Neuroleptic Malignant Syndrome

Written by: Maren Leibowitz, MD (NUEM ‘23) Edited by: Nick Wleklinski, MD (NUEM ‘22)
Expert Commentary by: Zachary Schmitz, MD (NUEM '21)

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Expert Commentary

This is an awesome, focused review of neuroleptic malignant syndrome (NMS). NMS is hard to diagnose because it's rare. There is no gold standard with respect to its definition, and it requires a medication history (which we typically don't do very well in the emergency department). A tricky cause of NMS is the removal of a dopamine agonist. For this reason, carbidopa/levodopa should never be discontinued during hospital admission - or ED boarding. [1]

Supportive care is more important than antidotal therapy during NMS management. The most acute cause of death from NMS is hyperthermia, which is induced both by D2 receptor antagonism leading to rigidity and impaired thermoregulation from the striatum and hypothalamus. Any life-threatening hyperthermia should be treated immediately with an ice bath.[2] Rigidity will lead to rhabdomyolysis with subsequent hyperkalemia and myoglobin-induced renal failure. Therefore, fluid resuscitation and maintenance are important. Profound immobility can precipitate DVT, so anticoagulation may be necessary.

In terms of pharmacotherapy, benzodiazepines are universally used. Dantrolene inhibits calcium-mediated muscle contraction to reduce muscle rigidity. However, it doesn't address the underlying central D2 antagonism, and its efficacy has only been shown in case reports. Bromocriptine acts more centrally as a dopamine agonist but should be used cautiously in patients with psychiatric diseases as it may exacerbate psychosis. Overall, benzodiazepine use and supportive care should get you through most cases of NMS, though additional therapies may be necessary in severe cases.

References

1. Institute for Safe Medication Practices. Delayed Administration and Contraindicated Drugs Place Hospitalized Parkinson’s Disease Patients at Risk. 12 March 2015. Accessed February 11, 2022.

2. Juurlink JN. Antipsychotics. In: Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. Page 1037-1039. McGraw Hill; 2019. Accessed February 11, 2022.

Zachary Schmitz, MD

Toxicology Fellow

Ronald O. Perelman Department of Emergency Medicine

NYU Langone Health

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How To Cite This Post:

[Peer-Reviewed, Web Publication] Leibowitz, M. Wleklinski, N. (2022, May 9). Neuroleptic Malignant Syndrome. [NUEM Blog. Expert Commentary by Schmitz, Z]. Retrieved from http://www.nuemblog.com/blog/neuroleptic-malignant-syndrome.

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How to Talk Like a Neurologist

Written by: Saabir Kaskar, MD (NUEM ‘23) Edited by: Nick Wleklinski (NUEM ‘22)
Expert Commentary by: Fan Caprio, MD

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Neurology Scores: LVO, NIHSS, and ICH

As first line providers, being able to effectively communicate with ancillary services and specialties is key to advancing patient care within the emergency department. When patients present with symptoms concerning for ischemic or hemorrhagic stroke, there are a variety of clinical decision tools available to help direct interventions and predict patient outcomes.  Having a basic understanding of these scoring systems helps ED providers communicate more effectively with our neurology colleagues. This post highlights indications, strengths, and limitations of common stroke assessment scales used in the prehospital and hospital setting.  

Cincinnati Prehospital Stroke Scale (CPSS)

The Cincinnati Prehospital Stroke Scale is a simple, easy to teach, three-part evaluation and is the most cited scale in statewide EMS protocols. Patients with one of these three findings, as a new event, will have 72% probability of ischemic stroke. If they have three of these deficits, that probability increases to 85%. Further, those scoring higher on this scale are more likely to have a large vessel occlusion (LVO) and warrant transfer to a comprehensive stroke center. One major limitation is that the CPSS does not identify features of posterior circulation strokes.

Figure 1: Cincinnati Prehospital Stroke Scale components

Predicting Large Vessel Occlusion 

There are many stroke severity scales that are useful in predicting large vessel occlusion (LVO) in the pre-hospital setting. Early LVO detection is useful as these patients have better outcomes if transported to comprehensive stroke centers (CSCs) which have endovascular interventions, such as thrombectomy, readily available. Such interventions are not available at primary stroke centers (PSC). LVO screening tools include the Rapid Arterial Occlusion Evaluation Scale (RACE), the Cincinnati Prehospital Stroke Severity Scale (CP-SSS/C-STAT), the Los Angeles Motor Scale (LAMS), and the Emergent Large Vessel Occlusion Scale (ELVO). While these scales are good, none have achieved an optimal sensitivity/specificity combination which is why there is no “gold standard” test per the most recent 2019 AHA guidelines (Powers et al. Guidelines for Early Mgmt of Patients with AIS. Stroke 2019). 

The Rapid Arterial Occlusion Evaluation Scale (RACE), for example, is one of these severity scales that predicts stroke caused by large vessel occlusion. It is based on the NIHSS but provides quicker assessment in the pre-hospital environment. It focuses on facial palsy, extremity motor function, head deviation, gaze deviation and aphasia or agnosia. The scale ranges from 0-9 with scores ≥ 5 being associated with detection of an LVO. RACE has a sensitivity of 85% and specificity of 68% for LVO at scores ≥ 5. 

Another example of a LVO screening tool is the Cincinnati Prehospital Stroke Severity Scale (CP-SSS/CSTAT) which is important to differentiate from the CPSS outlined above.  CSTAT focuses on gaze deviation, level of consciousness and arm weakness. Both RACE and CSTAT are validated in the prehospital setting and with external data sets. However, CSTAT is more convenient with fewer items to score. 

EMS protocol in Chicago (Region XI), utilizes a two-tier system that first involves the Cincinnati Stroke Scale and finger to nose test. If either aspect is abnormal, then stroke severity is assessed with the 3-Item Stroke Scale (3I-SS) which assesses level of consciousness, gaze preference and motor function, scored from 0-6. If the 3I-SS score is ≥4 and the last known normal is ≤6 hours ago then the patient is transported to the closest CSC instead of the closest primary stroke center (PSC), as long as the added transport time is not >15 minutes.  

National Institutes of Health Stroke Scale (NIHSS)

The NIHSS is a 11-part scoring tool and is the gold standard when assessing stroke patients in hospital (figure 3). Higher scores indicate a more severe stroke and usually correlate with infarct size on CT and MRI. Taken within the first 48 hours of acute stroke, the NIHSS helps predict three month and one-year clinical outcomes. For example, patients with a NIHSS of 1-4 have a high likelihood of functional independence and favorable outcome regardless of treatment. The NIHSS does not serve as the primary clinical guide in determining tPA administration. However, given that higher scores correlate with larger infarct size, caution is advised when considering tPA in patients with a NIHSS >22 as there is a higher risk of hemorrhagic conversion (see figure 2 for full tPA exclusion criteria). Analysis from subjects of the NINDS trials show that a NIHSS of >20 was associated with a 17% rate of intracranial hemorrhage with tPA when compared to 3% hemorrhage rate in patients with a score of <10.

Figure 2: Contraindications for tPA administration

Overall, the NIHSS is a reliable scoring tool to quicky assess the effects of stroke. Medical providers and nurses have been shown to have similar levels of accuracy when trained. Limitations include assessing posterior circulation stroke that involve gait abnormality, dizziness, or diplopia.

Figure 3: NIHSS, adopted from the American Stroke Association

Intracerebral Hemorrhage Score (ICH Score)

The ICH score is an important tool when evaluating a hemorrhagic stroke. This score was developed to standardize clinical grading of ICH and to improve communication between providers. This five-component scoring system (Figure 4) helps quantify ICH severity and subsequently 30-day mortality  (Figure 6) with a sensitivity of 66%. It is not used to determine treatment modality. This score helps universalize the grading of ICH severity, providing a standardized language that can be used between EM providers, neurologists, and neurosurgeons. Further, this score can help providers guide goals of care conversations with patient’s families and determine appropriate level of care or transfer.

Figure 4: ICH score, adapted from the American Stroke Association

Figure 5: Mortality rates based on ICH score

*No patients in the study scored 6, but estimated 100% mortality

Conclusion

In summary, it is important to understand how to utilize these scoring tools for ischemic and hemorrhagic stroke. Knowing how to interpret pre-hospital stroke scores and how to calculate a NIHSS score accurately and quickly is helpful in not only quantifying severity but also in improving communication between providers. Improved understanding and effective use of these tools can help better advance care of our stroke patients efficiently. These tools can also remind us of the severity of the neurologic deficit we observe on clinical exam. Subsequently, this can be helpful in guiding discussions with patients and their families regarding the severity of their condition.

References

Adams HP Jr, Davis PH, Leira EC, et al. Baseline NIH Stroke Scale score strongly predicts outcome after stroke: A report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology 1999; 53:126.

Goldstein, L. (2019). Use and utility of stroke scales and grading systems. Up To Date

Goldstein L, Bertels C, Davis JN. Interrater reliability of the NIH stroke scale. Arch Neurol 1989; 46:660.

Generalized efficacy of t-PA for acute stroke. Subgroup analysis of the NINDS t-PA Stroke Trial. Stroke 1997; 28:2119.

Hemphill JC 3rd, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke. 2001 Apr;32(4):891-7. PubMed PMID: 11283388.

Kothari RU, Pancioli A, Liu T, et al. Cincinnati Prehospital Stroke Scale: reproducibility and validity. Ann Emerg Med 1999; 33:373.

Pérez de la Ossa N, Carrera D, Gorchs M, et al. Design and validation of a prehospital stroke scale to predict large arterial occlusion: the rapid arterial occlusion evaluation scale. Stroke 2014; 45:87.

Schlemm L, Ebinger M, Nolte CH, Endres M. Impact of Prehospital Triage Scales to Detect Large Vessel Occlusion on Resource Utilization and Time to Treatment. Stroke 2018; 49:439.

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Expert Commentary

Thanks for writing this comprehensive summary of common screening tools used in stroke patients. Having a good handle on these tools will allow you to quickly and effectively communicate with comanaging care providers. It is also important to understand how and why each scale was developed, so they can be used in the appropriate setting to expedite care in extremely time-sensitive neurologic emergencies.

Keep in mind that scales are merely screening tools and are not meant to give a definitive diagnosis. No scale is perfect, but you have highlighted some that yield the highest sensitivity and specificity for identifying a potential stroke patient. In addition to leaning on these scales as decision support tools, always use your clinical judgement. A few things to remember in addition to the neurologic symptoms:

* Strokes are potentially intervenable within the first 24 hours:

1. Up to 4.5 hours – IV-TPA / tenecteplase.

2. Up to 6 hours – Thrombectomy with LVO on vessel imaging.

3. Up to 24 hours – Thrombectomy with LVO + favorable penumbra on perfusion imaging.

* Last known normal (LKN) starts the timer to when stroke patients are eligible for intervention (not to be confused with time of symptom discovery!)

* Strokes typically cause a sudden loss of function (in contrast to positive phenomena such as convulsive movements, tingling sensation, sparkling vision, which can point away from a stroke diagnosis)

* In patients with prior deficits, ask which symptoms are new or different in comparison to their baseline.

The NIHSS is widely accepted as THE stroke severity scale, and it has many strengths and some pitfalls. The NIHSS was initially developed to be used in research, and, as mentioned here, was designed to be reproducible between various groups – physicians, nurses, research staff. Higher scores correlate with bigger infarct volume. The NIHSS is not an accurate scale in that it does not necessarily capture each patient’s deficits, omitting brain functions such as gait, distal limb dexterity, and cognition. It also scores higher for dominant (L) hemispheric functions as many points depend on language function.

When screening for large vessel occlusion, remember key brain structures and functions from the L MCA, R MCA, and posterior circulation. Looking for cortical signs can be very helpful to identify larger stroke syndromes: aphasia, neglect, gaze deviation, visual field deficit.

Last but not least, keep in mind that hemorrhagic strokes (intracerebral hemorrhage, subarachnoid hemorrhage) account for about 15% of all strokes. The same screening tools for acute neurologic symptoms can be used to identify these patients, though they more often have concurrent headache or LOC than ischemic strokes (due to increased ICP and irritation from blood products). For SAH, two scales are commonly used to describe the clinical and radiographic severities: Hunt-Hess (surgical risk index) and modified Fisher scales (risk index for developing vasospasm).

Figure 1: Hunt-Hess Scale

Figure 2: Modified Fisher Scale

Fan Caprio, MD

Assistant Professor of Neurology (Stroke)

Department of Neurology

Northwestern Memorial Hospital

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How To Cite This Post:

[Peer-Reviewed, Web Publication] Kaskar, S. Wleklinski, N. (2021, Oct 25). How to Talk Like a Neurologist. [NUEM Blog. Expert Commentary by Caprio, F]. Retrieved from http://www.nuemblog.com/blog/neuro-scores

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What to expect when you're expecting a concussion

Written by: Kelsey Green, MD (NUEM ‘23) Edited by: Jordan Maivelett, MD (NUEM ‘20) Expert Commentary by: Jake Stelter, MD

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Expert Commentary

This is a great review of anticipatory guidance when counseling patients who have been diagnosed with a concussion.  As noted, “mild traumatic brain injury (mTBI)” is often used synonymously with “concussion.” A better way to conceptualize this is to view concussion as a form of mTBI, realizing that mTBI can represent a spectrum of conditions.  One of the most important treatments of concussion from the Emergency Department (ED) perspective is to counsel patients on what to expect and how to best control their symptoms.  Concussions can present with a wide range of symptoms as detailed and can be quite distressing and disruptive to patients. As correctly pointed out, the presence of vestibular symptoms (i.e. dizziness or gait instability) as well as pre-existing mental health diagnoses, such as depression or anxiety, are associated with a protracted symptom course. Setting expectations of the symptoms they may develop and the possible timeline of symptom duration is important for patients as they manage their condition.  Early conservative treatment with adequate sleep and relative cognitive and physical rest will help manage and reduce the intensity of symptoms.  In our current society, it is nearly impossible to completely avoid screens and reading.  Hence, “everything in moderation” is appropriate when counseling these patients.  If the patient has to work at a computer, advise them to take frequent breaks for at least 10 minutes for every 30 minutes of screen time.  In addition, it is recommended that patients with a concussion avoid alcohol.  It is also advisable to avoid excessive caffeine.  However, if a patient already uses caffeine on a daily basis, they should not stop completely, as that can lead to withdrawal headaches.  Over-the-counter pain relievers, such as naproxen, ibuprofen or acetaminophen are appropriate for headache treatment, provided there are no contraindications to use.

 There are multiple return-to-learn, -work and -play protocols that have been published.  This is particularly applicable to athletes who have sustained a sport-related concussion (SRC).  Most schools and athletic programs have protocols that have been developed in conjunction with athletic trainers and team physicians.  It is important to remember that as an ED provider, you should not clear a patient to return to play.  That process needs to be conducted by the school athletic trainer in collaboration with the team physician after they have had the opportunity to evaluate the patient. You should consider referring your concussion patients to a Primary Care Sports Medicine or Neurology provider for follow-up if they do not have a team physician to visit.

There are multiple free resources available to providers who are interested in learning more about concussion and educating patients.  The Sport Concussion Assessment Tool – 5th Edition (SCAT5) is an in-depth evaluation tool that is often used by Sports Medicine clinicians when evaluating the extent and severity of a patient’s concussion syndrome.  These resources are listed here:

References

American Medical Society for Sports Medicine position statement on concussion in sport:

https://bjsm.bmj.com/content/53/4/213

SCAT5:

https://bjsm.bmj.com/content/bjsports/early/2017/04/26/bjsports-2017-097506SCAT5.full.pdf

Jacob Stelter, MD

Emergency Medicine, Primary Care Sports Medicine

Division of Emergency Medicine

NorthShore University HealthSystem

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How To Cite This Post:

[Peer-Reviewed, Web Publication] Green, K. Maivelett, J. (2021, Feb 14). What to expect when you're expecting a concussion. [NUEM Blog. Expert Commentary by Stelter, J]. Retrieved from http://www.nuemblog.com/blog/concussion.

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Ultrasound Guidance for Lumbar Puncture

Written by: Maurey Hajjar, MD, MPH (NUEM ‘22) Edited by: Justin Seltzer, MD (NUEM ‘21) Expert Commentary by: Alex Ireland, MD (NUEM '20)

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Expert Commentary

Thank you to Dr. Hajjar and Dr. Seltzer for their excellent review of an underutilized ultrasound procedure. 

After several challenging lumbar punctures during my residency training, I began to adopt this technique as a supplemental tool to improve first-pass success. When beginning, the patient can be placed in either the lateral decubitus or the upright position. However, I have found that in the patients for whom you are looking for ultrasound guidance, the anatomy due to body habitus is already challenging, and upright positioning offers the best advantage of maintaining midline.

There are several approaches to identifying your target with ultrasound, and my preferred strategy is different than the one mentioned in this post. After palpating the bilateral anterior superior iliac spines and drawing lines inward towards the midline, I start with my probe in the transverse view to identify the spinous processes at L3, L4, and L5. I mark above and below my probe at each process to identify the midline.

I then rotate the probe 90 degrees into a longitudinal view, but I keep my probe in the midline to identify contiguous vertebral spinous processes and the intervertebral or interspinous spaces between them. I place a mark on both sides of my probe with it aligned in the middle of this intervertebral space, which will be the exact insertion point of my needle.

Another key advantage of ultrasound is the ability to measure the anticipated depth of needle insertion. After identifying the spinous processes and intervertebral space in longitudinal view, I increase the depth and the gain to view the mixed echogenicity soft tissue and ligaments, and then see the hypoechoic subarachnoid space underneath the dura mater. I measure the depth of this space and then have an estimate of how far to insert the needle before obtaining cerebrospinal fluid.

Lastly, I would highly recommend attempting this technique on several “easy” patients where you can also readily palpate the anatomy. Similar to using a bougie during difficult intubations, we need to be skilled with our rescue techniques through diligent preparation and repeated practice.

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References

Ultrasound Guided Lumbar Puncture. MGH Ultrasound. 

https://www.youtube.com/watch?v=DbqETxLurS0

 http://www.emdocs.net/ultrasound-lumbar-puncture-maximize-first-pass-success-patients-large-body-habitus/

Alex Ireland, MD

Emergency Medicine Physician

Vituity Group

Chicago, IL

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How To Cite This Post:

[Peer-Reviewed, Web Publication] Hajjar, M. Seltzer, J. (2020, Dec 7). Ultrasound Guidance for Lumbar Puncture. [NUEM Blog. Expert Commentary by Ireland, A]. Retrieved from http://www.nuemblog.com/blog/ultrasound-imaging-for-lumbar-puncture

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Non Contrast CT Head for the EM Physician

Written by: Philip Jackson, MD (NUEM ‘20) Edited by: Logan Weygandt, MD, MPH NUEM ‘17) Expert Commentary by: Katie Colton, MD

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Relying on in-house radiology reads of imaging is a habit that EM trainees are encouraged to avoid, but one that can be appealing when practicing in a busy, large academic facility with 24-hour radiologist staffing. By reading one’s own images, not only do EM physicians gain skills in diagnostic radiology, which they can employ when an attending radiology read is not readily available but more importantly, the EM physician can correlate history and physical with imaging and help detect subtle pathology. Recent studies have shown that even attending EM physicians are often deficient in reading non-contrast CT scans of the head, however, with minimal training residents have been shown to make significant improvements. [2,3]

An elderly male with a history of hypertension and Fuch’s corneal dystrophy presented to our ED the morning after developing acute on chronic worsening of the blurry vision in his R eye. He suffered from persistent blurry vision but stated that it had suddenly worsened while watching TV the previous night. He then developed a left-sided occipital headache that continued through the following morning. He also noticed that his thinking was “cloudy” and despite being a healthcare professional could not describe his own medical history or list of medications. He described blurriness especially on the right. On visual field confrontation, the patient was found to have a binocular R sided superior quadrantanopsia. The rest of his neurologic exam was unremarkable. As these findings were concerning for stroke specifically in the left temporooccipital region known as Myer’s loop, we obtained a STAT non-contrast head CT.

As the so-called green arrow-signs on the CT image indicate, there was indeed a significant amount of cerebral edema present in the L temporal lobe white matter, which  contains the anterior optic radiations carrying information from the R superior visual field and corresponds to our patient’s deficit. Upon discovering this lesion, our team immediately called our radiology colleagues who confirmed our concern for an acute ischemic infarct.

Like any other task in the ED, reading a head CT should be conducted as efficiently and accurately as possible using a standardized approach. EM residents have been found to be somewhat deficient in our ability to evaluate noncontrast head CTs; however, studies have shown that with adequate training, our skills can significantly improve. [3] Perron et al describe the simple but systematic approach “Blood Can Be Very Bad.” This mnemonic reminds residents to examine for the presence Blood, the shape and consistency of the Cisterns, the texture of the Brain parenchyma, the Ventricles, and the presence of fractures and symmetry of the Bony structures. 

• Blood:  In a non-contrast CT, blood will appear as hyperdense (bright/white) fluid.  As blood ages over weeks, it will become increasingly hypodense (darker).  Blood will present in one of the four following ways:

  • Subarachnoid hemorrhage - A dreaded complication of trauma, a ruptured aneurysm, or an arteriovenous malformation can lead to blood pooling in gravity-dependent areas correlating with the particular arterial defect. Rupture of the anterior communicating artery (ACA) will distribute blood in and around the interhemispheric fissure, suprasellar cistern, and brainstem.  Rupture of the middle cerebral artery (MCA) will distribute blood in the Sylvian and suprasellar cistern, while the posterior cerebral artery (PCA) will also distribute in the suprasellar cistern.

  • Subdural hemorrhage (SDH) – Caused by rupture of the bridging veins, SDHs will present as a crescentic lesions that often cross suture lines. SDHs can be acute, chronic, or mixed, and thus will have varying degrees of density.

  • Epidural Hemorrhage - Another serious complication of trauma, epidural hemorrhages will present as a lenticular (biconvex) areas of hyper-attenuation.     Caused by arterial laceration, with the most common being the middle meningeal artery, epidural hemorrhages can rapidly expand and cause significant and rapid mass effect.  Early identification is thus crucial to reducing mortality from these injuries.

  • Intraparenchymal/intraventricular hemorrhage - Often the result of hypertensive disease in elderly patients or as hemorrhagic strokes, intraparenchymal hemorrhage will most often be located in the basal ganglia. Amyloid angiopathy  (associated with Alzheimer’s dementia) often presents as wedge-shaped areas of hemorrhage in the outer cortex. Trauma leading to brain contusion can also present with intraparenchymal hemorrhage. All intraparenchymal hemorrhages (as well as subarachnoid hemorrhages) can potentially rupture into ventricles causing intraventricular hemorrhage and resultant hydrocephalus.

• Cisterns:  Cisterns are spaces surrounding and cushioning brain matter with cerebrospinal fluid. Each of the four major cisterns should be examined for blood or signs of mass effect: the sylvan fissure (in between temporal and parietal lobes), the circummesencephalic or peripontine cistern, the suprasellar (surrounding the circle of Willis), and the quadrigeminal (atop the midbrain).

• Brain matter: Always examine the gyri for and for distinct grey-white matter differentiation. Ischemic strokes, as in our case, will present with blurring of the grey-white differentiation and cerebral edema (areas of hypodensity).  Early strokes may not be apparent on CT, but after 6 or more hours hypodense lesions should be present with maximal edema occurring approximately 3-5 days after the event. Always examine the falx for midline shift through multiple slices.

• Ventricles:  Examining the third and fourth ventricles is crucial in determining the presence of blood hydrocephalus (dilation) or mass effect (asymmetry).

• Bone:  The bony structures of the head should all be examined for fractures, especially depressed skull fractures, which usually denote intracranial pathology. Also, examining the sphenoid, maxillary, ethmoid, and frontal sinuses for air fluid levels should raise suspicion for a skull fracture. Separate bony windows are available for close examination of these high-density structures. [1]

As our case illustrates, it is crucially important for EM physicians to interpret non-contrast CT scans in a systematic and accurate manner. Clinical correlation is a distinct advantage that we, as emergency physicians, possess and it should be exploited to allow for timely and effective patient care.

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Expert Commentary

Thanks to Drs. Jackson and Weygandt for this great primer to the emergent head CT.  One of the obvious challenges of EM is the breadth of pathology we see, and so having a strategic approach like this one will reveal most of the emergent diagnoses we are looking for.  I will never be a radiologist, but nothing is faster than looking at my own scan. A few thoughts: I start by scrolling a scan through quickly to identify obvious pathology (a bleed, midline shift, etc.) and then try to actively redirect my attention back to a systematic approach. It is easy to hone in on the obvious abnormality and miss smaller but crucial clues. Go through the same progression every time. Get comfortable with finding different windows for your imaging. If you only look in a brain window, you’ll miss critical diagnoses. Symmetry is your best friend - until it is not.  We are remarkably good at picking out asymmetry when looking at imaging, which reveals many of the emergent diagnoses, but keep some of the symmetric processes in the back of your mind.  Many of these can wait for a radiologist’s fine- tooth comb, but a few stand out.  Get used to finding the basilar artery, particularly in your unconscious patient; an acute occlusion in this midline structure is potentially devastating but quick intervention is life-saving. Similarly, acute hydrocephalus merits immediate intervention that can lead to dramatic clinical improvement. Bilateral or midline subdural hemorrhage can also be easily missed; finding these requires a level of comfort with windowing the images and identifying abnormal CSF spaces.

Katie Colton, MD

Instructor, Feinberg School of Medicine

Department of Neuro Critical Care and Department of Emergency Medicine

Northwestern Memorial Hospital

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How To Cite This Post:

[Peer-Reviewed, Web Publication] Philip, J. Weygandt, L. (2020, Feb 10). Non Contrast CT Head for the EM Physician. [NUEM Blog. Expert Commentary by Colton, K]. Retrieved from http://www.nuemblog.com/blog/non-contrast-ct-head-for-the-em-physician

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References

1. Adams, James, and Erik D. Barton. Emergency Medicine: Clinical Essentials. 2nd ed. N.p.: Elsevier Health Sciences, 2013;633-644.

2. Jamal K, Mandel L, Jamal L, Gilani S. 'Out of hours' adult CT head interpretation by senior emergency department staff following an intensive teaching session: a prospective blinded pilot study of 405 patients. Emergency medicine journal : EMJ. 2014;31(6):467-470.

3. Perron AD, Huff JS, Ullrich CG, Heafner MD, Kline JA. A multicenter study to improve emergency medicine residents' recognition of intracranial emergencies on computed tomography. Annals of emergency medicine. 1998;32(5):554-562.

4. Mayfield Brain & Spine. "Visual field test." Visual Field Test | Mayfield Brain & Spine. N.p., n.d. Web. 19 Dec. 2016.

Emergency Guide to Stroke Neuroimaging

Written by: Justin Seltzer, MD (PGY-3) Edited by: Luke Neill, MD (PGY-4) Expert commentary by: Babak Jahromi, MD, PhD

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According to the CDC, an ischemic stroke occurs approximately every 40 seconds in the US, with nearly 800,000 documented cases annually.[1] This, combined with an effective national stroke symptom public education program, has resulted in a large number of patients presenting to emergency departments for evaluation of stroke or stroke-like symptoms. Essential to this initial evaluation is neuroimaging, which in the emergency department is mainly CT based. 

However, despite frequent use, many emergency physicians are not familiar enough with stroke imaging to interpret images on their own. A prior post addressed the basics of reading a complete head CT, which you can find here. The goal of this article is to discuss the indications and limitations as well as to provide a basic guide to interpretation of noncontrast CT imaging of the brain (NCCT), CT angiography (CTA) of the head and neck, and CT perfusion (CTP) imaging in acute stroke evaluation.

Acute stroke imaging is obtained in the emergency department for two purposes. 

1. To evaluate rapidly for thrombolysis contraindications like hemorrhage and certain pathology such as vascular malformations and aneurysms. Thrombolysis has a high therapeutic benefit in stroke patients, with a number needed to treat of 10 within 3 hours of symptom onset and less than 20 if administered within 4.5 hours.[2,3] In addition, door to needle time of less than one hour is an established benchmark and quality measure.[3]

2. To identify a causative vascular lesion, which may or may not be amenable or contraindicatory to thrombolysis

Non-Contrast Head CT

NCCT is usually the first imaging modality obtained in the acute evaluation for stroke. Within the thrombolysis window (<4.5 hours), however, this scan is far more likely to detect hemorrhage than infarction. Chalela, et al., reviewed 356 patients evaluated for stroke symptoms at a single center over 18 months. They showed a sensitivity of 89% for detection of acute intracranial hemorrhage; conversely, the sensitivity for ischemic strokes less than 3 hours old was 12%, 16% for those older than 12 hours, and an overall sensitivity of 16%.[4] These findings are consistent with other studies and highlights the limitations of NCCT in acute stroke imaging. 

Despite the poor sensitivity for acute infarction, there are a few ways to improve detection. Windowing adjustments can enhance grey-white matter differentiation, as loss of this in an area anatomically associated with the presenting deficit is suggestive of acute infarction. A window width and center of approximately 50 each achieves adequate grey-white differentiation (Figure 1). Additionally, asymmetric, hyperdense section of cerebral vasculature, known as the “dense vessel” sign, is also highly suggestive of middle cerebral artery (MCA) occlusion.[5] As a side note, IV contrast should not be used outside of angiography to “enhance” the image as it may extravasate into the ischemic parenchyma mimicking hemorrhage.[6] 

Figure 1. NCCT of the brain in an acute right M1 occlusion with a last known well time was approximately 13 hours before. Windowing set at C50/W50 for improved grey-white differentiation. Official read: “A diffuse asymmetric hypodensity and subtle loss of gray-white matter differentiation in the right frontal and parietal region is highly concerning for an acute right MCA stroke.”

CT Angiography of the Head and Neck

The role of CTA in acute stroke evaluation is to identify the culprit vascular lesion and is an excellent addition to the emergent evaluation of acute ischemic stroke. A 2014 pooled analysis of 21 studies from 1993 to 2013 showed CTA has a sensitivity of 83.2% and specificity of 95% with a 97.1% negative predictive value for greater than 50% cerebral vascular stenosis;[7] a 2017 pooled analysis of 7 studies from 2003 to 2012 broadly reported a sensitivity of 93% and specificity of 100% for acute ischemic stroke.[8] CTA of the neck is also obtained to evaluate the contributing cervical vasculature. Since interpretation of angiography is dependent on knowledge of the relevant anatomy, the key structures are reviewed below. If a more detailed review is desired or necessary, several neuroanatomy texts may be found in the references. 

The major cerebral vasculature is supplied by the bilateral internal carotid arteries (ICA; “anterior circulation”) and the paired vertebral arteries (VA) that merge to form the basilar artery (BA; “posterior circulation”). The anterior circulation dominates perfusion of the cerebral hemispheres apart from the occipital lobe. The posterior circulation feeds the remaining structures, mainly the occipital lobe, cerebellum, and brain stem. 

Figure 2. CTA of the neck showing bilateral patent CCAs and VAs.

Anterior circulation

The anterior circulation starts with the ICA, which branches from the common carotid artery (CCA) in the upper neck at around the level of the fourth cervical vertebra. (Figures 2, 3). The ICA has four parts with seven defined segments; in general, segments assist with lesion localization and are provided in parenthesis. The cervical part (cervical segment, C1) is first and enters the skull at the carotid foramen (Figure 5). It is distinguished from its companion external carotid artery by a lack of extracranial branching. Once in the skull, the petrous part (petrous segment, C2) traverses the carotid canal within the petrous portion of the temporal bone (Figure 5). Moving out of the temporal bone, the ICA then crosses into the cavernous sinus, where it is known as the cavernous part (lacerum segment, C3, cavernous segment, C4, clinoid segment, C5). Navigating the bony turns in this area results in a characteristic curvature known as the “carotid siphon” (Figure 6). From here, the vessel passes through the dura, where it becomes the cerebral or supraclinoid part (ophthalmic segment, C6, communicating segment, C7) and gives off the ophthalmic, posterior communicating, and anterior choroidal arteries; these posterior communicating arteries (PCommA) run to the ipsilateral posterior cerebral arteries (PCA), thus connecting the anterior and posterior circulations and forming part of the circle of Willis (Figure 7). At the terminus, the internal carotid arteries bifurcate into the bilateral anterior cerebral arteries (ACA) and MCAs. Acute ICA lesions can cause dramatic symptoms due to restricted blood flow to the ipsilateral ACA and MCA and are large vessel occlusions.[9-12]

Figure 3. CTA of the neck showing the bilateral carotid bifurcations. Artifact from metal in the patient’s teeth.

Figure 4. CTA of the neck showing patent bilateral ICAs as well the the bilateral VAs entering the foramen magnum

The ACAs run between the frontal hemispheres in the longitudinal fissure and supply a large portion of the medial cerebral structures such as the medial frontal and parietal lobes as well as the basal ganglia and parts of the internal capsule. They are smaller than the MCAs and their course is recurrent frontal-occipital and inferior-superior, which can make visualization in the axial plane difficult to appreciate. The paired arteries are connected by the anterior communicating artery (ACommA) early in their course which is the final connection completing the circle of Willis (Figure 7). Lesions within the A1 segment, which runs from the carotid terminus to the ACommA are considered large vessel occlusions though may be better tolerated due to collateral flow through the anterior communicating artery.[9,10,12] 

Figure 5. CTA of the head showing the ICAs as they enter the skull and traverse the petrous portion of the temporal bone.

Figure 6. CTA of the head showing the ICA as it traverses the cavernous sinus; the carotid siphon is well visualized on the left.

The MCAs provide circulation to the remaining frontal and parietal lobes, basal ganglia, and internal capsules, as well as portions of the temporal lobes. They are larger and therefore more easily visualized than the ACAs (Figure 7). A lesion of the M1 segment, which runs from the carotid terminus to the bifurcation into the M2 segments, is considered a large vessel occlusion (Figures 8, 9).[9,10,12] 

Figure 7. CTA of the head showing an intact circle of Willis

Figure 8. CTA of the head showing an acute right M1 occlusion in the axial plane

Figure 9. Coronal MIPS of the same vascular occlusion noted in Figure 8 with clear deficit on the right compared with the left.

Posterior circulation

The posterior circulation starts with the VAs, which are subclavian branches that traverse the cervical spine via transverse foramina (Figures 2, 3). Prior to joining, each vertebral artery gives off an ipsilateral posterior inferior cerebellar arteries (PICA) as well as the contributing vessels that form the anterior and posterior spinal arteries. Upon entering the skull via the foramen magnum, the bilateral vertebral arteries join to form the basilar artery at about the level of the medullo-pontine junction (Figures 4, 5, 6). As the basilar artery moves superiorly it gives off the bilateral anterior inferior cerebellar arteries (AICA), multiple bilateral small perforating pontine arteries, the bilateral superior cerebellar arteries, and then finally terminates with a bifurcation into the bilateral posterior cerebral arteries (PCA). As noted prior, these PCAs connect with the ipsilateral posterior communicating arteries from the anterior circulation (Figure 7). Vertebral, basilar, and early posterior cerebral artery occlusions are considered large vessel occlusions but there is, as of now, limited data on mechanical thrombectomy in these territories.[9,10,12,13]

Application

Reading the scan itself is fairly straightforward based on the vascular anatomy. We recommend starting caudally (usually the aortic arch) in the axial plane and tracing all four cervical vessels cranially until they form the circle of Willis and from there extend out into the major branches. The coronal plane is particularly useful for evaluation of the anterior cervical vessels and the MCAs. Significant asymmetry or loss of contrast opacification in vascular beds anatomically consistent with the presenting symptoms should be considered strokes until proven otherwise. Make note of vascular abnormalities such as significant carotid stenosis, aneurysms, and malformations. 

Additional 2-D and 3-D post-processing images may also be provided. The most common is maximum intensity projection (MIP), which highlights high density structures over low density; this allows for improved visualization of the contrast enhanced vasculature at the expense of the surrounding brain tissue. However, MIP images can be falsely negative and should not be used alone for primary vascular evaluation.[14]

CT Perfusion

Though less common than CTA, CTP may also be acquired in the emergency setting to evaluate for territorial changes in cerebral blood flow suggestive of stroke. It is particularly valuable for identifying core infarct and salvageable ischemic penumbra and is becoming an important part of interventional decision making. It has a similar sensitivity and specificity for acute ischemic stroke as CTA, its use has been validated in multiple interventional stroke studies, and it has been shown to predict core infarct size accurately compared to the gold standard MRI.[7,8,15]

Basic concepts

While the specifics of CTP are complex and beyond the scope of this article, there are a few important concepts. CTP operates under the “central volume principle,” which is represented by the equation CBF = CBV/MTT and defines the relationship between cerebral blood volume (CBV; volume of flowing blood in a set volume of brain tissue), blood flow (CBF; per time unit rate of flowing blood in a set volume of brain tissue), and mean transit time (MTT;  average time for blood to transit a set volume of brain tissue). To illustrate this concept, imagine an acute arterial occlusion. The obstruction causes an immediate increase in MTT due to slowed arterial flow through the affected tissue. To maintain CBF a local compensatory vasodilation occurs, increasing CBV. However, this vasodilation may not be able to compensate for rising MTT, causing a progressively inadequate CBF that may result in infarction.[5,16]

Algorithms translate detected changes in MTT, CBV, and CBF into images that can be used in clinical decision-making. MTT is obtained by measuring the movement of contrast through the affected tissue; this also gives a value known as Tmax, which is the time to achieve peak contrast density. CBV and CBF are calculated relative values (rCBF, rCBV) and based off of the surrounding normal tissue. Composite metrics, such as mismatch ratio, the ratio of penumbra to the core infarct volumes, and mismatch volume, the penumbra volume minus the core infarct volume, are also generated.[11] Though there is no set rule, there is evidence that thrombolysis benefit is maximized and hemorrhage risk minimized with a mismatch ratio of 1.8 or greater, a mismatch volume of 15ml or greater, and a core infarct volume less than 70ml.[17]

Figure 10. Illustrative CTP report for the same acute right M1 occlusion from Figures 8 and 9 showing the core infarct (purple) and associated penumbra (green). Note the large mismatch volume and ratio, indicating a relatively small core infarct relative to the threatened penumbra.

Application

These values are then made into “parametric maps” superimposed onto axial CT slices, allowing for visual identification (Figures 10, 11). Different software may present the values and parametric maps differently; note that our institution uses RAPID (iSchemaView, Menlo Park, CA) and our example figures were generated by this software. Using Figure 10 as an example, we see purple and green areas as well as different volumes and ratios. The purple area corresponds to the volume of tissue with a rCBF less than 30% of the unaffected, healthy tissue and is considered the core infarct area. The green area corresponds to the volume of tissue with a Tmax longer than six seconds and is considered the ischemic penumbra. Though these threshold values were used and validated by the SWIFT PRIME and EXTEND-IA trials, they are not definitive or universal.[15,18] Familiarization with an institution’s software and threshold values is vital to interpreting CTP properly.

Importantly, CTP can be abnormal in other situations such as with chronic infarcts, vasospasm from subarachnoid hemorrhage, microvascular ischemia, and cerebral changes associated with seizure and feeding vessel stenosis.[16] Always interpret CTP in the context of the other imaging findings and anatomic consistency. 

Figure 11. Illustrative CTP report for the same acute right M1 occlusion from Figured 8, 9, and 10 showing territorially increased MTT with subtle reduction in CBF and a small area of asymmetrically elevated CBV in the area corresponding to infarction in Figure 10. This figure visually highlights the relationships between rCBV, cCBF, MTT, and Tmax.

Take Away Points

CT is the primary source of neuroimaging in the emergency department evaluation of stroke patients. NCCT is poor at detecting early acute infarcts directly, however it is excellent for hemorrhage detection. Use of CTA can demonstrate causative vascular lesions and addition of CTP can further delineate ischemia and determine how amenable it might be to intervention. Not all lesions identified by CTA and CTP will be amenable to thrombolysis or thrombectomy, but these are usually the only time effective ways available to emergency physicians to identify those that might be. Educating emergency physicians about these imaging modalities can both improve patient care through more rapid diagnosis in suspected stroke cases as well as help to streamline communication and treatment planning with consulting neurologists and neurointerventionalists. 

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Expert Commentary

This is a well-written synopsis of modern neuroimaging used today’s ED for workup and emergent treatment of acute stroke. The reader should keep in mind that the primary thrust of this blog segment is on acute ischemic stroke - while advanced CT imaging (i.e. CTA) also has a crucial role in hemorrhagic stroke, this is more thoroughly addressed elsewhere.

Practically speaking, today’s CT/CTP/CTA is to suspected stroke what an EKG is to chest pain in the ED. While confirmatory tests (MRI for stroke, troponin for MI) take more time, all actionable data depends on the initial CT/CTP/CTA in acute stroke. I would also categorize the purpose of acute stroke imaging in the ED into two categories, but with perhaps broader brush-strokes:

1. Determine if stroke is ischemic or hemorrhagic (“blood or no blood on CT”), and

2. Determine the next course of action:

   1. If ischemic, do temporal and anatomic criteria mandate IV tPA, endovascular thrombectomy, both, or neither, 

   2. If hemorrhagic, is there mass effect and/or an underlying vascular lesion (arterial or venous) that mandates urgent intervention beyond best medical care.

While NCCT is sufficient to determine whether to proceed with IV tPA in the 0-4.5 hour time-window (with an NNT of 10-20), CTP/CTA are key to determining whether the patient requires emergent endovascular thrombectomy in the 0-24 hour time-window (with an NNT of 2.6-4). As these two time-windows overlap, the most practical approach is increasingly to obtain multi-modality imaging up-front / as rapidly as possible in the ED. It is important to remember that as of 2015, both IV tPA and endovascular thrombectomy are considered standard-of-care, and any patient presenting with acute ischemic stroke must undergo full workup and consideration of both treatments based upon national society / consensus guidelines.

An added note on NCCT versus CTP: while NCCT is the oldest modality in the ED, it continues to have tremendous value in acute stroke imaging. Presence or absence of early stroke changes on NCCT (quantified by the ASPECT score) can at times trump CTP in the 0-6 hr time-window, and CTP within any time-window must be interpreted in context of NCCT findings. For example, CTP may show no abnormality (or even luxury perfusion) in an area of established stroke on NCCT in cases of spontaneous recanalization. On the other hand, CTP can be very helpful in detecting small areas of ischemia not well seen on CT/CTA (even when reading NCCT using optimized 35/35 or 40/40 “stroke windows”), and CTP has higher sensitivity for small/distal branch occlusions than either CT/CTA.

The approach to cerebrovascular arterial anatomy is nicely reviewed. A few additional comments:

1. ICA: acute ICA occlusions are most dramatic when reaching the terminus (thereby blocking the MCA/ACA), but those not reaching the supraclinoid ICA may at times be well-tolerated due to collaterals across the Circle of Willis,

2. VA: the course/anatomy of the VA is rather variable, with one VA (typically the right) being less dominant as we age; similarly, PICA can have a variable origin and territory of supply, and

3. BA: while randomized trials of endovascular thrombectomy for basilar occlusion have not been published, the natural history of BA occlusion is typically devastating/fatal, and a large body of non-randomized data (case series/cohorts) shows marked improvement over this natural history following endovascular thrombectomy for BA stroke in selected patients.

Vice Chair of Regional Neurosurgery

Professor of Neurological Surgery

Department of Neurological Surgery

Feinberg School of Medicine

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How to Cite this Post

[Peer-Reviewed, Web Publication] Seltzer J, Neill L. (2020, Jan 6). Emergency Guide to Stroke Neuroimaging. [NUEM Blog. Expert Commentary by Jahromi B]. Retrieved from http://www.nuemblog.com/blog/2018/4/20/stroke-neuroimaging

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References

1. National Center for Chronic Disease Prevention and Health Promotion , Division for Heart Disease and Stroke Prevention. “Stroke Fact Sheet.” Last Update: September 1, 2017. Accessed from https://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_stroke.htm

2. Emberson J, Lees KR, Lyden P, et al., for the Stroke Thrombolysis Trialists’ Collaborative Group. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014 Nov 29;384(9958):1929-35.

3. Filho JO, Samuels OB. Approach to reperfusion therapy for acute ischemic stroke. UpToDate. Last Update: September 14, 2018. Accessed from https://www.uptodate.com/contents/approach-to-reperfusion-therapy-for-acute-ischemic-stroke

4. Chaela JA, Kidwell CS, Nentwich LM, et al.. Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison. Lancet. 2007 Jan 27; 369(9558): 293–298.

5. Nadgir R, Yousef DM. “Vascular Diseases of the Brain.” In Neuroradiology: The requisites. 4th Ed. (2017). Philadelphia, PA: Mosby/Elsevier

6. Yoon W, Seo JJ, Kim JK, Cho KH, Park JG, Kang HK. Contrast enhancement and contrast extravasation on computed tomography after intra-arterial thrombolysis in patients with acute ischemic stroke. Stroke. 2004 Apr;35(4):876-81.

7. Sabarudin A, Subramaniam C, Sun Z. Cerebral CT angiography and CT perfusion in acute stroke detection: a systematic review of diagnostic value. Quant Imaging Med Surg. 2014 Aug;4(4):282-90.

8. Shen J, Li X, Li Y, Wu B. Comparative accuracy of CT perfusion in diagnosing acute ischemic stroke: A systematic review of 27 trials. PLoS One. 2017 May 17;12(5):e0176622. 

9. Mancall EL. “Vascular Supply of the Brain and Spinal Cord” In Gray's clinical neuroanatomy: The anatomic basis for clinical neuroscience. 1st Ed. (2011). Philadelphia, PA: Elsevier/Saunders.

10. Mtui E, Gruener G, Dockery P. “Blood Supply of the Brain.” In Fitzgerald’s Clinical Neuroanatomy and Neuroscience. 7th Ed. (2016). Edinburgh: Elsevier Saunders.

11. Bouthillier A, van Loveren HR, Keller JT. Segments of the internal carotid artery: a new classification. Neurosurgery. 1996 Mar;38(3):425-32.

12. The Joint Commission. Specifications Manual for Joint Commission National Quality Measures (v2018B). Last Updated: 2018. Accessed from https://manual.jointcommission.org/releases/TJC2018B/DataElem0771.html

13. Filho JO, Samuels OB. Mechanical thrombectomy for acute ischemic stroke. UpToDate. Last Update: March 22 2019. Accessed from https://www.uptodate.com/contents/mechanical-thrombectomy-for-acute-ischemic-stroke

14. Prokop M1, Shin HO, Schanz A, Schaefer-Prokop CM. Use of maximum intensity projections in CT angiography: a basic review. Radiographics. 1997 Mar-Apr;17(2):433-51. 

15. Mokin M, Levy EI, Saver JL, Siddiqui AH, Goyal M, Bonafé A, Cognard C, Jahan R, Albers GW; SWIFT PRIME Investigators. Predictive Value of RAPID Assessed Perfusion Thresholds on Final Infarct Volume in SWIFT PRIME (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment). Stroke. 2017 Apr;48(4):932-938.

16. Lui YW, Tang ER, Allmendinger AM, Spektor V. Evaluation of CT perfusion in the setting of cerebral ischemia: patterns and pitfalls. AJNR Am J Neuroradiol. 2010 Oct;31(9):1552-63.

17. Bivard A, Levi C, Krishnamurthy V, McElduff P, Miteff F, Spratt NJ, Bateman G, et al.. Perfusion computed tomography to assist decision making for stroke thrombolysis. Brain. 2015 Jul;138(Pt 7):1919-31. 

18. Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, Yan B,et al.; EXTEND-IA Investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015 Mar 12;372(11):1009-18.

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Approach to Double Vision in the ED

Written by: Andy Rogers, MD (NUEM PGY-2) Edited by: Dana Loke, MD (NUEM PGY-4) Expert commentary by: Quentin Reuter, MD

Seeing double: toil and trouble?

Introduction

Double vision, or diplopia, is a relatively infrequent presenting symptom in the emergency setting, representing 0.1% of Emergency Department (ED) complaints (1).  Diplopia can result from benign processes, such as dry eyes or idiopathic cranial nerve palsy, to emergent conditions with high morbidity, such as stroke, aneurysm, or inflammatory processes.   Given a wide range of possible outcomes for a less common presenting complaint, it is worth reviewing the neuroanatomy and etiologies of diplopia, as well as a generalized approach to the patient presenting to the ED with double vision.  

Neuroanatomy

The neuroanatomy underlying control of the extraocular muscles and their ability to provide gaze alignment is complex and worth a brief review.  Eye movements are governed by six extraocular muscles, which are controlled by four cranial nerves, summarized in Table 1 and Figure 1 below. The nuclei for the cranial nerves are located in the brainstem.  The nerves course from the brainstem, through the subarachnoid space, the cavernous sinus (Figure 2), the orbital apex, and finally to their respective extraocular muscles. Given the close proximity of nearby structures, lesions can often be localized based on associated symptoms, in addition to gaze palsies, to help guide workup and diagnosis.  For instance, an important additional function of CN III includes the parasympathetic fibers that travel along the oculomotor nerve that contribute to pupillary constriction.

Table 1: Summary of functions of the extraocular muscles, grouped by cranial nerve. (2)

Figure 1: Diagnostic positions of gaze with associated extraocular muscles contributing to movement. (3)

Figure 2: Cavernous sinus and its contents. Note that the cavernous sinus is symmetric about the pituitary fossa (only one side is shown above) (4)

Initial approach to diplopia

Dr. Margolin and Dr. Lam published an excellent review of the approach to diplopia in the ED, summarized in Figure 3 (5).  Critical to the diagnosis is a good history and neurologic exam. Their approach involves the follow steps:

1. Determine if symptoms are monocular or binocular

2. Determine if there are associated neurologic signs or symptoms

3. If isolated diplopia, determine if the palsy localizes to a third or sixth nerve palsy, or if it is a complex motility disorder

4. Screen for giant cell arteritis (also known as temporal arteritis) in all patients over the age of 60

Figure 3: Approach to patient with diplopia, from Margolin and Lam (5)

Monocular or Binocular

The first step in the approach to diplopia in the ED is to determine if the diplopia is monocular or binocular.  Some patients may not know or not have checked prior to presentation. Ask the patient “does the double vision resolve when you close one eye?” 

Monocular Diplopia

Monocular diplopia persists with one eye closed.  This localizes the lesions to the affected eye and reflects that the issue is not with misalignment of gaze.  It is almost always benign and most often due to dry eyes and refractive error (5, 6). Referral to an ophthalmologist is appropriate and no further imaging is indicated unless warranted by other features of the patient’s presentation.

Binocular diplopia

Binocular diplopia resolves with one eye closed.  This indicates ocular misalignment that can be due to an issue with the muscle, nerve, or CNS.  

Binocular diplopia with associated neurologic signs

Diplopia with other associated neurologic signs is concerning.  Acute onset of symptoms may be due to intracranial hemorrhage, cerebrovascular disease, or rapidly progressive neurologic disorder.  Initiation of stroke protocol is valuable for several reasons. It allows for rapid diagnosis of hemorrhagic or ischemic stroke, evaluates for cerebral aneurysm, and involves Neurology quickly in the patient’s care.  Some neurologic signs and symptoms, or clusters of signs and symptoms can help identify the etiology (5-7). See Table 2 below.

Binocular diplopia without associated neurologic signs (Isolated diplopia)

In all patients presenting with diplopia, careful examination of the extraocular movements and pupils are important to localizing the lesion.  Note that diplopia can be due to weakness in one direction or entrapment of the muscle limiting range of motion. Both etiologies must be kept in mind.  Figure 1 is a good reference to identify what muscles and nerves may be affected based on directional limitations in extraocular movements. Some important questions to ask include (6):

• Are the two images side by side, on top of each other, or on a diagonal? – helps to tease out the plane of action of the affected muscles and their respective nerves

• What field of gaze makes the double vision worse? – this represents the field of vision of a paretic muscle or opposite the field of action of a restricted muscle

• Can you move your head to correct the vision? – Oblique diplopia due to CN IV paresis often can be distinguished with tilting of the head. Vertical diplopia can be improved with neck extension or flexion. 

• Is there pain with eye movement? – suggests myopathy or orbital process

Isolated 4th nerve palsies:

The trochlear nerve innervates the superior oblique muscle.  Patients often complain of vertical or diagonal diplopia that may correct with head tilt.  CN IV palsies are most commonly due to trauma or are idiopathic in nature (6). In idiopathic CN IV palsies, the patient should be referred to ophthalmology. The palsy often resolves within two weeks.  Important neurologic signs to look for with a CN IV palsy are cerebellar signs. The trochlear nerve exits on the dorsum of the brainstem and may be compressed by a posterior fossa tumor.  

Isolated 6th nerve palsies:

The abducens nerve, or 6th cranial nerve, innervates the lateral rectus muscle. In a 6th nerve plasy, patients will complain of a horizontal diplopia.  There is often inward deviation of the affected eye (esotropia) and symptoms are made worse with lateral gaze to the affected side (6).  This nerve palsy is often idiopathic in etiology, with diabetes mellitus as a risk factor. Be careful to assess for bilateral 6th nerve palsy.  The abducens nerve has a long, isolated course intracranially; tumors can affect the bilateral abducens nerve before other areas of the brain are affected. 

Isolated 3rd nerve palsy:

The oculomotor nerve innervates four muscles and carries parasympathetic fibers that control pupil constriction.  Its course is closely related to the posterior cerebral artery and posterior communicating artery. A palsy of the 3rd nerve (especially with pupillary involvement) may be due to cerebral aneurysm and must emergently be evaluated with CTA, MRA, or intravascular angiography.   An acute isolated 3rd nerve palsy may be due to expanding aneurysm that is at risk of imminent rupture (7).  Pupil sparing 3rd nerve is rarely due to an aneurysm and more often ischemic injury (6,7).  

Internuclear ophthalmoplegia (INO) 

In the setting of horizonal diplopia, also look for internuclear ophthalmoplegia (INO).  An INO is impaired horizontal movement with weak adduction of the affected eye and abduction nystagmus of contralateral eye (8).  This localizes the lesion to the medial longitudinal fasciculous (MLF) in the dorsomedial brainstem tegmentum. The MLF connects the 6th nerve nucleus and medial rectus subnucleus of the 3rd nerve nucleus to coordinate lateral conjugate gaze movement.  In patients <45 years old, it is most commonly caused by multiple sclerosis and is often bilateral (73%) (9).  In older patients, especially those with vascular risk factors, it is caused by cerebrovascular disease and is usually unilateral.   Up to a third have other causes, including infection, tumor, trauma, myasthenia gravis, and Guillain-Barre. Look for historical clues and other neurologic exam findings.  Presence of an INO requires MRI workup. 

Complex motility abnormality

If the diplopia doesn’t isolate to a specific cranial nerve, consider what nerves may be involved and where they are close together to consider anatomic abnormalities. This includes the cavernous sinus, orbital apex, and brainstem.  Brainstem lesions will often have other neurologic deficits identified on exam.  

Cavernous sinus

Cavernous sinus lesions will affect multiple cranial nerves but should not affect visual acuity as the optic nerve does not pass through in relation to the other structures (5,7).  The pituitary gland also resides between the cavernous sinuses. Pituitary mass or apoplexy can compress laterally causing ophthalmoplegia. Another key concern is septic cavernous sinus thrombosis.  These patients will often be septic and febrile. Conversely, consider asking your septic patients if they have double vision! Consider CT and CT venogram of brain and orbits. 

Orbital apex

The orbital apex involves all extraocular muscles, sympathetic fibers, and cranial nerves 2/3/4/6/V1/V2.  Here, the optic nerve is in close anatomic relation to the nerves and muscles of ocular motility. Any ophthalmoplegia with decreased vision or numbness in V1 or V2 distribution should raise concern for orbital apex pathology (5,7).  Consider CT with contrast of the orbits.  

Giant Cell Arteritis

Giant cell arteritis (also known as temporal arteritis) is an important diagnosis to always consider in an elderly patient presenting with diplopia. Missing this diagnosis can lead to permanent vision loss. Diplopia is actually an uncommon finding in GCA, occurring in roughly 5% of cases. However, diplopia has the second highest positive likelihood ratio (LR 3.4) for GCA (the highest being jaw claudication – LR 4.2) (10).  In an elderly patient presenting with diplopia, be on the lookout for other signs and symptoms suggestive of GCA, such as jaw claudication, fevers, vision loss, temporal headaches, PMR, or elevated inflammatory markers.  

Key Points

• Diplopia is a relatively rare presenting complaint in the Emergency Department, and it can portend a wide range of disease, from the benign to the emergent

• A good history and physical exam are key to diagnosis

• Use your physical exam and the presence of other neurologic signs and symptoms to try to localize the lesion and guide imaging choice

• Screen for temporal arteritis in the >60 population

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Expert Commentary

Diplopia is a rare but potentially dangerous chief complaint, making up approximately 0.1% of all ED visits. [1]  In one study of 260 ED patients with non-traumatic, binocular diplopia, 64% had primary diplopia (i.e. no identifiable cause found, likely from microvascular ischemic disease) and 36% had secondary diplopia (i.e. caused by some discernible pathology).  Of patients with secondary diplopia, stroke accounted for nearly 50%, with multiple sclerosis (MS), tumor, aneurysm, myasthenia gravis (MG), and carotid cavernous fistula (CCF) accounting for the other diagnoses. [1]  Given the dangerous etiologies at play, clinicians must approach these patients in a systematic and cautious manner.  (Figure 1)

In patients presenting with diplopia, the first concern must be the possibility of stroke and the need to consider time-sensitive treatment with thrombolytics.  Cranial nerves (CN) 3, 4, and 6 are supplied by the vertebrobasilar arterial system and strokes affecting these nerves most often present with cerebellar dysfunction and/or “crossed signs” or contralateral hemiparesis from involvement of the corticospinal tracts. [2]  Thrombolytic treatment must be considered if the patient is presenting within the appropriate time window and stroke is suspected.  If the patient is outside of the tPA window but suspicion remains for an ischemic process, these patients may benefit from neurologic consultation and MR imaging.  

After considering stroke, look for other associated signs or symptoms that may lead to the correct diagnosis.  If a patient has fevers, facial infections, or meningismus one must consider orbital cellulitis, cavernous venous sinus thrombosis (CVST), meningitis, or encephalitis.  If a patient had a traumatic injury, consider orbital wall fractures, retrobulbar hematoma, increased intracranial pressure (ICP), and intracranial hemorrhage. If a patient has proptosis, chemosis, headaches, and/or facial sensory changes, consider cavernous sinus pathology such as CCF, aneurysm, CVST, mass, or Tolosa-Hunt syndrome (idiopathic inflammatory changes within the cavernous sinus).  If a patient has a severe headache, CN 6 palsy, and/or AMS, consider subarachnoid hemorrhage or other causes of increased ICP. Notably, up to 5% of ruptured PCOM aneurysms present with a CN 6 palsy. [3]  Lastly, if patients have concomitant vision changes/loss, consider pathology of the orbital apex such as mass, infection, and thyroid eye disease.  

If no associated signs or symptoms exists, evaluate the patient for an isolated CN palsy. (Figure 2)  The Margolin paper discusses the importance of obtaining a CTA brain in patients with isolated CN 3 palsy to rule out an intracranial aneurysm.  I would also highlight the importance of obtaining a CTA when patients have an isolated CN 6 palsy as 16% of patients with cavernous sinus carotid aneurysm presented with isolated CN 6 palsy in one study. [4]  In patients with internuclear ophthalmoplegia (INO), admission for MR and neurology consultation is appropriate to rule out stroke and MS, the most common causative pathologies.  Finally, clinicians must consider systemic disease entities such as giant cell arteritis (GCA), MS, and MG. GCA is a vision-threatening disease and must be considered in patients over the age of 60 with transient or persistent diplopia as it is a presenting complaint in 6-27% GCA patients. [5]

Finally, a word of caution when approaching patients with diplopia.  The Margolin article suggests that some patients with isolated diplopia can have non-emergent outpatient follow-up once an aneurysm has been excluded.  Others have also recommended that a CT brain is not useful in the setting of isolated diplopia citing one study showing CT had a sensitivity of 0% in 11 patients with isolated secondary diplopia as the rationale. [6]  I believe these recommendations are unrealistic for many reasons.  First, diplopia is encountered only infrequently in the ED, making the gains of avoiding a CT brain and inpatient neurologic workup minimal.  Furthermore, the neuro-ophthalmologic exam is challenging, and some patients can present with partial palsies or deficits involving multiple cranial nerves, making diagnosis of a specific CN challenging.  Clinicians must also be 100% confident that no other signs or symptoms exist such as jaw claudication in GCA or subtle vision changes and papilledema for pseudotumor cerebri prior to discharge, a difficult task in a busy ED.  Ensuring reliable and urgent neurologic follow-up and outpatient MR imaging can also be difficult or impossible in many health systems. Patients will also likely appreciate obtaining a definitive diagnosis for a concerning neurologic symptom like diplopia in a timely manner.   Moreover, of the 11 patients with isolated secondary diplopia for which CT was not useful in the Nazerian article, two had strokes, another patient had a mass, and another had a CFF that the CT missed. [1]  Diagnoses such as stroke, aneurysm, MS, GCA, and neoplasm can all have morbid ramifications if not expediently diagnosed.  

As such, in patients with isolated diplopia, it may be appropriate for ED clinicians to rule out aneurysm with vascular imaging and admit for neurology consultation and MR to evaluate for more sinister pathology.  ED clinicians should at the very least discuss the case with a consulting neurologist to ensure appropriate management. While the majority of patients with isolated diplopia will go on to be diagnosed with microangiopathic ischemia, given the above concerns, it would seem reasonable for ED clinicians to err on the side of caution and get help from their local neurology colleagues for these challenging patients. 

Citations:

1. Nazerian P, Vanni S, Tarocchi C, et al. Causes of diplopia in the emergency department: diagnostic accuracy of clinical assessment and of head computed tomography. Eur J Emerg Med 2014;21:118-24.

2. Rowe F, UK VISg. Prevalence of ocular motor cranial nerve palsy and associations following stroke. Eye (Lond) 2011;25:881-7.

3. Burkhardt JK, Winkler EA, Lasker GF, Yue JK, Lawton MT. Isolated abducens nerve palsy associated with subarachnoid hemorrhage: a localizing sign of ruptured posterior inferior cerebellar artery aneurysms. J Neurosurg 2018;128:1830-8.

4. Stiebel-Kalish H, Kalish Y, Bar-On RH, et al. Presentation, natural history, and management of carotid cavernous aneurysms. Neurosurgery 2005;57:850-7; discussion -7.

5. Haering M, Holbro A, Todorova MG, et al. Incidence and prognostic implications of diplopia in patients with giant cell arteritis. J Rheumatol 2014;41:1562-4.

6.Kisilevsky E, Kaplan A, Micieli J, McGowan M, Mackinnon D, Margolin E. Computed tomography only useful for selected patients presenting with primary eye complaints in the emergency department. Am J Emerg Med 2018;36:162-4.

Figure 1: Approach to the patient with diplopia

Figure 2: Clinical exam for CN 3 palsy, CN 6 palsy, and INO

Figure 2A: Complete CN 3 palsy

Figure 2B: Complete CN 6 palsy

Figure 2C: Internuclear Ophthalmoplegia

Quentin Reuter, MD

Assistant Professor of Emergency Medicine

Northeast Ohio Medical University

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Citations

Sources:

1. “Causes of Diplopia in the Emergency Department: Diagnostic Accuracy of Clinical Assessment and of Head Computed Tomography.” Nazerian et al. European Journal of Emergency Medicine. 21 April 2014 (2):118-24. Doi 10.097/MEJ.0b01323283636120

2. “Actions of Extraocular Muscles.” UpToDate.com. Accessed 11/22/18. 

3. Image adapted from: “Diagnostic Positions of Gaze.” UpToDate.com Accessed 11/22/18. 

4. Image from: “ZSFG Neuro Report: Multiple Cranial Neuropathies – Spotlight on the Cavernous Sinus.”  Stern, Rachel. UCSF Internal Medicine Chief Resident Hub. Published 28 Oct 2016. Accessed 20 November 2018. https://ucsfmed.wordpress.com/2016/10/28/zsfg-neuro-report-multiple-cranial-neuropathies-spotlight-on-the-cavernous-sinus/

5. “Approach to a Patient with Diplopia in the Emergency Department.” Margolin, Edward and Lam, Cindy.  Journal of Emergency Medicine. Volume 54, Issue 6. June 2018. pp799-806. Accessed 16 November 2018. 

6. “Overview of Diplopia.” Bienfang, Don. UpToDate. Last updated 20 June 2017. Accessed 17 November 2018. 

7. “Third Cranial Nerve (Oculomotor Nerve) Palsy in Adults.” Lee, Andrew. UpToDate. Last updated 19 June 2017. Accessed 17 November 2018. 

8. “Internuclear Ophthalmoparesis.” Frohman, Teresa; Frohman, Elliot.  UpToDate. Last updated 4 December 2017. Accessed 18 November 2018. 

9. “Internuclear Ophthalmoplegia Unusual Causes in 114 of 410 Patients.” Keane, James.  Arch Neurol. 2005;62(5):714–717. doi:10.1001/archneur.62.5.714

10. “Does This Patient Have Temporal Arteritis?” Smetana, Gerald; Shmerling, Robert. JAMA. 2002;287(1):92–101. doi:10.1001/jama.287.1.92

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How To Cite This Post

[Peer-Reviewed, Web Publication]  Rogers A, Loke D. (2019, Nov 18). Approach to Double Vision in the ED. [NUEM Blog. Expert Commentary by Reuter Q]. Retrieved from http://www.nuemblog.com/blog/double-vision.

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