EM Teaching Michael D. Hill, MD MSc FRCPC Calgary Stroke Program.

EM Teaching

Michael D. Hill, MD MSc FRCPCCalgary Stroke Program

Alcohol Warning LabelsIf the government really wants to help they should put useful warning labels on products. For instance alcohol should come with labels warning consumers of these unintended side effects:1.The consumption of alcohol may make you think you are whispering when you are not.2.The consumption of alcohol is a major factor in dancing like a retard.3.The consumption of alcohol may cause you to tell your friends over and over again that you love them.4.The consumption of alcohol may cause you to think you can sing.5.The consumption of alcohol may lead you to believe that ex-lovers are really dying for you to telephone them at four in the morning6.The consumption of alcohol may make you think you can logically converse with other members of the opposite sex without spitting7.The consumption of alcohol may make you think you have mystical Kung Fu powers, resulting in you getting your ass kicked8.The consumption of alcohol may cause you to roll over in the morning and see something really scary.9.The consumption of alcohol is the leading cause of inexplicable rug burns on the forehead.10.The consumption of alcohol may create the illusion that you are tougher, smarter, faster and better looking than most people.11.The consumption of alcohol may lead you to believe you are invisible.12.The consumption of alcohol may lead you to think people are laughing WITH you.13.The consumption of alcohol may cause a disturbance in the time-space continuum, whereby gaps of time may seem to literally disappear.

What is a stroke? (Important slide #1)

Stroke is a syndrome with multiple possible underlying etiologies. Stroke is a sudden vascular problem in the brain.

Stroke Types

• AIS – Acute Ischemic Stroke and TIA – Transient Ischemic Attack (85%)– Large vessel disease– Cardioembolic– Lacunar– Other

• ICH – Intracerebral hemorrhage (7-8%)– Lobar– Deep

• SAH – Sub-arachnoid hemorrhage (7-8%)• Sinovenous thrombosis (<<1%)

– Large sinus– Cortical vein

Cause of Death Worldwide

World Deaths x 10^6 % deaths

Coronary heart dx 7.20 12.2

Stroke 5.71 9.7

Lower resp infections 4.18 7.1

COPD 3.02 5.1

Diarrhoeal diseases 2.16 3.7

HIV/AIDS 2.04 3.5

Tuberculosis 1.46 2.5

Pulmonary cancers 1.32 2.3

MVA 2.27 2.2

Prematurity/LBW 1.18 2.0

Clinical Syndromes and Pathophysiology of Stroke

Michael D. Hill, MD, MSc, FRCPCAssociate ProfessorUniversity of CalgaryDirector, Stroke UnitStaff, Foothills Medical CentreCalgary, Alberta

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Learning Objectives

After reviewing this presentation, you will be better able to:

1. Understand that stroke is a syndrome consisting of multiple etiologies

2. Understand mechanisms of ischemia

3. Understand the pathophysiology of cardioembolic stroke

4. Understand mechanisms of intra-cranial cerebral atherosclerosis

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Stroke is a Syndrome

• Stroke (“apoplexy”)

– From the Greek – “to cripple by a stroke”

– A sudden vascular event leading to focal neurological dysfunction

– The clinical presentation alone does not allow differentiation between hemorrhage or ischemia

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Stroke Types

• Ischemia [85% of all stroke]– Transient ischemic attack

• “mini-stroke”– Acute ischemic stroke

• Intracerebral hemorrhage (ICH) [7-8% of stroke]

• Sub-arachnoid hemorrhage (SAH) [7-8% of stroke]

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Mechanisms of Ischemia

• Ischemia lack of blood flow resulting in tissue deprivation of nutrients

• The brain can tolerate hypoxia for many tens of minutes or hours; the brain does not tolerate ischemia for more than a few minutes

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Brain Ischemia

ThrombusThrombus

Collateral FlowCollateral Flow

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Thresholds of Blood Flow leading to Infarction

Cell deathCell death

CBF pml/100g/minCBF pml/100g/min

NormalNormal

OligaemicOligaemic

Electrocortical function Electrocortical function affectedaffected

Electrical failureElectrical failureIonic pump failureIonic pump failure

3535

2020

1515

1010

6060

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Reversible Reversible reduced reduced functionfunction

0

20

50

Normal flow, normal function

Low flow, raised O2 extraction, normal function

Irreversible Irreversible reduced reduced functionfunctionC

BF

(m

l/100

g br

ain)

Time

Cerebral Ischemia and Time

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Cerebral Ischemia

• Plumbing problem

• Blocked artery in the brain

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TIA vs. Stroke

• TIA stroke where all symptoms have resolved within 24h (WHO definition)

• Recent call for modified definition using 1 hour as the time point and modified by MR findings.

• Ischemic Stroke residual findings after 24 hours, however minor

N Engl J Med 2002: 347(21): 1713-1720N Engl J Med 2002: 347(21): 1713-1720

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“TIA”

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Mechanism of Ischemic Stroke

• Classification• Large Artery• Cardioembolic• Lacunar/small artery• Other known cause• Two or more causes• Cryptogenic• Unknown

Ann Neurol 2005;58:688–697Ann Neurol 2005;58:688–697

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Large Artery Stroke (20%)

• Arteroembolic Stroke

– Thrombus in carotid or vertebral artery on an atherosclerotic plaque which embolises to the brain – arteroembolic event – COMMON

– Thrombus on an intracranial arterial stenosis (akin to an acute coronary syndrome) – UNCOMMON

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Unstable plaque Stable plaque

Thin fibrous cap

Thrombus

Thick fibrous cap

Smooth muscle cells

Lipid rich coreand

macrophages

Media

Pathophysiology of Stable and Unstable Plaques

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Cardioembolic Stroke (25-30%)

• Proximal embolic event

– Cardiac source• Atrial fibrillation/flutter• Valvular heart disease (eg. endocarditis, prosthetic valve)• Post-MI mural thrombus• Proximal aortic atheromatous disease causing arteroembolic

stroke (most often classified in the cardioembolic group even though large artery disease is the true mechanism)

• Paradoxical embolus via RL intra-cardiac shunt as seen in large PFO with atrial septal aneurysm

• A thrombus breaks off and embolises to a brain artery blocking an intracranial artery

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Lacunar Stroke (25%)

• Small vessel disease– Occlusion of small, deep end-arteries– Associated strongly with hypertension and diabetes

mellitus– Mechanisms are:

• Lipohyalinosis with arterial wall collapse• Microatheroma with in situ thrombus• Small embolic material to these penetrating arteries

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Other Known Causes (<5%)

• Multiplicity of other causes:– Dissection– Metabolic stroke

• Fabry’s disease• MELAS• Hypercoagulable states

(eg. essential thrombocytosis)

55 yo woman with a dissected ICA seen here on angiogram55 yo woman with a dissected ICA seen here on angiogram

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Cryptogenic (20%)

• Despite complete and thorough investigation, the cause of stroke is unknown

– Commoner in younger patients

– ~20% of patients will have no cause identified

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Pathology of Stroke Mechanism

• Atherosclerosis

– Relevant directly to about 20% of strokes – the large artery strokes

– In these patients, the analogy to coronary artery disease is direct

– Typical risk factors contribute to cerebral atherosclerosis – elevated lipids, smoking, hypertension, diabetes mellitus

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Intra-cranial Cerebral Atherosclerosis

• Intracranial atherosclerosis is uncommon in western populations; greater prevalence in Asia

• When present in Caucasians it is most often seen in diabetics who smoke

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Pathology: Cardioembolic Stroke

• Commonest cardioembolic source in the western world is atrial fibrillation– Hypertension as risk factor– Heart failure (most often due to CAD) as a risk factor

• Thus, indirectly atherosclerosis of the coronary arteries has an effect on stroke via the heart

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Cardioembolic Stroke

• Multiple other causes of cardioembolic stroke– Infective endocarditis – blood cultures

and ESR should be done acutely on all patients with fever at stroke onset

– Marantic endocarditis

– Rheumatic heart disease

– Mitral stenosis

– Mural thrombus due to MI, dilated cardiomyopathy

– Cardiac tumours (atrial myxoma, fibroelastoma)

TTE showing atrial myxomaTTE showing atrial myxoma

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Cardioembolic Stroke

• Mitral valve prolapse not a risk factor for stroke

• Mitral annual calcification weakly associated with stroke

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Pathology Lacunar Stroke

• Small artery disease lacunar stroke

• End arteries

• Susceptible to occlusion due to lipohyalinosis of the relatively thin muscular arterial layer

• Embolism (arteroembolism, cardioembolism) to the perforating arteries is known to occur but is less common a cause of lacunar stroke

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Other Causes of Stroke

• Dissection

– Tear in the intima of the artery wall

– Most commonly spontaneous

– Associated with trauma in some cases

– May be iatrogenic due to endovascular treatment

– May occur in vertebral or carotid artery systems; 15% of the time dissection occurs in two or more arteries concurrently

N Engl J Med 2001: 344 (12): 898-906N Engl J Med 2001: 344 (12): 898-906

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Other Causes: Hypercoagulable States

• Myeloproliferative disorders :

– essential thrombocytosis, polycythemia rubra vera, CML

• Antiphospholipid Antibody syndrome

• Genetic deficiencies (eg. AT3, protein C, S, APC resistance, prothrombin and factor XII mutations) are not a direct cause of arterial ischemic stroke. They may be relevant in paradoxical embolus due to their well-defined role in venous thromboembolism.

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Other Causes: Vasculitis

• Intracranial cerebral vasculitis– Idiopathic granulomatous angiitis of the CNS

– Amyloid angiopathy vasculitis

– Systemic angiitis affecting the CNS• Lympomatoid granulomatosis• Wegener’s• PAN

• Distinguish from segmental vasospasm induced by drugs, blood

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Key Concept: Determining Ischemic Stroke Mechanism

• Stroke mechanism is determined by inference based upon investigations completed after the fact– Eg. atrial fibrillation with normal carotid arteries

infer that the mechanism is cardioembolic

• Only about 20% of stroke is akin to coronary artery disease – ie. large artery

• The term atherothrombotic stroke is not a useful way to think about the cause of stroke because atherosclerosis is only relevant in a minority of ischemic stroke

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ICH Type

• Anatomic Classification– Lobar

• Superficial hemorrhage extending to the cortical surface

– Sub-cortical• Basal ganglia• Thalamus• Dentate• Pontine

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Mechanism of ICH

• Mechanistic classification– Primary (=spontaneous,

idiopathic)

• Amyloid angiopathy

• Hypertensive hemorrhage– Secondary

• AVM

• Cavernoma (venous angioma)

• Tumour

• Coagulopathy-associated

• Sympathomimetic drug-related (eg. cocaine, pseudoephedrine)

• Vasculitis

• Iatrogenic

• Traumatic

Typical deep hypertensive hemorrhage in the putamen

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Massive ICH: > 200 cc

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Mechanisms of SAH

• SAH – the most common cause is blunt trauma to the head

• Usually, when we discuss SAH, we are speaking of atraumatic SAH

• Cause rupture of an aneurysm of a proximal intracranial artery, usually at the circle Willis (“Berry Aneurysm”)

N Engl J Med 2006;354:387-96N Engl J Med 2006;354:387-96

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SAH

• Atraumatic SAH

– Angiogram negative ~15% of the time (no aneurysm or arterial abnormality)

• Perimesencepalic may be the commonest angio-negative SAH

• Superficial cortical SAH may occur secondary to:

– amyloid angiopathy, venous occlusion and ischemic stroke (with and without thrombolysis). This is a relatively rare phenomenon.

• Angiography may be negative and repeat studies may show a ruptured aneurysm

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Angiogram Negative SAH

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ADDITIONAL RESOURCE SLIDES

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Multiple Causes of Ischemic Stroke

Stroke 2001;32:2735Neurology 1994;44:626

Large Artery Disease Small Vessel Disease

Cardioembolic Disease

Other or No Cause Found

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Small Vessel Arteriosclerosis – Hypertension

Occlusion

Leakage

Lacunar stroke

ICH

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Noncardioembolic Stroke Causes

Stroke 2001;32:2735Neurology 1994;44:626

Large Artery Disease Small Vessel Disease

Other or No Cause Found

Agenda1) We best learn from our mistakes, and I have had a few of them! A few

cases of where the ED md's could have done a better job is always of high interest to residents and ED staff.

2) Risk stratification is always on the top of our minds as we see people

presenting with a miriad of symptoms and we can always get better at risk stratifying.

3) Stroke mimics and how to differentiate these from the real deal. 4) Basilar stroke presentations and how to identify them, especially when

there are bilateral symptoms. A second to that, a discussion on bilateral findings and when they are not worrying and when they are not.

5) Up and coming stroke therapies and protocols.

Risk Stratification

• Prognosis exercise

• Distinguish clearly between:– Prognostic factors– Effect modifying factors

Risk Stratification: Therapy and disposition

• Is an acute intervention warranted?

• What is the correct disposition of my patient?– Discharge home?– Outpatient clinic? If so, when?– Admit –ie. consult

Risk Stratification: Therapy and disposition

• Thrombolysis• BP treatment

– ICH– AIS / TIA– SAH

• Antithrombotic therapy (ASA, heparin)• TIA / minor stroke stratification

CT – 4.5h into stroke77yo man, tourist visiting Banff

~4h into his stroke

Intubated, coma, L hemiplegia

CTA-SI-not salvageable-palliated

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Stroke Mimics: Diagnosing Stroke

Michael “give the juice” Hill, MD MSc FRCPC

a “get on with it” productionby “I like the smell of tPA in the morning” studio

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Stroke Mimics

1. Migrainous phenomena2. Somatization3. Seizure4. Old stroke with emergent symptoms

Less commonly:5. Space occupying lesion – subdural, glioma, metastasis6. Metabolic toxic – hypoglycemia, alcohol, drugs7. Other stroke type – SAH8. Local – hip #, brachial or sup fem artery occlusion

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Cases

54 yo man presents with --history of sudden collapse but no witness and so the etiology and timing is uncertain-awake, alert, mute, staring-eyes straight ahead (no gaze deviation)-plegic L side

Discussion?

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Case

25 yo woman

-visiting from New Zealand

-presents with sudden onset diplopia, headache, neck stiffness, dysphagia, inability to move the tongue

-awake, alert, distraught affect, moves all limbs actively against gravity

-agitated, hard to get consistent exam, possibly ataxic in all four limbs, unable to walk

Thoughts?

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Case

75 yo woman-visiting a friend in hospital-on way out of the hospital going to her car, she collapses, can’t get up-witnessed; brought to ER within 20 min-awake and alert, speaking normally, no evident hemispatial neglect-cannot move L leg

Thoughts?

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Pitfalls

Age of patientTake a social historyExamine the patient

Remember – Most people will present with an unusual presentation of a common disease rather than an unusual disease (with a common or uncommon presentation). [Corollary of Occam’s razor but of course, Occam died of multiple causes]

Stroke Mimics in the ER

Saturday Morning Workshops

Learning Objectives:

1. To review the other conditions that present like acute ischemic stroke (mimics)

2. To have a bedside strategy to quickly and efficiently rule out these stroke “mimics” a. To avoid incorrectly over-treating a stroke mimic

b. To avoid delays in correctly treating true acute ischemic strokes and stroke mimics

Stroke is often initially a clinical diagnosis aided by a standard imaging modality that has limitations

There is a better imaging modality but it has its own limitations (mainly availability)

There is overlap in the signs of true stroke and stroke mimics

There is a treatment for true stroke that has constraints (time) and risks (hemorrhage)

The Challenge !

10. What is the risk of thrombolyzing a stroke mimic?

True stroke

(n = 243)

Stroke mimics

(n = 7)

Angioedema 3 (1.2 %) 0

Symptomatic ICH

13 (5.3%) 0

Asymptomatic ICH

30 (12.3 %) 0

Thrombolysis in Stroke Mimics. Stroke 2009

Misdiagnosis of Stroke in TPA Treated Patients. Ann Emerg Med 2003.

66 yr female brought to ER by husband

Sudden onset (~ 2 hrs ago) of slurred speech, right facial droop, and right arm weakness Headache & mild nausea earlier in the day; c/o “chills” Hx of hypertension; remote hx of complex migraine; moderate

Alzheimer’s On ASA, amlodipine, donepezil

BP = 173/94 HR = irreg (80 - 120) RR = 20 T = 38.2 PERL, normal EOM (but eyes favor the left), no carotid bruits Right lower facial droop (UMN) 3/5 strength right arm, 4/5 strength right leg Speech slurred and slightly confused

1. What should be done immediately next?

a. Complete & comprehensive neurological examination

b. Administration of 160 mg acetylsalicylic acid (ASA)

c. Blood glucose & SaO2

d. CT scan

e. ECG

5th & 6th VITAL SIGNS:

2. What is going on here?

a. Ischemic stroke

b. Subarachnoid hemorrhage

c. Stroke mimic

d. Stroke chameleon

e. Any of the above

3. What is the difference between a stroke & a stroke mimic?

Stroke ~ sudden onset of a focal neurological deficit in a recognizable intracranial vascular distribution resulting in a common clinical syndrome due to vascular occlusion or hemorrhage

Stroke mimic ~ a nonvascular condition that may simulate stroke

4. What are some common stroke mimics?

METABOLIC / SYSTEMIC CONDITIONS: Hypoglycemia / hyperglycemia Hepatic encephalopathy Hypertensive encephalopathy

CNS CONDITIONS: Post-ictal state with focal neurological signs (Todd’s paresis) Nonconvulsive status epilepticus Hemiplegic migraine Subdural hematoma Brain abscess Intracranial tumour (primary / metastatic) Multiple sclerosis

PSYCHIATRIC CONDITIONS: Conversion disorder Factitious disorder

5. How common are stroke mimics?

a. 9%

b. 4%

c. 13%

d. 1.2%

e. All of the above

Norris(1982)

Libman (1995)

Kothari(1995)

Alder(1999)

Ay (1999)

When was diagnosis made?

At stroke unit admission

After initial ED

assessment

At admission from ED

Within 6 hrs of onset

Unclear

Who diagnosed the stroke?

Intern, family physician, neurology resident

Emergency physician

Emergency physician

Unclear; likely

neurologists

Neurologists

What studies were done to arrive at the diagnosis?

History, physical

History, physical

History, physical, labs, CT

Unclear CT, labs

Were other studies eventually performed?

Multiple, few CTs

Some CTs Unclear MRI, MRA, DMI, PMI

MRI, DMI

How many stroke mimics were there? 13% 19% 4% 9% 1.2%

Huff. Emerg Med Clin N Am. 2002

6. What features suggest that this is a stroke? Age? Risk factors? Current BP? Irregular heart rate? Recognizable vascular distribution / clinical pattern?

7. What features suggest that this is a mimic? Headache & nausea? Chills & fever? Migraine history? Workshop title?

Incidence of Stroke Mimics by Age Groups. J Stroke Cerebrovasc Dis 2008.

Nearly 1/3 of older patients with true stroke had features of stroke mimic

Hand et al. The Brain Attack Study. Stroke 2006;37:769

Prospective observational study, single center, N = 350 Univariate analysis = 47 parameters

FAVORING MIMIC: Hx of cognitive impairment Confusion, loss of consciousness, seizure at onset No neurological signs, signs that do not lateralize/localize, or signs that do

not fit a vascular territory or clinical syndrome Abnormal findings in other systems

FAVORING STROKE: Hx of CAD or PVD Exact time of onset Definite lateralizing /localizing neurological symptoms, demonstrable

neurological signs Signs consistent with clinical stroke syndrome

The Brain Attack Study. Stroke 2006

Recognition of Stroke in the Emergency Room (ROSIER). Lancet Neurol 2005

FAVORING MIMIC:

Confusion Loss of consciousness Seizure at onset No neurological signs Signs that do not

lateralize Signs that do not fit a

vascular territory or clinical syndrome

Signs in other systems

FAVORING STROKE:

CVD history IHD, PVD Exact time of onset Definite neurological

symptoms Demonstrable

neurological signs Signs consistent with

clinical stroke syndrome

Glucose = 6.6 Normal routine chemistry Platelets = 455 INR = 1.2 ECG = atrial fibrillation Prior to CT she vomits once & receives 10 mg IV

metoclopramide On return from CT her neurological symptoms are

rapidly improving CT is normal Subsequent MRI & MRA is normal

Migraine Equivalent:

Migraine without pain (5%)AKA migraine variantProlonged aura (can be atypical)Focal neurological signs ICHD-2 (2004)

Hemiplegic migraine Opthalmoplegic migraine Retinal migraine Vertiginous migraine Acute confusional migraine

8. How long can hemiplegic migraine last?

a. Less than 1 hr

b. Less than 4.5 hrs

c. Less than 24 hrs

d. Less than 72 hrs

e. More than 72 hrs

9. What is the longest hemiplegic migraine reported on the internet?

77 days

Summary (cont’d):

Differentiation of some can be difficult Consult liberally Where feasible MR can be diagnostic

Neurologist on-call Radiologist on-call

52 yr male

EMS Report: Found on floor in restaurant restroom Mâitre-d’ recognizes him having walked in alone 50

minutes ago; he was walking and talking “okay” Waiter reports that he seemed “normal” when he

ordered a drink 30 minutes ago, asked where the restrooms were, and walked there “like normal”

Incontinent of urine & stoolWallet – businessman from Alberta; home phone

number ~ no answer; no NOK listed

EMS ~ “code-stroke” ~ stroke center bypass

No previous chart; only history is from EMS BP = 158/84 HR = 100 RR = 12 SaO2 = 98% T = 36.4

Markedly slurred speech; appears confused PERL, normal EOM (but eyes favor the left) 3/5 strength left arm, 2/5 strength leg Strong odor of alcohol on his breath Very large BMI

60

1. What should be done immediately next?

a. Blood glucose

b. Mobilize staff for CT scan

c. Venous access

d. CBC, INR, routine chemistry

e. All of the above can be done concurrently

2. What is going on here?

a. Ischemic stroke

b. Subarachnoid hemorrhage

c. Stroke mimic

d. Too many martinis at today’s business lunch

e. Any of the above

3. What features suggest that this is a mimic? Confusion? Incontinence? Alcohol on breath? His age?

4. So, is this a mimic?

Glucose = 11.5 Normal routine chemistry Platelets = 125 INR = 1.1 CT is normal ECG = minor LV strain His neuro exam is

unchanged

5. What will you do next?

90

Collateral from local businessman who was to meet him at restaurant Just met at conference today Patient was upset

Brother had recently had a stroke and is bed-ridden Hated seeing him that way (“better off dead”)

Said he himself was healthy

His neuro exam is unchanged

6. What will you do next?120

Search of his briefcase (brought by local businessman) Bottle of pills His neuro exam is unchanged

7. What might this be & what will you do next?

145

8. What is Todd’s paresis? Occurs in up to 13% of seizures Most common after GM seizures Mechanism unclear

9. How long can it last? Usually hours, but rare cases up to several

days

11. Why do both patients look left?

III III

VI VI

III III

VI VI

Away from a seizure . . .

III III

VI VI

Towards a stroke . . .

A few more mimics not to miss . . . what

are these?

Any questions????

Summary:

Stroke mimics occur in 2 – 20% of acute neurologic deficits

Most commonly hypoglycemia, migraine equivalent, Todd’s paresis

Most others will be diagnosed by imaging & labs

Most important is to efficiently identify those with true strokes who may benefit from thrombolytic therapy

Approach to Coma