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Ischemic stroke mimics: A comprehensive review

      Highlights

      • Peripheral vertigo, toxic/metabolic changes, seizure, migraine and functional disorders are the most common stroke mimics.
      • One out of four mimics is thrombolyzed with a very good outcome.
      • Patient evaluation by should be carried by physicians experienced in the diagnosis of both ischemic stroke stroke and mimics.

      Abstract

      Background

      Ischemic stroke is the leading cause of disability and one of the leading causes of death. Ischemic stroke mimics (SMs) can account for a noteble number of diagnosed acute strokes and even can be thrombolyzed.

      Methods

      The aim of our comprehensive review was to summarize the findings of different studies focusing on the prevalence, type, risk factors, presenting symptoms, and outcome of SMs in stroke/thrombolysis situations.

      Results

      Overall, 61 studies were selected with 62.664 participants. Ischemic stroke mimic rate was 24.8% (15044/60703). Most common types included peripheral vestibular dysfunction in 23.2%, toxic/metabolic in 13.2%, seizure in 13%, functional disorder in 9.7% and migraine in 7.76%. Ischemic stroke mimic have less vascular risk factors, younger age, female predominance, lower (nearly normal) blood pressure, no or less severe symptoms compared to ischemic stroke patients (p < 0.05 in all cases). 61.7% of ischemic stroke patients were thrombolysed vs. 26.3% among SMs (p < 0.001). (p < 0.001). Overall intracranial hemorrhage was reported in 9.4% of stroke vs. 0.7% in SM patients (p < 0.001). Death occurred in 11.3% of stroke vs 1.9% of SM patients (p < 0.001). Excellent outcome was (mRS 0–1) was reported in 41.8% ischemic stroke patients vs. 68.9% SMs (p < 0.001). Apart from HINTS manouvre or Hoover sign there is no specific method in the identification of mimics. MRI DWI or perfusion imaging have a role in the setup of differential diagnosis, but merit further investigation.

      Conclusion

      Our article is among the first complex reviews focusing on ischemic stroke mimics. Although it underscores the safety of thrombolysis in this situation, but also draws attention to the need of patient evaluation by physicians experienced in the diagnosis of both ischemic stroke and SMs, especially in vertigo, headache, seizure and conversional disorders.

      Keywords

      1. Introduction

      Ischemic stroke is the leading cause of disability and one of the leading causes of death. Enourmous efforts have been recently made to improve the clinical outcome of stroke patients including testing up comprehensive stroke units and the introducting endovascular procedures [
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      ]. The benefit of revascularisation procedures (both intravenous thrombolysis and endovascular procedures) is time-dependent, therefore shortening door-to-needle time is crucial in the emergency department [
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      ]. Ischemic stroke is usually an exclusionary clinical diagnosis in the emergency room, usually supported by noncontrast computed tomography (NCCT), which is the first step in the evaluation of ischemic stroke patients due to its widespread availability and relatively short imaging time [
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      ,

      2018 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. 2018;49:e46–e99.

      ].
      However, the increased availability of systemic thrombolysis and shortened door-to-needle time have lead to inappropiate inclusion and treatment of so-called ischemic stroke mimics (ie. non-stroke patients) [
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      ]. Ischemic stroke mimics can account for approximately one in five clinically diagnosed acute ischemic strokes and the rate of thrombolyzed mimics can be as high as 17% [
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      ]. Based on literature data mimics are most likely to be identified as seizures, complicated migraines or conversion disorders [
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      ].
      Multimodal patient imaging (both CT and MR perfusion techniques) is an important part of acute ischemic stroke imaging to delineate the infarct from ischemic penumbra in specific situations such as stroke of unknown time of onset (SUTO) or in endovascular intervention with extended time window [
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      ]. Perfusion techniques may play a vital role in diagnosing SMs in the stroke/thrombolysis pathway (if the etiology is doubtful) [
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      ,
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      ].
      Despite of increasing number of publications in the last three decades, no comprehensive review has summarized the complex etiology, potential maltreatment and outcome of ischemic stroke mimics, especially in emergency situations.
      The aim of our review article was to summarize the findings of different studies focusing on the prevalence, type, risk factors, presenting symptoms, and outcome of mimics in ischemic stroke/thrombolysis situations.

      2. Methods

      We searched PubMed, MEDLINE, and the Cochrane Library restricted to English language publications to January 2020. We used these search items in the following combinations: stroke, ischemic stroke, mimic, thrombolysis, rt-PA, alteplase, imaging, outcome, and mortality. After reviewing the abstracts, we obtained and reviewed the full text and reference lists of relevant articles.

      3. Statistical analysis

      Participants of the relevant studies were divided into two groups: (1) ischemic stroke patients, and (2) ischemic stroke mimics. Ischemic stroke mimic types, clinical findings, risk factors, thrombolysis rates and outcomes were compared between the two groups. Data were evaluated as means ± SD (standard deviation) by Student’s t-test or chi square test to detect significant differences among the examined parameters. Data analysis was performed using SPSS (version 22.0, IBM, New York, NY, USA).

      4. Results

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      ]. There were five prospective multicenter, one observational prospective, 17 prospective single center, 9 retrospective multicenter and 30 retrospective single center study (Supplementary Table 1).
      Stroke mimic rate was 24.9% overall (15595/62664). Stroke mimic rate based on study type can be seen in Supplementary Table 1.

      4.1 Mimic types

      Ischemic stroke mimic types were the following: peripheral vestibular dysfunction in 23.2% (1109/4769 based on 15 studies /11, 16, 22, 26, 30, 32, 44, 46, 51, 61,65, 66, 69, 70, 71/), toxic/metabolic in 13.2% (1053/7985, based on 15 studies /11, 16, 22, 26, 30, 32, 44, 46, 51, 61, 65, 66, 69, 70, 71/), seizure in 13% (1257/9629, based on 11 studies /11, 25, 26, 28, 32, 33, 36, 53, 64, 68, 71/), functional disorder in 9.7% (373/3822 based on 12 studies /11, 14, 16, 17, 22, 41, 51, 59, 61, 69, 70, 71/) and migraine in 7.76% (697/8983, based on 36 studies /11, 14, 16, 17, 18, 20, 22–25, 27, 28, 30, 32, 33–47, 71/). Other etiologies were collapse/presyncope in 5.95% (464/7858 /11, 16, 18, 20, 22, 25–27, 30, 32, 35, 37, 38, 43, 44, 46, 47, 51, 53, 54, 59, 61, 62, 66, 69, 70/), sepsis in 5.3% (265/4823 /11, 16, 17, 23–25, 32, 33, 37, 38, 42, 43, 54, 60, 61, 69, 70,71/), mononeuropathy in 5% (including those with Bell's palsy, radial nerve palsy, oculomotor or abducens nerve palsies, but proper data are lacking) (162/3213 /11, 14, 16, 41, 61, 66, 70/), space-occupying lesion in 4.3% (299/6897 /11,16–18, 24, 26–28, 30, 34, 37, 38, 43, 46–48, 51, 54, 61, 64–66, 69, 70/), acute confusion in 1.9% (84/4344 /11, 14, 16, 34, 38, 44, 59, 70/). dementia in 1.2% (54/4577 /11, 16, 23, 33, 34, 38, 43, 46, 51, 54, 55, 61, 69, 70/) and spinal lesion in 0.7% (22/2939 /11, 16, 20, 25, 43, 61/) (Fig. 2). 9.69 % had non defined etiology which was not entirely clarified including Susac syndrome, obstructive hydrocephalus, transient global amnesia etc. (Fig. 1).
      Figure thumbnail gr2
      Fig. 2Clinical findings in the examined subgroups (%). Abbreviations: WOS: woke up symptoms, LOC: loss of consciousness, ATW: able to walk. *p < 0.05.

      4.2 Clinical findings

      SM patients had significantly lower NIHSS (4.99 ± 5.65 vs. 8.06 ± 6.37, p < 0.001 /11, 14, 15, 19, 20–22, 24, 26, 28, 30, 34, 37, 41, 42, 45, 47, 49, 52, 53, 55, 58, 59, 61, 63–67, 69, 70/)), they were younger (60.9 ± 10.4 vs. 68.4 ± 9.7 years, p < 0.001 /11, 14, 15, 18–31, 33–50, 52, 53, 55–59, 61–71/) with female predominance (68 vs 56 %, p < 0.001 /11, 14, 15, 17–30, 32–53, 5–57, 59, 61–71/). The median time to onset from presentation was not significant between SM and ischemic stroke patients (116.75 ± 53.03 vs. 134.45 ± 58.27 min, p = 0.5 /11, 22, 26, 30, 31, 41, 42, 55, 56, 65, 70/).
      Average blood pressure was 153.75/86.45 Hgmm in ischemic stroke and 140.25/83.1 Hgmm in SM patients (p < 0.001) [

      Pearson C, Przyklenk K, Mika VH, Ayaz SI, Ellis M, Varade P, Tolomello R, Welch RD. Utility of point of care assessment of platelet reactivity (using the PFA-100®) to aid in diagnosis of stroke. Am J Emerg Med. 2017;35(5):802.e1‐802.e5.

      ,
      • Lewandowski C.
      • Mays-Wilson K.
      • Miller J.
      • Penstone P.
      • Miller D.J.
      • Bakoulas K.
      • et al.
      Safety and outcomes in stroke mimics after intravenous tissue plasminogen activator administration: a single-center experience.
      ,
      • Sivakumaran P.
      • Gill D.
      • Mahir G.
      • Baheerathan A.
      • Kar A.
      A Retrospective Cohort Study on the Use of Intravenous Thrombolysis in Stroke Mimics.
      ,
      • Amort M.
      • Fluri F.
      • Schäfer J.
      • Weisskopf F.
      • Katan M.
      • Burow A.
      • et al.
      Transient ischemic attack versus transient ischemic attack mimics: frequency, clinical characteristics and outcome.
      ,
      • Suzuki J.
      • Nakai N.
      • Kondo N.
      • Tsuji H.
      • Inagaki R.
      • Furukawa S.
      • et al.
      Ten-Year Evaluation of the TOYOTA Prehospital Stroke Scale for Tissue Plasminogen Activator Intravenous Therapy in the Real World.
      ,
      • Okano Y.
      • Ishimatsu K.
      • Kato Y.
      • Yamaga J.
      • Kuwahara K.
      • Okumoto K.
      • et al.
      Clinical features of stroke mimics in the emergency department.
      ,
      • Bath P.M.
      • Scutt P.
      • Appleton J.P.
      • Dixon M.
      • Woodhouse L.J.
      • Wardlaw J.M.
      • et al.
      Baseline characteristics of the 1149 patients recruited into the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) randomized controlled trial.
      ,
      • Bliden K.P.
      • Raviv G.
      • Tantry U.S.
      • Chaudhary R.
      • Cochran J.W.
      • Navarese E.P.
      • et al.
      “Blueprinting” thrombogenicity and antithrombotic drug response at the bedside in patients presenting emergently with symptoms of acute stroke.
      ,
      • Kvistad C.E.
      • Novotny V.
      • Næss H.
      • Hagberg G.
      • Ihle-Hansen H.
      • Waje-Andreassen U.
      • et al.
      Safety and predictors of stroke mimics in The Norwegian Tenecteplase Stroke Trial (NOR-TEST).
      ,
      • Zinkstok S.M.
      • Engelter S.T.
      • Gensicke H.
      • Lyrer P.A.
      • Ringleb P.A.
      • Artto V.
      • et al.
      Safety of thrombolysis in stroke mimics: results from a multicenter cohort study.
      ,
      • Chang P.
      • Ruff I.
      • Mendelson S.J.
      • Caprio F.
      • Bergman D.L.
      • Prabhakaran S.
      The 2CAN Score.
      ]. Unrevealed AF on admission was 15.6 % (17/109) in SM and 24.6 % (55/224) in ischemic stroke patients based on one study (p = 0.06) [
      • Hand P.J.
      • Kwan J.
      • Lindley R.I.
      • Dennis M.S.
      • Wardlaw J.M.
      Distinguishing between stroke and mimic at the bedside: the brain attack study.
      ] (Table 1).
      Table 1Clinical findings in the examined subgroups.
      StrokeStroke mimicp value
      NIHSS (points)8.06 ± 6.374.99 ± 5.65<0.001
      Age (years)68.4 ± 9.760.9 ± 10.4<0.001
      Female gender (%)56%68%<0.001
      Median time (min)134.45 ± 58.27116.75 ± 53.030.5
      Blood pressure (Hgmm)153.75/86.45140.25/83.1<0.001
      Unrevealed atrial fibrillation (%)24.615.60.06
      Woke up symptoms were presented in 27.9% (211/757) in SM vs. 24.6% (278/1132) in ischemic stroke patients (p = 0.1 /11, 38, 61, 62/). Loss of consciousness was more common in SM (14.7%, 275/1876) than in ischemic stroke (10.2%, 390/3831) patients (p < 0.001 /11, 28, 34, 45, 46, 49, 52, 62, 64, 69/). Vomiting was also more common in SM patients 28.5% (162/569) vs. 18.8% (73/388) (p < 0.001 /11, 17, 36, 62/). Headache occured more frequently in SM patients 21.3% (269/1263) vs. 9.8% (202/2061) (p < 0.001) [
      • Hand P.J.
      • Kwan J.
      • Lindley R.I.
      • Dennis M.S.
      • Wardlaw J.M.
      Distinguishing between stroke and mimic at the bedside: the brain attack study.
      ,
      • DeLaroche A.M.
      • Sivaswamy L.
      • Farooqi A.
      • Kannikeswaran N.
      Pediatric Stroke and Its Mimics: Limitations of a Pediatric Stroke Clinical Pathway.
      ,
      • Sharma R.
      • Macy S.
      • Richardson K.
      • Lokhnygina Y.
      • Laskowitz D.T.
      A blood-based biomarker panel to detect acute stroke.
      ,
      • Ifergan H.
      • Amelot A.
      • Ismail M.
      • Gaudron M.
      • Cottier J.P.
      • Narata A.P.
      Stroke-mimics in stroke-units. Evaluation after changes imposed by randomized trials.
      ,
      • Amort M.
      • Fluri F.
      • Schäfer J.
      • Weisskopf F.
      • Katan M.
      • Burow A.
      • et al.
      Transient ischemic attack versus transient ischemic attack mimics: frequency, clinical characteristics and outcome.
      ,
      • Quenardelle V.
      • Lauer-Ober V.
      • Zinchenko I.
      • Bataillard M.
      • Rouyer O.
      • Beaujeux R.
      • et al.
      Stroke Mimics in a Stroke Care Pathway Based on MRI Screening.
      ,
      • Michelson E.A.
      • Hanley D.
      • Chabot R.
      • Prichep L.S.
      • Goldstein J.
      Identification of acute stroke using quantified brain electrical activity.
      ,
      • Esmaeili S.
      • Afrakhteh M.
      • Bahadori M.
      • Shojaei S.F.
      • Ashayeri R.
      • Mehrpour M.
      Thrombolytic treatment in stroke mimic, inevitable but fortunately safe: An observational study from Iran.
      ] and more of them were able to walk comparing to ischemic stroke patients: 51.38% (56/109) vs. 37.5% (84/224) (p = 0.016) although it was based on the results of one study [
      • Hand P.J.
      • Kwan J.
      • Lindley R.I.
      • Dennis M.S.
      • Wardlaw J.M.
      Distinguishing between stroke and mimic at the bedside: the brain attack study.
      ]. Glasgow Coma Scale (GCS) < 15 was 91.9% (1152/1267) in ischemic stroke and 88.8% (688/775) in SM patients (p = 0.43) [
      • Hand P.J.
      • Kwan J.
      • Lindley R.I.
      • Dennis M.S.
      • Wardlaw J.M.
      Distinguishing between stroke and mimic at the bedside: the brain attack study.
      ,
      • Sharma R.
      • Macy S.
      • Richardson K.
      • Lokhnygina Y.
      • Laskowitz D.T.
      A blood-based biomarker panel to detect acute stroke.
      ,
      • Bath P.M.
      • Scutt P.
      • Appleton J.P.
      • Dixon M.
      • Woodhouse L.J.
      • Wardlaw J.M.
      • et al.
      Baseline characteristics of the 1149 patients recruited into the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) randomized controlled trial.
      ,
      • Mackay M.T.
      • Yock-Corrales A.
      • Churilov L.
      • Monagle P.
      • Donnan G.A.
      • Babl F.E.
      Differentiating Childhood Stroke From Mimics in the Emergency Department.
      ].
      Confusion could be detected in 11.2% (87/775) in SM and 8.9% (115/1284) in ischemic stroke patients (p = 0.09) [
      • Hand P.J.
      • Kwan J.
      • Lindley R.I.
      • Dennis M.S.
      • Wardlaw J.M.
      Distinguishing between stroke and mimic at the bedside: the brain attack study.
      ,
      • Asaithambi G.
      • Castle A.L.
      • Sperl M.A.
      • Ravichandran J.
      • Gupta A.
      • Ho B.M.
      • et al.
      Thrombolytic treatment to stroke mimic patients via telestroke.
      ,
      • Kim S.J.
      • Kim D.W.
      • Kim H.Y.
      • Roh H.G.
      • Park J.-J.
      Seizure in code stroke: Stroke mimic and initial manifestation of stroke.
      ,
      • Quenardelle V.
      • Lauer-Ober V.
      • Zinchenko I.
      • Bataillard M.
      • Rouyer O.
      • Beaujeux R.
      • et al.
      Stroke Mimics in a Stroke Care Pathway Based on MRI Screening.
      ,
      • Hansson P.-O.
      • Andersson Hagiwara M.
      • Herlitz J.
      • Brink P.
      • Wireklint Sundström B.
      Prehospital assessment of suspected stroke and TIA: An observational study.
      ,
      • Dawson A.
      • Cloud G.C.
      • Pereira A.C.
      • Moynihan B.J.
      Stroke mimic diagnoses presenting to a hyperacute stroke unit.
      ,
      • Avellaneda-Gómez C.
      • Rodríguez Campello A.
      • Giralt Steinhauer E.
      • Gómez González A.
      • Serra Martínez M.
      • de Ceballos C.P.
      • et al.
      Description of stroke mimics after complete neurovascular assessment.
      ,
      • Yaghi S.
      • Rayaz S.
      • Bianchi N.
      • Hall-Barrow J.C.
      • Hinduja A.
      Thrombolysis to stroke mimics in telestroke.
      ]. No signs of stroke on physical examination could be found 33.7% (131/389) in SM and 10.5% (36/343) in ischemic stroke patients (p < 0.001) (Fig. 2).
      CT was diagnostic in 80.2% (3481/4338) in ischemic stroke and 57.8% (884/1529) in SM patiens (p < 0.001 /11, 25, 26, 28, 32, 33, 36, 53, 64, 68/), while MRI was carried out in 41.5% (3098/7470) in ischemic stroke and 50% (787/1575) in SM patients (p < 0.001 /11,25,26,28, 32, 33, 36, 53, 59, 61, 64/). CT perfusion may help to differentiate between ischemic stroke and SM patients based on two studies [
      • Hopyan J.
      • Ciarallo A.
      • Dowlatshahi D.
      • Howard P.
      • John V.
      • Yeung R.
      • et al.
      Certainty of stroke diagnosis: incremental benefit with CT perfusion over noncontrast CT and CT angiography.
      ,
      • Siegler J.E.
      • Rosenberg J.
      • Cristancho D.
      • Olsen A.
      • Pulst-Korenberg J.
      • Raab L.
      • et al.
      Computed tomography perfusion in stroke mimics.
      ]. CT perfusion was more likely to enable confirmation of clinical ischemic stroke diagnosis (odds ratio, 13.3) than was noncontrast CT and CT angiography (odds ratio, 6.4) or noncontrast CT alone (odds ratio, 3.3) [
      • Hopyan J.
      • Ciarallo A.
      • Dowlatshahi D.
      • Howard P.
      • John V.
      • Yeung R.
      • et al.
      Certainty of stroke diagnosis: incremental benefit with CT perfusion over noncontrast CT and CT angiography.
      ].

      4.3 Risk factors

      Hypertension 66.8% (20074/30035) vs. 41.1% (3434/8347) [
      • Hand P.J.
      • Kwan J.
      • Lindley R.I.
      • Dennis M.S.
      • Wardlaw J.M.
      Distinguishing between stroke and mimic at the bedside: the brain attack study.
      ,
      • Asaithambi G.
      • Castle A.L.
      • Sperl M.A.
      • Ravichandran J.
      • Gupta A.
      • Ho B.M.
      • et al.
      Thrombolytic treatment to stroke mimic patients via telestroke.
      ,

      Pearson C, Przyklenk K, Mika VH, Ayaz SI, Ellis M, Varade P, Tolomello R, Welch RD. Utility of point of care assessment of platelet reactivity (using the PFA-100®) to aid in diagnosis of stroke. Am J Emerg Med. 2017;35(5):802.e1‐802.e5.

      ,
      • Sharma R.
      • Macy S.
      • Richardson K.
      • Lokhnygina Y.
      • Laskowitz D.T.
      A blood-based biomarker panel to detect acute stroke.
      ,
      • Lewandowski C.
      • Mays-Wilson K.
      • Miller J.
      • Penstone P.
      • Miller D.J.
      • Bakoulas K.
      • et al.
      Safety and outcomes in stroke mimics after intravenous tissue plasminogen activator administration: a single-center experience.
      ,
      • Goyal N.
      • Male S.
      • Al Wafai A.
      • Bellamkonda S.
      • Zand R.
      Cost burden of stroke mimics and transient ischemic attack after intravenous tissue plasminogen activator treatment.
      ,
      • Neves Briard J.
      • Zewude R.T.
      • Kate M.P.
      • Rowe B.H.
      • Buck B.
      • Butcher K.
      • et al.
      Stroke Mimics Transported by Emergency Medical Services to a Comprehensive Stroke Center: The Magnitude of the Problem.
      ,
      • Garg R.
      • Rech M.A.
      • Schneck M.
      Stroke Mimics: An Important Source of Bias in Acute Ischemic Stroke Research.
      ,
      • Ifergan H.
      • Amelot A.
      • Ismail M.
      • Gaudron M.
      • Cottier J.P.
      • Narata A.P.
      Stroke-mimics in stroke-units. Evaluation after changes imposed by randomized trials.
      ,
      • Okano Y.
      • Ishimatsu K.
      • Kato Y.
      • Yamaga J.
      • Kuwahara K.
      • Okumoto K.
      • et al.
      Clinical features of stroke mimics in the emergency department.
      ,
      • Hansson P.-O.
      • Andersson Hagiwara M.
      • Herlitz J.
      • Brink P.
      • Wireklint Sundström B.
      Prehospital assessment of suspected stroke and TIA: An observational study.
      ,
      • Geisler F.
      • Ali S.F.
      • Ebinger M.
      • Kunz A.
      • Rozanski M.
      • Waldschmidt C.
      • et al.
      Evaluation of a score for the prehospital distinction between cerebrovascular disease and stroke mimic patients.
      ,
      • Noureddine A.
      • Ghandehari K.
      • Taghi S.M.
      Differentiation of true transient ischemic attack versus transient ischemic attack mimics.
      ,
      • Williams J.B.
      • Jauch E.C.
      • Lindsell C.J.
      • Campos B.
      Endothelial microparticle levels are similar in acute ischemic stroke and stroke mimics due to activation and not apoptosis/necrosis.
      ,
      • Ali S.F.
      • Viswanathan A.
      • Singhal A.B.
      • Rost N.S.
      • Forducey P.G.
      • Davis L.W.
      • et al.
      Partners Telestroke Network. The TeleStroke mimic (TM)-score: a prediction rule for identifying stroke mimics evaluated in a Telestroke Network.
      ,
      • Neves Briard J.
      • Zewude R.T.
      • Kate M.P.
      • Rowe B.H.
      • Buck B.
      • Butcher K.
      • et al.
      Stroke Mimics Transported by Emergency Medical Services to a Comprehensive Stroke Center: The Magnitude of the Problem.
      ,
      • Natteru P.
      • Mohebbi M.R.
      • George P.
      • Wisco D.
      • Gebel J.
      • Newey C.R.
      Variables That Best Differentiate In-Patient Acute Stroke from Stroke-Mimics with Acute Neurological Deficits.
      ,
      • Winkler D.T.
      • Fluri F.
      • Fuhr P.
      • Wetzel S.G.
      • Lyrer P.A.
      • Ruegg S.
      • et al.
      Thrombolysis in stroke mimics: frequency, clinical characteristics, and outcome.
      ,
      • Zinkstok S.M.
      • Engelter S.T.
      • Gensicke H.
      • Lyrer P.A.
      • Ringleb P.A.
      • Artto V.
      • et al.
      Safety of thrombolysis in stroke mimics: results from a multicenter cohort study.
      ,
      • Chang P.
      • Ruff I.
      • Mendelson S.J.
      • Caprio F.
      • Bergman D.L.
      • Prabhakaran S.
      The 2CAN Score.
      ,
      • Zerna C.
      • Yu A.Y.X.
      • Hong Z.M.
      • Penn A.M.
      • Lesperance M.L.
      • Croteau N.S.
      • et al.
      SpecTRA Study Group. White Matter Hyperintensity Volume Influences Symptoms in Patients Presenting With Minor Neurological Deficits.
      ,
      • Yaghi S.
      • Rayaz S.
      • Bianchi N.
      • Hall-Barrow J.C.
      • Hinduja A.
      Thrombolysis to stroke mimics in telestroke.
      ,
      • Wilkins S.S.
      • Bourke P.
      • Salam A.
      • Akhtar N.
      • D'Souza A.
      • Kamran S.
      • et al.
      Functional Stroke Mimics: Incidence and Characteristics at a Primary Stroke Center in the Middle East.
      ,
      • Penn A.M.
      • Croteau N.S.
      • Votova K.
      • Sedgwick C.
      • Balshaw R.F.
      • Coutts S.B.
      • et al.
      Systolic blood pressure as a predictor of transient ischemic attack/minor stroke in emergency department patients under age 80: a prospective cohort study.
      ,
      • Uchino K.
      • Massaro L.
      • Hammer M.D.
      Transient ischemic attack after tissue plasminogen activator: aborted stroke or unnecessary stroke therapy?.
      ,
      • Ghia D.
      • Thomas P.R.
      • Cordato D.J.
      • Worthington J.M.
      • Cappelen-Smith C.
      • Griffith N.
      • et al.
      Validation of emergency and final diagnosis coding in transient ischemic attack: South Western Sydney transient ischemic attack study.
      ,
      • Amort M.
      • Fluri F.
      • Schäfer J.
      • Weisskopf F.
      • Katan M.
      • Burow A.
      • et al.
      Transient ischemic attack versus transient ischemic attack mimics: frequency, clinical characteristics and outcome.
      ,
      • Quenardelle V.
      • Lauer-Ober V.
      • Zinchenko I.
      • Bataillard M.
      • Rouyer O.
      • Beaujeux R.
      • et al.
      Stroke Mimics in a Stroke Care Pathway Based on MRI Screening.
      ,
      • Bliden K.P.
      • Raviv G.
      • Tantry U.S.
      • Chaudhary R.
      • Cochran J.W.
      • Navarese E.P.
      • et al.
      “Blueprinting” thrombogenicity and antithrombotic drug response at the bedside in patients presenting emergently with symptoms of acute stroke.
      ,
      • Kostulas N.
      • Larsson M.
      • Kall T.-B.
      • von Euler M.
      • Nathanson D.
      Safety of thrombolysis in stroke mimics: an observational cohort study from an urban teaching hospital in Sweden.
      ,
      • Foerch C.
      • Niessner M.
      • Back T.
      • Bauerle M.
      • De Marchis G.M.
      • Ferbert A.
      • et al.
      BE FAST Study Group. Diagnostic accuracy of plasma glial fibrillary acidic protein for differentiating intracerebral hemorrhage and cerebral ischemia in patients with symptoms of acute stroke.
      ,
      • Liberman A.L.
      • Liotta E.M.
      • Caprio F.Z.
      • Ruff I.
      • Maas M.B.
      • Bernstein R.A.
      • et al.
      Do efforts to decrease door-to-needle time risk increasing stroke mimic treatment rates?.
      ,
      • Gioia L.C.
      • Zewude R.T.
      • Kate M.P.
      • Liss K.
      • Rowe B.H.
      • Buck B.
      • et al.
      Prehospital systolic blood pressure is higher in acute stroke compared with stroke mimics.
      ,
      • Merino J.G.
      • Luby M.
      • Benson R.T.
      • Davis L.A.
      • Hsia A.W.
      • Latour L.L.
      • et al.
      Predictors of acute stroke mimics in 8187 patients referred to a stroke service.
      ,
      • Ali S.F.
      • Hubert G.J.
      • Switzer J.A.
      • Majersik J.J.
      • Backhaus R.
      • Shepard L.W.
      • et al.
      Validating the TeleStroke Mimic Score: A Prediction Rule for Identifying Stroke Mimics Evaluated Over Telestroke Networks.
      ,
      • Avellaneda-Gómez C.
      • Rodríguez Campello A.
      • Giralt Steinhauer E.
      • Gómez González A.
      • Serra Martínez M.
      • de Ceballos C.P.
      • et al.
      Description of stroke mimics after complete neurovascular assessment.
      ], dyslipidaemia 38% (9891/26005) vs. 23.6% (1585/6717) [
      • Asaithambi G.
      • Castle A.L.
      • Sperl M.A.
      • Ravichandran J.
      • Gupta A.
      • Ho B.M.
      • et al.
      Thrombolytic treatment to stroke mimic patients via telestroke.
      ,

      Pearson C, Przyklenk K, Mika VH, Ayaz SI, Ellis M, Varade P, Tolomello R, Welch RD. Utility of point of care assessment of platelet reactivity (using the PFA-100®) to aid in diagnosis of stroke. Am J Emerg Med. 2017;35(5):802.e1‐802.e5.

      ,
      • Sharma R.
      • Macy S.
      • Richardson K.
      • Lokhnygina Y.
      • Laskowitz D.T.
      A blood-based biomarker panel to detect acute stroke.
      ,
      • Lewandowski C.
      • Mays-Wilson K.
      • Miller J.
      • Penstone P.
      • Miller D.J.
      • Bakoulas K.
      • et al.
      Safety and outcomes in stroke mimics after intravenous tissue plasminogen activator administration: a single-center experience.
      ,
      • Neves Briard J.
      • Zewude R.T.
      • Kate M.P.
      • Rowe B.H.
      • Buck B.
      • Butcher K.
      • et al.
      Stroke Mimics Transported by Emergency Medical Services to a Comprehensive Stroke Center: The Magnitude of the Problem.
      ,
      • Ifergan H.
      • Amelot A.
      • Ismail M.
      • Gaudron M.
      • Cottier J.P.
      • Narata A.P.
      Stroke-mimics in stroke-units. Evaluation after changes imposed by randomized trials.
      ,
      • Okano Y.
      • Ishimatsu K.
      • Kato Y.
      • Yamaga J.
      • Kuwahara K.
      • Okumoto K.
      • et al.
      Clinical features of stroke mimics in the emergency department.
      ,
      • Bliden K.P.
      • Raviv G.
      • Tantry U.S.
      • Chaudhary R.
      • Cochran J.W.
      • Navarese E.P.
      • et al.
      “Blueprinting” thrombogenicity and antithrombotic drug response at the bedside in patients presenting emergently with symptoms of acute stroke.
      ,
      • Kostulas N.
      • Larsson M.
      • Kall T.-B.
      • von Euler M.
      • Nathanson D.
      Safety of thrombolysis in stroke mimics: an observational cohort study from an urban teaching hospital in Sweden.
      ,
      • Noureddine A.
      • Ghandehari K.
      • Taghi S.M.
      Differentiation of true transient ischemic attack versus transient ischemic attack mimics.
      ,
      • Williams J.B.
      • Jauch E.C.
      • Lindsell C.J.
      • Campos B.
      Endothelial microparticle levels are similar in acute ischemic stroke and stroke mimics due to activation and not apoptosis/necrosis.
      ,
      • Ali S.F.
      • Viswanathan A.
      • Singhal A.B.
      • Rost N.S.
      • Forducey P.G.
      • Davis L.W.
      • et al.
      Partners Telestroke Network. The TeleStroke mimic (TM)-score: a prediction rule for identifying stroke mimics evaluated in a Telestroke Network.
      ,
      • Kvistad C.E.
      • Novotny V.
      • Næss H.
      • Hagberg G.
      • Ihle-Hansen H.
      • Waje-Andreassen U.
      • et al.
      Safety and predictors of stroke mimics in The Norwegian Tenecteplase Stroke Trial (NOR-TEST).
      ,
      • Avellaneda-Gómez C.
      • Rodríguez Campello A.
      • Giralt Steinhauer E.
      • Gómez González A.
      • Serra Martínez M.
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      ], smoking 25.7% (5002/19433) vs. 22.2% (853/3841) [
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      Pearson C, Przyklenk K, Mika VH, Ayaz SI, Ellis M, Varade P, Tolomello R, Welch RD. Utility of point of care assessment of platelet reactivity (using the PFA-100®) to aid in diagnosis of stroke. Am J Emerg Med. 2017;35(5):802.e1‐802.e5.

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      ,

      2018 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. 2018;49:e46–e99.

      ,
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      ,
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      Description of stroke mimics after complete neurovascular assessment.
      ,
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      • George P.
      • Wisco D.
      • Gebel J.
      • Newey C.R.
      Variables That Best Differentiate In-Patient Acute Stroke from Stroke-Mimics with Acute Neurological Deficits.
      ,
      • Winkler D.T.
      • Fluri F.
      • Fuhr P.
      • Wetzel S.G.
      • Lyrer P.A.
      • Ruegg S.
      • et al.
      Thrombolysis in stroke mimics: frequency, clinical characteristics, and outcome.
      ,
      • Zinkstok S.M.
      • Engelter S.T.
      • Gensicke H.
      • Lyrer P.A.
      • Ringleb P.A.
      • Artto V.
      • et al.
      Safety of thrombolysis in stroke mimics: results from a multicenter cohort study.
      ,
      • Zerna C.
      • Yu A.Y.X.
      • Hong Z.M.
      • Penn A.M.
      • Lesperance M.L.
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      • et al.
      SpecTRA Study Group. White Matter Hyperintensity Volume Influences Symptoms in Patients Presenting With Minor Neurological Deficits.
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      ,
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      • et al.
      Transient ischemic attack versus transient ischemic attack mimics: frequency, clinical characteristics and outcome.
      ,
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      • et al.
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      ] and diabetes 24.3% (6970/28689) vs. 17.8% (1373/7695) [
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      ,
      • Asaithambi G.
      • Castle A.L.
      • Sperl M.A.
      • Ravichandran J.
      • Gupta A.
      • Ho B.M.
      • et al.
      Thrombolytic treatment to stroke mimic patients via telestroke.
      ,
      • Sharma R.
      • Macy S.
      • Richardson K.
      • Lokhnygina Y.
      • Laskowitz D.T.
      A blood-based biomarker panel to detect acute stroke.
      ,
      • Lewandowski C.
      • Mays-Wilson K.
      • Miller J.
      • Penstone P.
      • Miller D.J.
      • Bakoulas K.
      • et al.
      Safety and outcomes in stroke mimics after intravenous tissue plasminogen activator administration: a single-center experience.
      ,
      • Neves Briard J.
      • Zewude R.T.
      • Kate M.P.
      • Rowe B.H.
      • Buck B.
      • Butcher K.
      • et al.
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      ,
      • Garg R.
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      ,
      • Ifergan H.
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      • Narata A.P.
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      ,
      • Okano Y.
      • Ishimatsu K.
      • Kato Y.
      • Yamaga J.
      • Kuwahara K.
      • Okumoto K.
      • et al.
      Clinical features of stroke mimics in the emergency department.
      ,
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      ,
      • Williams J.B.
      • Jauch E.C.
      • Lindsell C.J.
      • Campos B.
      Endothelial microparticle levels are similar in acute ischemic stroke and stroke mimics due to activation and not apoptosis/necrosis.
      ,
      • Ali S.F.
      • Viswanathan A.
      • Singhal A.B.
      • Rost N.S.
      • Forducey P.G.
      • Davis L.W.
      • et al.
      Partners Telestroke Network. The TeleStroke mimic (TM)-score: a prediction rule for identifying stroke mimics evaluated in a Telestroke Network.
      ,
      • Kvistad C.E.
      • Novotny V.
      • Næss H.
      • Hagberg G.
      • Ihle-Hansen H.
      • Waje-Andreassen U.
      • et al.
      Safety and predictors of stroke mimics in The Norwegian Tenecteplase Stroke Trial (NOR-TEST).
      ,
      • Avellaneda-Gómez C.
      • Rodríguez Campello A.
      • Giralt Steinhauer E.
      • Gómez González A.
      • Serra Martínez M.
      • de Ceballos C.P.
      • et al.
      Description of stroke mimics after complete neurovascular assessment.
      ,
      • Natteru P.
      • Mohebbi M.R.
      • George P.
      • Wisco D.
      • Gebel J.
      • Newey C.R.
      Variables That Best Differentiate In-Patient Acute Stroke from Stroke-Mimics with Acute Neurological Deficits.
      ,
      • Yaghi S.
      • Rayaz S.
      • Bianchi N.
      • Hall-Barrow J.C.
      • Hinduja A.
      Thrombolysis to stroke mimics in telestroke.
      ,
      • Wilkins S.S.
      • Bourke P.
      • Salam A.
      • Akhtar N.
      • D'Souza A.
      • Kamran S.
      • et al.
      Functional Stroke Mimics: Incidence and Characteristics at a Primary Stroke Center in the Middle East.
      ,
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      ,
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      • Cappelen-Smith C.
      • Griffith N.
      • et al.
      Validation of emergency and final diagnosis coding in transient ischemic attack: South Western Sydney transient ischemic attack study.
      ,
      • Amort M.
      • Fluri F.
      • Schäfer J.
      • Weisskopf F.
      • Katan M.
      • Burow A.
      • et al.
      Transient ischemic attack versus transient ischemic attack mimics: frequency, clinical characteristics and outcome.
      ,
      • Quenardelle V.
      • Lauer-Ober V.
      • Zinchenko I.
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      Do efforts to decrease door-to-needle time risk increasing stroke mimic treatment rates?.
      ,
      • Gioia L.C.
      • Zewude R.T.
      • Kate M.P.
      • Liss K.
      • Rowe B.H.
      • Buck B.
      • et al.
      Prehospital systolic blood pressure is higher in acute stroke compared with stroke mimics.
      ,
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      • Luby M.
      • Benson R.T.
      • Davis L.A.
      • Hsia A.W.
      • Latour L.L.
      • et al.
      Predictors of acute stroke mimics in 8187 patients referred to a stroke service.
      ,
      • Winkler D.T.
      • Fluri F.
      • Fuhr P.
      • Wetzel S.G.
      • Lyrer P.A.
      • Ruegg S.
      • et al.
      Thrombolysis in stroke mimics: frequency, clinical characteristics, and outcome.
      ,
      • Zinkstok S.M.
      • Engelter S.T.
      • Gensicke H.
      • Lyrer P.A.
      • Ringleb P.A.
      • Artto V.
      • et al.
      Safety of thrombolysis in stroke mimics: results from a multicenter cohort study.
      ,
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      • Prabhakaran S.
      The 2CAN Score.
      ,
      • Zerna C.
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      • Hong Z.M.
      • Penn A.M.
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      • Croteau N.S.
      • et al.
      SpecTRA Study Group. White Matter Hyperintensity Volume Influences Symptoms in Patients Presenting With Minor Neurological Deficits.
      ] were more common in ischemic stroke patients (p < 0.001 in all cases) (Table 2).
      Table 2Distribution of risk factors in the study subgroups.
      StrokeStroke mimicP values
      Smoking25.722.2<0.001
      Hypertension66.841.1<0.001
      Dyslipidaemia3823.6<0.001
      Diabetes24.317.8<0.001
      IHD15.99.1<0.001
      AF238.4<0.001
      PVD9.96.7<0.001
      Previous stroke19.319.70.42
      Cognitive impairment11.125.4<0.001
      Migraine in anamnesis11.316.5<0.001
      Seizure in anamnesis1.52.30.23
      Known malignancy8.79.10.88
      Abbreviations: IHD: ischemic heart disease, AF: atrial fibrillation, PVD: peripheral vascular disease.
      Ischemic heart disease (IHD) 15.9 % (3388/21237) vs. 9.1% (507/5542) [
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      ,
      • Asaithambi G.
      • Castle A.L.
      • Sperl M.A.
      • Ravichandran J.
      • Gupta A.
      • Ho B.M.
      • et al.
      Thrombolytic treatment to stroke mimic patients via telestroke.
      ,

      Pearson C, Przyklenk K, Mika VH, Ayaz SI, Ellis M, Varade P, Tolomello R, Welch RD. Utility of point of care assessment of platelet reactivity (using the PFA-100®) to aid in diagnosis of stroke. Am J Emerg Med. 2017;35(5):802.e1‐802.e5.

      ,
      • Lewandowski C.
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      • Penstone P.
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      • Bakoulas K.
      • et al.
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      ,
      • Neves Briard J.
      • Zewude R.T.
      • Kate M.P.
      • Rowe B.H.
      • Buck B.
      • Butcher K.
      • et al.
      Stroke Mimics Transported by Emergency Medical Services to a Comprehensive Stroke Center: The Magnitude of the Problem.
      ,
      • Uchino K.
      • Massaro L.
      • Hammer M.D.
      Transient ischemic attack after tissue plasminogen activator: aborted stroke or unnecessary stroke therapy?.
      ,
      • Amort M.
      • Fluri F.
      • Schäfer J.
      • Weisskopf F.
      • Katan M.
      • Burow A.
      • et al.
      Transient ischemic attack versus transient ischemic attack mimics: frequency, clinical characteristics and outcome.
      ,
      • Quenardelle V.
      • Lauer-Ober V.
      • Zinchenko I.
      • Bataillard M.
      • Rouyer O.
      • Beaujeux R.
      • et al.
      Stroke Mimics in a Stroke Care Pathway Based on MRI Screening.
      ,
      • Hansson P.-O.
      • Andersson Hagiwara M.
      • Herlitz J.
      • Brink P.
      • Wireklint Sundström B.
      Prehospital assessment of suspected stroke and TIA: An observational study.
      ,
      • Williams J.B.
      • Jauch E.C.
      • Lindsell C.J.
      • Campos B.
      Endothelial microparticle levels are similar in acute ischemic stroke and stroke mimics due to activation and not apoptosis/necrosis.
      ,
      • Ali S.F.
      • Viswanathan A.
      • Singhal A.B.
      • Rost N.S.
      • Forducey P.G.
      • Davis L.W.
      • et al.
      Partners Telestroke Network. The TeleStroke mimic (TM)-score: a prediction rule for identifying stroke mimics evaluated in a Telestroke Network.
      ,
      • Gioia L.C.
      • Zewude R.T.
      • Kate M.P.
      • Liss K.
      • Rowe B.H.
      • Buck B.
      • et al.
      Prehospital systolic blood pressure is higher in acute stroke compared with stroke mimics.
      ,
      • Merino J.G.
      • Luby M.
      • Benson R.T.
      • Davis L.A.
      • Hsia A.W.
      • Latour L.L.
      • et al.
      Predictors of acute stroke mimics in 8187 patients referred to a stroke service.
      ,
      • Avellaneda-Gómez C.
      • Rodríguez Campello A.
      • Giralt Steinhauer E.
      • Gómez González A.
      • Serra Martínez M.
      • de Ceballos C.P.
      • et al.
      Description of stroke mimics after complete neurovascular assessment.
      ,
      • Natteru P.
      • Mohebbi M.R.
      • George P.
      • Wisco D.
      • Gebel J.
      • Newey C.R.
      Variables That Best Differentiate In-Patient Acute Stroke from Stroke-Mimics with Acute Neurological Deficits.
      ,
      • Winkler D.T.
      • Fluri F.
      • Fuhr P.
      • Wetzel S.G.
      • Lyrer P.A.
      • Ruegg S.
      • et al.
      Thrombolysis in stroke mimics: frequency, clinical characteristics, and outcome.
      ,
      • Zinkstok S.M.
      • Engelter S.T.
      • Gensicke H.
      • Lyrer P.A.
      • Ringleb P.A.
      • Artto V.
      • et al.
      Safety of thrombolysis in stroke mimics: results from a multicenter cohort study.
      ,
      • Zerna C.
      • Yu A.Y.X.
      • Hong Z.M.
      • Penn A.M.
      • Lesperance M.L.
      • Croteau N.S.
      • et al.
      SpecTRA Study Group. White Matter Hyperintensity Volume Influences Symptoms in Patients Presenting With Minor Neurological Deficits.
      ] previously known atrial fibrillation 23% (6611/28723) vs. 8.4% (670/7929) [
      • Hand P.J.
      • Kwan J.
      • Lindley R.I.
      • Dennis M.S.
      • Wardlaw J.M.
      Distinguishing between stroke and mimic at the bedside: the brain attack study.
      ,
      • Asaithambi G.
      • Castle A.L.
      • Sperl M.A.
      • Ravichandran J.
      • Gupta A.
      • Ho B.M.
      • et al.
      Thrombolytic treatment to stroke mimic patients via telestroke.
      ,

      Pearson C, Przyklenk K, Mika VH, Ayaz SI, Ellis M, Varade P, Tolomello R, Welch RD. Utility of point of care assessment of platelet reactivity (using the PFA-100®) to aid in diagnosis of stroke. Am J Emerg Med. 2017;35(5):802.e1‐802.e5.

      ,
      • Sharma R.
      • Macy S.
      • Richardson K.
      • Lokhnygina Y.
      • Laskowitz D.T.
      A blood-based biomarker panel to detect acute stroke.
      ,
      • Lewandowski C.
      • Mays-Wilson K.
      • Miller J.
      • Penstone P.
      • Miller D.J.
      • Bakoulas K.
      • et al.
      Safety and outcomes in stroke mimics after intravenous tissue plasminogen activator administration: a single-center experience.
      ,
      • Neves Briard J.
      • Zewude R.T.
      • Kate M.P.
      • Rowe B.H.
      • Buck B.
      • Butcher K.
      • et al.
      Stroke Mimics Transported by Emergency Medical Services to a Comprehensive Stroke Center: The Magnitude of the Problem.
      ,
      • Garg R.
      • Rech M.A.
      • Schneck M.
      Stroke Mimics: An Important Source of Bias in Acute Ischemic Stroke Research.
      ,
      • Ifergan H.
      • Amelot A.
      • Ismail M.
      • Gaudron M.
      • Cottier J.P.
      • Narata A.P.
      Stroke-mimics in stroke-units. Evaluation after changes imposed by randomized trials.
      ,
      • Okano Y.
      • Ishimatsu K.
      • Kato Y.
      • Yamaga J.
      • Kuwahara K.
      • Okumoto K.
      • et al.
      Clinical features of stroke mimics in the emergency department.
      ,
      • Hansson P.-O.
      • Andersson Hagiwara M.
      • Herlitz J.
      • Brink P.
      • Wireklint Sundström B.
      Prehospital assessment of suspected stroke and TIA: An observational study.
      ,
      • Bliden K.P.
      • Raviv G.
      • Tantry U.S.
      • Chaudhary R.
      • Cochran J.W.
      • Navarese E.P.
      • et al.
      “Blueprinting” thrombogenicity and antithrombotic drug response at the bedside in patients presenting emergently with symptoms of acute stroke.
      ,
      • Kostulas N.
      • Larsson M.
      • Kall T.-B.
      • von Euler M.
      • Nathanson D.
      Safety of thrombolysis in stroke mimics: an observational cohort study from an urban teaching hospital in Sweden.
      ,
      • Topiwala K.
      • Tarasaria K.
      • Staff I.
      • Beland D.
      • Schuyler E.
      • Nouh A.
      Identifying Gaps and Missed Opportunities for Intravenous Thrombolytic Treatment of Inpatient Stroke.
      ,
      • Geisler F.
      • Ali S.F.
      • Ebinger M.
      • Kunz A.
      • Rozanski M.
      • Waldschmidt C.
      • et al.
      Evaluation of a score for the prehospital distinction between cerebrovascular disease and stroke mimic patients.
      ,
      • Williams J.B.
      • Jauch E.C.
      • Lindsell C.J.
      • Campos B.
      Endothelial microparticle levels are similar in acute ischemic stroke and stroke mimics due to activation and not apoptosis/necrosis.
      ,
      • Ali S.F.
      • Viswanathan A.
      • Singhal A.B.
      • Rost N.S.
      • Forducey P.G.
      • Davis L.W.
      • et al.
      Partners Telestroke Network. The TeleStroke mimic (TM)-score: a prediction rule for identifying stroke mimics evaluated in a Telestroke Network.
      ,
      • Kvistad C.E.
      • Novotny V.
      • Næss H.
      • Hagberg G.
      • Ihle-Hansen H.
      • Waje-Andreassen U.
      • et al.
      Safety and predictors of stroke mimics in The Norwegian Tenecteplase Stroke Trial (NOR-TEST).
      ,
      • Natteru P.
      • Mohebbi M.R.
      • George P.
      • Wisco D.
      • Gebel J.
      • Newey C.R.
      Variables That Best Differentiate In-Patient Acute Stroke from Stroke-Mimics with Acute Neurological Deficits.
      ,
      • Yaghi S.
      • Rayaz S.
      • Bianchi N.
      • Hall-Barrow J.C.
      • Hinduja A.
      Thrombolysis to stroke mimics in telestroke.
      ,
      • Uchino K.
      • Massaro L.
      • Hammer M.D.
      Transient ischemic attack after tissue plasminogen activator: aborted stroke or unnecessary stroke therapy?.
      ,
      • Ghia D.
      • Thomas P.R.
      • Cordato D.J.
      • Worthington J.M.
      • Cappelen-Smith C.
      • Griffith N.
      • et al.
      Validation of emergency and final diagnosis coding in transient ischemic attack: South Western Sydney transient ischemic attack study.
      ,
      • Amort M.
      • Fluri F.
      • Schäfer J.
      • Weisskopf F.
      • Katan M.
      • Burow A.
      • et al.
      Transient ischemic attack versus transient ischemic attack mimics: frequency, clinical characteristics and outcome.
      ,
      • Quenardelle V.
      • Lauer-Ober V.
      • Zinchenko I.
      • Bataillard M.
      • Rouyer O.
      • Beaujeux R.
      • et al.
      Stroke Mimics in a Stroke Care Pathway Based on MRI Screening.
      ,
      • Suzuki J.
      • Nakai N.
      • Kondo N.
      • Tsuji H.
      • Inagaki R.
      • Furukawa S.
      • et al.
      Ten-Year Evaluation of the TOYOTA Prehospital Stroke Scale for Tissue Plasminogen Activator Intravenous Therapy in the Real World.
      ,
      • Gioia L.C.
      • Zewude R.T.
      • Kate M.P.
      • Liss K.
      • Rowe B.H.
      • Buck B.
      • et al.
      Prehospital systolic blood pressure is higher in acute stroke compared with stroke mimics.
      ,
      • Merino J.G.
      • Luby M.
      • Benson R.T.
      • Davis L.A.
      • Hsia A.W.
      • Latour L.L.
      • et al.
      Predictors of acute stroke mimics in 8187 patients referred to a stroke service.
      ,
      • Ali S.F.
      • Hubert G.J.
      • Switzer J.A.
      • Majersik J.J.
      • Backhaus R.
      • Shepard L.W.
      • et al.
      Validating the TeleStroke Mimic Score: A Prediction Rule for Identifying Stroke Mimics Evaluated Over Telestroke Networks.
      ,
      • Avellaneda-Gómez C.
      • Rodríguez Campello A.
      • Giralt Steinhauer E.
      • Gómez González A.
      • Serra Martínez M.
      • de Ceballos C.P.
      • et al.
      Description of stroke mimics after complete neurovascular assessment.
      ,
      • Winkler D.T.
      • Fluri F.
      • Fuhr P.
      • Wetzel S.G.
      • Lyrer P.A.
      • Ruegg S.
      • et al.
      Thrombolysis in stroke mimics: frequency, clinical characteristics, and outcome.
      ,
      • Zinkstok S.M.
      • Engelter S.T.
      • Gensicke H.
      • Lyrer P.A.
      • Ringleb P.A.
      • Artto V.
      • et al.
      Safety of thrombolysis in stroke mimics: results from a multicenter cohort study.
      ,
      • Wendt M.
      • Ebinger M.
      • Kunz A.
      • Rozanski M.
      • Waldschmidt C.
      • Weber J.E.
      • et al.
      Copeptin Levels in Patients With Acute Ischemic Stroke and Stroke Mimics.
      ,
      • Chang P.
      • Ruff I.
      • Mendelson S.J.
      • Caprio F.
      • Bergman D.L.
      • Prabhakaran S.
      The 2CAN Score.
      ,
      • Zerna C.
      • Yu A.Y.X.
      • Hong Z.M.
      • Penn A.M.
      • Lesperance M.L.
      • Croteau N.S.
      • et al.
      SpecTRA Study Group. White Matter Hyperintensity Volume Influences Symptoms in Patients Presenting With Minor Neurological Deficits.
      ] and peripheral vascular disease (PVD) 9.9% (468/4719) vs. 6.7% (45/669) [
      • Hand P.J.
      • Kwan J.
      • Lindley R.I.
      • Dennis M.S.
      • Wardlaw J.M.
      Distinguishing between stroke and mimic at the bedside: the brain attack study.
      ,
      • Amort M.
      • Fluri F.
      • Schäfer J.
      • Weisskopf F.
      • Katan M.
      • Burow A.
      • et al.
      Transient ischemic attack versus transient ischemic attack mimics: frequency, clinical characteristics and outcome.
      ,
      • Avellaneda-Gómez C.
      • Rodríguez Campello A.
      • Giralt Steinhauer E.
      • Gómez González A.
      • Serra Martínez M.
      • de Ceballos C.P.
      • et al.
      Description of stroke mimics after complete neurovascular assessment.
      ,
      • Chang P.
      • Ruff I.
      • Mendelson S.J.
      • Caprio F.
      • Bergman D.L.
      • Prabhakaran S.
      The 2CAN Score.
      ] were more common in ischemic stroke patients also (p < 0.01 in all cases) (Table 2).
      The prevalence of previous ischemic stroke was not statistically different between the two groups (19.3%, 4906/25481 vs. 19.7%, 1412/7141, p = 0.42) [
      • Hand P.J.
      • Kwan J.
      • Lindley R.I.
      • Dennis M.S.
      • Wardlaw J.M.
      Distinguishing between stroke and mimic at the bedside: the brain attack study.
      ,
      • Asaithambi G.
      • Castle A.L.
      • Sperl M.A.
      • Ravichandran J.
      • Gupta A.
      • Ho B.M.
      • et al.
      Thrombolytic treatment to stroke mimic patients via telestroke.
      ,

      Pearson C, Przyklenk K, Mika VH, Ayaz SI, Ellis M, Varade P, Tolomello R, Welch RD. Utility of point of care assessment of platelet reactivity (using the PFA-100®) to aid in diagnosis of stroke. Am J Emerg Med. 2017;35(5):802.e1‐802.e5.

      ,
      • Neves Briard J.
      • Zewude R.T.
      • Kate M.P.
      • Rowe B.H.
      • Buck B.
      • Butcher K.
      • et al.
      Stroke Mimics Transported by Emergency Medical Services to a Comprehensive Stroke Center: The Magnitude of the Problem.
      ,
      • Sugii N.
      • Zaboronok A.
      • Fujimori H.
      • Sato N.
      • Fujita K.
      • Ishikawa E.
      • et al.
      Stroke Mimics and Accuracy of Referrals Made by Emergency Department Doctors in Japan for Patients with Suspected Stroke.
      ,
      • Ifergan H.
      • Amelot A.
      • Ismail M.
      • Gaudron M.
      • Cottier J.P.
      • Narata A.P.
      Stroke-mimics in stroke-units. Evaluation after changes imposed by randomized trials.
      ,
      • Uchino K.
      • Massaro L.
      • Hammer M.D.
      Transient ischemic attack after tissue plasminogen activator: aborted stroke or unnecessary stroke therapy?.
      ,
      • Amort M.
      • Fluri F.
      • Schäfer J.
      • Weisskopf F.
      • Katan M.
      • Burow A.
      • et al.
      Transient ischemic attack versus transient ischemic attack mimics: frequency, clinical characteristics and outcome.
      ,
      • Quenardelle V.
      • Lauer-Ober V.
      • Zinchenko I.
      • Bataillard M.
      • Rouyer O.
      • Beaujeux R.
      • et al.
      Stroke Mimics in a Stroke Care Pathway Based on MRI Screening.
      ,
      • Hansson P.-O.
      • Andersson Hagiwara M.
      • Herlitz J.
      • Brink P.
      • Wireklint Sundström B.
      Prehospital assessment of suspected stroke and TIA: An observational study.
      ,
      • Bliden K.P.
      • Raviv G.
      • Tantry U.S.
      • Chaudhary R.
      • Cochran J.W.
      • Navarese E.P.
      • et al.
      “Blueprinting” thrombogenicity and antithrombotic drug response at the bedside in patients presenting emergently with symptoms of acute stroke.
      ,
      • Kostulas N.
      • Larsson M.
      • Kall T.-B.
      • von Euler M.
      • Nathanson D.
      Safety of thrombolysis in stroke mimics: an observational cohort study from an urban teaching hospital in Sweden.
      ,
      • Williams J.B.
      • Jauch E.C.
      • Lindsell C.J.
      • Campos B.
      Endothelial microparticle levels are similar in acute ischemic stroke and stroke mimics due to activation and not apoptosis/necrosis.
      ,
      • Ali S.F.
      • Viswanathan A.
      • Singhal A.B.
      • Rost N.S.
      • Forducey P.G.
      • Davis L.W.
      • et al.
      Partners Telestroke Network. The TeleStroke mimic (TM)-score: a prediction rule for identifying stroke mimics evaluated in a Telestroke Network.
      ,
      • Kvistad C.E.
      • Novotny V.
      • Næss H.
      • Hagberg G.
      • Ihle-Hansen H.
      • Waje-Andreassen U.
      • et al.
      Safety and predictors of stroke mimics in The Norwegian Tenecteplase Stroke Trial (NOR-TEST).
      ,
      • Avellaneda-Gómez C.
      • Rodríguez Campello A.
      • Giralt Steinhauer E.
      • Gómez González A.
      • Serra Martínez M.
      • de Ceballos C.P.
      • et al.
      Description of stroke mimics after complete neurovascular assessment.
      ,
      • Natteru P.
      • Mohebbi M.R.
      • George P.
      • Wisco D.
      • Gebel J.
      • Newey C.R.
      Variables That Best Differentiate In-Patient Acute Stroke from Stroke-Mimics with Acute Neurological Deficits.
      ,
      • Siegler J.E.
      • Rosenberg J.
      • Cristancho D.
      • Olsen A.
      • Pulst-Korenberg J.
      • Raab L.
      • et al.
      Computed tomography perfusion in stroke mimics.
      ,
      • Zinkstok S.M.
      • Engelter S.T.
      • Gensicke H.
      • Lyrer P.A.
      • Ringleb P.A.
      • Artto V.
      • et al.
      Safety of thrombolysis in stroke mimics: results from a multicenter cohort study.
      ,
      • Chang P.
      • Ruff I.
      • Mendelson S.J.
      • Caprio F.
      • Bergman D.L.
      • Prabhakaran S.
      The 2CAN Score.
      ,
      • Zerna C.
      • Yu A.Y.X.
      • Hong Z.M.
      • Penn A.M.
      • Lesperance M.L.
      • Croteau N.S.
      • et al.
      SpecTRA Study Group. White Matter Hyperintensity Volume Influences Symptoms in Patients Presenting With Minor Neurological Deficits.
      ,
      • Wilkins S.S.
      • Bourke P.
      • Salam A.
      • Akhtar N.
      • D'Souza A.
      • Kamran S.
      • et al.
      Functional Stroke Mimics: Incidence and Characteristics at a Primary Stroke Center in the Middle East.
      ,
      • Sharma R.
      • Macy S.
      • Richardson K.
      • Lokhnygina Y.
      • Laskowitz D.T.
      A blood-based biomarker panel to detect acute stroke.
      ,
      • Lewandowski C.
      • Mays-Wilson K.
      • Miller J.
      • Penstone P.
      • Miller D.J.
      • Bakoulas K.
      • et al.
      Safety and outcomes in stroke mimics after intravenous tissue plasminogen activator administration: a single-center experience.
      ,
      • Goyal N.
      • Male S.
      • Al Wafai A.
      • Bellamkonda S.
      • Zand R.
      Cost burden of stroke mimics and transient ischemic attack after intravenous tissue plasminogen activator treatment.
      ,
      • Liberman A.L.
      • Liotta E.M.
      • Caprio F.Z.
      • Ruff I.
      • Maas M.B.
      • Bernstein R.A.
      • et al.
      Do efforts to decrease door-to-needle time risk increasing stroke mimic treatment rates?.
      ,
      • Gioia L.C.
      • Zewude R.T.
      • Kate M.P.
      • Liss K.
      • Rowe B.H.
      • Buck B.
      • et al.
      Prehospital systolic blood pressure is higher in acute stroke compared with stroke mimics.
      ,
      • Merino J.G.
      • Luby M.
      • Benson R.T.
      • Davis L.A.
      • Hsia A.W.
      • Latour L.L.
      • et al.
      Predictors of acute stroke mimics in 8187 patients referred to a stroke service.
      ].
      Cognitive impairment 25.4% (31/122) vs. 11.1% (40/359) [
      • Hand P.J.
      • Kwan J.
      • Lindley R.I.
      • Dennis M.S.
      • Wardlaw J.M.
      Distinguishing between stroke and mimic at the bedside: the brain attack study.
      ,
      • Asaithambi G.
      • Castle A.L.
      • Sperl M.A.
      • Ravichandran J.
      • Gupta A.
      • Ho B.M.
      • et al.
      Thrombolytic treatment to stroke mimic patients via telestroke.
      ], and history of migraine 16.5% (151/916) vs. 11.3% (215/1900) [
      • Hand P.J.
      • Kwan J.
      • Lindley R.I.
      • Dennis M.S.
      • Wardlaw J.M.
      Distinguishing between stroke and mimic at the bedside: the brain attack study.
      ,
      • Asaithambi G.
      • Castle A.L.
      • Sperl M.A.
      • Ravichandran J.
      • Gupta A.
      • Ho B.M.
      • et al.
      Thrombolytic treatment to stroke mimic patients via telestroke.
      ,

      Pearson C, Przyklenk K, Mika VH, Ayaz SI, Ellis M, Varade P, Tolomello R, Welch RD. Utility of point of care assessment of platelet reactivity (using the PFA-100®) to aid in diagnosis of stroke. Am J Emerg Med. 2017;35(5):802.e1‐802.e5.

      ,
      • Ifergan H.
      • Amelot A.
      • Ismail M.
      • Gaudron M.
      • Cottier J.P.
      • Narata A.P.
      Stroke-mimics in stroke-units. Evaluation after changes imposed by randomized trials.
      ,
      • Gargalas S.
      • Weeks R.
      • Khan-Bourne N.
      • Shotbolt P.
      • Simblett S.
      • Ashraf L.
      • et al.
      Incidence and outcome of functional stroke mimics admitted to a hyperacute stroke unit.
      ,
      • Zerna C.
      • Yu A.Y.X.
      • Hong Z.M.
      • Penn A.M.
      • Lesperance M.L.
      • Croteau N.S.
      • et al.
      SpecTRA Study Group. White Matter Hyperintensity Volume Influences Symptoms in Patients Presenting With Minor Neurological Deficits.
      ] were more common is SM patients (p < 0.001 in both cases).
      History of seizures/epilepsy (1.5%, 13/871 vs. 2.3%, 15/643, p = 0.23) [
      • Hand P.J.
      • Kwan J.
      • Lindley R.I.
      • Dennis M.S.
      • Wardlaw J.M.
      Distinguishing between stroke and mimic at the bedside: the brain attack study.
      ,
      • Asaithambi G.
      • Castle A.L.
      • Sperl M.A.
      • Ravichandran J.
      • Gupta A.
      • Ho B.M.
      • et al.
      Thrombolytic treatment to stroke mimic patients via telestroke.
      ,

      Pearson C, Przyklenk K, Mika VH, Ayaz SI, Ellis M, Varade P, Tolomello R, Welch RD. Utility of point of care assessment of platelet reactivity (using the PFA-100®) to aid in diagnosis of stroke. Am J Emerg Med. 2017;35(5):802.e1‐802.e5.

      ,
      • Ifergan H.
      • Amelot A.
      • Ismail M.
      • Gaudron M.
      • Cottier J.P.
      • Narata A.P.
      Stroke-mimics in stroke-units. Evaluation after changes imposed by randomized trials.
      ] and malignancy (8.7%, 21/241 vs. 9.1%, 10/109, p = 0.88) [
      • Hand P.J.
      • Kwan J.
      • Lindley R.I.
      • Dennis M.S.
      • Wardlaw J.M.
      Distinguishing between stroke and mimic at the bedside: the brain attack study.
      ] were not different in the two groups.
      Pre-existing psychological disturbace was more common in ischemic stroke vs. SM patients (12.5%, 233/1857 vs. 9.2%, 121/1318, p = 0.003) [
      • Hand P.J.
      • Kwan J.
      • Lindley R.I.
      • Dennis M.S.
      • Wardlaw J.M.
      Distinguishing between stroke and mimic at the bedside: the brain attack study.
      ,
      • Asaithambi G.
      • Castle A.L.
      • Sperl M.A.
      • Ravichandran J.
      • Gupta A.
      • Ho B.M.
      • et al.
      Thrombolytic treatment to stroke mimic patients via telestroke.
      ,
      • Zerna C.
      • Yu A.Y.X.
      • Hong Z.M.
      • Penn A.M.
      • Lesperance M.L.
      • Croteau N.S.
      • et al.
      SpecTRA Study Group. White Matter Hyperintensity Volume Influences Symptoms in Patients Presenting With Minor Neurological Deficits.
      ].

      4.4 Thrombolysis

      20 studies reported thrombolysis rates between ischemic stroke and SM patients [
      • Garg R.
      • Rech M.A.
      • Schneck M.
      Stroke Mimics: An Important Source of Bias in Acute Ischemic Stroke Research.
      ,
      • Chtaou N.
      • Bouchal S.
      • Midaoui A.E.l.
      • Souirti Z.
      • Tachfouti N.
      • Belahsen M.F.
      Stroke Mimics: Experience of a Moroccan Stroke Unit.
      ,
      • Ifergan H.
      • Amelot A.
      • Ismail M.
      • Gaudron M.
      • Cottier J.P.
      • Narata A.P.
      Stroke-mimics in stroke-units. Evaluation after changes imposed by randomized trials.
      ,
      • Uchino K.
      • Massaro L.
      • Hammer M.D.
      Transient ischemic attack after tissue plasminogen activator: aborted stroke or unnecessary stroke therapy?.
      ,
      • Kostulas N.
      • Larsson M.
      • Kall T.-B.
      • von Euler M.
      • Nathanson D.
      Safety of thrombolysis in stroke mimics: an observational cohort study from an urban teaching hospital in Sweden.
      ,
      • Geisler F.
      • Ali S.F.
      • Ebinger M.
      • Kunz A.
      • Rozanski M.
      • Waldschmidt C.
      • et al.
      Evaluation of a score for the prehospital distinction between cerebrovascular disease and stroke mimic patients.
      ,
      • Esmaeili S.
      • Afrakhteh M.
      • Bahadori M.
      • Shojaei S.F.
      • Ashayeri R.
      • Mehrpour M.
      Thrombolytic treatment in stroke mimic, inevitable but fortunately safe: An observational study from Iran.
      ,
      • Kvistad C.E.
      • Novotny V.
      • Næss H.
      • Hagberg G.
      • Ihle-Hansen H.
      • Waje-Andreassen U.
      • et al.
      Safety and predictors of stroke mimics in The Norwegian Tenecteplase Stroke Trial (NOR-TEST).
      ,
      • Liberman A.L.
      • Liotta E.M.
      • Caprio F.Z.
      • Ruff I.
      • Maas M.B.
      • Bernstein R.A.
      • et al.
      Do efforts to decrease door-to-needle time risk increasing stroke mimic treatment rates?.
      ,
      • Avellaneda-Gómez C.
      • Rodríguez Campello A.
      • Giralt Steinhauer E.
      • Gómez González A.
      • Serra Martínez M.
      • de Ceballos C.P.
      • et al.
      Description of stroke mimics after complete neurovascular assessment.
      ,
      • Siegler J.E.
      • Rosenberg J.
      • Cristancho D.
      • Olsen A.
      • Pulst-Korenberg J.
      • Raab L.
      • et al.
      Computed tomography perfusion in stroke mimics.
      ,
      • Winkler D.T.
      • Fluri F.
      • Fuhr P.
      • Wetzel S.G.
      • Lyrer P.A.
      • Ruegg S.
      • et al.
      Thrombolysis in stroke mimics: frequency, clinical characteristics, and outcome.
      ,
      • Zinkstok S.M.
      • Engelter S.T.
      • Gensicke H.
      • Lyrer P.A.
      • Ringleb P.A.
      • Artto V.
      • et al.
      Safety of thrombolysis in stroke mimics: results from a multicenter cohort study.
      ,
      • Yaghi S.
      • Rayaz S.
      • Bianchi N.
      • Hall-Barrow J.C.
      • Hinduja A.
      Thrombolysis to stroke mimics in telestroke.
      ,
      • Wilkins S.S.
      • Bourke P.
      • Salam A.
      • Akhtar N.
      • D'Souza A.
      • Kamran S.
      • et al.
      Functional Stroke Mimics: Incidence and Characteristics at a Primary Stroke Center in the Middle East.
      ,
      • Hemmen T.M.
      • Meyer B.C.
      • McClean T.L.
      • Lyden P.D.
      Identification of nonischemic stroke mimics among 411 code strokes at the University of California, San Diego.
      ,
      • Sharma R.
      • Macy S.
      • Richardson K.
      • Lokhnygina Y.
      • Laskowitz D.T.
      A blood-based biomarker panel to detect acute stroke.
      ,
      • Lewandowski C.
      • Mays-Wilson K.
      • Miller J.
      • Penstone P.
      • Miller D.J.
      • Bakoulas K.
      • et al.
      Safety and outcomes in stroke mimics after intravenous tissue plasminogen activator administration: a single-center experience.
      ,
      • Goyal N.
      • Male S.
      • Al Wafai A.
      • Bellamkonda S.
      • Zand R.
      Cost burden of stroke mimics and transient ischemic attack after intravenous tissue plasminogen activator treatment.
      ,
      • Sivakumaran P.
      • Gill D.
      • Mahir G.
      • Baheerathan A.
      • Kar A.
      A Retrospective Cohort Study on the Use of Intravenous Thrombolysis in Stroke Mimics.
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