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Clinical Mimics: An Emergency Medicine-Focused Review of Stroke Mimics
The Journal of Emergency Medicine, Vol. -, No. -, pp. 1–8, 2016 Published by Elsevier Inc. 0736-4679/$ - see front matter
http://dx.doi.org/10.1016/j.jemermed.2016.09.021
Clinical Review CLINICAL MIMICS: AN EMERGENCY MEDICINE-FOCUSED REVIEW OF STROKE MIMICS Brit Long, MD* and Alex Koyfman, MD† *Department of Emergency Medicine, San Antonio Military Medical Center, Fort Sam Houston, Texas and †Department of Emergency Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas Reprint Address: Brit Long, MD, Department of Emergency Medicine, San Antonio Military Medical Center, 3551 Roger Brooke Dr, Fort Sam Houston, TX 78234
, Abstract—Background: Stroke is a leading cause of death and disability and most commonly presents with focal neurologic deficit within a specific vascular distribution. Several other conditions may present in a similar manner. Objectives: This review provides emergency providers with an understanding of stroke mimics, use of thrombolytics in these mimics, and keys to differentiate true stroke from mimic. Discussion: Stroke has significant morbidity and mortality, and the American Heart Association emphasizes rapid recognition and aggressive treatment for patients with possible stroke-like symptoms, including thrombolytics. However, many conditions mimic the presentation of stroke, with up to a 31% rate of misdiagnosis, leading to potentially harmful treatment. Stroke mimics are conditions that present with stroke-like symptoms, including seizures, headaches, metabolic, infection, space-occupying lesion, neurodegenerative disorder, peripheral neuropathy, syncope, vascular disorder, and functional disorder. Factors of history and physical examination supporting stroke vs. mimic are discussed, though any sudden-onset, objective, focal neurologic deficit in a patient should be assumed acute stroke until proven otherwise. Head computed tomography noncontrast is the first-line imaging modality. Magnetic resonance imaging is the most sensitive and specific imaging modality. Neurology consultation is recommended in the majority of patients. If stroke is suspected after evaluation, shared decision-making for further management and consideration of thrombolytics is recommended. Conclusions: Stroke mimics present a conundrum for emergency providers. A new focal neurologic deficit warrants rapid
evaluation for stroke with neuroimaging and neurology consultation. Several mimics found on assessment may resolve with treatment. Published by Elsevier Inc. , Keywords—stroke; cerebrovascular accident; thrombolytics; mimic; headache; seizure; encephalopathy; hypoglycemia; peripheral neuropathy; neurodegenerative; chameleon
INTRODUCTION Cerebrovascular accident (CVA) is among the top five causes of death and the number one cause of disability in the United States (1,2). Acute ischemic attack affects over 600,000 patients per year, with three-quarters of these presenting with a first-time stroke (1–5). With the potential morbidity and mortality of stroke, the American Heart Association (AHA) recommends rapid recognition and potentially aggressive treatment of patients presenting with possible stroke symptoms (3–7). A significant push exists to rapidly diagnose CVA and obtain glucose and head computed tomography (CT) in patients with concern for CVA, as thrombolytics require specific time criteria and contraindication considerations (6,7). Literature suggests that for every 15-min interval reduction in time to thrombolytics, patients demonstrate improved
RECEIVED: 7 September 2016; ACCEPTED: 12 September 2016 1
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morbidity and decreased risk of intracranial hemorrhage, the primary concern of providing thrombolytics (8,9). Classically, strokes present as the sudden onset of a focal neurologic deficit in a vascular distribution (6,7,10). There are multiple diagnoses that may mimic this presentation. Misdiagnosis of stroke ranges from 5% to 31% of patients, which can potentially lead to unnecessary and harmful treatments if patients present within the thrombolytic time window (11–17). Patients can experience many conditions that may present as stroke, often confounding the clinical picture. These conditions are known as stroke mimics. DISCUSSION A stroke mimic is defined as a nonvascular disease that presents with stroke-like symptoms, often indistinguishable from an actual CVA. The harmful side effects of thrombolytics, most commonly bleeding, are not insignificant; thus, accurate diagnosis is essential. Rates of mimic treated with intravenous thrombolytics vary from 1% to 20% (11–17). The rate of bleeding approaches 1–2% in these patients (14,15). Acute CVA may present with a variety of symptoms including weakness, sensory changes, vision changes, dysarthria, dysphagia, vision abnormalities, seizures, and many others (11–13,17). Due to this wide variety of symptoms, many other conditions may, on initial impression, be diagnosed as acute stroke (17–23). Table 1 lists these common conditions (6–8,13,17–48). Stroke Chameleons A stroke chameleon is a CVA that presents as a different condition (23,25,49). Movement disorders such as acute hemiballismus can occur with acute lesions in the subthalamic nucleus. This condition will present with wild movements, often uncontrollable, that are one sided. Confusion, agitation, and delirium may occur with acute lesions of temporal lobe limbic cortex, as well as the orbitofrontal regions (23,25,49). This can be difficult to differentiate from stroke syndromes with neglect or aphasia, as the patient may appear altered. Lesions affecting the parietal or thalamic regions may result in sensory loss. Cortical blindness is rare, but examination demonstrates normal pupillary light response and normal optic disks (23,25,49). One key to differentiation and diagnosis of the stroke chameleon is evaluating for symptoms with abrupt onset. Risk factors for cerebrovascular disease such as cardiovascular disease, diabetes, hypertension, and hyperlipidemia can suggest stroke with atypical presentation, but by no means are they definitive (11,17–20,25). Another
key difference is the presentation of negative symptoms or deficit in strokes (25). Differentiating Stroke vs. Mimic Diagnosis of stroke, compared to mimic, depends on the complaint, risk factors, onset time, vascular distribution of symptoms, and imaging modalities available to the provider. A variety of studies have evaluated signs or symptoms that can indicate stroke vs. mimic. One study found convulsions (odds ratio [OR] 4.59) and aphasia (OR 2.55) to predict mimic, whereas dysarthria (0.25), hemiparesis (OR 0.26), facial palsy (OR 0.22), and visual field neglect (0.15) predict stroke (20,50). A separate study suggests that chest pain (OR 16.7) and paresthesias (OR 10) more commonly suggest mimic (20,22). Ultimately, studies display conflicting results. Two or three focal findings (acute facial paralysis, arm drift/weakness, change in speech) with abrupt onset suggest CVA, whereas the lack of these findings suggest mimic (11,17–23,25,32,50–52). This history is also vital, as younger age is more commonly associated with mimic in most studies, though one study by Winkler et al. finds it to be inconclusive (52). Risk factors such as atrial fibrillation (OR 11.4) are often associated with stroke, though other studies have found conflicting results (16–20,50). Other risk factors such as coronary artery disease, hypertension, hyperlipidemia, and diabetes are inconsistent, with some studies suggesting improved likelihood of stroke and others suggesting no correlation (11,16–23,25,32,51–54). A prior history of epilepsy, baseline cognitive impairment, and migraine can suggest mimic, but beware of contributing all conditions to these factors. Time of onset is a necessary part of the evaluation. A suddenonset deficit in a vascular distribution suggests CVA, and several deficits fitting a specific anatomic distribution supports a diagnosis of acute ischemic stroke as well (11,16–23,25,32,51–53). Table 2 depicts factors supporting stroke and mimic (11,16–23,25,32,51–53). Management The goals of care in evaluation of the patient with concern for CVA are rapid recognition of the deficit and rapid imaging. Stroke is one of the most life-threatening and timesensitive conditions associated with focal deficit requiring diagnosis in the ED. The diagnosis of stroke mimic is most commonly completed only after advanced imaging, laboratory investigation, and neurology consultation (6–8). Any focal deficit should be assumed CVA. A focused history and physical examination must be completed in a rapid manner with assessment of the National Institutes of Health Stroke Scale (NIHSS)
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Table 1. Common Stroke Mimics Condition
Presentation
Management
Seizure (6–8,13,17–26)
–Accounts for 20% of mimics. –May originate from prior stroke foci. –Generalized convulsions, involuntary movements, postictal confusion, incontinence, tongue biting more frequent. –Up to 8% of strokes may present with seizure. –Postictal paresis occurs in up to 10% of seizures, usually lasting 180 s. May last for several hours. –Account for 10% of mimics. –Patients often present with positive prior history and no evidence of focal deficit. –Hemiplegic migraine is autosomal disorder, often teenagers with first episode. –Classic migraine features are common, though nearly 30% of stroke patients may have headache at stroke onset. –Migraine with aura accounts for 20–30% of migraine headaches. Auras typically have a gradual onset over 5 min and last under 60 min. –Auras usually have visual symptoms, rather than motor or sensory disturbances. –Basilar migraines present with vision changes, vertigo, dysarthria, and altered mentation. –Serum glucose levels < 55 mg/dL in healthy individuals defines hypoglycemia, whereas levels < 70 mg/dL in diabetics is significant. –Neuroglycopenic episodes commonly present with confusion and autonomic symptoms, but can uncommonly present with paresis. –Autonomic symptoms are often first in hypoglycemia with diaphoresis and tachycardia. –Glucose level is often 30 mg/dL in patients with hemiparesis. Right-sided symptoms more common. –Hyperglycemia may produce focal deficits. Hyperosmolar, nonketotic hyperglycemia can present with movement disorders such as hemichorea-hemiballismus. –Hyper-/hyponatremia and hepatic encephalopathy may result in focal deficit, commonly through cerebral edema. –Sepsis accounts for 6–20% of mimics. –Encephalopathy including coma, weakness, and speech changes may occur. –Due to neuroinflammatory response and blood brain barrier dysfunction –Fever many not be present in elderly patients with sepsis. –Hyperthermia/hypothermia, tachycardia, and altered mental status may occur in sepsis. –Brain abscess, meningitis, and encephalitis may present with focal deficits. –Include CNS tumors, metastases, and abscesses. –Mass effect and alteration in vascular blood flow may result in focal neurologic deficit. –These deficits often present over 24–48 h.
–Active seizures require treatment with benzodiazepines and second-line agents such as levetiracetam, fosphenytoin, or valproate. –MRI with diffusion-weighted imaging can assist in differentiation. –Seizure at time of stroke onset is a contraindication to tPA administration.
Headache (13,17–20,25,27,28)
Metabolic (13,17–20,25,29–33)
Infection (13,17–20,34)
Space-occupying lesion (13,17–20,25,34–36)
–Headache with a focal deficit should be considered CVA until proven otherwise. –Patients with focal deficit require neuroimaging. –Treat headache with medications including antidopaminergic agents, nonsteroidal antiinflammatory medications, and other treatments as indicated. –Focal deficit requires neurology consultation.
–Rapid assessment of blood glucose is needed in any neurologic complaint including altered mental status. –A variety of causes of hypoglycemia such as insulin or sulfonylurea overdose, alcohol intoxication, Addison crisis. –Hypoglycemia is rapidly correctable with provision of glucose. Correction of neurologic deficit is usually rapid, though it may take hours.
–Evaluate for sepsis with systemic inflammatory response and source of infection. –Seek a baseline functional status from patient, family member, or nursing facility. –Without baseline status, any neurologic deficit should be assumed to be stroke. –Timeframe of onset may assist, because sepsis is more often gradual. –Neuroimaging is required with any focal deficit or altered mental status. –Neuroimaging is required, with noncontrast head CT able to rapidly diagnose mass or acute intracranial hemorrhage. –Mass lesions likely require neurosurgery consultation. (Continued )
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Table 1. Continued Condition Peripheral neuropathy (13,17–20,25)
Neurodegenerative disorder (13,17–20,25,37–40)
Syncope (13,17–20,35,40)
Cerebrovascular narrowing (13,41–44)
Functional (17,25,45,46)
Toxin/ingestion (13,47,48)
Presentation
Management
–Less common mimic. –Due to cellular changes in distal nerves, causing axonal degeneration, segmental degeneration, or Wallerian degeneration. –Mononeuropathies often cause focal sensorimotor deficits and can occur acutely. –Peripheral nerve injury may result in sensorimotor dysfunction, muscle atrophy, and areflexia, whereas stroke often results in hyperreflexia and no atrophy. –Rare mimic. –May present with variety of deficits including hemiparesis or cranial nerve deficits. –Multiple sclerosis (MS) may present with focal deficits that worsen with heat and stress. –Optic neuritis presents with sudden vision loss and is the first symptom in 20% of cases of MS. –Guillain-Barre´ syndrome progressive, ascending bilateral paralysis characterized by peripheral motor weakness, hyporeflexia. –Accounts for 20% of mimics. –Strokes of the vertebrobasilar system may cause altered consciousness. –Syncope is defined by loss of consciousness with rapid return to baseline. –Consists of neurogenic, orthostatic, cardiogenic, and other serious causes such as heat syncope, hypoglycemia, subarachnoid hemorrhage, and subclavian steal. –Rare cause of mimic. –Includes vasculitis, reversible cerebral vasoconstriction syndrome (RCVS), subarachnoid hemorrhage (SAH), idiopathic intracranial hypertension (IIH), and atherosclerosis. –Onset varies from acute to chronic, with ataxia, weakness, and vision changes. –RCVS and SAH often present with sudden, maximal headache. –IIH most commonly affects young, obese women, often with chronic headache and vision changes (35–70%). Abducens nerve palsy is present in 80%. –One of the most common mimics, with conversion disorder accounting for 75% in one study. –Focal deficit in the setting of some trigger is common. –Variety of complaints including paralysis, aphonia, seizures, ataxia, blindness, paresthesias. –Physical examination may be inconsistent with repeated evaluations. –Deficits often do not fit a specific vascular territory. –Patients may present with confusion and atypical neurologic examination. –Include anticholinergic toxidrome, salicylates, acetaminophen, ethanol, antidopaminergic medications, tricyclic antidepressants, and strychnine poisoning. –Strychnine poisoning results from competitive antagonism of glycine at postsynaptic receptors and presents with twitching, spasms, trismus, and opisthotonos.
–History and chronicity assist in differentiating stroke vs. neuropathy, as this condition is more gradual in onset. –Examination with decreased reflexes and atrophy may be found. –Neurology consultation is recommended; diagnosis often requires electromyography, nerve biopsy. –All focal deficits warrant neuroimaging. –History is essential to evaluate for other medical conditions and prior exacerbations. –Neurology consultation is needed for patients with neurodegenerative conditions.
–Vertebrobasilar strokes will have unilateral cranial nerve deficits in association with alteration in mental status. –Syncope should not demonstrate focal neurologic deficits. –Syncope may have transient tonic clonic movements lasting approximately 30 s. –Focal deficits suggest CVA. –Imaging with noncontrast head CT and CT angiography is recommended. –Lumbar puncture may be needed for definitive diagnosis of SAH and IIH. –Vasculitis syndromes may result in true ischemia and stroke. High-dose steroids may be needed for treatment. –Neurology consultation is advised. Vasculitis affecting the nervous system.
–Conversion disorder is rare, and focal deficits require neuroimaging. –History and physical examination can assist providers. –CVA will more likely have vascular territory deficits, with consistent examinations. –If functional disorder is diagnosed, reassurance and efforts to remove stressor are needed. –Evaluation of electrocardiogram for QRS and QT prolongation. –Seizure should be treated with benzodiazepines. –Specific treatments warranted for the agent ingested (bicarbonate for tricyclic or salicylates). –Sedation may be required for agitated patients.
MRI = magnetic resonance imaging; tPA = tissue plasminogen activator; CVA = cerebrovascular accident; CNS = central nervous system; CT = computed tomography.
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Table 2. History and Examination Findings in Stroke vs. Mimic (11,16–23,25,32,51–53) Assessment
Suggests Mimic
Suggests Stroke
History
Prior seizures/epilepsy Migraine Cognitive impairment
Atrial fibrillation
Symptom/sign
Altered mental status Chest pain Speech change/aphasia without hemiparesis
Focal weakness Hemiparesis Dysarthria Gaze palsy Focal symptom in anatomic vascular distribution
Inconclusive Age Gender Hypertension Hyperlipidemia Coronary artery disease Smoking Prior stroke Peripheral vascular disease Psychiatric disease Kidney disease Paresthesias Headache Dizziness/vertigo Less severe deficit (NIHSS < 10) Convulsions at onset
NIHSS = National Institutes of Health Stroke Scale.
(6–8). If unable to complete the NIHSS, a focused assessment for facial paralysis, arm drift/weakness, or speech change should occur (6–8,16–20). Table 3 depicts goals of care for these patients. A blood glucose level should be obtained, as hypoglycemia is a common mimic that is easily correctable. Ancillary laboratories include electrolytes, blood urea nitrogen/creatinine, complete blood count, troponin, coagulation studies, and 12-lead electrocardiogram. Noncontrast CT of the head is often the first-line imaging modality, though this test and its interpretation may not be always reliable. Location of deficit. Anterior circulation deficits involve the middle cerebral or anterior cerebral arteries, often presenting with clear focal deficits such as upper extremity weakness, aphasia, or leg weakness. Anterior cerebral artery lesions will cause leg weakness that is worse compared to arm weakness, often with aphasia and cognitive or behavioral alterations. Middle cerebral artery infarction will present with contralateral hemiparesis and speech changes and gaze preferences. Posterior circulation strokes affect posterior cerebral artery and present with more confusion symptoms such as dizziness,
vertigo, cranial nerve deficit, altered mental status, or visual field deficit. Lacunar strokes affect the deep cerebral penetrating arteries and will more likely be confused with other conditions, or a stroke chameleon, with pure motor, sensorimotor, pure sensory, ataxic hemiparesis, or dysarthria-clumsy hand syndrome (6–8,20). Imaging. Noncontrast head CT is easily available and the most feasible test in the ED for patients with focal deficit or concern for CVA. However, imaging modalities vary based on institution. The sensitivity and specificity of certain modalities have significant differences. Head CT has the lowest sensitivity, ranging from 12% to 52%, though large anterior circulation strokes are often easily discovered on this modality. Distal lesions due to small emboli often require the use of angiography and perfusion imaging (20,53). CT angiography can assist in demonstrating focal obstructions or diffuse atherosclerosis, which has an OR of 23.6 for ischemic stroke identification (53). Large-vessel occlusions on this modality indicate worse outcomes. CT angiography in addition to noncontrast head CT increases the sensitivity to over 70%, with specificity approaching 88% (20,53).
Table 3. Goals of Assessment and Management – Obtain focused history and physical examination evaluating for speech deficit, weakness, or facial paralysis. Conduct NIHSS if able. – Rapid blood glucose measurement is needed. Other tests, including ECG, function as adjuncts. – Obtain noncontrast head CT within 25 min of patient arrival, with interpretation complete by 45 min. Other imaging warranted per anatomic distribution. – Assume CVA in patient with focal neurologic deficit and sudden onset or combination of objective findings. – Symptoms with more gradual onset, inconsistent physical examination findings, and nonvascular territory complaints suggest mimic. – Concern for stroke within thrombolytic time window requires consideration of tPA in shared decision-making. – Obtain neurologic consultation for patients with focal deficit or concern for stroke vs. mimic. NIHSS = National Institutes of Health Stroke Scale; ECG = electrocardiogram; CT = computed tomography; CVA = cerebrovascular accident; tPA = tissue plasminogen activator.
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Unfortunately, agreement on diagnosis of acute stroke based on head CT is poor between separate physicians, and head CT possesses a sensitivity of 12% for small lesions and transient ischemic events (20,53). Posterior circulation symptoms require the use of magnetic resonance imaging (MRI). MRI possesses sensitivities over 80% and specificities over 95% (12,16,17,20,54– 58). Diffusion-weighted imaging evaluates ischemic tissue more readily, as well as demonstrating damaged but not ischemic areas (6–8,54–58). If anterior circulation deficits involving the middle cerebral artery are present, including unilateral weakness with aphasia or neglect, noncontrast head CT followed by angiography is warranted. If there is concern for anterior circulation deficits, including leg more than arm weakness, noncontrast head CT and angiography are efficacious. On the other hand, patients with posterior circulation symptoms should undergo MRI, though if this is not available, angiography may be used (20). Treatment.If the history, physical examination, and investigations suggest CVA, thrombolytics should be considered as long as the patient is in the AHA time window. Shared decision-making with the patient and family is advised. Several mimics such as hypoglycemia are easily discernable and rapidly corrected. Mass found on CT or the patient with systemic inflammatory response syndrome criteria and definitive source are reasons to withhold tissue plasminogen activator (tPA) (17–22,25). Symptoms that rapidly resolve, witnessed seizure, and history of epilepsy suggest seizure. With focal deficit, emergent neuroimaging is needed. A well-conducted history and physical examination is essential. Careful evaluation of subjective and objective factors in the patient’s symptoms is recommended. A deficit that remains and does not change over several reevaluations strongly suggests organic disease, whereas deficits that do not fit a specific anatomical region or those that change over several reevaluations suggest functional disorder (11,15–22,25,32,56–60). Neurology consultation is advised in patients with objective neurologic findings, no matter the history. Patients with sudden-onset deficits and objective findings within the AHA thrombolytic time window may improve with tPA (6–8,15,20–22,25). The risks and benefits of thrombolytic treatment should be discussed with the management team and the patient using shared decision-making. CONCLUSIONS Stroke is a condition associated with significant morbidity and mortality, often presenting with focal neurologic deficit within defined vascular distribution.
Stroke mimic is any condition that presents with stroke-like symptoms and includes seizures, headaches, metabolic, infection, space-occupying lesion, neurodegenerative disorder, peripheral neuropathy, syncope, and functional disorder. This review evaluates stroke mimics, differentiation between stroke and mimic, and provides an approach to evaluation and management. Few historical factors support either, though migraine history, seizure history, psychiatric history, altered mental status, speech alteration without weakness, and chest pain suggest mimic. A history of atrial fibrillation, focal weakness, hemiparesis, dysarthria, gaze palsy, and focal symptom in anatomic vascular distribution suggest stroke. However, any new, focal neurologic deficit or combination of deficits should be assumed to be stroke until proven otherwise. Head CT noncontrast is the first-line imaging modality, though MRI with diffusion-weighted imaging possesses greater diagnostic abilities. Neurologic consultation should be completed for patients with focal deficit. REFERENCES 1. Centers for Disease Control and Prevention, National Center for Health Statistics. CDC Wonder Online Database, compiled for compressed mortality file 1999–2009, Series 20, No. 20, 2012. Underlying cause-of-death 1999–2009. Available at: wonder.cdc.gov/ Mortsql.html. Accessed July 14, 2016. 2. Kochanek KD, Murphy SL, Xu JQ, Arias E. Mortality in the United States, 2013. NCHS Data Brief 2014;1–8. 3. Mozzafarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics — 2015 update: a report from the American Heart Association. Circulation 2015;131:e29–322. 4. Go AS, Mozzafarian D, Roger VL, et al., American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics — 2014 update: a report from the American Heart Association. Circulation 2014;129:e28–292. 5. Centers for Disease Control and Prevention (CDC). Prevalence and most common causes of disability among adults—United States, 2005. MMWR Morb Mortal Wkly Rep 2009;58:421–6. 6. Goldstein LB, Bushnell CD, Adams RJ, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2010;42:517–84. 7. Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:870–947. 8. Saver JL. Time is brain—quantified. Stroke 2006;37:263–6. 9. Saver JL, Fonarow GC, Smith EE, et al. Time to treatment with intravenous tissue plasminogen activator and out- come from acute ischemic stroke. JAMA 2013;309:2480–8. 10. Goldstein LB, Simel DL. Is this patient having a stroke? JAMA 2005;293:2391–402. 11. Merino JG, Luby M, Benson RT, et al. Predictors of acute stroke mimics in 8187 patients referred to a stroke service. J Stroke Cerebrovasc Dis 2013;22:397–403. 12. Ali SF, Viswanathan A, Singhal AB, et al. The telestroke mimic (TM)-Score: a prediction rule for identifying stroke mimics evaluated in a telestroke network. J Am Heart Assoc 2014;3:e000838. 13. Magauran BG, Nitka M. Stroke mimics. Emerg Med Clin North Am 2012;30:795–804. 14. Tsivgoulis G, Alexandrov AV, Chang J, et al. Safety and outcomes of intravenous thrombolysis in stroke mimics: a 6-year, single-care
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7 40. Kose A, Inal T, Armagan E, Kiyak R, Demir AB. Conditions that mimic stroke in elderly patients admitted to the emergency department. J Stroke Cerebrovasc Dis 2013;22:e522–7. 41. Calabrese LH, Duna GF, Lie JT. Vasculitis in the central nervous system. Arthritis Rheum 1997;40:1189–201. 42. Salvarani C, Brown RD Jr, Calamia KT, et al. Primary central nervous system vasculitis: analysis of 101 patients. Ann Neurol 2007; 62:442–51. 43. Sattar A, Manousakis G, Jensen MB. Systematic review of reversible cerebral vasoconstriction syndrome. Expert Rev Cardiovasc Ther 2010;8:1417–21. 44. Friedman DI, Jacobson DM. Diagnostic criteria for idiopathic intracranial hypertension. Neurology 2002;59:1492–5. 45. Feinstein F. Conversion disorder: Advances in our understanding. CMAJ 2011;183:915–20. 46. Stone J, Warlow C, Sharpe M. Functional weakness: clues to mechanism from the nature of onset. J Neurol Neurosurg Psychiatry 2012;83:67–9. 47. Greene S. General management of poisoned patients. In: Tintinalli J, Stapczynski J, Ma OJ, Yealy D, Meckler G, Cline D, eds. Tintinalli’s emergency medicine: a comprehensive study guide. 8th edn. Chapel Hill, NC: McGraw-Hill Holdings, LLC; 2016. Available at: http://accessemergencymedicine.mhmedical. com/content.aspx?bookid=1658§ionid=109437481. Accessed July 27, 2016. 48. Burillo-Putze G, Xarau SN. Pesticides. In: Tintinalli J, Stapczynski J, Ma OJ, Yealy D, Meckler G, Cline D, eds. Tintinalli’s emergency medicine: a comprehensive study guide. 8th edn. Chapel Hill, NC: McGraw-Hill Holdings, LLC; 2016. Available at: http:// accessemergencymedicine.mhmedical.com/content.aspx?section id=109415903&bookid=1658&jumpsectionID=109416056&Result click=2. Accessed July 24, 2016. 49. Dupre CM, Libman R, Dupre SI, Katz JM, Rybinnik I, Kwiatkowski T. Stroke chameleons. J Stroke Cerebrovasc Dis 2014;23:374–8. 50. Chang J, Teleb M, Yang JP, et al. A model to prevent fibrinolysis in patients with stroke mimics. J Stroke Cerebrovasc Dis 2012;21: 839–43. 51. Gibson LM, Whiteley W. The differential diagnosis of suspected stroke: a systematic review. J R Coll Physicians Edinb 2013;43: 114–8. 52. Winkler DT, Fluri F, Fuhr P, et al. Thrombolysis in stroke mimics: frequency, clinical characteristics, and outcome. Stroke 2009;40: 1522–5. 53. Hopyan J, Ciarallo A, Dowlatshahi D, et al. Certainty of stroke diagnosis: incremental benefit with CT perfusion over noncontrast CT and CT angiography. Radiology 2010;255:142–53. 54. Ay H, Buonanno FS, Rordorf G, et al. Normal diffusion-weighted MRI during stroke-like deficits. Neurology 1999;52:1784–92. 55. Rajajee V, Kidwell C, Starkman S, et al. Early MRI and outcomes of untreated patients with mild or improving ischemic stroke. Neurology 2006;67:980–4. 56. Chalela 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;369:293–8. 57. Moreau F, Asdaghi N, Modi J, Goyal M, Coutts SB. Magnetic resonance imaging versus computed tomography in transient ischemic attack and minor stroke: the more you see the more you know. Cerebrovasc Dis Extra 2013;3:130–6. 58. Hemmen TM, Meyer BC, McClean TL, et al. Identification of nonischemic stroke mimics among 411 code strokes at the University of California, San Diego, Stroke Center. J Stroke Cerebrovasc Dis 2008;18:23–5. 59. Artto V, Putaala J, Strbian D, et al. Stroke mimics and intravenous thrombolysis. Ann Emerg Med 2012;59:27–32. 60. Vroomen PC, Buddingh MK, Luijckx GJ, et al. The incidence of stroke mimics among stroke admissions in relation to age group. J Stroke Cerebrovasc Dis 2008;17:418–22.
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ARTICLE SUMMARY 1. Why is this topic important? Acute stroke is a major cause of morbidity and mortality. It often presents with focal neurologic deficit, and many conditions may present with stroke-like symptoms, known as stroke mimic. 2. What does this review attempt to show? This review evaluates stroke mimics, use of thrombolytics in mimics, and keys in differentiating acute stroke vs. mimic. 3. What are the key findings? Stroke possesses significant morbidity and mortality, and the American Heart Association emphasizes rapid recognition and potentially aggressive treatment for acute stroke. Many conditions can mimic stroke. Conditions include seizures, headaches, metabolic conditions, infection, space-occupying lesion, neurodegenerative disorder, peripheral neuropathy, syncope, and functional disorder. Through utilizing several history and physical examination factors, the differential can be narrowed. Focal neurologic deficit requires imaging, with noncontrast computed tomography of the head first line. Magnetic resonance imaging with diffusion-weighted imaging provides greater diagnostic capability. Neurology consultation and shared decision-making should be utilized in consideration of stroke vs. mimic. 4. How is patient care impacted? Stroke mimics can be challenging to diagnose, and any focal neurologic deficit or combination of deficits warrants evaluation for acute stroke with neuroimaging and neurology consultation.
http://dx.doi.org/10.1016/j.jemermed.2016.09.021
Clinical Review CLINICAL MIMICS: AN EMERGENCY MEDICINE-FOCUSED REVIEW OF STROKE MIMICS Brit Long, MD* and Alex Koyfman, MD† *Department of Emergency Medicine, San Antonio Military Medical Center, Fort Sam Houston, Texas and †Department of Emergency Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas Reprint Address: Brit Long, MD, Department of Emergency Medicine, San Antonio Military Medical Center, 3551 Roger Brooke Dr, Fort Sam Houston, TX 78234
, Abstract—Background: Stroke is a leading cause of death and disability and most commonly presents with focal neurologic deficit within a specific vascular distribution. Several other conditions may present in a similar manner. Objectives: This review provides emergency providers with an understanding of stroke mimics, use of thrombolytics in these mimics, and keys to differentiate true stroke from mimic. Discussion: Stroke has significant morbidity and mortality, and the American Heart Association emphasizes rapid recognition and aggressive treatment for patients with possible stroke-like symptoms, including thrombolytics. However, many conditions mimic the presentation of stroke, with up to a 31% rate of misdiagnosis, leading to potentially harmful treatment. Stroke mimics are conditions that present with stroke-like symptoms, including seizures, headaches, metabolic, infection, space-occupying lesion, neurodegenerative disorder, peripheral neuropathy, syncope, vascular disorder, and functional disorder. Factors of history and physical examination supporting stroke vs. mimic are discussed, though any sudden-onset, objective, focal neurologic deficit in a patient should be assumed acute stroke until proven otherwise. Head computed tomography noncontrast is the first-line imaging modality. Magnetic resonance imaging is the most sensitive and specific imaging modality. Neurology consultation is recommended in the majority of patients. If stroke is suspected after evaluation, shared decision-making for further management and consideration of thrombolytics is recommended. Conclusions: Stroke mimics present a conundrum for emergency providers. A new focal neurologic deficit warrants rapid
evaluation for stroke with neuroimaging and neurology consultation. Several mimics found on assessment may resolve with treatment. Published by Elsevier Inc. , Keywords—stroke; cerebrovascular accident; thrombolytics; mimic; headache; seizure; encephalopathy; hypoglycemia; peripheral neuropathy; neurodegenerative; chameleon
INTRODUCTION Cerebrovascular accident (CVA) is among the top five causes of death and the number one cause of disability in the United States (1,2). Acute ischemic attack affects over 600,000 patients per year, with three-quarters of these presenting with a first-time stroke (1–5). With the potential morbidity and mortality of stroke, the American Heart Association (AHA) recommends rapid recognition and potentially aggressive treatment of patients presenting with possible stroke symptoms (3–7). A significant push exists to rapidly diagnose CVA and obtain glucose and head computed tomography (CT) in patients with concern for CVA, as thrombolytics require specific time criteria and contraindication considerations (6,7). Literature suggests that for every 15-min interval reduction in time to thrombolytics, patients demonstrate improved
RECEIVED: 7 September 2016; ACCEPTED: 12 September 2016 1
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morbidity and decreased risk of intracranial hemorrhage, the primary concern of providing thrombolytics (8,9). Classically, strokes present as the sudden onset of a focal neurologic deficit in a vascular distribution (6,7,10). There are multiple diagnoses that may mimic this presentation. Misdiagnosis of stroke ranges from 5% to 31% of patients, which can potentially lead to unnecessary and harmful treatments if patients present within the thrombolytic time window (11–17). Patients can experience many conditions that may present as stroke, often confounding the clinical picture. These conditions are known as stroke mimics. DISCUSSION A stroke mimic is defined as a nonvascular disease that presents with stroke-like symptoms, often indistinguishable from an actual CVA. The harmful side effects of thrombolytics, most commonly bleeding, are not insignificant; thus, accurate diagnosis is essential. Rates of mimic treated with intravenous thrombolytics vary from 1% to 20% (11–17). The rate of bleeding approaches 1–2% in these patients (14,15). Acute CVA may present with a variety of symptoms including weakness, sensory changes, vision changes, dysarthria, dysphagia, vision abnormalities, seizures, and many others (11–13,17). Due to this wide variety of symptoms, many other conditions may, on initial impression, be diagnosed as acute stroke (17–23). Table 1 lists these common conditions (6–8,13,17–48). Stroke Chameleons A stroke chameleon is a CVA that presents as a different condition (23,25,49). Movement disorders such as acute hemiballismus can occur with acute lesions in the subthalamic nucleus. This condition will present with wild movements, often uncontrollable, that are one sided. Confusion, agitation, and delirium may occur with acute lesions of temporal lobe limbic cortex, as well as the orbitofrontal regions (23,25,49). This can be difficult to differentiate from stroke syndromes with neglect or aphasia, as the patient may appear altered. Lesions affecting the parietal or thalamic regions may result in sensory loss. Cortical blindness is rare, but examination demonstrates normal pupillary light response and normal optic disks (23,25,49). One key to differentiation and diagnosis of the stroke chameleon is evaluating for symptoms with abrupt onset. Risk factors for cerebrovascular disease such as cardiovascular disease, diabetes, hypertension, and hyperlipidemia can suggest stroke with atypical presentation, but by no means are they definitive (11,17–20,25). Another
key difference is the presentation of negative symptoms or deficit in strokes (25). Differentiating Stroke vs. Mimic Diagnosis of stroke, compared to mimic, depends on the complaint, risk factors, onset time, vascular distribution of symptoms, and imaging modalities available to the provider. A variety of studies have evaluated signs or symptoms that can indicate stroke vs. mimic. One study found convulsions (odds ratio [OR] 4.59) and aphasia (OR 2.55) to predict mimic, whereas dysarthria (0.25), hemiparesis (OR 0.26), facial palsy (OR 0.22), and visual field neglect (0.15) predict stroke (20,50). A separate study suggests that chest pain (OR 16.7) and paresthesias (OR 10) more commonly suggest mimic (20,22). Ultimately, studies display conflicting results. Two or three focal findings (acute facial paralysis, arm drift/weakness, change in speech) with abrupt onset suggest CVA, whereas the lack of these findings suggest mimic (11,17–23,25,32,50–52). This history is also vital, as younger age is more commonly associated with mimic in most studies, though one study by Winkler et al. finds it to be inconclusive (52). Risk factors such as atrial fibrillation (OR 11.4) are often associated with stroke, though other studies have found conflicting results (16–20,50). Other risk factors such as coronary artery disease, hypertension, hyperlipidemia, and diabetes are inconsistent, with some studies suggesting improved likelihood of stroke and others suggesting no correlation (11,16–23,25,32,51–54). A prior history of epilepsy, baseline cognitive impairment, and migraine can suggest mimic, but beware of contributing all conditions to these factors. Time of onset is a necessary part of the evaluation. A suddenonset deficit in a vascular distribution suggests CVA, and several deficits fitting a specific anatomic distribution supports a diagnosis of acute ischemic stroke as well (11,16–23,25,32,51–53). Table 2 depicts factors supporting stroke and mimic (11,16–23,25,32,51–53). Management The goals of care in evaluation of the patient with concern for CVA are rapid recognition of the deficit and rapid imaging. Stroke is one of the most life-threatening and timesensitive conditions associated with focal deficit requiring diagnosis in the ED. The diagnosis of stroke mimic is most commonly completed only after advanced imaging, laboratory investigation, and neurology consultation (6–8). Any focal deficit should be assumed CVA. A focused history and physical examination must be completed in a rapid manner with assessment of the National Institutes of Health Stroke Scale (NIHSS)
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Table 1. Common Stroke Mimics Condition
Presentation
Management
Seizure (6–8,13,17–26)
–Accounts for 20% of mimics. –May originate from prior stroke foci. –Generalized convulsions, involuntary movements, postictal confusion, incontinence, tongue biting more frequent. –Up to 8% of strokes may present with seizure. –Postictal paresis occurs in up to 10% of seizures, usually lasting 180 s. May last for several hours. –Account for 10% of mimics. –Patients often present with positive prior history and no evidence of focal deficit. –Hemiplegic migraine is autosomal disorder, often teenagers with first episode. –Classic migraine features are common, though nearly 30% of stroke patients may have headache at stroke onset. –Migraine with aura accounts for 20–30% of migraine headaches. Auras typically have a gradual onset over 5 min and last under 60 min. –Auras usually have visual symptoms, rather than motor or sensory disturbances. –Basilar migraines present with vision changes, vertigo, dysarthria, and altered mentation. –Serum glucose levels < 55 mg/dL in healthy individuals defines hypoglycemia, whereas levels < 70 mg/dL in diabetics is significant. –Neuroglycopenic episodes commonly present with confusion and autonomic symptoms, but can uncommonly present with paresis. –Autonomic symptoms are often first in hypoglycemia with diaphoresis and tachycardia. –Glucose level is often 30 mg/dL in patients with hemiparesis. Right-sided symptoms more common. –Hyperglycemia may produce focal deficits. Hyperosmolar, nonketotic hyperglycemia can present with movement disorders such as hemichorea-hemiballismus. –Hyper-/hyponatremia and hepatic encephalopathy may result in focal deficit, commonly through cerebral edema. –Sepsis accounts for 6–20% of mimics. –Encephalopathy including coma, weakness, and speech changes may occur. –Due to neuroinflammatory response and blood brain barrier dysfunction –Fever many not be present in elderly patients with sepsis. –Hyperthermia/hypothermia, tachycardia, and altered mental status may occur in sepsis. –Brain abscess, meningitis, and encephalitis may present with focal deficits. –Include CNS tumors, metastases, and abscesses. –Mass effect and alteration in vascular blood flow may result in focal neurologic deficit. –These deficits often present over 24–48 h.
–Active seizures require treatment with benzodiazepines and second-line agents such as levetiracetam, fosphenytoin, or valproate. –MRI with diffusion-weighted imaging can assist in differentiation. –Seizure at time of stroke onset is a contraindication to tPA administration.
Headache (13,17–20,25,27,28)
Metabolic (13,17–20,25,29–33)
Infection (13,17–20,34)
Space-occupying lesion (13,17–20,25,34–36)
–Headache with a focal deficit should be considered CVA until proven otherwise. –Patients with focal deficit require neuroimaging. –Treat headache with medications including antidopaminergic agents, nonsteroidal antiinflammatory medications, and other treatments as indicated. –Focal deficit requires neurology consultation.
–Rapid assessment of blood glucose is needed in any neurologic complaint including altered mental status. –A variety of causes of hypoglycemia such as insulin or sulfonylurea overdose, alcohol intoxication, Addison crisis. –Hypoglycemia is rapidly correctable with provision of glucose. Correction of neurologic deficit is usually rapid, though it may take hours.
–Evaluate for sepsis with systemic inflammatory response and source of infection. –Seek a baseline functional status from patient, family member, or nursing facility. –Without baseline status, any neurologic deficit should be assumed to be stroke. –Timeframe of onset may assist, because sepsis is more often gradual. –Neuroimaging is required with any focal deficit or altered mental status. –Neuroimaging is required, with noncontrast head CT able to rapidly diagnose mass or acute intracranial hemorrhage. –Mass lesions likely require neurosurgery consultation. (Continued )
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Table 1. Continued Condition Peripheral neuropathy (13,17–20,25)
Neurodegenerative disorder (13,17–20,25,37–40)
Syncope (13,17–20,35,40)
Cerebrovascular narrowing (13,41–44)
Functional (17,25,45,46)
Toxin/ingestion (13,47,48)
Presentation
Management
–Less common mimic. –Due to cellular changes in distal nerves, causing axonal degeneration, segmental degeneration, or Wallerian degeneration. –Mononeuropathies often cause focal sensorimotor deficits and can occur acutely. –Peripheral nerve injury may result in sensorimotor dysfunction, muscle atrophy, and areflexia, whereas stroke often results in hyperreflexia and no atrophy. –Rare mimic. –May present with variety of deficits including hemiparesis or cranial nerve deficits. –Multiple sclerosis (MS) may present with focal deficits that worsen with heat and stress. –Optic neuritis presents with sudden vision loss and is the first symptom in 20% of cases of MS. –Guillain-Barre´ syndrome progressive, ascending bilateral paralysis characterized by peripheral motor weakness, hyporeflexia. –Accounts for 20% of mimics. –Strokes of the vertebrobasilar system may cause altered consciousness. –Syncope is defined by loss of consciousness with rapid return to baseline. –Consists of neurogenic, orthostatic, cardiogenic, and other serious causes such as heat syncope, hypoglycemia, subarachnoid hemorrhage, and subclavian steal. –Rare cause of mimic. –Includes vasculitis, reversible cerebral vasoconstriction syndrome (RCVS), subarachnoid hemorrhage (SAH), idiopathic intracranial hypertension (IIH), and atherosclerosis. –Onset varies from acute to chronic, with ataxia, weakness, and vision changes. –RCVS and SAH often present with sudden, maximal headache. –IIH most commonly affects young, obese women, often with chronic headache and vision changes (35–70%). Abducens nerve palsy is present in 80%. –One of the most common mimics, with conversion disorder accounting for 75% in one study. –Focal deficit in the setting of some trigger is common. –Variety of complaints including paralysis, aphonia, seizures, ataxia, blindness, paresthesias. –Physical examination may be inconsistent with repeated evaluations. –Deficits often do not fit a specific vascular territory. –Patients may present with confusion and atypical neurologic examination. –Include anticholinergic toxidrome, salicylates, acetaminophen, ethanol, antidopaminergic medications, tricyclic antidepressants, and strychnine poisoning. –Strychnine poisoning results from competitive antagonism of glycine at postsynaptic receptors and presents with twitching, spasms, trismus, and opisthotonos.
–History and chronicity assist in differentiating stroke vs. neuropathy, as this condition is more gradual in onset. –Examination with decreased reflexes and atrophy may be found. –Neurology consultation is recommended; diagnosis often requires electromyography, nerve biopsy. –All focal deficits warrant neuroimaging. –History is essential to evaluate for other medical conditions and prior exacerbations. –Neurology consultation is needed for patients with neurodegenerative conditions.
–Vertebrobasilar strokes will have unilateral cranial nerve deficits in association with alteration in mental status. –Syncope should not demonstrate focal neurologic deficits. –Syncope may have transient tonic clonic movements lasting approximately 30 s. –Focal deficits suggest CVA. –Imaging with noncontrast head CT and CT angiography is recommended. –Lumbar puncture may be needed for definitive diagnosis of SAH and IIH. –Vasculitis syndromes may result in true ischemia and stroke. High-dose steroids may be needed for treatment. –Neurology consultation is advised. Vasculitis affecting the nervous system.
–Conversion disorder is rare, and focal deficits require neuroimaging. –History and physical examination can assist providers. –CVA will more likely have vascular territory deficits, with consistent examinations. –If functional disorder is diagnosed, reassurance and efforts to remove stressor are needed. –Evaluation of electrocardiogram for QRS and QT prolongation. –Seizure should be treated with benzodiazepines. –Specific treatments warranted for the agent ingested (bicarbonate for tricyclic or salicylates). –Sedation may be required for agitated patients.
MRI = magnetic resonance imaging; tPA = tissue plasminogen activator; CVA = cerebrovascular accident; CNS = central nervous system; CT = computed tomography.
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Table 2. History and Examination Findings in Stroke vs. Mimic (11,16–23,25,32,51–53) Assessment
Suggests Mimic
Suggests Stroke
History
Prior seizures/epilepsy Migraine Cognitive impairment
Atrial fibrillation
Symptom/sign
Altered mental status Chest pain Speech change/aphasia without hemiparesis
Focal weakness Hemiparesis Dysarthria Gaze palsy Focal symptom in anatomic vascular distribution
Inconclusive Age Gender Hypertension Hyperlipidemia Coronary artery disease Smoking Prior stroke Peripheral vascular disease Psychiatric disease Kidney disease Paresthesias Headache Dizziness/vertigo Less severe deficit (NIHSS < 10) Convulsions at onset
NIHSS = National Institutes of Health Stroke Scale.
(6–8). If unable to complete the NIHSS, a focused assessment for facial paralysis, arm drift/weakness, or speech change should occur (6–8,16–20). Table 3 depicts goals of care for these patients. A blood glucose level should be obtained, as hypoglycemia is a common mimic that is easily correctable. Ancillary laboratories include electrolytes, blood urea nitrogen/creatinine, complete blood count, troponin, coagulation studies, and 12-lead electrocardiogram. Noncontrast CT of the head is often the first-line imaging modality, though this test and its interpretation may not be always reliable. Location of deficit. Anterior circulation deficits involve the middle cerebral or anterior cerebral arteries, often presenting with clear focal deficits such as upper extremity weakness, aphasia, or leg weakness. Anterior cerebral artery lesions will cause leg weakness that is worse compared to arm weakness, often with aphasia and cognitive or behavioral alterations. Middle cerebral artery infarction will present with contralateral hemiparesis and speech changes and gaze preferences. Posterior circulation strokes affect posterior cerebral artery and present with more confusion symptoms such as dizziness,
vertigo, cranial nerve deficit, altered mental status, or visual field deficit. Lacunar strokes affect the deep cerebral penetrating arteries and will more likely be confused with other conditions, or a stroke chameleon, with pure motor, sensorimotor, pure sensory, ataxic hemiparesis, or dysarthria-clumsy hand syndrome (6–8,20). Imaging. Noncontrast head CT is easily available and the most feasible test in the ED for patients with focal deficit or concern for CVA. However, imaging modalities vary based on institution. The sensitivity and specificity of certain modalities have significant differences. Head CT has the lowest sensitivity, ranging from 12% to 52%, though large anterior circulation strokes are often easily discovered on this modality. Distal lesions due to small emboli often require the use of angiography and perfusion imaging (20,53). CT angiography can assist in demonstrating focal obstructions or diffuse atherosclerosis, which has an OR of 23.6 for ischemic stroke identification (53). Large-vessel occlusions on this modality indicate worse outcomes. CT angiography in addition to noncontrast head CT increases the sensitivity to over 70%, with specificity approaching 88% (20,53).
Table 3. Goals of Assessment and Management – Obtain focused history and physical examination evaluating for speech deficit, weakness, or facial paralysis. Conduct NIHSS if able. – Rapid blood glucose measurement is needed. Other tests, including ECG, function as adjuncts. – Obtain noncontrast head CT within 25 min of patient arrival, with interpretation complete by 45 min. Other imaging warranted per anatomic distribution. – Assume CVA in patient with focal neurologic deficit and sudden onset or combination of objective findings. – Symptoms with more gradual onset, inconsistent physical examination findings, and nonvascular territory complaints suggest mimic. – Concern for stroke within thrombolytic time window requires consideration of tPA in shared decision-making. – Obtain neurologic consultation for patients with focal deficit or concern for stroke vs. mimic. NIHSS = National Institutes of Health Stroke Scale; ECG = electrocardiogram; CT = computed tomography; CVA = cerebrovascular accident; tPA = tissue plasminogen activator.
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Unfortunately, agreement on diagnosis of acute stroke based on head CT is poor between separate physicians, and head CT possesses a sensitivity of 12% for small lesions and transient ischemic events (20,53). Posterior circulation symptoms require the use of magnetic resonance imaging (MRI). MRI possesses sensitivities over 80% and specificities over 95% (12,16,17,20,54– 58). Diffusion-weighted imaging evaluates ischemic tissue more readily, as well as demonstrating damaged but not ischemic areas (6–8,54–58). If anterior circulation deficits involving the middle cerebral artery are present, including unilateral weakness with aphasia or neglect, noncontrast head CT followed by angiography is warranted. If there is concern for anterior circulation deficits, including leg more than arm weakness, noncontrast head CT and angiography are efficacious. On the other hand, patients with posterior circulation symptoms should undergo MRI, though if this is not available, angiography may be used (20). Treatment.If the history, physical examination, and investigations suggest CVA, thrombolytics should be considered as long as the patient is in the AHA time window. Shared decision-making with the patient and family is advised. Several mimics such as hypoglycemia are easily discernable and rapidly corrected. Mass found on CT or the patient with systemic inflammatory response syndrome criteria and definitive source are reasons to withhold tissue plasminogen activator (tPA) (17–22,25). Symptoms that rapidly resolve, witnessed seizure, and history of epilepsy suggest seizure. With focal deficit, emergent neuroimaging is needed. A well-conducted history and physical examination is essential. Careful evaluation of subjective and objective factors in the patient’s symptoms is recommended. A deficit that remains and does not change over several reevaluations strongly suggests organic disease, whereas deficits that do not fit a specific anatomical region or those that change over several reevaluations suggest functional disorder (11,15–22,25,32,56–60). Neurology consultation is advised in patients with objective neurologic findings, no matter the history. Patients with sudden-onset deficits and objective findings within the AHA thrombolytic time window may improve with tPA (6–8,15,20–22,25). The risks and benefits of thrombolytic treatment should be discussed with the management team and the patient using shared decision-making. CONCLUSIONS Stroke is a condition associated with significant morbidity and mortality, often presenting with focal neurologic deficit within defined vascular distribution.
Stroke mimic is any condition that presents with stroke-like symptoms and includes seizures, headaches, metabolic, infection, space-occupying lesion, neurodegenerative disorder, peripheral neuropathy, syncope, and functional disorder. This review evaluates stroke mimics, differentiation between stroke and mimic, and provides an approach to evaluation and management. Few historical factors support either, though migraine history, seizure history, psychiatric history, altered mental status, speech alteration without weakness, and chest pain suggest mimic. A history of atrial fibrillation, focal weakness, hemiparesis, dysarthria, gaze palsy, and focal symptom in anatomic vascular distribution suggest stroke. However, any new, focal neurologic deficit or combination of deficits should be assumed to be stroke until proven otherwise. Head CT noncontrast is the first-line imaging modality, though MRI with diffusion-weighted imaging possesses greater diagnostic abilities. Neurologic consultation should be completed for patients with focal deficit. REFERENCES 1. Centers for Disease Control and Prevention, National Center for Health Statistics. CDC Wonder Online Database, compiled for compressed mortality file 1999–2009, Series 20, No. 20, 2012. Underlying cause-of-death 1999–2009. Available at: wonder.cdc.gov/ Mortsql.html. Accessed July 14, 2016. 2. Kochanek KD, Murphy SL, Xu JQ, Arias E. Mortality in the United States, 2013. NCHS Data Brief 2014;1–8. 3. Mozzafarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics — 2015 update: a report from the American Heart Association. Circulation 2015;131:e29–322. 4. Go AS, Mozzafarian D, Roger VL, et al., American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics — 2014 update: a report from the American Heart Association. Circulation 2014;129:e28–292. 5. Centers for Disease Control and Prevention (CDC). Prevalence and most common causes of disability among adults—United States, 2005. MMWR Morb Mortal Wkly Rep 2009;58:421–6. 6. Goldstein LB, Bushnell CD, Adams RJ, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2010;42:517–84. 7. Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:870–947. 8. Saver JL. Time is brain—quantified. Stroke 2006;37:263–6. 9. Saver JL, Fonarow GC, Smith EE, et al. Time to treatment with intravenous tissue plasminogen activator and out- come from acute ischemic stroke. JAMA 2013;309:2480–8. 10. Goldstein LB, Simel DL. Is this patient having a stroke? JAMA 2005;293:2391–402. 11. Merino JG, Luby M, Benson RT, et al. Predictors of acute stroke mimics in 8187 patients referred to a stroke service. J Stroke Cerebrovasc Dis 2013;22:397–403. 12. Ali SF, Viswanathan A, Singhal AB, et al. The telestroke mimic (TM)-Score: a prediction rule for identifying stroke mimics evaluated in a telestroke network. J Am Heart Assoc 2014;3:e000838. 13. Magauran BG, Nitka M. Stroke mimics. Emerg Med Clin North Am 2012;30:795–804. 14. Tsivgoulis G, Alexandrov AV, Chang J, et al. Safety and outcomes of intravenous thrombolysis in stroke mimics: a 6-year, single-care
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ARTICLE SUMMARY 1. Why is this topic important? Acute stroke is a major cause of morbidity and mortality. It often presents with focal neurologic deficit, and many conditions may present with stroke-like symptoms, known as stroke mimic. 2. What does this review attempt to show? This review evaluates stroke mimics, use of thrombolytics in mimics, and keys in differentiating acute stroke vs. mimic. 3. What are the key findings? Stroke possesses significant morbidity and mortality, and the American Heart Association emphasizes rapid recognition and potentially aggressive treatment for acute stroke. Many conditions can mimic stroke. Conditions include seizures, headaches, metabolic conditions, infection, space-occupying lesion, neurodegenerative disorder, peripheral neuropathy, syncope, and functional disorder. Through utilizing several history and physical examination factors, the differential can be narrowed. Focal neurologic deficit requires imaging, with noncontrast computed tomography of the head first line. Magnetic resonance imaging with diffusion-weighted imaging provides greater diagnostic capability. Neurology consultation and shared decision-making should be utilized in consideration of stroke vs. mimic. 4. How is patient care impacted? Stroke mimics can be challenging to diagnose, and any focal neurologic deficit or combination of deficits warrants evaluation for acute stroke with neuroimaging and neurology consultation.