the patient’s right maxillary epidural hematoma (B), air (C) has entered the calvarium and is sinus (A) has an air (black) – fluid (gray) level. The left maxillary visible as a small black area on brain windows. On this setting, sinus (B) is completely opacified. The fractures of the sinuses CSF and air both appear black, so fine adjustment of the window themselves are hard to identify, though a right zygomatic arch setting may sometimes be necessary to confirm that this finding is fracture is visible (C). air. In some cases, air may be more visible on bone windows. In The mastoid air cells (D) are normal and have no fluid. Follow- this case, the location (adjacent to the fracture) and the rounded ing trauma, opacification of the mastoid air-cells is a sign of shape (typical of air bubbles) are confirmatory. © 2007 Joshua temporal bone fracture. © 2007 Joshua Broder. Broder.

Emergency Medicine Practice® 6 December 2007 • EBMedicine.net calcification, which may also be present as an inciden- assessment for masses, infarction, edema, and tal finding (Figures 13 and 14). Although the specific midline shift. type of hemorrhage is important to recognize, the end Masses may be visible due to calcifications results of mass effect may be more important determi- (Figure 14), surrounding vasogenic edema (Figure 15 nants of acute management. on page 8), or solely due to their mass effect on surrounding structures. Vasogenic edema refers to B Is For Brain edema occurring in the presence of abnormally leaky Inspection of the brain parenchyma should include blood vessels (such as those seen in the setting of Figure 11. Subarachnoid Hemorrhage neoplasm), perhaps in response to vascular endothe- lial growth factor. Edema reduces the density of tissues toward that of water (zero on the Hounsfield scale), resulting in a “hypodense” (darker/blacker) appearance on CT. Ischemic infarction (Figure 17 on page 8) results in a number of abnormalities (Table 2), including loss of gray-white matter differentiation, vasogenic and cytogenic edema, and the frank hypodensity of infarction, depending on time elapsed from onset. Table 2. Prevalence Of Early Ischemic CT Changes Within Three Hours, Possibly Contraindicating TPA Use, From NINDS Subarachnoid hemorrhage appears white on non-contrast CT. In Any change 31% this case of diffuse subarachnoid hemorrhage, note the presence of Loss of GWMD* 27% subarachnoid blood filling the sulci, as well as extending into the Hypodensity 9% cisterns, Sylvian fissures, and even lateral ventricles. Compression of CSF spaces 14% A. Blood in basilar cistern Loss of GWMD > 1/3 MCA 13% B. Blood in Sylvian fissure Hypodensity > 1/3 MCA 2% C. Blood in posterior horns of lateral ventricles Compression of CSF spaces > 1/3 MCA 9% D. Blood in sulci © 2007 Joshua Broder. *GWMD = gray-white matter differentiation

Figure 12. CT Of An Epidural Hematoma Figure 13. CT Of An Intraparenchymal Hemorrhage

Classic features of epidural hematoma (arrowheads) are visible: • Lens-like or biconvex disc shape • Temporal location, with associated depressed temporal bone Acute intraparenchymal hemorrhage appears white on CT. fracture (A) Hemorrhage in the patient’s left frontal region is creating mass • Does not cross suture lines (B - expected location of suture) effect with midline shift. The left lateral ventricle has been effaced. • Mass effect with midline shift (C) A calcified mass in the right occipital region must be differenti- • “Swirl sign” – heterogeneous appearance suggesting active ated from acute hemorrhage. Calcifications are extremely bright bleeding (D) white on brain windows – as white and dense as bone. On bone • Elevated ICP, with small ventricles (E) and no visible sulci (F) windows, they remain visible, while hemorrhage does not. © 2007 Joshua Broder. © 2007 Joshua Broder.

EBMedicine.net • December 2007 7 Emergency Medicine Practice® Normal gray-white matter differentiation (Figure 16) higher content than gray matter; therefore, it is the result of the normal density difference between normally appears less dense and darker gray on CT. gray matter and white matter in the brain. White As ischemia or infarction develops, ATP-dependent matter, representing myelinated structures, has a ion pumps fail, and fluid shifts result in the development of interstitial edema in the affected Figure 14. Calcifications region. Affected tissue becomes hypodense on CT, compared with normal tissues. The earliest manifes- tation of this change on CT is loss of the normal differentiation between gray and white matter, progressing ultimately to the appearance of infarct (Figure 17). Localized brain edema may be evident as hypo- density of brain parenchyma (Figures 15 and 17). In addition, local edema may result in local mass effect, including the effacement of ventricles (Figure 15,

Figure 16. Gray And White Matter

Calcification of the choroid plexi (A) is a frequent incidental finding which may resemble punctate intraparenchymal hemorrhage. Clues are a bright white density (equal to that of bone), location in the posterior horns of the lateral ventricle, and frequent bilaterality. This patient also has a calcified meningioma (B). Meningiomas are common benign neoplasms which may become quite large. A well-circumscribed rounded appearance and calcification are common. © 2007 Joshua Broder.

Figure 15. Masses This shows normal gray-white matter differentiation. Myelinated regions (white matter) have a greater fat content than unmyelinated regions (gray matter). As a consequence, white matter is lower density and appears darker on CT. When ischemia renders this interface less discrete, the CT appearance is called loss of gray- white differentiation. © 2007 Joshua Broder.

Figure 17. Progression Of Ischemic Hypodensity Over Days

This image shows a mass with surrounding vasogenic edema (arrowheads). Neoplasms are frequently associated with vasogenic edema, named for the putative cause, which is abnormal vessels A left MCA distribution stroke, day two (A) and day four (B) after that allow extravasation of edema fluid. symptom onset. Early ischemic changes may be visible within This form of edema appears hypodense, like an ischemic three hours of symptom onset. The rate of progression of CT infarct, but is not restricted to a vascular territory. An findings may depend on the degree of ischemia or infarction and might appear similar. © 2007 Joshua Broder. thus may vary between patients. © 2007 Joshua Broder.

Emergency Medicine Practice® 8 December 2007 • EBMedicine.net effacement of the posterior horn of the lateral ventri- rather than a more selective imaging policy based on cle), and effacement of sulci as adjacent gyri expand in clinical criteria.17 However, with an annual cost of size (Figure 17). emergency head CTs in the U.S. estimated to exceed As described previously, midline shift should be $130 million, others have estimated the savings from carefully assessed during inspection of the brain on selective use of CT to be high and the risk of missed “brain” windows (Figures 6, 12, and 13). injury to be low using validated clinical decision rules such as the Canadian CT Head Rule.18 C Is For CSF Spaces Normal cerebrospinal fluid (CSF) spaces (Figure 5 on Figure 18. Cerebral Atrophy page 5) show symmetrical lateral ventricles that are neither enlarged nor effaced, patent sulci, and patent basilar cisterns. Deviations from this norm are best appreciated by understanding the normal pattern. In cerebral atrophy (Figure 18), all CSF spaces are enlarged. In obstructive hydrocephalus (Figure 19), the enlarging ventricles compress other CSF spaces, causing effacement of the sulci and basilar cisterns. In diffuse cerebral edema (Figure 20), the swelling brain parenchyma compresses and effaces all CSF spaces, including sulci, ventricles, and cisterns. Figure 21 In cerebral atrophy, all CSF spaces become prominent. The basilar compares various combinations of CSF spaces and cisterns (A, arrow) are open, and the lateral ventricles are enlarged (B). Sulci (C) are equally prominent, helping to distinguish this their diagnostic correlates. condition from hydrocephalus. © 2007 Joshua Broder. Costs Of Neuroimaging Figure 19. Hydrocephalus Costs of CT and MR tests are listed in Table 3 on page 10. These Medicare reimbursement figures may dramatically underestimate the cost billed to the patient. An industry survey of imaging costs in New Jersey found a wide variation in consumer costs, ranging from $1000 to $4750 for brain MRI/MRA.15 The American Hospital Directory reports the national average charge to be $996 for head CT and $2283 for MRI.16 Additional radiologist physician fees may apply. Some authors have concluded that, in the In hydrocephalus, the basilar cisterns (A, arrow) are effaced, as are setting of , the extreme cost of a the sulci (C). The lateral and third ventricle are enlarged (B). missed injury justifies the use of CT in all patients, © 2007 Joshua Broder. Figure 20. Cerebral Edema

In cerebral edema, the basilar cistern (A, arrow) becomes effaced. The lateral ventricles become compressed and slit-like (B), or even completely effaced. Sulci (C) become effaced. © 2007 Joshua Broder.

EBMedicine.net • December 2007 9 Emergency Medicine Practice® Radiation while large (over 2000 subjects followed over time) The radiation dose from a head CT is approximately was retrospective and therefore can demonstrate only 60 mGray.19,20 Attributable mortality risk varies, an association, not causation. In general, the radiation depending on age of exposure. A single head CT in a exposure from head CT likely poses a very low level neonate would be expected to contribute less than a 1 of risk for deleterious biological effects, but care in 2000 attributable risk of fatal cancer; the risk in should be taken to perform testing only when indi- adults declines even further, to less than 1 in 10,000.20 cated, as radiation effects are cumulative and not fully However, head CT may have other risks — one study understood. of patients undergoing external beam radiation for scalp hemangiomas, with a radiation Emergency Department Evaluation exposure similar to that from CT, found an association with lower high school graduation rates.21 This study, Before neuroimaging can be considered, basic princi- ples of emergency medicine must be applied, includ- Table 3. Costs Of CT And MR Imaging, Based On 2007 ing management of the patient’s airway and hemody- Medicare Reimbursement National Averages namic stabilization as indicated. An unstable patient is not appropriate for imaging tests that will take the Hospital Outpatient patient out of the ED for extended periods of time Diagnostic Procedure Department (such as MRI). The history and physical examination CT head or brain without contrast $230.54 can guide imaging decisions. A thorough neurological CT angiography head, without contrast followed by contrast, further sections, examination, including assessment of orientation, and post-processing $382.19 strength, sensation, deep tendon reflexes, cerebellar MR angiography, head with contrast $386.64 function, and language, may help localize the neuro- MR angiography, neck with contrast $386.64 logic lesion and assist in choosing the imaging modal- MRI brain w/contrast $386.64 ity. Motor and sensory deficits that are unilateral may MR angiography, neck without contrast material(s), followed by contrast be more suggestive of an anterior fossa brain abnor- material(s) and further sequences $522.54 mality, imaged by CT or MRI, whereas a bilateral motor and sensory level may suggest a spinal lesion. Figure 21. A Comparison Of CSF Spaces Symptoms of vertigo, ataxia, and dysmetria may suggest posterior fossa cerebellar abnormalities, best imaged by MRI. Acute onset of these symptoms could suggest posterior circulation stroke, for which imaging options would include MRI/MRA and CTA of the head and neck. Symptoms of cranial nerve dysfunction, including dysarthria, dysphagia, and abnormalities of extraocular muscles suggest brain- stem pathology which is better imaged with MRI than with CT. A motor deficit with ptosis and miosis may suggest carotid artery aneurysm or dissection, imaged by CTA, MRA, or carotid ultrasound. Table 4 corre- lates chief complaints, differential diagnosis, and suggested initial imaging test. A complete review of neuroanatomic localization is beyond the scope of this article. Stroke Stroke is the leading cause of disability in the U.S.22 and may be ischemic (85%) or hemorrhagic (15%) in nature. When presented with signs and symptoms suggestive of stroke, the emergency physician (EP) must take steps to differentiate ischemic stroke from An overview of CSF spaces: intraparenchymal hemorrhage while entertaining the • Normal brain possibility of “stroke mimics” (e.g., hypoglycemia or o All CSF spaces are present, neither effaced nor enlarged Todd’s paralysis). To aid in this task, a number of • Atrophy neuroimaging studies exist. Some techniques may o All CSF spaces are enlarged yield additional information, including localization of • Hydrocephalus o The ventricles expand the vascular territory affected, the extent of injury, o The sulci and cisterns are compressed clues to the underlying precipitant cause(s), and identi- • Edema fication of tissue that might be ischemic but still viable. o All CSF spaces are compressed This information is critical when contemplating the © 2007 Joshua Broder. use of thrombolytic or neuroprotective .

Emergency Medicine Practice® 10 December 2007 • EBMedicine.net Unfortunately, many imaging modalities are not (hyperattenuation of the MCA) may also be present;28 currently available at all institutions during all hours although, it is only visible in 30-40% of patients with of the day. Furthermore, many options remain stroke affecting the MCA territory, and its relevance to untested or inconclusive with regard to their utility in clinical outcome is equivocal.28,29 The presence of one guiding intervention and disposition. or more of these signs during the early stages (within six hours of stroke onset) of brain ischemia is impor- Computed Tomography (CT) For Stroke tant since it correlates with worse functional out- CT is the most widely available immediate imaging comes,27 but it must be emphasized that a truly technique for patients presenting to the ED with signs normal non-contrast head CT is still consistent with and symptoms of stroke. Non-contrast head CT is the diagnosis of acute ischemic stroke in a patient rapid, taking less than five seconds for image acquisi- presenting with suggestive signs and symptoms. This tion using some 64 slice scanners.23 It is sensitive for is because, although the sensitivity increases beyond detecting intracranial hemorrhage,24 and immediate 24 hours, the sensitivity for ischemia-induced changes imaging is more cost effective than either delayed or in the early stages is relatively low at 66%.27 selective imaging strategies.25 Limitations do exist, For the emergency physician, several points about however. For example, the surrounding bone can early ischemic changes should be emphasized. First, obscure evidence of ischemic stroke, an artifact effect in contrast to the assertion in some emergency medi- known as “beam hardening.” This problem can be cine texts that ischemic stroke becomes visible on non- minimized by requesting fine thickness cuts (~ 1 mm); contrast head CT only after six hours,30 the NINDS however, the risk of false negatives for stroke detec- trial upon which TPA therapy is largely based demon- tion still exists, particularly when a vertebral-basilar strates that 31% of patients had early findings of distribution is present since beam hardening is ischemia within three hours of symptom onset (Table worsened by the thick bone surrounding the posterior 2 on page 7).31 Although early ischemic changes were fossa.26 not an exclusion criterion for TPA in the original In response to cell damage and associated edema, NINDS trial,32 subsequent research has shown a ischemic brain typically appears as a lower density heightened risk of hemorrhagic conversion of signal on non-contrast head CT. A variety of early ischemic stroke, poor neurological outcomes, and ischemic changes have been described (Figures 17, 22, death in patients with these changes.27,33 As a conse- 23). These include hypoattenuation of the middle quence, the FDA, the American Heart Association, cerebral artery (MCA) territory, obscuration or shad- and the American Academy of recommend owing of the lentiform nucleus, loss of the insular against the use of TPA in patients with major early ribbon or obscuration of the Sylvian fissure, efface- ischemic changes.34 Specifically, early ischemic ment of the cortical sulcus, focal parenchymal hypoat- changes occupying an area one-third the size of the tenuation, or loss of gray-white matter differentiation MCA territory or one-third of a cerebral hemisphere, in the basal ganglia.27 The much publicized cerebral edema, and midline shift are considered “hyperdense MCA sign” (Figure 24 on page 12)

Table 4. Neurological Complaints, Differential Diagnoses, And Initial Imaging Modality

Neurological Complaint Differential Diagnosis Initial Imaging Modality

Headache Mass, traumatic or spontaneous hemorrhage, Non-contrast CT , brain abscess, sinusitis, hydrocephalus Altered mental status or coma Mass, traumatic or spontaneous hemorrhage, Non-contrast CT meningitis, brain abscess, hydrocephalus Fever Meningitis (assessment of ICP), brain abscess Non-contrast CT Focal neurological deficit – motor, Mass, ischemic infarct, traumatic or Non-contrast CT – possibly followed by sensory, or language deficit spontaneous hemorrhage, meningitis, brain MRI/MRA or CTA, depending on context abscess, sinusitis, hydrocephalus Focal neurological complaint – ataxia, Posterior fossa or brainstem abnormalities, MRI/MRA of brain and neck; CT/CTA of brain cranial nerve abnormalities vascular dissections and neck if MR not rapidly available Seizure Mass, traumatic or spontaneous hemorrhage, Non-contrast CT, possibly followed by MR meningitis, brain abscess, sinusitis, hydrocephalus Syncope Trauma Little indication for imaging for cause of syncope, only for resulting trauma Trauma Hemorrhage, mass-effect, cerebral edema Non-contrast CT Traumatic loss of consciousness (LOC) Hemorrhage, diffuse axonal injury, mass-effect, Little indication when transient LOC is isolated cerebral edema complaint Planned lumbar puncture Increased intracranial pressure Non-contrast head CT – limited indications

EBMedicine.net • December 2007 11 Emergency Medicine Practice® relative contraindications to TPA due to increased risk Figure 23. Early Ischemic Changes of hemorrhage.35 The more extensive the ischemic changes on CT, the higher the risk of bleeding — as demonstrated in the multinational ECASS II trial.33 When discussing the head CT findings with a radiolo- gist prior to administration of TPA, it is important to ask specifically about the presence and extent of these changes, in addition to asking about hemorrhage. Standard contrast-enhanced head CT is rarely used since it provides little additional information compared with non-contrast head CT. With the advent of multi-detector CT scanners and spiral CT

Figure 22. Early Ischemic Changes

Normal gray-white matter differentiation is subtle. Gray matter has lower lipid content than myelinated white matter and therefore appears brighter on CT. This leads to the unexpected fact that, on CT, gray matter looks white and white matter looks gray. Normal gray matter areas include the cerebral cortex (A), lentiform nucleus (B), caudate (C), and thalamus (D). White matter tracks separate these structures (E). © 2007 Joshua Broder.

Figure 24. CT Angiography

Early ischemic changes may be visible within three hours of onset of ischemic stroke. They include sulcal effacement, loss of gray- white matter differentiation, and the “insular ribbon sign.” Sulci are simply CSF-containing spaces between gyri. Sulcal effacement occurs when the adjacent gyri swell, displacing CSF from the sulci. Loss of gray-white matter differentiation occurs as ion pumps fail, leading to equilibration of diffusion gradients and shift of fluid. The normal ability of CT to differentiate gray from white matter relies on differences in their density, due to differences in their fluid and lipid content. White matter contains more fat, is less dense, and therefore appears darker on CT. Gray matter contains less lipid, is denser, and therefore appears whiter on CT. Local edema in the region of a developing infarct renders the region darker on CT, due to the presence of increasing amounts of fluid. This masks the normal differentiation between white and gray matter. The “insular The hyperdense MCA (middle cerebral artery) sign is a CT finding ribbon” sign is another manifestation of this loss of gray-white of thrombosis of the MCA. It can be seen in the immediate matter differentiation. The insula is a region of gray matter lining the hyperacute stages of thrombotic/ischemic stroke and may guide lateral sulcus, in which ischemic of the MCA distribution therapy (such as intra-arterial TPA administration). On CT, the may demonstrate early abnormalities. In this patient, both sulcal hyperdense MCA appears as a white line or point representing the effacement (A) and loss of gray-white matter differentiation (B) have thrombosed vessel. Care must be taken not to confuse this with occurred. The frank hypodensity of ischemic stroke is also the white appearance of fresh extravascular blood in hemorrhagic becoming visible. The abnormalities on the patient’s left side are stroke. In this patient, who presented within 30 minutes of onset of particularly evident when compared with similar normal regions on right hemiplegia, the normal MCA is not visible (A) while the left the patient’s right side (normal sulci [C] and normal gray-white MCA is thrombosed and demonstrates the hyperdense MCA sign matter differentiation [D]). © 2007 Joshua Broder. (B). © 2007 Joshua Broder.

Emergency Medicine Practice® 12 December 2007 • EBMedicine.net technology, however, CT angiography (CTA) can be injected contrast over time, CTPS are capable of even performed to obtain images of the extra- and intracra- more direct estimates of cerebral perfusion than CTA, nial vasculature from the aortic arch to the cranial including measurements of cerebral blood volume vertex (Figure 25). Images are acquired by adminis- (CBV) and cerebral blood flow (CBF) (Figure 26). By tering a rapid bolus of IV contrast immediately after quantifying these variables, the goal is to allow standard non-contrast head CT. The raw images can clinicians to identify areas of the brain that, although be acquired in as little as 60 seconds, and three- ischemic, are potentially still viable – the so-called dimensional computer reconstructions can be per- “ischemic penumbra.” This has implications for the formed in fifteen minutes. The results can profoundly clinician attempting to weigh the benefits of adminis- alter the course of management since large artery tering intravenous or intra-arterial thrombolytics occlusions correlate with NIH Stroke Scale scores36 versus the risk of intracranial hemorrhage. Routine and may indicate a need for endovascular interven- use of CTPS could potentially allow a more precise tion. Generally, agreement between CTA and catheter prediction of outcome40 and could even herald a angiography — still the gold standard for diagnosis of paradigm shift in one of the indications for throm- vessel stenosis — approaches 95%. For severe carotid bolytic administration: rather than excluding the use artery stenosis, sensitivity for CTA approaches 100%, of thrombolytics in patients presenting after an while the sensitivity for diminished flow in the Circle arbitrary time interval (e.g., three hours), thrombolytic of Willis is 89%.37 Although traditional angiography therapy could be initiated or excluded based on actual may have subtle, additional benefits related to charac- visualization or absence of a penumbral area likely to terization of the plaque lesion (and the relatively non- benefit from such intervention. invasive and rapid nature of CTA) render it an Routine use of CTPS in the hospital setting (much attractive option to the EP (assuming that the risks of less in the ED) is not without challenges. First, the exposure to contrast and additional radiation are usual difficulties of imaging the posterior fossa with acceptable to the patient). CT techniques persist.26,41 Second, only limited CTA uses enhancement of the cerebral vasculature volumes of brain can be imaged at one time with each as a surrogate for estimating perfusion of the bolus of contrast so ischemia located outside the parenchyma. CT perfusion studies (CTPS) can be scanning level of interest can be missed,42 although performed simultaneously using the same bolus of this is partially alleviated by the use of multi-slice contrast38 and have a sensitivity and specificity for scanners or using repeated contrast boluses. Third, detecting ischemia of 95% and 100%, respectively.39 despite the theoretical appeal, only small studies in By measuring the rise and fall in concentration of limited populations exist that confirm the ability of CTPS to detect infarct,43 predict infarct location44 and Figure 25. CT Angiography size,45 and predict final outcomes.43,45 Confirmation of these studies is needed before their use in routine clinical practice can be recommended.

Figure 26. CT Perfusion Scan

A CT perfusion scan provides a map of blood flow in ischemic stroke, potentially identifying ischemic areas which could be sal- vaged by reperfusion. Here, blood flow in similar regions of the two cerebral hemispheres is compared. This is an imaging technique In this patient with carotid artery dissection, a CT angiogram allows which continues to be developed in the research setting but is not a three dimensional reconstruction of the vessel, with cross- a routine part of most clinical practice. © 2007 Joshua Broder. sections displayed at intervals around the periphery. An intimal flap Note: Subscribers can view the full color version of this image is faintly visible on several of these cross-sections (arrows). © 2007 by logging in to their free online subscription at Joshua Broder. http://ebmedicine.net/redirect/?topic=emp

EBMedicine.net • December 2007 13 Emergency Medicine Practice® Magnetic Resonance Imaging (MRI) For Acute Stroke spending more time per study as compared to CT. Standard MRI imaging for stroke includes scout Additionally, expert-level radiologists with extensive images, T1- and T2-weighted images, and MRA. training in MRI interpretation must be employed since Increasingly available new generation scanners interpretation is still not reproducible (though advo- incorporate additional high sensitivity methods such cates of DWI point out that there is virtually no intra- as diffusion-weighted imaging (DWI), gradient echo or inter-observer variability with this modality).48 pulse sequencing (GEPS), and perfusion-weighted Similar to the ability of CTPS to identify the imaging (PWI). ischemic penumbra, the combination of DWI and PWI Obtaining DWI has been possible since 1985.46 In makes it possible to make inferences about ischemia brief, the technique involves detecting and processing before injury has occurred. PWI is performed with a signal in response to the movement of water mole- standard MRI and MRA using gadolinium and cules caused by two pulses of radio frequency. requires a total imaging time of less than 15 minutes. Ischemic changes can be detected in as little as 3-30 PWI can be performed on patients with contraindica- minutes after insult. In a small study of 22 patients tions to gadolinium (a rare event, as gadolinium has who presented within six hours of symptom onset, been found to be safe in most instances, though recent DWI was found to be 100% sensitive and 100% fatal nephrogenic systemic fibrosis has been noted in specific.47 In a subsequent study, DWI was found to patients with advanced renal disease)57 by magneti- have a far superior sensitivity compared to CT (91% cally labeling the blood as the blood enters the brain, vs. 61%).48 When MRA is done simultaneous with a technique known as continuous arterial spin label- DWI as part of a fast protocol to detect vascular ing (CASL).58 The benefits of using DWI and PWI (so- stenosis, their combined usage within 24 hours of called diffusion/perfusion mismatch) have started to hospitalization substantially improved the early accrue. Large perfusion defects59,60 and patients with diagnostic accuracy of ischemic stroke subtypes.49 occluded arteries61 are at heightened risk for enlarging The utility of DWI to detect ischemia may also be lesions, leading some to suggest that these findings present when the clinician encounters a patient with should prompt early revascularization, either pharma- remote onset defects. In patients presenting with a cologically with thrombolytic agents or with mechani- median delay of 17 days after symptom onset, clini- cal devices. Volume abnormalities on DWI and PWI cians gained additional clinical information one-third during acute stroke correlate with acute NIH stroke of the time (including clarification of the vascular scales and with chronic neurological scores, and lesion territory affected) by performing DWI in addition to size may be predictive with respect to early neurologi- conventional T2. Of this third, the information was cal deterioration.62,63 Still another benefit of advanced designated as “highly likely” to affect management techniques like DWI and PWI is, as is the case for strategy in 38%.50 CTPS, the potential to identify areas of ischemia MRI is superior to CT at detecting acute ischemic which have not yet progressed to infarction, poten- change46,48 and visualizing the posterior fossa.26,41 tially permitting extension of the traditional three- However, MRI has failed to supplant CT as the hour window for thrombolytic administration and/or imaging modality of choice for stroke in the ED due to a paradigm shift to ruling in/out stroke based on cost considerations, availability of the requisite perfusion/diffusion mismatch.64,65 However, PWI personnel, time, and a long-standing belief that MRI is and DWI have yet to prove practical and reliable in not reliable for detecting intracerebral hemorrhage. defining the ischemic penumbra and infarct core,66 At least the last two factors are being surmounted. and head-to-head trials comparing diffusion/perfu- New scanners are increasingly faster — with acquisi- sion studies performed with MRI versus CTPS are tion times in the range of three to five minutes, limited. compared to 15-20 minutes previously.51 With respect Figure 27 shows images from a single patient in to hemorrhage, DWI has been proven to be sufficient various modalities, including CT, CTA, MRI, and to exclude intracerebral hemorrhage.52 Additionally, MRA. in studies comparing GEPS with CT, the former was at least as useful for detecting acute intracranial Ultrasonography For Ischemic Stroke hemorrhage and actually better at elucidating chronic Ultrasound techniques include Doppler (used to hemorrhagic changes,53-55 with sensitivity approach- assess flow rate and the presence of stenosis), bright- ing 100% when interpreted by trained personnel.53 ness-mode (permitting anatomical and structural The issues of cost and personnel are more complex, details of the tissue to be illuminated), and duplex (a however. MRI hardware costs and costs associated combination of the two). Carotid duplex ultrasound with imaging are roughly double that of CT.56 has traditionally been deployed on an elective basis Whether these costs will fall in the future or if they (i.e., non-emergent) to investigate whether the origin can be justified in the form of better outcomes, shorter of an acute ischemic event in a given patient could be hospital stays, or other measurable endpoints is due to carotid artery stenosis. Studies show conflict- unknown. Personnel issues are related not only to ing results, with some showing poorer performance of sheer manpower, but also to qualitative training ultrasound (65% sensitivity, 95% specificity) compared demands. MRI requires specially trained technicians with MRA (sensitivity 82-100%, specificity 95-100%)

Emergency Medicine Practice® 14 December 2007 • EBMedicine.net and the gold standard of digital subtraction contralateral stenosis can result in reassuring flow angiography (as the gold standard, by definition 100% velocities (false negatives for stenosis) ipsilaterally.73-76 sensitive and specific).67,68 Transcranial ultrasound Conventional Catheter Angiography For Stroke can be used to visualize the vessels in and near the Circle of Willis. Here, it is possible to identify stenosis Still considered the gold standard for diagnosing with reasonable success, though less well for the arterial stenosis, conventional catheter angiography vertebral-basilar system. In the internal carotid artery has been substantially improved with the advent of (ICA), distribution of the respective sensitivity and digital subtraction techniques which enable visualiza- specificity for this task is 85% and 95%, but falls to tion of even small, cortical branches of intracranial 75% and 85% in the vertebral-basilar. Additional arteries. Endovascular techniques permit administra- benefits of transcranial ultrasound reportedly include tion of intra-arterial thrombolytics and some users the ability to identify collateral pathways, visualize have the ability to perform clot retrieval and angio- 77 harmful emboli in real time, and judge the success of plasty with or without stenting. However, despite therapy in the post-thrombolysis state.69-71 In addi- its utility when noninvasive techniques are equivocal tion, ultrasound is being used therapeutically in trials or conflicting, it is still used only sparingly in the to augment the thrombolytic effect of medications.72 acute stroke setting due to its invasive nature and the Whether an acute indication for ultrasound exists approximate 1% risk of iatrogenic stroke associated 78 has received some attention, particularly with the aim with the procedure. of selecting patients for thrombolytics or endovascular Stroke Neuroimaging Summary treatment. The inexpensive and non-invasive nature The goals of neuroimaging in the ED patient present- of ultrasound is obviously attractive, but the integrity ing with signs and symptoms consistent with stroke of the results is highly operator-dependent. In include the exclusion of intraparenchymal hemor- addition, it is impossible to differentiate reliably rhage, space-occupying lesions, and other stroke between complete versus high-grade stenosis, and “mimics.” Ideally, the imaging technique would also Figure 27. Multi-modality Assessment Of Stroke

This patient presented with dizziness, nausea, and vomiting. The brain CT (A) was interpreted as normal but symptoms were concerning for posterior circulation stroke. CTA (B) suggested right vertebral artery dissection (arrow). MRI (C) confirmed posterior inferior cerebellar artery (PICA) territory ischemic stroke (arrows), and MRA (D) showed vertebral dissection (arrow). © 2007 Joshua Broder.

EBMedicine.net • December 2007 15 Emergency Medicine Practice® highlight areas of ischemia, possible underlying CT Angiography For Aneurismal SAH etiologies of ischemia (i.e., vessel occlusion), and potentially identify those areas that, although When non-contrast head CT is negative in a patient ischemic, are still potentially salvageable. Currently, suspected of SAH, is additional neuroimaging warranted to there is no single imaging modality that can accom- assess for aneurismal disease (i.e., is there a role for CT plish all of these goals quickly and at a low cost, and angiography)? there is no combination of studies that is widely The precise role is, as yet, undefined. A small study available in all centers. found aneurysms in 5.1% (6/116) of patients with a When confronted with a patient for whom stroke negative CT and positive LP and in 2.5% (3/116) is the suspected diagnosis, the patient must be imaged following a normal CT/LP. Given the incidence of as quickly as possible with the most readily available berry aneurysms in the general population, believed neuroimaging modality to rule out hemorrhage and to be approximately 1-5%,85-87 it is possible that the other stroke “mimics.” Typically, this is with non- aneurysms detected in these patients were incidental, contrast CT. In the absence of contraindication to the not the acute cause of the patients’ symptoms. Wide use of contrast agents, it seems prudent to perform use of CTA might result in detection of large numbers simultaneous CTA to rule out large vessel occlusion. of asymptomatic aneurysms, resulting in unneeded If available and if it will not delay other indicated procedures, including formal angiography and therapy, CTPS may be useful for prognosis and to endovascular coiling of aneurysms, with associated guide therapeutic decisions (i.e., the use of throm- morbidity and mortality. Perhaps the best role of CTA bolytics). In specialized centers with the required would be in patients in whom LP is not feasible — expertise and resources, MR stroke protocols includ- those with coagulopathy, for example. CTA might ing MRI, MRA, DWI, and PWI may be feasible from also be useful in patients with a particularly high the ED without the need for prior CT imaging. pretest probability of disease but negative non- contrast CT and LP.88 Suspected Subarachnoid Hemorrhage (SAH) Imaging Of Vascular Dissections Traditional practice in the evaluation for suspected SAH has been LP following negative CT, a practice Vascular dissections of the carotid and vertebral still advocated by major emergency medicine text- arteries are a relatively rare cause of acute headache books.93 The reported sensitivity of CT (third genera- and neurological symptoms; they account for only tion or higher) for SAH is in the range of 90% in the about 2% of all ischemic strokes but as many as 20% first 24 hours, declining after 24 or more hours.79 A of strokes in young adults.89-91 Non-contrast head CT recent study of fifth generation CT found no SAHs in is expected to be negative in the setting of these patients undergoing LP after negative CT.80 However, lesions, unless ischemic stroke has resulted. In this retrospective review examined only 177 ED addition, dissection of the vertebral arteries would be patients undergoing both CT and LP. Records and expected to result in ischemia in the region of the follow-up were not reviewed for patients who under- basilar artery (which forms from the confluence of the went CT but not lumbar puncture, so it is possible vertebral arteries), and the territories supplied by the that cases of SAH with negative head CT occurred but basilar artery lie within the posterior fossa, an area were not detected. In addition, the interval between poorly seen on non-contrast CT. Multiple imaging headache onset and CT/LP was not recorded, so this techniques are available for this diagnosis. CTA, study provides no information on any time depend- MRA, and conventional angiography all have greater ency of CT sensitivity for SAH. Given an incidence of than 95% sensitivity and specificity.92 Imaging of the SAH of only 3.4% of ED acute severe non-traumatic head and neck should be ordered when these diag- headache patients compared with previously reported noses are suspected, to ensure that the lesion is within numbers in the range of 12%, the true sensitivity of the imaged field (Figure 25 on page 13). fifth generation CT may be as low as 61%.24,80,81 A prospective study of patients presenting with the Imaging In Acute Hydrocephalus And Shunt Failure worst headache of their life reported a sensitivity of Non-contrast head CT is the initial study of choice 97.5%; again, the small number of patients (107) for diagnosis of acute obstructive hydrocephalus. As yielded a confidence interval as low as 91%.24 Sensi- the ventricles enlarge due to obstruction of the tivity of CT is thought to decline with the passage of normal outflow of CSF, other CSF spaces become time due to clearance of blood, and it is reported to be progressively effaced due to the fact that the total as low as 50% at seven days.82 EPs are only moder- volume of all skull contents is fixed (Figures 19 and ately accurate at predicting SAH based on clinical 21 on page 9 and 10). Large ventricles with small or history,83 so a conservative approach including LP completely effaced sulci and cisterns are consistent after negative head CT is probably still warranted with hydrocephalus. In contrast, all CSF spaces are based on CT sensitivity. Even the authors of studies enlarged in atrophy, while all spaces are effaced in of CT sensitivity are reluctant to state that LP is not cerebral edema. Occasionally a mixed picture can needed after negative CT.84 Future advances in CT occur, with both obstructing hydrocephalus and may eliminate this need.

Emergency Medicine Practice® 16 December 2007 • EBMedicine.net diffuse cerebral edema. A number of radiographic patients with new onset seizure, 17.7% had an abnor- criteria for hydrocephalus have been described (Table mal head CT – 26.6% of those undergoing head CT. 5). Among patients with AIDS and new-onset seizure, the risk appears higher still (30%), with frequent CT How common is shunt obstruction among children present- diagnoses including cerebral toxoplasmosis, progres- ing with suspected obstruction undergoing CT? sive multifocal leukoencephalopathy, and CNS Among children presenting with suspected shunt lymphoma.99 Risk factors for life-threatening lesions malfunction, up to 25% may have malfunction requir- include new focal deficits, persistent altered mental ing surgical intervention. status, fever, trauma, persistent headache, cancer history, anticoagulation, AIDS or immunocompro- How sensitive and specific is the CT in a patient with an mise, or age greater than 40. Whether seizure is new existing ventricular shunt suspected of shunt failure? onset or recurrent, emergent CT scanning is recom- The sensitivity of non-contrast head CT is reported to mended for patients with any of these findings.100 be 83%, with a specificity of 76%. Traditionally, a Non-contrast CT is the initial neuroimaging method shunt series (a series of plain x-rays without contrast as the majority of life-threatening lesions (hemor- following the course of the shunt from head to rhage, edema, mass effect, hydrocephalus) would be destination, usually the peritoneum) is also per- expected to be found with this modality. Enhanced formed. Shunt series have low sensitivity (20%) but high specificity (98%). Studies do not suggest high Figure 28. Shunt Failure utility of this test in patients with normal non-contrast head CT, but the shunt series may occasionally be positive in these patients (Figure 28). In one series, 3 of 233 patients undergoing imaging had normal head CTs but abnormal shunt series and documented shunt obstruction.93,94 Neuroimaging In Patients With Seizures Neuroimaging of patients with new onset seizure who have returned to a normal neurological baseline is a Level B recommendation in the 2004 ACEP Clinical Policy on seizures (Table 6).95 Level B recommenda- tions generally reflect evidence with moderate cer- tainty based on class II studies (e.g., nonrandomized trials, retrospective or observational studies, case- control studies) directly addressing a clinical question or broad consensus among experts based on class III studies (e.g., case reports and case series).

What is the basis of the ACEP recommendation? Studies on patients with new-onset seizure show a high rate of abnormal neuroimaging results, as high as 41%, often unsuspected on the basis of history or examination.96-98 It is not clear that there is a causal relationship between some of the CT abnormalities found in these studies and acute seizure or that any change in management resulted from CT imaging. A systematic review found that among all adult ED

Table 5. Radiographic Findings Of Acute Hydrocephalus

• Dilated lateral ventricles • Effaced sulci • Both temporal horns > 2 mm • Sylvian and interhemispheric fissures effaced • Ratio largest width of frontal horns: internal diameter from A VP shunt series is a series of plain x-ray images documenting the inner table to inner table > 0.5 course of a shunt from brain to abdomen. Rarely, a shunt series • Ratio of largest width of frontal horns to maximum biparietal may reveal an abnormality not revealed by brain CT. Much more diameter > 30% frequently, the shunt series will be abnormal only if the head CT • Periventricular low density due to transependymal absorption shows hydrocephalus. • Ballooning of frontal horns of lateral ventricles and third In this patient, a discontinuity is faintly visible between the ventricle, also known as “Mickey Mouse” ventricles — shunt catheter in the chest and abdomen (double arrow). © 2007 aqueductal obstruction Joshua Broder.

EBMedicine.net • December 2007 17 Emergency Medicine Practice® CT or MRI may be indicated if unenhanced CT is Neuroimaging In Syncope normal and suspicion remains of a structural lesion. Head CT is commonly obtained as part of the evalua- Febrile Seizures And Typical Recurrent Seizures tion of a patient with syncope, despite little evidence Neither emergent nor urgent neuroimaging is recom- supporting its use. Syncope is a brief, non-traumatic mended for patients with typical simple febrile loss of consciousness with loss of postural tone. Most seizure (Table 7) or recurrent seizures with typical syncope is due to global cerebral hypoperfusion, but features compared with the patient’s prior seizure the brain is generally the “victim” of syncope, not the history.100 cause. Syncope is rarely due to stroke, as loss of consciousness requires loss of blood flow to both Do complex febrile seizures require emergent neuroimaging? cerebral hemispheres or to the medullary reticular A recent study found that although 16% of children activating system in the brainstem. Studies of the presenting with new onset complex febrile seizure diagnostic yield of head CT performed for syncope had abnormal CT or MR findings, none required show little pathology clearly related to the syncope 103 emergent intervention (0%, 95% CI 0-4%).101 episode. In one retrospective study, 34% of patients presenting to a community ED underwent head CT, Do partial seizures suggest a focal structural brain abnor- with only one patient (0.7%) having the etiology mality and thus mandate imaging? identified by imaging (posterior circulation infarct).104 A study from South Africa in a region with a high A second retrospective study found that 283/649 incidence of tuberculosis and neurocysticercosis calls (44%) patients admitted with syncope at two commu- this tenet into question. This prospective cohort study nity teaching hospitals from 1994 to 1998 underwent of 118 children with new onset partial seizure found head CT, with five (2%) revealing an apparent causal abnormal CT scans in only eight (7%) patients, all of diagnosis; 10 patients underwent MRI without a whom were suspected prospectively of having the CT diagnosis of a cause of syncope. Utilization of head diagnosis. The investigators concluded that routine CT fell from 61% of syncope patients to 33% from scanning would require 11 scans and 5 courses of anti- 1994 to 1998, but diagnostic yield remained extremely 105 helminthic therapy to prevent one case of childhood low, under 1% for both groups. A prospective seizure disorder, versus no scans and 11 courses of observational study found a 39% rate of head CT in drug therapy if all seizure patients were empirically ED syncope patients at Harvard’s Beth Israel Dea- treated.102 Of course, this study is from a population coness Medical Center, with only 5% having head CT quite different from the U.S. population, and its abnormalities. That research group proposed that a results must be viewed in this context. decision rule for head CT in syncope might reduce utilization by 25-50%, although such a rule has not been prospectively validated (Table 8).106 Head CT may be warranted when the history and examination Table 6. Indications For Neuroimaging In Adult Patients With do not fully exclude other diagnoses such as seizure New Onset Seizure or stroke, or when trauma results from a syncope 107 • Recommended for all patients, even with return to episode. baseline neurological status • New focal deficits Neuroimaging Of Traumatic Brain Injury • Persistent altered mental status • Fever For evaluation of traumatic brain injury (TBI), non- • Trauma contrast CT remains the primary imaging modality. • Persistent headache Brain injuries can include traumatic subarachnoid • Cancer history hemorrhage, subdural hematoma, epidural • Anticoagulation hematoma, intraparenchymal hemorrhage, diffuse • AIDS or immunocompromise • Age older than 40 years axonal injury, and traumatic cerebral edema. Concur- rent injuries may include bony injuries such as skull Table 7. Simple Febrile Seizure (Neuroimaging Not Generally fracture. More rarely, head and neck trauma may Indicated) result in vascular dissection of the intracranial or extracranial arteries (carotid or vertebral), with • Three months to five years of age • Generalized • Duration < 15 min Table 8. Proposed Decision Rule For CT Head In Syncope, • Does not recur within 24 hours Not Yet Validated

Complex febrile seizure (neuroimaging may be indicated, though Head CT indicated only for patients with: recent studies suggest low risk of emergent intervention) • Signs or symptoms of neurologic disease, including • Less than three months or greater than five years of age headache • Focal, with or without secondary generalization • Trauma above the clavicles • Duration > 15 min • Coumadin use • Recur within 24 hours • Age > 60 years

Emergency Medicine Practice® 18 December 2007 • EBMedicine.net potential catastrophic neurological outcomes such as radiographs are obtained in approximately 20% of ischemic stroke. blunt head injury patients, a decrease from nearly 50% in the past.115 Some investigators have argued that Epidemiology Of Traumatic Brain Injury this diagnostic test may play a limited role when CT is The incidence of an acute intracranial injury seen on not available.116,117 CT following a “mild” TBI (GCS score 13-15) is approximately 6-9%, but not all detected injuries Clinical Decision Rules For Blunt Head Trauma result in a clinically meaningful change in manage- Clinical decision rules have been derived by several ment.108,109 Eight percent of patients in the derivation groups in the United States and Canada, with moder- phase of the Canadian CT Head Rule had potentially ate success. These rules differ in their definitions of important CT head findings, yet only 1% underwent a clinically significant injuries, the neurological neurosurgical intervention.109 The NEXUS-II study inclusion criteria (GCS, loss of consciousness, and enrolled 13,728 patients at 21 medical centers in the neurological examination), and the time from injury to United States, including all ED patients undergoing imaging. Table 10 compares the three rules, while head CT after blunt head trauma, regardless of GCS Tables 11-15 list the specific inclusion and exclusion or neurological examination. There was clinically criteria and specified outcomes of interest. In general, significant traumatic blunt head injury (prospectively the New Orleans Criteria seeks to identify any acute defined, Table 9) in 6.7-8.7%.110,111 For purposes of the intracranial injury, while NEXUS-II and the Canadian NEXUS-II study, a clinically significant traumatic CT Head Rule seek to identify injuries most likely to brain injury was defined based on prior research as an require neurosurgical intervention or to result in injury that may require neurosurgical intervention serious neurological deficits. It is a matter of debate (such as craniotomy, invasive ICP monitoring, or as to which definition is most appropriate. For mechanical ventilation) or an injury with potential for example, is it important to know of the existence of a rapid deterioration or long-term neurological dysfunc- traumatic brain injury that does not require neurosur- tion.112 Based on the NEXUS-II study, the average gical intervention in order to follow cognitive function emergency physician evaluating patients with a range long-term? Moreover, some clinical interventions may of GCS and neurological examination findings might not have truly been “needed,” but rather may have expect to find a potentially important head CT abnor- been driven by the judgment of individual physicians mality in between 1 in 20 and 1 in 10 patients in once they became aware of imaging findings. whom head CT was ordered after blunt trauma.110,111 Stiehl and collaborators in Canada showed a 6% incidence of head injuries in ED patients undergoing CT following blunt head injury, although they also Table 9. NEXUS II: Intracranial Injuries Considered demonstrated great heterogeneity in the ordering Significant practices of ED physicians, with 6.5-80% of patients • Mass effect or sulcal effacement with head trauma undergoing CT depending on the • Signs of herniation treating physician.113 A variety of decision rules have • Basal cistern compression or midline shift been investigated to target neuroimaging to patients • Substantial epidural or subdural hematomas (greater the with a high risk of intracranial injury. 1.0 cm in width or causing mass effect) • Substantial cerebral contusion (more than 1.0 cm in diameter Skull Films For Blunt Head Trauma or more than one site) • Extensive subarachnoid hemorrhage The ACEP clinical policy on altered mental status and • Hemorrhage in the posterior fossa mild blunt head trauma states that “plain films of the • Intraventricular hemorrhage skull have essentially no utility in [the emergent • Bilateral hemorrhage of any type evaluation of patients with altered mental status].”114 • Depressed or diastatic skull fracture Surprisingly, they are still widely used in international • Pneumocephalus • Diffuse cerebral edema emergency practice. In the United Kingdom, skull • Diffuse axonal injury

Table 10. A Comparison Of Three Clinical Decision Rules For Blunt Head Injury

GCS/Neurological Examination Time To Imaging Outcome Of Interest NEXUS-II Any GCS/any examination/with Within 24 hours of injury Clinically important traumatic injuries or without LOC† New Orleans Criteria LOC, GCS 15, normal Within 24 hours of injury Any intracranial injury neurological examination € Canadian CT Head Rule GCS 13-15 with LOC For patients with GCS < 15, Injuries requiring neurosurgical two hour post-injury observation intervention required to observe for improvement in GCS †LOC = loss of consciousness € Normal neuro examination = normal strength, sensation, and cranial nerves

EBMedicine.net • December 2007 19 Emergency Medicine Practice® New Orleans Criteria criticized for relative complexity, as well as for end- The New Orleans Criteria (Table 13) investigators points which might be considered unacceptable in sought a rule with 100% sensitivity, citing prior some medical practice settings, including the United surveys of emergency physicians indicating that a States, where fears of litigation might make it undesir- clinical decision rule with anything less than perfect able to miss any CT abnormality. Nonetheless, in sensitivity would be unacceptable. Their rule multiple validation studies and subanalyses, the rule achieved the sensitivity goal (100%, 95% CI 95-100%) appears to perform well in identifying patients who but with a low specificity (25%, 95% CI 22-28%).108 present with normal mental status but require emer- This rule has been challenged for its lack of specificity, gent neurosurgical intervention, including in U.S. 123 which might lead to increased utilization of CT for populations. Remarkably, despite numerous patients with no other indication for neuroimaging studies in multiple settings, emergency physician beyond headache, vomiting, or minor head and neck awareness of the rule remains low. A recent study trauma (such as facial abrasions). found that only 35% of U.S. emergency physicians were aware of the rule.124 Canadian CT Head Rule (CCHR) NEXUS II Rule The Canadian CT Head Rule (Table 14) found 100% sensitivity and 52% specificity for patients with blunt The NEXUS II investigators identified a decision rule trauma and a GCS 15.18,118-122 This rule has been with high sensitivity (98.3%, 95% CI 97.2-99.0%) but low specificity (13.7%, 95% CI 13.1-14.3%) for signifi- 110 Table 11. “Positive” CT Findings, New Orleans Criteria cant intracranial injury. This rule (Table 15) has limited clinical utility because it would mandate brain Any acute traumatic intracranial lesion CT in the majority of patients following blunt trauma • Subdural hematoma and thus might actually increase CT utilization when • Epidural hematoma • Parenchymal hematoma compared with current physician practice. Its clinical • Subarachnoid hemorrhage outcome benefit is uncertain — no study to date has • Cerebral contusion demonstrated whether application of the NEXUS II • Depressed skull fracture rule would identify important injuries that would otherwise have been missed. Another difficulty with Table 12. Outcomes, Canadian Head CT Rule Table 14. Canadian CT Head Rule* Primary Outcomes: Neurosurgical Intervention • Death within seven days secondary to head injury For patients with GCS 13 to 15 after witnessed traumatic loss of • Any of the following procedures within seven days: consciousness, CT is only required for patients with any one of the o Craniotomy following findings: o Elevation of skull fracture High Risk For Neurosurgical Intervention o Intracranial pressure monitoring 1. Glasgow Coma Scale score lower than 15 at two hours after o Intubation for head injury (demonstrated on CT) injury 2. Suspected open or depressed skull fracture Secondary Outcomes: Clinically Important Brain Injury On CT 3. Any sign of basal skull fracture† • Any acute brain finding revealed on CT that would normally 4. Two or more episodes of vomiting require admission to hospital and neurosurgical follow-up 5. 65 years or older • Not clinically important: o Patient was neurologically intact and had one of the Medium Risk For Brain Injury Detection By Computed following Tomographic Imaging (1) Solitary contusion of less than 5 mm in diameter 1. Amnesia before impact of 30 or more minutes (2) Localized subarachnoid blood less than 1 mm thick 2. Dangerous mechanism‡ (3) Smear subdural hematoma less than 4 mm thick *Exclusion criteria: no history of trauma, GCS < 13, age < 16 years, (4) Closed depressed skull fracture not through the warfarin use or coagulopathy, obvious open skull fracture. inner table †Signs of basal skull fracture include hemotympanum, raccoon eyes, cerebrospinal fluid, otorrhea or rhinorrhea, and Battle’s sign. Table 13. New Orleans Criteria ‡Dangerous mechanism is a pedestrian struck by a motor vehicle, an occupant ejected from a motor vehicle, or a fall from an Head CT is required for blunt trauma patients with loss of elevation of ≥ three feet or five stairs. consciousness, GCS 15, a normal neurological examination*, and any of the following: Table 15. Variables Associated With Significant Head Injury • Headache In NEXUS II • Vomiting • Age over 60 years 1. Evidence of significant skull fracture • Drug or alcohol intoxication 2. Scalp hematoma • Deficits in short-term memory 3. Neurologic deficit • Physical evidence of trauma above the clavicles 4. Altered level of alertness • Seizure 5. Abnormal behavior *Normal cranial nerves and normal strength and sensation in the 6. Coagulopathy (includes aspirin use) arms and legs, as determined by a physician on the patient’s 7. Persistent vomiting arrival at the emergency department 8. Age greater than 65 years

Emergency Medicine Practice® 20 December 2007 • EBMedicine.net this proposed rule is the potential variability in utilization or could actually increase utilization. application of terms such as “scalp hematoma” or Can We “Mix And Match” The Rules? “abnormal behavior” by different observers. In addition, coagulopathy – found to be a high risk It may be tempting to adopt a combination of features factor – included aspirin use, potentially increasing of the above decision rules in order to manufacture a the need for head imaging among patients who do not superior decision rule. Unfortunately, there is little otherwise appear at risk of brain injury. One impor- evidence to support this practice. The NEXUS investi- tant finding of NEXUS II is a lack of association gators and the New Orleans investigators tested a between several clinical variables which have tradi- variety of other combinations of clinical criteria 108,110 tionally been considered as potential markers of besides the final suggested rule. Eliminating significant clinical injury, including loss of conscious- criteria not surprisingly improved specificity but ness, seizure, severe headache, and vomiting. impaired sensitivity, and adding additional criteria improved sensitivity but impaired specificity. A rule External Validity Of Decision Rules For Blunt Head Trauma with large numbers of criteria fails the original The Canadian CT Head Rule and the New Orleans purpose of developing a clinical decision rule; it Criteria have been prospectively tested in other detects all injuries by mandating CT for all blunt head populations with less success; in Australia, the rules trauma patients. fail to exclude injury while reducing utilization.125 In Some Commonalities Among The Rules Britain, the CCHR would increase CT utilization and associated costs.126,127 In German populations, the An important take-home point for all of the decision rules appear to reduce utilization.128 A prospective rules described here is the notable absence of loss of Dutch study validated the high sensitivity of both consciousness alone as an indication for head CT. In rules but found that the New Orleans Criteria would each study, loss of consciousness was a required decrease utilization by only 3% and the CCHR by inclusion criterion, but in none of the studies did only 37.3%.119 These reductions in utilization are isolated loss of consciousness identify patients at risk smaller than the estimates from the original New of significant injury. Prior studies had shown little Orleans Criteria publication (20%)108 and CCHR (50- association between loss of consciousness and signifi- 129 70%).109 These findings reflect the existing practices in cant traumatic brain injury. In fact, neither NEXUS other countries; when baseline CT utilization for blunt II nor the Canadian CT Head Rule found post- head injury is low, the NEXUS, Canadian, and New traumatic headache to be an indication for head CT. Orleans rules may result in smaller decreases in The New Orleans Criteria did identify headache as a

Key Points For Imaging Of Acute Neurological Conditions

1. For stroke, CT is sensitive for ruling out these, not just for the presence or absence of hemorrhage. MRI may be even better for chronic hemorrhage. hemorrhage. 6. For patients presenting with apparent TIA, the 2. For cervical artery dissections, CTA and MRA risk of progression to stroke is high. Some have have similar high sensitivity and specificity. advocated admission, while others have recommended rapid outpatient evaluation. The 3. Following an episode of syncope, head CT is modifiable structural risk factors for stroke not routinely indicated unless head trauma is include carotid stenosis and cardiac defects. One suspected. The diagnostic yield of CT for imaging strategy from the emergency department syncope appears to be less than 1%. is imaging of the carotids (by CTA, ultrasound, or MRA), and echocardiography to evaluate cardiac 4. A negative non-contrast head CT is not widely causes of stroke. accepted to rule out subarachnoid hemorrhage without lumbar puncture. Although CT appears 7. Neuroimaging is not indicated for simple to be very sensitive, it is thought to become less febrile seizures or a single occurrence of the sensitive with elapsed time since symptom onset, typical seizure of a patient with prior seizure and the decline in sensitivity is not fully disorder. Imaging findings relevant to understood for new generation scanners. management are unlikely in this setting.

5. Extensive early ischemic changes, especially 8. Following blunt traumatic head injury, loss of those in an area greater than one-third of the consciousness alone is not an indication for middle cerebral artery territory, are a head CT. Clinical decision rules exist for contraindication to TPA administration. The selecting patients to forgo CT following closed radiologist should be specifically queried about head injury.

EBMedicine.net • December 2007 21 Emergency Medicine Practice® high-risk criterion, though a decision rule omitting “severe headache,” so emergency physicians must headache would have had 97% sensitivity in their scrupulously apply the rules if they expect the rules to derivation phase.108 Because the New Orleans investi- function as described in the original studies.130-134 gators desired 100% sensitivity, they did not further Decision Rules For Elderly validate such a rule. Single post-traumatic seizure also does not appear to be a high risk feature by the The elderly have a high rate of injury with few clinical 135 CCHR or NEXUS II; though, again, it is considered predictors. NEXUS-II found that the rate of high risk by the New Orleans Criteria. clinically significant injury in patients 65 years of age or older was 12.6%, compared with 7.8% in patients Decision Rules For Children under 65 years of age.111 The CCHR classifies patients Clinical decision rules for children following blunt greater than 65 years of age as high risk and therefore head injury have failed to perform well. In general, in need of imaging in the case of traumatic loss of acceptably high sensitivity in these studies comes at consciousness. the price of extremely low specificity, resulting in very Is A Repeated Head CT Required For Patients With Abnormal little reduction in the utilization of CT in pediatric Head CT After Blunt Trauma? populations. In fact, in some settings, application of these rules could actually increase utilization. These A wide range of reported progression in CT findings rules may also be very sensitive to the care with has been published, with few clear-cut indications for which they are applied; the NEXUS II rule, for exam- safely omitting repeat scan. A systematic review from ple, falls in sensitivity from approximately 99% to 2006 found that the range of reported progression of only 90% when the word “headache” is replaced with injury on repeat head CT varied from 8 to 67%, with

Risk Management Pitfalls For Neurological Conditions

1. Ruling out subarachnoid hemorrhage based on during non-contrast head CT is not considered to normal non-contrast head CT without lumbar pose significant fetal threat. The mother’s health puncture. Although some recent studies suggest is paramount. that modern CT scanners may be able to detect 7. Ruling out intracranial injury based on normal subarachnoid hemorrhage with extremely high skull films. Although skull films are still widely sensitivity, the sensitivity of CT is thought to used internationally, they are insensitive for decline with the passage of time, and lumbar intracranial injury and are not advised by the puncture is still recommended. American College of Emergency Physicians 2. Failure to obtain head CT after blunt head injury (ACEP). with loss of consciousness in an anticoagulated 8. Relying on a normal head CT to determine patient. The existing head CT clinical decision safety for lumbar puncture. Head CT may not rules for blunt trauma all exclude anticoagulated accurately estimate intracranial pressure. patients or classify them as high-risk for clinically Lumbar puncture may be contraindicated in significant injury. patients with examination evidence of high 3. Obtaining head CT in all patients with traumatic intracranial pressure, such as obtundation, even loss of consciousness. Traumatic loss of con- if CT appears normal. sciousness alone does not appear to be associated 9. Mistaking complex febrile seizure for simple with clinically significant head injury. febrile seizure. Simple febrile seizures are 4. Discharging a patient with TIA symptoms after a generalized, last less than 15 minutes, and do not normal head CT and without further diagnostic recur within 24 hours. Febrile seizures which are testing. Head CT is often normal in TIA, and a focal, last greater than 15 minutes, or recur substantial minority of TIA patients will progress within 24 hours are complex and may require to stroke in the 48 hours after symptoms. Addi- neuroimaging – although a recent study suggests tional imaging of the carotid arteries and heart are a very low rate of neuroimaging findings requir- advised. ing emergent intervention. 5. Administering TPA to patients with early 10. Relying on a point estimate of sensitivity when ischemic changes in greater than one-third of the 95% confidence intervals are wide. The point middle cerebral artery territory. The greater the estimate is frequently the value cited in an extent of early ischemic changes, the greater the abstract or manuscript conclusions, but the 95% risk of hemorrhage. Early ischemic changes of this confidence intervals provide best and worst case magnitude are associated with high risk of intrac- scenarios. A diagnostic test with a high point erebral hemorrhage, and TPA is contraindicated. estimate of sensitivity but confidence intervals 6. Advising a pregnant patient not to undergo from 60-100%, such as the ABCD score for TIA head CT for a suspected serious neurological progression to stroke, may have sensitivity as low condition. The radiation exposure to the fetus as 60%.

Emergency Medicine Practice® 22 December 2007 • EBMedicine.net resulting neurosurgical intervention in 0-54% of with MR substantially more sensitive for DAI.141 patients.136 The review’s authors cited a variety of Subsequent studies have often compared new MR explanations for this dramatic variability in study image sequences such as FLAIR (fluid attenuated outcomes, including selection bias, spectrum bias inversion recovery) and diffusion-weighted imaging (studies with more severely injured patients being to other MR sequences, using as a gold standard a more likely to show unfavorable outcomes), and poor clinical definition of DAI (loss of consciousness definitions of injury progression. Risk factors such as persisting greater than six hours after injury, no coagulopathy, poor GCS, and high overall injury hemorrhage on CT) plus imaging criteria (presence of severity appear to be associated with worsening CT white matter injury on MRI). This type of study, in abnormalities, but methodologic flaws in the studies which the gold standard or reference used to deter- reviewed make more specific recommendations mine the accuracy of the experimental test incorpo- impossible. Since the publication of that review, a rates that test, suffers from incorporation bias.142 prospective study of level I trauma center patients with an abnormal head CT addressed some of the Controversies And Cutting Edge issues raised by that review. The study stratified patients by GCS (mild: GCS 13-15; moderate: GCS 9- 12; and severe: GCS < 9) and indication for repeat CT Is Emergency Physician Reading Of Head CTs (routine versus indicated by neurological deteriora- Becoming A "Best Practice" In Emergency Care? tion). Among patients undergoing CT for neurologi- Head CT is rapid to obtain but delays in interpreta- cal deterioration, a medical or surgical intervention tion could result in adverse patient outcomes if followed CT in 38%. In contrast, among patients clinical treatment decisions cannot be made in a undergoing routine repeat CT, 1% underwent an timely fashion. Surveys of emergency medicine intervention – in both cases in patients with GCS < 9. residency programs suggest that, in many cases, The authors concluded that repeat CT is warranted in radiology interpretation is not rapidly available for any patient with neurological deterioration, and clinical decisions and that emergency physicians often routine repeat CT may be warranted among patients perform the initial interpretation of radiographic with GCS < 9. No interventions occurred in patients studies. A study simulating a teleradiology support with GCS 9 or higher undergoing routine head CT, system estimated the time to interpretation of a non- but this study is too small to conclude with certainty contrast head CT at 39 minutes, potentially wasting that routine repeat CT is never necessary in this precious time in patients with intracranial hemorrhage group.137 Other recent retrospective studies also or ischemic stroke.143 The ability of the on-scene suggest that routine repeat head CT is not likely to emergency physician to interpret the CT could be change clinical management in the absence of a extremely valuable. deteriorating neurological examination, but a larger prospective study will be needed to more stringently Can Emergency Physicians Accurately Interpret define those patients with abnormal CT after blunt Head CTs? 138 trauma in whom repeat CT can be deferred. Multiple studies have examined the ability of emer- What Is The Best Imaging Modality For Diffuse Axonal gency medicine residents and attending physicians to Injury? interpret head CTs. A 1995 study showed that, in an As the name implies, diffuse axonal injury (DAI) is EM residency program, although up to 24% of poten- damage to white matter tracts throughout the brain, tially significant CT abnormalities were not identified by the EM residents, only 0.6% of patients appear to thought to occur as the result of shearing from rapid 144 deceleration, often with a rotational component.139 have been mismanaged as a result. Studies have There is some debate as to the clinical scenarios in shown that substantial and sustained improvements in which this injury occurs, with some arguing that DAI interpretation ability can occur with brief training. is a feature only of severe injury while others suggest Perron et al showed an improvement from 60% to 78% accuracy after a two hour training session based on a it as a mechanism underlying post-concussive syn- 12 dromes in patients with normal CT.140 Studies in mnemonic, sustained at three months. In the setting patients with mild head injury are problematic, as it is of stroke, emergency medicine attendings perform unclear whether MR abnormalities are truly evidence relatively poorly in the recognition of both hemorrhage of CT-negative DAI or rather false-positive MR and early ischemic changes which may contraindicate findings. CT is generally thought to be poor in TPA administration, with accuracy of approximately detecting these changes, though a gold standard for 60%, but neurologists and general radiologists achieve only about 80% accuracy compared with the gold comparison is often lacking or limited to comparison 145,146 with MRI. A prospective study in 1988 compared CT standard interpretation by neuroradiologists. and MR for identification of blunt traumatic head Undoubtedly, improvements in training are needed, injuries, but advances in both modalities have ren- but the pragmatic limitations on the availability of dered its results invalid. A 1994 study found the subspecialist radiologists, even with teleradiology, modalities to be complementary for head trauma, mean that emergency physicians must become

EBMedicine.net • December 2007 23 Emergency Medicine Practice® proficient first-line readers of emergent CT. 5. The Nobel Prize in Physiology or Medicine 2003. 2003 [cited; Available from: http://nobelprize.org/nobel_prizes/medicine/laureates/2003/pres Case Conclusions s.html. (Nobel Organization webpage) 6. De Wilde, J.P., A.W. Rivers, and D.L. Price. A Review of the Current use of Magnetic Resonance Imaging in Pregnancy and Safety … the 75-year-old male with hemiplegia had greater Implications for the Fetus. Progress in Biophysics and Molecular than one-third of the MCA territory showing ischemic Biology. 2005;87(2-3):335-353. (Review and survey) 7. Shellock, F.G. and J.V. Crues. MR Procedures: Biologic Effects, changes. You held TPA and admitted the patient to the Safety, and Patient Care. Radiology. 2004;232(3):635-52. (Review) ICU where he experienced an intracranial hemorrhage in 8. Loewy, J., A. Loewy, and E.J. Kendall. Reconsideration of the region of his infarct. The neurologist commended you Pacemakers and MR Imaging. Radiographics. 2004;24(5):1257-1267. (Metaanalysis; 232 patients from prospective trials) for recognizing the patient’s risk of hemorrhage and the 9. Tope, W.D. and F.G. Shellock. Magnetic Resonance Imaging and family was grateful that you withheld thrombolysis. Permanent Cosmetics (Tattoos): Survey of Complications and Adverse Events. J Magn Reson Imaging. 2002;15(2):180-184. (Survey) … the 55-year-old male with syncope was reassured 10. Ratnapalan, S., M. Greenberg, and D. Armstrong. Tattoos and MRI. when you told him that he did not require a CT, given the Am. J. Roentgenol. 2004;183(2):541. (Case report) extremely low likelihood of abnormal findings. He was 11. Franiel, T., S. Schmidt, and R. Klingebiel. First-Degree Burns on MRI due to Nonferrous Tattoos. Am. J. Roentgenol. 2006;187(5):W556. admitted for telemetry and was found to have non-sus- (Case report) tained ventricular tachycardia as the cause of his event. 12. Perron, A.D., et al. A Multicenter Study to Improve Emergency Medicine Residents’ Recognition of Intracranial Emergencies on … the 19-year-old female with a thunderclap headache Computed Tomography. Ann Emerg Med. 1998;32(5):554-562. underwent lumbar puncture at your urging, since you (Prospective trial; 83 emergency medicine residents at 5 sites) recalled that the sensitivity of CT for SAH declines with 13. Broder, J. Midnight Radiology: Head CT Interpretation. emedhome.com. 2006. (Review) time. Her LP showed xanthochromia, and angiography 14. Broder, J., L.A. Fordham, and D.M. Warshauer. Increasing confirmed an aneurysm which was treated with endovascu- Utilization of Computed Tomography in the Pediatric Emergency lar coil placement. Department, 2000-2006. Emerg Radiol. 2007. (Retrospective study) 15. Reginald D. Williams II, A.R., and and J. Glaudemans. Pricing …the 20-year-old male with new onset seizure had a Variations in the Consumer Market for Diagnostic Imaging Services. completely normal, well documented, neurological exam, as Avalere Health LLC, CareCore National. December 2005. 16. American Hospital Directory. [cited; Available from: well as normal serum glucose and electrolytes. His history http://www.ahd.com/sample_outpatient.html did not reveal any potential etiologies for the event. A 17. Stein, S.C., M.G. Burnett, and H.A. Glick. Indications for CT decision to initiate anti-epileptic drug therapy will likely Scanning in Mild Traumatic Brain Injury: A Cost-effectiveness Study. J Trauma. 2006;61(3):558-566. (Cost effectiveness model) depend on the findings of a MRI and an EEG. Although he 18. Stiell, I.G., et al. The Canadian CT Head Rule for Patients with is at a relatively low risk for seizure recurrence, ACEP Minor Head Injury. The Lancet. 2001;357(9266):1391-1396. policy recommends neuroimaging for first-time seizure 19. Koller, C.J., J.P. Eatough, and A. Bettridge. Variations in radiation dose between the same model of multislice CT scanner at different patients and you decide to perform a CT since the scanner hospitals. Br J Radiol. 2003;76(911):798-802. (Prospective study is now available. comparing standard CT exam doses at 7 centers) 20. Brenner, D., et al. Estimated risks of radiation-induced fatal cancer … the 52-year-old male with transient loss of con- from pediatric CT. AJR Am J Roentgenol. 2001;176(2):289-296. sciousness after a collision was evaluated using the Cana- (

Emergency Medicine Practice® 24 December 2007 • EBMedicine.net 31. Patel, S.C., et al. Lack of clinical significance of early ischemic 50. Schulz, U.G., et al. Diffusion-weighted MRI in 300 patients changes on computed tomography in acute stroke. Jama. presenting late with subacute transient ischemic attack or minor 2001;286(22):2830-2838. (Interpretation, blinded to treatment arm; stroke. Stroke. 2004;35(11):2459-2465. (Prospective study; 300 616 CTs taken from the previously randomized NINDS trial) patients with acute TIA or minor stroke) 32. Tissue plasminogen activator for acute ischemic stroke. The 51. JM, U.K.-I., et al. Utility of an ultrafast magnetic resonance imaging National Institute of Neurological Disorders and Stroke rt-PA Stroke protocol in recent and semi-recent strokes.[see comment]. J Neurol, Study Group. N Engl J Med. 1995;333(24):1581-1587. (Multicenter & . 2005;76(7):1002-1005. (Prospective randomized placebo-controlled double blind trial, in 2 phases, 291 observational comparative study; 23 patients with suspected patient in phase 1 and 333 in phase 2) recent stroke) 33. Dzialowski, I., et al. Extent of early ischemic changes on computed 52. Kang, D.W., et al. MRI screening before standard tissue tomography (CT) before thrombolysis: prognostic value of the plasminogen activator therapy is feasible and safe. Stroke. Alberta Stroke Program Early CT Score in ECASS II. Stroke. 2005;36(9):1939-1943 2006;37(4):973-978. (Retrospective analysis of 800 patients 53. Fiebach, J.B., et al. Stroke magnetic resonance imaging is accurate in previously prospectively enrolled and randomized to rTPA or hyperacute intracerebral hemorrhage: a multicenter study on the placebo in ECASS II trial) validity of stroke imaging.[see comment]. Stroke. 2004;35(2):502-506. 34. Adams, H.P., Jr., et al. Guidelines for the early management of (Prospective multicenter comparative study of 6 image adults with ischemic stroke: a guideline from the American Heart interpreters; 124 patient cases) Association/American Stroke Association Stroke Council, Clinical 54. Kidwell, C.S., et al. Comparison of MRI and CT for detection of Council, Cardiovascular Radiology and Intervention acute intracerebral hemorrhage.[see comment]. JAMA. Council, and the Atherosclerotic Peripheral Vascular Disease and 2004;292(15):1823-1830 Quality of Care Outcomes in Research Interdisciplinary Working 55. Patel, M.R., R.R. Edelman, and S. Warach. Detection of hyperacute Groups: the American Academy of Neurology affirms the value of primary intraparenchymal hemorrhage by magnetic resonance this guideline as an educational tool for neurologists. Stroke. imaging. Stroke. 1996;27(12):2321-2324. (Retrospective; 35 patients 2007;38(5):1655-1711. (Peer-reviewed evidence-based consensus with MR for acute stroke within 6 hours of onset) guidelines) 56. Tatlisumak, T. Is CT or MRI the method of choice for imaging 35. FDA product labelling for Genetech Alteplase. 2002. (FDA product patients with acute stroke? Why should men divide if fate has labeling based on multiple studies) united?[see comment]. Stroke. 2002;33(9):2144-2145. (Editorial) 36. Sims, J.R., et al. Arterial occlusion revealed by CT angiography 57. FDA warning on gadolinium associated fatal nephrogenic systemic predicts NIH stroke score and acute outcomes after IV tPA fibrosis. 2006. (FDA warning based on case series) treatment. AJNR Am J Neuroradiol. 2005;26(2):246-251. (Retrospective 58. Chalela, J.A., et al. Magnetic resonance perfusion imaging in acute review of prospectively collected stroke data; 47 patients) ischemic stroke using continuous arterial spin labeling. Stroke. 37. Katz, D.A., et al. Circle of Willis: evaluation with spiral CT 2000;31(3):680-687. (Prospective observational study; 15 acute angiography, MR angiography, and conventional angiography. ischemic stroke patients) Radiology. 1995;195(2):445-449. (Prospective blinded comparative 59. Neumann-Haefelin, T., et al. Diffusion- and perfusion-weighted study; 17 patients) MRI. The DWI/PWI mismatch region in acute stroke. Stroke. 38. Hunter, G.J., et al. Assessment of cerebral perfusion and arterial 1999;30(8):1591-1597. (Prospective observational study; 20 patients anatomy in hyperacute stroke with three-dimensional functional CT: with acute stroke) early clinical results.[see comment]. AJNR Am J Neuroradiol. 60. Sorensen, A.G., et al. Hyperacute stroke: simultaneous measurement 1998;19(1):29-37. (Prospective observational study of 22 patients of relative cerebral blood volume, relative cerebral blood flow, and with suspected acute stroke) mean tissue transit time. Radiology. 1999;210(2):519-527 39. Wintermark, M., et al. Comparison of admission perfusion 61. Rordorf, G., et al. Regional ischemia and ischemic injury in patients computed tomography and qualitative diffusion- and perfusion- with acute middle cerebral artery stroke as defined by early weighted magnetic resonance imaging in acute stroke patients.[see diffusion-weighted and perfusion-weighted MRI. Stroke. comment]. Stroke. 2002;33(8):2025-2031. (Prospective observational 1998;29(5):939-943 study; 13 patients) 62. Beaulieu, C., et al. Longitudinal magnetic resonance imaging study 40. Grotta, J.C., et al. Agreement and variability in the interpretation of of perfusion and diffusion in stroke: evolution of lesion volume and early CT changes in stroke patients qualifying for intravenous rtPA correlation with clinical outcome.[see comment]. Annals of therapy.[see comment]. Stroke. 1999;30(8):1528-1533 Neurology. 1999;46(4):568-578. (Prospective longitudinal 41. Teasdale, G.M., et al. Comparison of magnetic resonance imaging observational study; 21 stroke patients at 5 time points) and computed tomography in suspected lesions in the posterior 63. Lovblad, K.O. Diffusion-weighted MRI: back to the cranial fossa.BMJ. 1989;299(6695):349-355. (Randomized future.[comment]. Stroke. 2002;33(9):2204-2205. (Editorial and prospective study; 1020 patients) review) 42. Michel, P. and J. Bogousslavsky. Penumbra is brain: no excuse not to 64. Fiehler, J., et al. Are there time-dependent differences in diffusion perfuse.[comment]. Annals of Neurology. 2005;58(5):661-663. and perfusion within the first 6 hours after stroke onset? Stroke. (Editorial) 2004;35(9):2099-2104. (Retrospective study; 112 patients with acute 43. Kilpatrick, M.M., et al. CT-based assessment of acute stroke: CT, CT ischemic stroke) angiography, and xenon-enhanced CT cerebral blood flow.[see 65. Hacke, W., et al. The Desmoteplase in Acute Ischemic Stroke Trial comment]. Stroke. 2001;32(11):2543-2549 (DIAS): a phase II MRI-based 9-hour window acute stroke 44. Ezzeddine, M.A., et al. CT angiography with whole brain perfused thrombolysis trial with intravenous desmoteplase. Stroke. blood volume imaging: added clinical value in the assessment of 2005;36(1):66-73. (Placebo-controlled, double-blind, randomized, acute stroke. Stroke. 2002;33(4):959-966. (Comparative study of dose-finding phase II trial; 104 patients) radiologist interpretations of imaging studies; 40 patients) 66. Sobesky, J., et al. Does the mismatch match the penumbra? Magnetic 45. Levatter, R.E. Radiation risk of body CT: what to tell our patients resonance imaging and positron emission tomography in early and other questions. Radiology. 2005;234(3):968-970 ischemic stroke. Stroke. 2005;36(5):980-985. (Prospective study; 13 46. Warach, S., et al. Acute human stroke studied by whole brain echo stroke patients) planar diffusion-weighted magnetic resonance imaging. Annals of 67. D’Onofrio, M., et al. Doppler ultrasound and contrast-enhanced Neurology. 1995;37(2):231-241. (Prospective study; 40 patients) magnetic resonance angiography in assessing carotid artery 47. Gonzalez, R.G., et al. Diffusion-weighted MR imaging: diagnostic stenosis. Radiol Med (Torino). 2006;111(1):93-103. (Prospective accuracy in patients imaged within 6 hours of stroke symptom comparative study; 32 patients) onset. Radiology. 1999;210(1):155-162 68. Johnson, M.B., et al. Comparison of Doppler ultrasound, magnetic 48. Fiebach, J.B., et al. CT and diffusion-weighted MR imaging in resonance angiographic techniques and catheter angiography in randomized order: diffusion-weighted imaging results in higher evaluation of carotid stenosis. Clin Radiol. 2000;55(12):912-920. accuracy and lower interrater variability in the diagnosis of (Prospective comparative study; 40 patients with symptomatic hyperacute ischemic stroke.[see comment]. Stroke. 2002;33(9):2206- carotid stenosis) 2210. (Prospective randomized trial; 54 consecutive stroke and TIA 69. Alexandrov, A.V., et al. Yield of transcranial Doppler in acute patients) cerebral ischemia. Stroke. 1999;30(8):1604-1609. (Prospective study; 49. Lee, L.J., et al. Impact on stroke subtype diagnosis of early 130 patients) diffusion-weighted magnetic resonance imaging and magnetic 70. Gao, S., et al. Microembolic signal predicts recurrent cerebral resonance angiography. Stroke. 2000;31(5):1081-1089. (Retrospective ischemic events in acute stroke patients with middle cerebral artery review of registry data; 46 consecutive patients with acute stenosis. Stroke. 2004;35(12):2832-2836. (Prospective observational ischemic stroke) study; 114 consecutive acute ischemic stroke patients)

EBMedicine.net • December 2007 25 Emergency Medicine Practice® 71. Saqqur, M., et al. Derivation of transcranial Doppler criteria for 95. Clinical policy: Critical issues in the evaluation and management of rescue intra-arterial thrombolysis: multicenter experience from the adult patients presenting to the emergency department with Interventional Management of Stroke study. Stroke. 2005;36(4):865- seizures. Ann Emerg Med. 2004;43(5):605-625. (Evidence-based 868. (Observational study; 29 patient subgroup in prospective consensus guidelines) Interventional Management of Stroke study) 96. Henneman, P.L., F. DeRoos, and R.J. Lewis. Determining the need 72. Siegel, R.J. Ultrasound augmentation of thrombolysis and tissue for admission in patients with new-onset seizures. Ann Emerg Med. perfusion. Clin Physiol Funct Imaging. 2004;24(3):156-163. (Review) 1994;24(6):1108-1114. (Retrospective review; 325 emergency 73. Grolimund, P., et al. Evaluation of cerebrovascular disease by department patients with new onset seizure) combined extracranial and transcranial Doppler sonography. 97. Tardy, B., et al. Adult first generalized seizure: etiology, biological Experience in 1,039 patients. Stroke. 1987;18(6):1018-1024. tests, EEG, CT scan, in an ED. Am J Emerg Med. 1995;13(1):1-5. (Retrospective study; 1,039 ultrasound examinations) (Retrospective review; 247 patients over 3 years) 74. Camerlingo, M., et al. Transcranial Doppler in acute ischemic stroke 98. Earnest, M.P., et al. Intracranial lesions shown by CT scans in 259 of the middle cerebral artery territories. Acta Neurologica cases of first alcohol-related seizures. Neurology. 1988;38(10):1561- Scandinavica. 1993;88(2):108-111. (Prospective study; 48 patients 1565. (Study of 259 apparent alcohol-related seizures) with acute ischemic stroke) 99. Pesola, G.R. and R.E. Westfal. New-onset generalized seizures in 75. Iannuzzi, A., et al. Ultrasonographic correlates of carotid patients with AIDS presenting to an emergency department. Acad in transient ischemic attack and stroke. Stroke. Emerg Med. 1998;5(9):905-911. (Retrospective review; 26 HIV 1995;26(4):614-619. (Retrospective analysis; 242 stroke and 336 positive patients and 120 HIV negative patients with new-onset transient ischemic attack (TIA) patients) seizures) 76. Razumovsky, A.Y., et al. TCD, MRA and MRI in acute cerebral 100. Greenberg, M.K., W.G. Barsan, and S. Starkman. Neuroimaging in ischemia. Acta Neurologica Scandinavica. 1999;99(1):65-76. the emergency patient presenting with seizure. Neurology. (Prospective comparative study; 30 patients) 1996;47(1):26-32. (Evidence-based consensus guidelines/practice 77. Flint, A.C., et al. Mechanical Thrombectomy of Intracranial Internal parameter) Carotid Occlusion: Pooled Results of the MERCI and Multi MERCI 101. Teng, D., et al. Risk of intracranial pathologic conditions requiring Part I Trials. Stroke. 2007;38(4):1274-1280. (Prospective emergency intervention after a first complex febrile seizure episode interventional study; 80 patients) among children. . 2006;117(2):304-308. (Retrospective 78. Biondi, A., et al. Fatal hemorrhagic complication following review of prospectively collected data; 71 pediatric patients) endovascular treatment of a cerebral arteriovenous malformation.J 102. Swingler, G.H., A.T. Westwood, and K. Iloni. The utility of Neuroradiol. 2006;33(2):96-104. (Case report and review) computed tomography for recent-onset partial seizures in 79. Sames, T.A., et al. Sensitivity of new-generation computed childhood. S Afr Med J. 2006;96(9 Pt 2):941-944. (Prospective cohort tomography in subarachnoid hemorrhage. Acad Emerg Med. study; 94 patients) 1996;3(1):16-20. (Retrospective chart review; 181 patients) 103. Goyal, N., et al. The utility of head computed tomography in the 80. Boesiger, B.M. and J.R. Shiber. Subarachnoid hemorrhage diagnosis emergency department evaluation of syncope. Intern Emerg Med. by computed tomography and lumbar puncture: Are fifth 2006;1(2):148-150. (Retrospective review; 117 patients undergoing generation CT scanners better at identifying subarachnoid head CT for syncope) hemorrhage? J Emerg Med. 2005;29(1):23-27. (Retrospective chart 104. Giglio, P., et al. Syncope and head CT scans in the emergency review; 177 patients) department. Emergency Radiology. 2005;12(1):44-46. (Retrospective 81. Linn, F.H.H., et al. Prospective study of sentinel headache in review; 128 patients) aneurysmal subarachnoid haemorrhage. The Lancet. 105. Pires, L.A., et al. Diagnostic patterns and temporal trends in the 1994;344(8922):590-593. (Prospective observational study; 148 evaluation of adult patients hospitalized with syncope. Arch Intern patients) Med. 2001;161(15):1889-1895. (Retrospective review; 649 patients) 82. Suarez, J.I., R.W. Tarr, and W.R. Selman. Aneurysmal Subarachnoid 106. Grossman, S.A., et al. The yield of head CT in syncope: a pilot Hemorrhage. N Engl J Med. 2006;354(4):387-396. (Review) study. Intern Emerg Med. 2007;2(1):46-49 83. Perry, J.J., et al. Attitudes and Judgment of Emergency Physicians in 107. Kapoor, W.N. Evaluation and outcome of patients with syncope. the Management of Patients with Acute Headache. Acad Emerg Med. Medicine (Baltimore). 1990;69(3):160-175. (Retrospective study; 433 2005;12(1):33-37. (Prospective cohort study; 51 physicians treating syncope patients) 747 patients) 108. Haydel, M.J., et al. Indications for computed tomography in patients 84. Storrow, A.B., et al. Aneurysmal Subarachnoid Hemorrhage. N Engl with minor head injury. N Engl J Med. 2000;343(2):100-105. J Med. 2006;354(16):1755-1757. (Review) (Retrospective derivation (520 patients) and validation (909 85. Brisman, J.L., J.K. Song, and D.W. Newell. Cerebral Aneurysms.N patients) of a clinical decision rule) Engl J Med. 2006;355(9):928-939. (Review) 109. Stiell, I.G., et al. The Canadian CT Head Rule for patients with 86. Unruptured intracranial aneurysms—risk of rupture and risks of minor head injury. Lancet. 2001;357(9266):1391-1396. (Prospective surgical intervention. International Study of Unruptured study; 3121 patients) Intracranial Aneurysms Investigators. N Engl J Med. 110. Mower, W.R., et al. Developing a decision instrument to guide 1998;339(24):1725-1733. (Two part observational study, computed tomographic imaging of blunt head injury patients. J retrospective and prospective phases; 2621 patients at 53 Trauma. 2005;59(4):954-959. (Prospective observational study; 13,728 participating centers in the United States, Canada, and Europe) patients) 87. Wiebers, D.O., et al. Unruptured intracranial aneurysms: natural 111. Holmes, J.F., et al. Epidemiology of blunt head injury victims history, clinical outcome, and risks of surgical and endovascular undergoing ED cranial computed tomographic scanning. Am J treatment. Lancet. 2003;362(9378):103-110. (Prospective study; 4060 Emerg Med. 2006;24(2):167-173. (Prospective, multicenter, patients) observational study; 13728 ED patients undergoing cranial CT 88. Carstairs, S.D., et al. Computed Tomographic Angiography for the after blunt head injury) Evaluation of Aneurysmal Subarachnoid Hemorrhage. Acad Emerg 112. Atzema, C., et al. Defining “therapeutically inconsequential” head Med. 2006;13(5):486-492. (Prospective observational study; 131 computed tomographic findings in patients with blunt head trauma. patients) Annals of Emergency Medicine. 2004;44(1):47-56. (Prospective 89. Lee, V.H., et al. Incidence and outcome of cervical artery dissection: observational study; 8,374 patients at 18 US medical centers) a population-based study. Neurology. 2006;67(10):1809-1812 113. Stiell, I.G., et al. Variation in ED Use of Computed Tomography for 90. Schievink, W.I., B. Mokri, and J.P. Whisnant. Internal carotid artery Patients With Minor Head Injury. Annals of Emergency Medicine. dissection in a community. Rochester, Minnesota, 1987-1992. Stroke. 1997;30(1):14-22. (Retrospective review; 1,699 adult patients) 1993;24(11):1678-1680 114. Clinical policy for the initial approach to patients presenting with 91. Dziewas, R., et al. Cervical artery dissection—clinical features, risk altered mental status. Ann Emerg Med. 1999;33(2):251-281. (Best- factors, therapy and outcome in 126 patients. J Neurol. evidence practice guideline) 2003;250(10):1179-1184. (Retrospective study; 126 patients) 115. Mossop, D. and S. Soysa. The use of skull X-rays in head injury in 92. Elijovich, L., et al. The emerging role of multidetector row CT the emergency department—a changing practice. Ann R Coll Surg angiography in the diagnosis of cervical arterial dissection: Engl. 2005;87(3):188-190. (Retrospective chart review; 278 patients) preliminary study. Neuroradiology. 2006;48(9):606-612. (Review and 116. Andronikou, S., et al. Skull fracture as a herald of intracranial retrospective study; 7 patients using multislice CTA) abnormality in children with mild head injury: Is there a role for 93. Eide, P.K. The relationship between intracranial pressure and size of skull radiographs? Australasian Radiology. 2003;47(4):381-385. cerebral ventricles assessed by computed tomography. Acta (Retrospective review; 381 patients) Neurochirurgica. 2003;145(3):171-179. (Retrospective study; 184 117. Windolf, J., et al. [Roentgen studies of the skull in head injuries—a patients) multicenter study]. Unfallchirurgie. 1992;18(1):10-18. (Multicenter 94. Zorc, J.J., et al. Radiographic evaluation for suspected cerebrospinal prospective observational study) fluid shunt obstruction. Pediatr Emerg Care. 2002;18(5):337-340. (Retrospective study; 233 patients)

Emergency Medicine Practice® 26 December 2007 • EBMedicine.net 118. Clement, C.M., et al. Clinical Features of Head Injury Patients 140. Mittl, R.L., et al. Prevalence of MR evidence of diffuse axonal injury Presenting With a Glasgow Coma Scale Score of 15 and Who in patients with mild head injury and normal head CT findings. Require Neurosurgical Intervention. Annals of Emergency Medicine. AJNR Am J Neuroradiol. 1994;15(8):1583-1589. (Prospective study; 20 2006;48(3):245-251. (Retrospective nested cohort study; 4551 consecutive patients with normal head CT and GCS 13-15) patients from the CCHR study) 141. Gentry, L.R., et al. Prospective comparative study of intermediate- 119. Smits, M., et al. External validation of the Canadian CT Head Rule field MR and CT in the evaluation of closed head trauma. AJR Am J and the New Orleans Criteria for CT scanning in patients with Roentgenol. 1988;150(3):673-682. (Prospective comparative study; 40 minor head injury. JAMA. 2005;294(12):1519-1525. (Prospective closed head trauma patients) study; 3181 patients) 142. Ezaki, Y., et al. Role of Diffusion-Weighted Magnetic Resonance 120. Stiell, I.G., et al. Comparison of the Canadian CT Head Rule and the Imaging in Diffuse Axonal Injury. Acta Radiologica. 200647(7):733- New Orleans Criteria in Patients With Minor Head Injury. JAMA. 740. (Prospective study; 21 DAI patients) 2005;294(12):1511-1518. (Prospective cohort study; 2707 adult 143. Kalyanpur, A., et al. Emergency radiology coverage: technical and patients) clinical feasibility of an international teleradiology model. Emerg 121. Stiell, I.G., et al. Canadian CT head rule study for patients with Radiol. 2003;10(3):115-118. (Prospective study; 102 consecutive ED minor head injury: methodology for phase II (validation and patients undergoing head CT 11pm to 7am) economic analysis). Annals of Emergency Medicine. 2001;38(3):317-322. 144. Alfaro, D., et al. Accuracy of Interpretation of Cranial Computed (Methodology description) Tomography Scans in an Emergency Medicine Residency Program. 122. Stiell, I.G., et al. The canadian CT head rule study for patients with Annals of Emergency Medicine. 1995;25(2):169-174. (Prospective minor head injury: Rationale, objectives, and methodology for phase observational cohort study; 555 patients) I (derivation). Annals of Emergency Medicine. 2001;38(2):160-169. 145. Schriger, D.L., et al. Cranial computed tomography interpretation in (Methodology description) acute stroke: physician accuracy in determining eligibility for 123. Papa, L., et al. Sensitivity and Specificity of the Canadian CT Head thrombolytic therapy. JAMA. 1998;279(16):1293-1297. (Prospective Rule and the New Orleans Criteria in a US Trauma Center. Acad study; 103 physicians interpreting head CT) Emerg Med. 2007;14(5 Suppl 1):S46-47. (Prospective observational 146. Kalafut, M.A., et al. Detection of early CT signs of >1/3 middle cohort study; 314 patients) cerebral artery infarctions : interrater reliability and sensitivity of CT 124. Eagles, D., et al. An International Survey of Emergency Physicians interpretation by physicians involved in acute stroke care. Stroke. Knowledge, Use, and Attitudes Towards the Canadian CT Head 2000;31(7):1667-1671. (Prospective study of interpretations of Rule. Acad Emerg Med. 2007;14(5 Suppl 1):S86. (Survey of noncontrast CT by 3 neuroradiologists) international emergency physicians) 125. Rosengren, D., et al. The application of North American CT scan criteria to an Australian population with minor head injury. Emerg Med Australas. 2004;16(3):195-200. (Retrospective chart review; 240 CME Questions patients) 126. Boyle, A., L. Santarius, and C. Maimaris. Evaluation of the impact of the Canadian CT head rule on British practice. Emerg Med J. 1. A patient presents with symptoms and signs of 2004;21(4):426-428. (Retrospective review; 1489 patients) 127. Sultan, H.Y., et al. Application of the Canadian CT head rules in ischemic stroke. Early ischemic changes in what managing minor head injuries in a UK emergency department: portion of the middle cerebral artery distribution implications for the implementation of the NICE guidelines. Emerg contraindicate TPA? Med J. 2004;21(4):420-425. (Before and after observational study; 597 patients) a. Early ischemic changes do not contraindicate 128. Schlegel, P.M., et al. [Is the Canadian CT head rule for minor head TPA administration injury applicable for patients in Germany?]. Rofo. 2005;177(6):872- 876. (Retrospective study; 122 patients) b. > 33% 129. Falimirski, M.E., et al. The need for head computed tomography in c. > 25% patients sustaining loss of consciousness after mild head injury.J d. > 10% Trauma. 2003;55(1):1-6. (Prospective observational study; 331 patients) e. Any early ischemic change 130. Haydel, M.J. and A.D. Shembekar. Prediction of intracranial injury in children aged five years and older with loss of consciousness 2. A patient presents with sudden onset of headache after minor head injury due to nontrivial mechanisms. Annals of three days prior. Non-contrast head CT is normal. Emergency Medicine. 2003;42(4):507-514. (Prospective study; 175 patients) Subarachnoid hemorrhage can be ruled out: 131. Palchak, M.J., et al. A decision rule for identifying children at low a. After a negative lumbar puncture risk for brain injuries after blunt head trauma. Annals of Emergency Medicine. 2003;42(4):492-506. (Prospective observational cohort; b. Based on the CT findings 1271 patients) c. After CT angiography 132. Greenes, D.S. Decisionmaking in pediatric minor head trauma. d. After conventional angiography Annals of Emergency Medicine. 2003;42(4):515-518. (Editorial) 133. Simon, B., et al. Pediatric minor head trauma: indications for e. After MR angiography computed tomographic scanning revisited. J Trauma. 2001;51(2):231- 237. (Retrospective review; 429 pediatric trauma patients) 3. A patient presents with a GCS 15 after blunt head 134. Oman, J.A., et al. Performance of a decision rule to predict need for trauma. According to the Canadian CT Head computed tomography among children with blunt head trauma. Pediatrics. 2006;117(2):e238-246. (Nested cohort study from Rule, CT is indicated if: prospective observational multicenter study; 1666 children) a. Loss of consciousness occurred 135. Mack, L.R., et al. The use of head computed tomography in elderly b. A severe headache is present patients sustaining minor head trauma. J Emerg Med. 2003;24(2):157- 162. (Retrospective review; 133 patients) c. A single posttraumatic seizure occurred 136. Wang, M.C., et al. Utility of repeat head computed tomography after d. Persistent vomiting is present blunt head trauma: a systematic review. J Trauma. 2006;61(1):226-233. (Systematic review) e. The patient is greater than 50 years of age 137. Brown, C.V., et al. Indications for routine repeat head computed tomography (CT) stratified by severity of traumatic brain injury. J 4. A simple febrile seizure does not require Trauma. 2007;62(6):1339-1344. (Prospective study; 241 patients neuroimaging. Features of simple febrile seizures undergoing repeat CT after an abnormal brain CT for blunt trauma) include all of the following EXCEPT: 138. Smith, J.S., et al. The role of early follow-up computed tomography a. Age three months to five years imaging in the management of traumatic brain injury patients with b. Generalized seizure intracranial hemorrhage. J Trauma. 2007;63(1):75-82. (Retrospective review; 116 blunt head trauma patients) c. Duration < 15 minutes 139. Gadda, D., et al. Traumatic lesions of corpus callosum: early d. No recurrence within 24 hours multidetector CT findings. Neuroradiology. 2004;46(10):812-816. (Retrospective review; 3 patients) e. Preceding history of seizure

EBMedicine.net • December 2007 27 Emergency Medicine Practice® 5. A patient presents with syncope. When should Physician CME Information

head CT be ordered? Date of Original Release: December 1, 2007. Date of most recent review: a. When head trauma is suspected November 8, 2007. Termination date: December 1, 2010. Accreditation: This activity has been planned and implemented in accordance b. When other diagnoses such as stroke or with the Essentials and Standards of the Accreditation Council for Continuing seizure are suspected Medical Education (ACCME) through the joint sponsorship of Mount Sinai School of Medicine and Emergency Medicine Practice. The Mount Sinai School c. In every patient with syncope of Medicine is accredited by the ACCME to provide continuing medical d. Answers a and b education for physicians. Credit Designation: The Mount Sinai School of Medicine designates this e. Head CT should not be ordered for evaluation educational activity for a maximum of 48 AMA PRA Category 1 Credit(s)™ per year. Physicians should only claim credit commensurate with the extent of their of syncope participation in the activity. ACEP Accreditation: Emergency Medicine Practice is approved by the American 6. Non-contrast head CT may detect early ischemic College of Emergency Physicians for 48 hours of ACEP Category 1 credit per annual subscription. changes in stroke within: AAFP Accreditation: Emergency Medicine Practice has been reviewed and is a. 3 hours acceptable for up to 48 Prescribed credits per year by the American Academy of Family Physicians. AAFP Accreditation begins August 1, 2006. Term of b. 6 hours approval is for two years from this date. Each issue is approved for 4 Prescribed credits. Credits may be claimed for two years from the date of this c. 8 hours issue. d. 12 hours AOA Accreditation: Emergency Medicine Practice has been approved for 48 e. 24 hours Category 2B credit hours per year by the American Osteopathic Association. Needs Assessment: The need for this educational activity was determined by a survey of medical staff, including the editorial board of this publication; review 7. In stroke, MRI with comparison of DWI and PWI of morbidity and mortality data from the CDC, AHA, NCHS, and ACEP; and evaluation of prior activities for emergency physicians. sequences may allow identification of the Target Audience: This enduring material is designed for emergency medicine ischemic penumbra with what potential clinical physicians, physician assistants, nurse practitioners, and residents. advantage? Goals & Objectives: Upon completion of this article, you should be able to: (1) demonstrate medical decision-making based on the strongest clinical evidence; a. Extension of the window for thrombolytic (2) cost-effectively diagnose and treat the most critical ED presentations; and therapy (3) describe the most common medicolegal pitfalls for each topic covered. Discussion of Investigational Information: As part of the newsletter, faculty may b. Triage to ICU or floor status be presenting investigational information about pharmaceutical products that is outside Food and Drug Administration approved labeling. Information presented c. Identification of patients with possible TIA as part of this activity is intended solely as continuing medical education and is not intended to promote off-label use of any pharmaceutical product. d. Measurement of intracranial pressure Disclosure of Off-Label Usage: This issue of Emergency Medicine Practice e. Decreased hospital length of stay discusses no off-label use of any pharmaceutical product. Faculty Disclosure: It is the policy of Mount Sinai School of Medicine to ensure objectivity, balance, independence, transparency, and scientific rigor in all CME- 8. The ACEP clinical policy for adult ED patients sponsored educational activities. All faculty participating in the planning or with new-onset seizure and return to baseline implementation of a sponsored activity are expected to disclose to the audience any relevant financial relationships and to assist in resolving any neurological status recommends neuroimaging conflict of interest that may arise from the relationship. Presenters must also make a meaningful disclosure to the audience of their discussions of unlabeled for: or unapproved drugs or devices. a. Fever In compliance with all ACCME Essentials, Standards, and Guidelines, all faculty for this CME activity were asked to complete a full disclosure statement. The b. Immunocompromise information received is as follows: Dr. Broder, Dr. Preston, Dr. Chan, and Dr. Perron report no significant financial interest or other relationship with the c. Age greater than 50 years manufacturer(s) of any commercial product(s) discussed in this educational d. History of anticoagulation presentation. e. All patients Method of Participation: • Print Subscription Semester Program: Paid subscribers with current and valid licenses in the United States who read all CME articles during each Emergency Medicine Practice six-month testing period, complete the post-test and the Subscribers: CME Evaluation Form distributed with the June and December issues, and return it according to the published instructions are eligible for up to 4 hours of CME credit for each issue. You must complete both the post test and CME Your subscription includes free online access and Evaluation Form to receive credit. Results will be kept confidential. CME 48 AMA/ ACEP Category 1, AAFP Prescribed, or certificates will be delivered to each participant scoring higher than 70%. • Online Single-Issue Program: Current, paid subscribers with current and valid AOA Category 2B CME credits per year, plus 144 licenses in the United States who read this Emergency Medicine Practice CME article and complete the online post-test and CME Evaluation Form at additional credits online. EBMedicine.net are eligible for up to 4 hours of Category 1 credit toward the AMA Physician’s Recognition Award (PRA). You must complete both the post- test and CME Evaluation Form to receive credit. Results will be kept You can now take the CME quizzes, view the confidential. CME certificates may be printed directly from the Web site to each correct answers, submit feedback, and print your participant scoring higher than 70%. Hardware/Software Requirements: You will need a Macintosh or PC to access certificates instantly upon passing online at the online archived articles and CME testing. Adobe Reader is required to view www.ebmedicine.net/redirect. the PDFs of the archived articles. Adobe Reader is available as a free download at www.adobe.com.

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CEO: Robert Williford President and Publisher: Stephanie Williford Director of Member Services & Continuing Education: Liz Alvarez Direct all editorial or subscription-related questions to EB Medicine: 1-800-249-5770 • Fax: 1-770-500-1316 • Non-U.S. subscribers, call: 1-678-366-7933 5550 Triangle Parkway, Suite 150 • Norcross, GA 30092 E-mail: [email protected] • Web Site: EBMedicine.net Emergency Medicine Practice (ISSN Print: 1524-1971, ISSN Online: 1559-3908) is published monthly (12 times per year) by EB Practice, LLC, 5550 Triangle Parkway, Suite 150, Norcross, GA 30092. Opinions expressed are not necessarily those of this publication. Mention of products or services does not constitute endorsement. This publication is intended as a general guide and is intended to supplement, rather than substitute, professional judgment. It covers a highly technical and complex subject and should not be used for making specific medical decisions. The materials contained herein are not intended to establish policy, procedure, or standard of care. Emergency Medicine Practice is a trademark of EB Practice, LLC. Copyright © 2007 EB Practice, LLC. All rights reserved. No part of this publication may be reproduced in any format without written consent of EB Practice, LLC. Individual subscription price: $299, Institutional subscription price: $899 U.S. funds. (Call for international shipping prices.)

Emergency Medicine Practice® 28 December 2007 • EBMedicine.net