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Stroke Mimics and Chameleons�Differential Diagnosis

J. Stephen Huff, MD

Professor of Emergency Medicine and Neurology

University of Virginia, Charlottesville, Virginia USA

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Stroke - Questions

What historical or physical examination findings suggest ischemic stroke?

What processes may simulate ischemic stroke?

What are unusual stroke presentations?

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Stroke Differential Diagnosis

Differential diagnostic process

Formulation of the problem

Traditional neurologic process…

Is there a problem of the neurologic system?

Where is the problem?

What is the problem?

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Stroke Definition

“Stroke”- what does this mean?

Signs and symptoms with abrupt onset

Vascular disease

Often focal examination findings

Often loss of function / negative symptoms

Variety of etiologies…mostly common causes

…but what is causing the symptoms?

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Stroke Subtypes

Unifying theme

interruption of brain blood flow

disruption of brain blood flow

Common-ischemic stroke

many mechanisms

many etiologies

embolic, thrombotic, hemorrhage

dural sinus thrombosis, dissection

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Stroke

Aneurysmal hemorrhage

with intraparenchymal

bleeding

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Stroke

Ischemic stroke

Early CT

Dense vessel sign

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Stroke

Early ischemic stroke

CT mimic

Ischemic damage

left occipital

CT insensitive for

acute Ischemic stroke

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Think Stroke Subtypes

Ischemic stroke

-embolic

-thrombotic

Lacunar infarction

Intraparenchymal hemorrhage

-intracerebral hemorrhage

-aneurysmal hemorrhage / subarachnoid

-arteriovenous malformation

Venous thrombosis

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Case presentation 1

A 72-year old man is brought to the emergency department by EMS with altered behavior. After Sunday dinner, he was found to be “confused.” According to his family, “He could not find his way about the house…he was bumping into things.”

There is a history of stroke two years ago with residua of very mild left-sided hemiparesis. There is no recent history of trauma or seizures. The patient has a history of hypertension for which he takes a diuretic.

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Case presentation

On physical examination his vital signs are blood pressure of 120/80, pulse 90, respiratory rate of 14 per minute. He is afebrile. Pulse oximetry is 96% on room air.

He is awake, alert, articulate and conversant. He looks toward the examiner when questioned. He is insistent that there is nothing wrong with him. There is a pronator drift with mild weakness of the left arm. Mild facial asymmetry is present with weakness of the left face. He is able to walk unassisted but seems to have trouble turning to his left….

A diagnostic procedure was performed….

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Case presentation

Here’s what really happened….

The patient wished to leave. He disagreed with his family’s assessment and claimed that nothing was wrong. We tried to talk him into staying for further evaluation but he insisted on getting up and walked rather briskly to the restroom….

…and he could not find the restroom. He would not turn to his left and seemed unable to appreciate things to his left.

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Case presentation

Abrupt onset of symptoms

Risk factors for stroke / history of stroke

Physical examination

trouble turning to left…

would not turn to left…

three right turns to reach restroom

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Noncontrast CT

Ischemic changes

likely old stroke

Right occipital area

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MRI DWI

“Light bulb sign”

Acute ischemic stroke

Right occipital area

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Case presentation

Chief complaint – “confusion”

In reality, occipital lobe stroke

Non-dominant hemisphere

Visual field cut and neglect syndrome

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“Stroke”

Looks like a stroke

Is a stroke

Looks like a stroke

Is not a stroke

“MIMICS”

Does not look like stroke

Is a stroke

“CHAMELEONS”

Does not look like stroke

Is not a stroke

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Stroke Differential Diagnosis

Stroke Chameleon

-stroke appears as something else

-disguised or hidden stroke

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Stroke chameleon

Retrospective chart review for one year at one center

Dupree CM et al. J Stroke and Cardiovasc Dis 2014;23:374

Abrupt onset seemed to be key…

Consider stroke chameleon / disguised stroke

Altered mental status

Syncope

Hypertensive emergency

Possible cardiac syndrome

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Stroke chameleons�Initial diagnoses

Dupree CM et al. J Stroke and Cardiovasc Dis 2014;23:374

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Case presentation 2

A 35-year old woman is brought to the emergency department by EMS with suspected stroke. She had the abrupt onset of right-sided weakness and inability to speak late in the morning.

There is no history of stroke, trauma, or seizures. History is limited but the patient is thought to be diabetic.

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Case presentation

On physical examination vital signs are blood pressure 120/76, pulse 90, respiratory rate 14, with pulse oximetry of 98% on room air. She is afebrile. She appears alert but seemingly cannot hear or speak. She looks about the room and is in no distress.

A flaccid right hemiparesis is present.

What needs to be done immediately?

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Stroke Mimic

Hypoglycemic hemiplegia syndrome

Rapid glucose determination performed

- less than 40 mg/dl

- (very low)

Rapid resolution of hemiparesis and aphasia with administration of intravenous dextrose

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“Stroke”

Looks like a stroke

Is a stroke

Looks like a stroke

Is not a stroke

“MIMICS”

Does not look like stroke

Is a stroke

“CHAMELEONS”

Does not look like stroke

Is not a stroke

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Stroke Mimics

Unusual manifestation of nonvascular disease with clinical picture of stroke

May result from systemic or CNS events

May be indistinguishable from stroke

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Stroke Mimics

Why is this important?

As we move toward stroke therapies, increasingly important to have correct diagnosis…

Misapplied therapy costly, risky

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Stroke Mimics

Metabolic problems

hypoglycemia

hyperglycemia

hepatic

hypertensive

Psychiatric problems

factitious

conversion

CNS problems

seizure/postictal

migraine

subdural hematoma

brain abscess

tumor

multiple sclerosis

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How frequent are Stroke Mimics?

Stroke mimics are discovered at different times during clinical investigation

Stroke misdiagnosis rates (mimic rate) will vary depending on when the diagnosis of stroke is assigned

Stroke diagnosis after history and physical?

Stroke diagnosis after laboratory work?

Stroke diagnosis after neuroimaging?

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Stroke Mimic articles

Norris JW. Misdiagnosis of Stroke Lancet 1982;1:1523

821 patients consecutively admitted to a stroke unit from an emergency room

Evaluators –interns, then neurology

Initial studies not clear – history, physical

Further studies – LP, EEG, brain scan

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Stroke Mimic articles

Norris JW. Misdiagnosis of Stroke. Lancet 1982;1:1523

Stroke mimic rate 13%

Postictal state, nonconvulsive status epilepticus

Confusional states –metabolic, toxic

Subdural hematoma

CNS tumor

Radial nerve palsy

Vertigo

Encephalitis

Cardiac failure

Multiple sclerosis

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Stroke Mimic articles

Norris JW. Misdiagnosis of Stroke. Lancet 1982;1:1523

Stroke mimic rate 13%

Most common misdiagnosis seizures

Unwitnessed or unrecognized (5%)

Most had postictal confusion

Focal neurologic signs in about half

1/3 had previous history of stroke

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Stroke Mimic articles

Libman RB. Conditions that mimic stroke in the emergency department. Arch Neurol 1995; 52:111.

411 consecutive patients to ER with initial diagnosis of stroke

Evaluators-neurologists, EPs (75%)

Definition – sudden onset deficit >1 hour

Initial studies – history and physical

Further studies – CT. laboratory work

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Stroke Mimic articles

Libman RB. Conditions that mimic stroke in the emergency department. Arch Neurol 1995; 52:111.

Four conditions – majority of stroke mimics

Unrecognized seizures / postictal

Systemic infections

Brain tumor

Toxic-metabolic

14 others

(Cerebral hemorrhage counted as stroke)

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Stroke Mimic rate 19%

Seizure and postictal state

Systemic infection

Brain tumor

Toxic-metabolic

Positional vertigo

Cardiac

Syncope

Trauma

Subdural hematoma

Herpes encephalitis

Transient global amnesia

Dementia

Multiple sclerosis

Cervical spine fracture

Myasthenia gravis

Parkinsonism

Hypertensive encephalopathy

Conversion disorder

Libman RB. Conditions that mimic stroke in the emergency department. Arch Neurol 1995; 52:111.

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Stroke Mimic rate 19%

Libman RB. Conditions that mimic stroke in the emergency department. Arch Neurol 1995; 52:111.

Increased chance of stroke mimic

IF level of consciousness decreased

AND normal extraocular eye movements

Increased chance of true stroke if abnormal visual fields, DBP >90, atrial fibrillation, or history of angina

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Stroke Mimic articles

Kothari RU. Emergency physician’s accuracy in diagnosis of stroke. Stroke 1995;26:2238.

446 patients admitted to hospital with diagnosis of ischemic stroke; compared admission and discharge diagnoses.

Evaluators- EPs at teaching hospital

Initial studies – H&P, CT, labs

95% agreement between diagnoses

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Stroke Mimic articles

Kothari RU. Emergency physician’s accuracy in diagnosis of stroke. Stroke 1995;26:2238.

All patients with intracerebral hemorrhage and subarachnoid hemorrhage were correctly diagnosed by EPs

19/351 patients with final diagnosis of stroke or TIA diagnosed by EPs had a final discharge diagnosis other than stroke.

5% disagreement between diagnoses

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Stroke Mimic articles

Conclusion: EPs could accurately diagnosis stroke, particularly hemorrhages

Incongruent diagnoses

Paresthesias of unknown cause

Seizure

Migraine

Neuropathy

Psychogenic

Others

Kothari RU. Emergency physician’s accuracy in diagnosis of stroke. Stroke 1995;26:2238.

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Stroke Mimic articles

Allder SJ. Limitations of diagnosis in acute stroke.

Lancet 1999; 354:1523

Found 9% of patients diagnosed with stroke (by neurologists) had a normal detailed MRI with probably alternative diagnoses

Metabolic causes

Hemiplegic migraine

Psychogenic

Alcohol withdrawal

Moving to tissue based / imaging diagnosis

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Stroke Mimics

When is a stroke mimic present?

The time a diagnosis is assigned affects the frequency of stroke mimics and eliminates many alterative diagnoses

�Rate of mimics – 1-19%

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Hypoglycemia

Known as a stoke mimic for many years

Patients may be drowsy or alert

Patients may not show confusion

Reported in alcoholics as well as diabetics

Usually defined as glucose < 45mg/dl

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Hypoglycemia

Hemiplegia may resolve immediately but recovery over hours is also reported

Aphasia may make discovery challenging

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Mass lesions

Counterintuitive that a slowly expanding mass should cause abrupt symptoms…

Subdural hematoma

Cerebral Abscess

Tumor – primary and metastatic

6% had symptoms less one day

edema

hemorrhage into tumor

obstructive hydrocephalus

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Seizures and postictal states

Theory-seizure induced alteration in neuronal function

Postictal paralysis (Todd’s paralysis)

Usually follows partial motor seizure

May follow a generalized seizure

Duration is usually brief

Cases of paralysis lasting 48 hours

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Seizures and postictal states

Rare inhibitory seizures with weakness representing the seizure are reported

Beware-seizures may follow a stroke either acutely or remotely

Most studies that identified seizures as a stroke mimic either used additional history or observation to make diagnosis

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Migraine mimicking stroke

Hemiplegic migraine

Hemiplegia may outlast headache

Diagnosis of exclusion

First diagnosis difficult

Family history may be present

Attacks often stereotypic but alternating hemiplegia reported

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Functional hemiparesis

Little written on factitious stroke

Most case series do include a few patients

Psychiatric disorder

Conversion disorder – unaware

Malingering-conscious feigning

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Encephalopathies�Toxic-metabolic conditions

Hypoglycemia

Hyperglycemia with hyperosmolar state

Aphasia, hemiplegia, hemiparesis, visual field cuts, hemisensory deficits, unilateral hyperreflexia, Babinski’s signs reported

Hyponatremia

Hepatic encephalopathy

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“Stroke”

Looks like a stroke

Is a stroke

Looks like a stroke

Is not a stroke

“MIMICS”

Does not look like stroke

Is a stroke

“CHAMELEONS”

Does not look like stroke

Is not a stroke

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Atypical presentation of stroke

“Chameleons”

Uncommon manifestation of an uncommon clinical problem

Abrupt onset of symptoms

Risk factors for stroke often present

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Atypical presentation of stroke

Stroke commonly presents with negative symptoms or deficits

Unusually, positive symptoms are present

Movement disorders

Hemiballismus

Unilateral dyskinesia

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Atypical presentation of stroke

Other stroke chameleons

Confusional states, agitation, delirium

Limbic structures may be involved

Temporal and frontal regions

Aphasias-fluent

Neglect syndromes

Sensory complaints

Cortical blindness, neglect

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Atypical presentation of stroke

Aphasias

Fluent

Non-fluent

Adequate sample of speech

Ask to name objects

Ask to repeat words short sentences

Ask to write

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Fluent aphasia

Patients may seem confused

Look for other signs…

Paraphasic errors

Trouble naming

Trouble repeating

Trouble writing

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Other stroke chameleons

Sensory complaints

-paresthesias

-chest pain mimicking MI

-thalamic, medullary infarcts

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Other stroke chameleons

Visual symptoms

Visual field cuts

Neglect

Cortical blindness

-may appear to be feigning

-may deny to be blind

-pupils will be reactive to light

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“Stroke”

Looks like a stroke

Is a stroke

Looks like a stroke

Is not a stroke

“MIMICS”

Does not look like stroke

Is a stroke

“CHAMELEONS”

Does not look like stroke

Is not a stroke

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Questions?

Why is this important?

As we move toward stroke therapies, increasingly important to have correct diagnosis…

Misapplied therapy costly, risky

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Final thoughts…

Remember, noncontrast CT is insensitive for acute ischemic stroke.

Noncontrast CT severs mainly to exclude hemorrhages and mass lesions.

Stroke diagnosis is become a imaging tissue-level diagnosis. Distinction between TIA and stroke is blurring…

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Questions?

“Errors of judgment must occur in the practice of an art which consists largely in balancing probabilities.”

-Sir William Osler

J. Stephen Huff, MD

University of Virginia, Charlottesville

jshuff@virginia.edu