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• To Join: • Text KERRYAHRENS516 to 37607 • For all future texts, you text your choice A-E Kerry Ahrens MD, MS BayCare Clinic Emergency Physician Associate Professor EM UW School of Medicine Medflight Physician Medical Director Oshkosh Fire Dept Co-Chair Wisconsin Coalition Disclosures:

• On speakers bureau Genentech Stroke Mimics OBJECTIVES

• Discuss & learn the pathologies behind various stroke mimics • Distinguish stroke mimic vs ‘chameleon’ • Objective & subjective methods to distinguish a mimic from a stroke • Discuss medical & financial ramifications of mimics

!5

Stroke is an Emergency!

• 795,000/year

!6 You wake up in the morning, look in the mirror…

•

!7 !8 = Rapid Stroke Activation

!9 Target Stroke Best Practices

Initial Patient Evaluation →10 min Stroke Team Available →15 min CT Scan & Lab initiated →25 min CT Scan & Lab eval →45 min Evaluate t-PA inclusion/exclusion criteria Administer t-PA → DTN goal 60 min *Target Stroke Elite DTN <45 min Pt transferred to inpatient setting → <3 hrs

!10 !11 Case • 37 yo F pmh obesity, anxiety & depression here with numbness to her R hand/arm, with inability to move hand in addition to difficulty getting her words out. All symptoms began suddenly around 7:30am. Symptoms lasted 10 minutes then are now resolving - after numbness improved, her speech slowly returned. She also had some visual symptoms. Denies fevers, chills. no h/o cardiac issues. Denies abdominal pain, nausea, vomiting or diarrhea. No recent head injuries.

!12 Stroke Mimics - a lot to consider… • Rate ranges from 9-31% of CVAs • 60% of TIAs • Approx 8-17% admissions Hyper-Acute Stroke Unit • Several Mimics • difficult to distinguish during Code Stroke! • $$Cost$$ • unnecessary use of healthcare $$, resources, practitioners • OMG! I tPA’d that !!!

Allder et al 1999, Dawson 2016

!13 ~20-40% • One of most common stroke mimic in ED pts • tend to present in POST-ICTAL phase • + symptoms • motor changes • paresthesias • neg symptoms ~40% occurrence • postictal • paresis • Tend to occur MORE after PARTIAL SEIZURESβ • HOWEVER: HAVE occurred in CVA⍺ • 40% after ischemic stroke, 57% after ICH βGallmetzer et al. 2004, ⍺Bladin et al 2000

!14 Conversion Disorder 0-47% • ‘They know not what they do…’ • Often have documented psychiatric Hx • depression • fibromyalgia

Lewandowski et al 2015 !15 Glycemic Abnormalities • Hypoglycemic ~ 32mg/dL • seizure • hemiplegia ~2% ( R>>L…don’t know why) • Hyperglycemia - DKA, HHS • theory: caused by cellular hyperosmolarity • homonymous hemianopsia • hemiplegia • hemisensory deficits • aphasia • hemichorea- • Corrects w Glucose correction

!16 Toxic Ingestions

• Can cause: • sedation • altered behaviors • 1 reason ECG is key in CVA work up • Alcohol intoxication known to cause lateralizing sx • Salicylate OD (chronic) • → confusion

!17 Other Metabolic Abnormalities • Hyper, Hyponatremia • Hepatic • , hemiplegia • seen in ~ 17.4% liver patients

Combined Toxic + Metabolic ~ 38.0%

Cadranel et al 2001

!18 Sepsis ~6-20%

• Causes • Encephalopathy • delirium→coma • Anamnestic reaction • person w prior stroke history weakened by infection

!19 Migraine ~10-19.6%

• ~25% patients have focal neuro deficits • Theory: due to cortical spreading depression • aka: excitation of neurons leads to inhibition • Hemiplegic migraine • aura accompanied by motor weakness • Other Sx • dysarthria, focal weakness, vertigo, , AMS • a small # pts have permanent neuro changes � • BUT: 30% stroke patients may have at CVA onset!! �

Goldstein et al 2005 !20 Syncopal Episode ~ 13% mimics

• Can be 1st sign of subarachnoid hemorrhage

• Often confused with vestibulobasilar artery • →AMS

!21 Neoplasm ~2.8%

• 12% diagnosed CVA’s @ presentation→tumors • Most Common Presenting Sx • vision changes • aphasia • pure motor hemiparesis • Tend to be Gliomas • also NS lymphoma • Anaplastic astrocytoma

!22 Degenerative Neurologic Disorders

• • brief paroxysmal sx • dysarthria • ataxia • diplopia, • VF deficit • sensory deficits • Leukoencephalopathy ($5 word) due to viruses • ADEM (acute demyelination ) • post-viral, immune-mediated process • shorter onset sx than MS • pediatric population

!23 Bell’s Palsy

• A peripheral neurologic issue - NOT Central • est 20/100,000 annually • Symptoms: • unilateral facial weakness: • ptosis • facial droop • slurred speech • Exact cause unknown • infectious causes • HSV-1 reactivation

!24 Bell’s Palsy

Janjua 2011 !25 Bell’s Palsy

• Tends to occur > age 40 • but… • So, if there’s no frontal sparing = woot! Bell’s?! …not necessarily • Some Brain stem strokes have isolated eye w facial weakness • Rapidity of onset

• Age/Risk factors From: Janjua HS, Ayoob R, Spencer JD

Janjua 2011 !26 Degenerative Neurologic Disorders

• Myelopathy • affects • → motor/sensory loss • causes: • inflammation • infections • trauma • vascular lesions • compressive lesions

!27 Degenerative Neurologic Disorders

• Myelopathy • affects spinal cord • → motor/sensory loss • causes: inflammation, infections, trauma, vascular lesions, compressive lesions • Vasculitis • rare • often CAUSES CVA

!28 Stroke Chameleon? • A CVA that presents as a different condition… • Acute Hemiballismus? https://www.youtube.com/watch?v=fCL7RWaC3RA • = subthalamic nucleus CVA • Confusion, agitation, & delirium? • temporal lobe, limbic cortex lesions • How to tell the difference? • if ACUTE in onset - work it up!

Fernandes et al 2013 !29 Predictors Stroke vs Mimic

!30 Stroke Predictors

1.Strongest predictor: lateralizing weakness • PPV 90% • NPV 43% � 2.Atrial Fib History 3.Hypertension 4.Focal Deficits 5.Age > 50

Ali et al 2018

!31 Mimic Predictors

1. Younger, female 2. ↓NIHSS • median 5, range 1-15 3. Hx 4. Migraine Hx 5. Paresthesias 6. Sx INCONSISTENT w vascular territory 7. NO Vascular risk factors - HTN, hyperlipidemia, etc 8. Decreased Mental status @ presentation

Hand 2006, Chang 2012

!32 In-hospital Risk Factors

• A fib • in-patients ↑likelihood A Fib-related CVA vs outpatient • 31% of CVA pts SUBTHERAPEUTIC on anticoag • 6.9% had anti-thrombotics d/c’d for surg procedures • Make sure to restart ⍺-coags early • Stroke Alerts for AMS = MIMIC >>> CVA • ~ metabolic vs infectious cause

Vera et al 2011

!33 Imaging to help w diagnosis?

• CT head • LEAST sensitive test • ~12-52% • CTA? • can visualize vascular obstructions • increases Sn 70%, Sp~88% • MRI? of course • BUT Sn >80%, Sp 95% • ~1/3 non-disabling CVA had neg DWI 4 days post event • 4-29% miss rate of CVA Nguyen 2015, Makin 2015

!34 What IF we tPA a Mimic?!?!?

• ~1-20% mimics treated with IV tPA • Harm? • hemorrhagic conversion rate: ~1.8 - 5% • 5% study - n=2, 1 was 8d post cath w femoral bleed • most studies report none • Typically seizure or tumor • per Lewandowski et al. • Chernyshev, Chen recommend tPA w ANY patient suspected of Acute CVA w/in 3 hours of onset • …regardless if later we determine it was a mimic…

Lewandowski 2015, Zinkstok 2013, Tsivgoulis 2011 Chernyshev et al 2010. Chen 2011

!35 Co�t of Mimics • 74 pts diagnosed w Mimics 2009-2013 • Median cost per admission: $5401 • CT head, basic labs • tPA • ICU observation stay >24hrs • Median LOS: 1 day • Direct Hospital Cost $288,277 (=meds, food, consults, tx, devices, supplies) • Indirect Hospital Cost: $257,975 (utilities, facilities, labor) • Extrapolate to USA: $15,000,000/year

Goyal et al 2015

!36 So…how do we tell? 1.TIMING!! ➡ If acute onset - consider stroke until proven otherwise 2.Risk Factors • some suggest mimic • some suggest CVA 3.Neuroanatomy - more likely stroke if it occurs in particular vascular distribution - Work to understand it

!37 There is NO • 15% stroke patients had NO LATERALIZING SYMPTOMS • 6% Sx NOT in Vascular territory • NIHSS? • NIH>10 occurred in 19% mimics

Hand et al 2006 !38 Now Back to Our Case… • 37 yo F pmh depression, anxiety here with 10 minutes of numbness to her R hand/arm, with inability to move hand in addition to difficulty getting her words out. Visual symptoms described as a ‘flashing zig zag’ when looking to the right. Shortly after resolution of hand numbness, a headache began. Does have hx of rare .

What symptoms push away from CVA and towards a mimic?

!39 Now Back to Our Case… 37 yo F with pmh depression, anxiety here with 10 min of numbness to her R hand/arm, with inability to move hand in addition to difficulty getting her words out. Visual symptoms described as a ‘flashing zig zag’ when looking to the right. Shortly after resolution of hand numbness, a headache began. Does have hx of rare migraines.

• DDX? Complex migraine, IC hemorrhage, IC Mass, CVA • Seen by neurology in house • Negative CT head/CTA • Likely migraine → NOT tPA candidate • D/c home

!40 Recap:

Mimics are a reality we can’t escape • Look at the entire clinical context • Risk factors ?a fib?? • age • prior dx • epilepsy/psych hx • It does cost the system ~$5400/mimic • BUT if real CVA benefit outweighs cost • When in doubt, tPA if you are in the window • 23 yo (Dr. Cady) !41 Thank you! Questions? [email protected]

!42 References

• Ali et al. Validating the TeleStroke Mimic Score: A prediction rule for identifying stroke mimics evaluated over telestroke networks. Stroke 2018;49:688-692. • Allder et al. Limitations of clinical diagnosis in acute stroke. The Lancet 1999;354(9189):1523. • Bladin et al. Seizures after stroke: a prospective multi center study. Arch Neurol 2000;57:1617-22. • Cadranel et al. Focal neurological signs in in cirrhotic patients: an underestimated entity? Am J Gastroenterol 2001;96(2):515-8. • Dawson et al. Stroke mimic diagnoses presenting to a hyperacute stroke unit. Clin Med 2016; 16:423-426. • Loomis & Mullen. Differentiating Facial Weakness Caused by Bell’s Palsy vs Acute Stroke. Journal of Emergency Medical Services. May 2014. https://www.jems.com/articles/ print/volume-39/issue-5/features/differentiating-facial-weakness-caused-b.html. Accessed March 29, 2019. • Janjua et al. Hypertension in a boy with Bell palsy. Consultant for Pediatricians. 2011; 10(6): 203-206. • Chang et al. A model to prevent fibrinolysis in patients with stroke mimics. J Stroke Cerebrovasc Dis. 2012 Nov;21(8):839-43

!43 References

• Chernyshev et al. Safety of tPA in stroke mimics and neuroimaging-negative cerebral ischemia. Neurology 2010;74:1340-1345. • Fernandes et al. Strokes: Mimics and chameleons. Pract Neurol 2013; 13:2108. • Gallmetzer et al. Postictal paresis in focal - incidence, duration, and causes: a video-EEG monitoring study. Neurology 2004; 62:2160-4. • Goldstein et al. Is this patient having a stroke? JAMA 2005;293(19):2391-402. • Goyal et al. Cost Burden of Stroke Mimics and Transient Ischemic Attack after Intravenous Tissue Plasminogen Activator Treatment. J of Stroke & Cerebrovasc Dis 2015; 24: 828-833 • Hand et al. Distinguishing Between Stroke and Mimic at the Bedside. Stroke 2006;37:769-775. • Chen et al. Intravenous thrombolytic therapy in patients with stroke mimics: baseline characteristics and safety profile. Eur. J Neurol 2011; 18(10): 1246-50 • Lewandowski et al. Safety and Outcomes in Stroke Mimics after Intravenous Tissue Plasminogen Activator Administration: A Single-center Experience. J of Stroke and Cerebrovasc Dis 2015;24: 48-52.

!44 References

• Makin et al. Clinically confirmed stroke with negative diffusion-weighted imaging magnetic resonance imaging longitudinal study of clinical outcomes, stroke recurrence and systematic review. Stroke 2015;46:3142-3148. • Nguyen and Chang. Stroke mimics and acute stroke evaluation: clinical differentiation and complications after intravenous tissue plasminogen activator. J of Emerg Med 2015;49(2):244-252. • Tsivgoulis et al. Safety and outcomes of intravenous thrombolysis in stroke mimics: a 6- year, single-care center study and a pooled analysis of reported series. Stroke 2011:42:1771-4 • Vera et al. In-hospital ischemic strokes in patients admitted to cardiology and cardiac surgery departments. Multi-centre registry. Medicina Clinica 2011; 137(11):479-483. • Zinkstok et al. Safety of thrombolysis in stroke mimics: results from a multi center cohort study: stroke 2-13;44:1080-1084.

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