16.10.2019

Stroke Mimics Mimics

Carolina Tramontini, M.D. Neuroradiologist Clínica Universitaria Colombia, Bogotá Disclosure: I have nothing to disclose Neuroradiology Professor Fundación Universitaria Sanitas, Bogotá

ECNR Rovinj, October 16th, 2019

Stroke Mimics Stroke Mimics

• Introduction • Introduction • Topographic distribution patterns • Topographic distribution patterns • Imaging approach in stroke mimics • Imaging approach in stroke mimics • Take home messages • Take home messages

Introduction Introduction

• Stroke is a clinical diagnosis • For the clinician it is not always an easy Dx • Stroke mimics in – 9‐31% of suspected Two different types of diagnostic error – 2.8‐17% of strokes treated with IV‐tPA • Many different causes

Presentations sugesting • Imaging facilitates diagnosis Conditions resembling stroke another condition but are but are no real stroke stroke • But brain imaging, even DWI, are not infallible

STROKE MIMICS STROKE CHAMELEON

Kamalian S et all. Applied Radiology, 2015 Dupre et all, J Stroke Cerebrovasc Dis, 2017 Hand PJ et all. Stroke, 2006 Boulter TJ,Schaeffer PW, Seminars in Radiology 2014 Boulter TJ,Schaeffer PW, Seminars in Radiology 2014

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Predictor for Stroke and Mimics Causes of stroke Mimics Stroke Mimic predictors predictors Most frequent causes are:

Seizure 21%‐ 17% • Exact time of onset • Cognitive impairment • Definite focal symptoms • Abnormal signs in other Sepsis 17%‐13% • Abnormal vascular findings systems • Presence of neurological signs • Loss of consciousness or Toxic/metabolic 13%‐ 11% • at onset Being able to lateralize the signs Space occupying lesions 15%‐9% to left or right side of the brain • Complete abscence of • Being able to determine a neurological signs Syncope 9% clinical stroke subclassification Hand PJ et all. Stroke, 2006 Kamalian S et all. Applied Radiology, 2015 Liberman AL, Prabhakaran S. Curr Neurol Neurosci Rep 2017 Hand PJ et all. Stroke, 2006.

Causes of stroke Mimics Stroke Mimics and Thrombolysis

• 57% of mimics were neurological conditions • Stroke mimics account for 2 to 17% of Iv‐tPA treated patients • In +18% of mimics neurological conditions were in the DDX • Incidence of sICH – Stroke mimics 0.5‐ 1% • • 75% of mimics with 42% of mimics had – Confirmed stroke patients 4‐ 7.9% neurological conditions previous stroke • Median excess cost was approximately US$ 5400 per admission Many had normal brain Most had abnormal imaging brain imaging “The benefit of rapid treatment with tPA likely outweighs the minimal risk of complications associated with tPA in stroke mimics”

Liberman AL, Prabhakaran S. Curr Neurol Neurosci Rep 2017 Daniere F et all. Journal of Neuroradiology 2014 Hand PJ et all. Stroke, 2006. Goyal N, Journal of Stroke and Cerebrovascular Diseases, 2015 Zinkstok SM et all, Stroke 2013

Stroke Mimics Approach based on topographic distribution patterns

Large artery territory Regional grey and white infarction matter Deep grey matter and Perforating vessel infarction • Introduction brain stem Vascular watershed • Topographic distribution patterns Border zone pattern border zones • Imaging approach in stroke mimics Hypoxic ischemic Cortical and deep gray • Take home messages encephalopathy matter Ischemic white matter White matter disease

Central embolization Scattered foci

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Approach based on topographic Regional grey and white matter distribution patterns Large artery territory infarct

Seizures • Regional grey and white matter • Cortical and deep gray matter Brain tumors • Deep grey matter Herpes simplex • White matter Hypoglicemia • Scattered foci Transient global • Border zone pattern MELAS Venous infarctions

Regional grey and white matter Seizures Seizures

• One‐third of stroke mimics are due to seizures or postictal deficits • Seizures may cause T2 hyperintensity and restricted diffusion • Distinguishing features – Nonvascular distribution – Earlier edema and gyral enhancement – Normal or elevated perfusion Three patterns of diffusion restriction: – Absence of vascular occlusion • Hypocampus: Ipsilateral to side of onset – Sometimes simultaneous restricted cortical and elevated subcortical • Cortical: Hypoxia, reduced energy suply, cytotoxic edema diffusion

Boulter TJ,Schaeffer PW, Seminars in Radiology 2014 • Splenial: excitotoxic damage due to status epilepticus Milligan T et all, Seizure 2009 Daniere F et all, Journal of Neuroradiology, 2014 Milligan T et all, Seizure 2009

Regional grey and white matter Regional grey and white matter Migraine Brain tumors • Causes 5‐10% of stroke mimics • May present with acute neurologic deficits • May show restricted diffusion • Low‐grade glial tumor • Distinguishing factors – Mild mass effect – Long history of – Cortical involvement – Involvement of multiple arterial territories – May be confused with subacute infarction – Absence of vascular occlusion • High‐grade gliomas with hemorrhage • Perfusion decreases in acute‐onset aura – Can show areas of restricted diffusion • Perfusion is normal or elevated in prolonged episodes – Heterogeneous enhancement • The lesions are usually reversible – Mass effect – May be confused with subacute infarction But remember : 15% of strokes in patients younger than 45 years of age are due to migraine

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Brain tumors Brain tumors

Distinguishing features

Nonvascular distribution Lack of significant restricted diffusion Lack of gyral enhancement

Regional grey and white matter Herpes simplex encephalitis Herpes simplex encephalitis

• Most common cause of viral encephalitis • Predilection for the limbic system • Restricted diffusion is observed in early stages

Irreversible neuronal damage • Hyperintense on FLAIR images • Cause of restricted diffusion: glutamate excitotoxic pathway • Frequently hemorrhagic transformation • DWI shows concurrent areas with decreased

Kamalian S et all. Applied Radiology, 2015 and increased diffusivity Boulter TJ,Schaeffer PW, Seminars in Radiology 2014

Regional grey and white matter Hypoglicemia Hypoglicemia

• Can present with focal neurologic deficits • Restricted diffusion may be seen in the cerebral cortex (occipital lobes), corona radiata and centrum semiovale • Basal ganglia, hippocampi, internal capsules and splenium may be involved • Cerebellum, brain stem and hypothalamus are usually spared

Kang, AJNR, 2010

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Hypoglicemia Cortical and deep gray matter Hypoxic‐ischemic encephalopathy

Wernicke’s encephalopathy

Cause of diffusion restriction: Hepatic encephalopathy

Creutzfeldt‐Jakob disease Energy failure due to lack of glucose Excitotoxic edema Eastern equine encephalitis Asymmetric cerebral blood flow

Cortical and deep gray matter Wernicke’s encephalopathy Wernicke’s encephalopathy

• In alcoholics and other malnourished patients with thiamine deficiency • Clinically presents with: – Altered mental status – Memory impairment – Ophthalmoplegia Symmetric T2/FLAIR hyperintensity in : • Mammillary bodies – Ataxia • Hypothalami • Medial thalami • Tectal plate and periaqueductal area • Cerebral cortex may also be involved

Wernicke’s encephalopathy Wernicke’s encephalopathy

• Early stages: restricted diffusion due to cytotoxic edema • Later stages: no diffusion restriction

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Cortical and deep gray matter Hepatic encephalopathy Hepatic encephalopathy

• Neuropsychiatric abnormalities, potentially reversible • In chronic and acute hepatic failure • Clinical severity: West Haven Criteria grades 1‐4 • Diffuse cortical involvement can be reversible, but is associated with an increased risk of permanent neurologic sequela • Decrease in ADC values due to the excitotoxic injury and osmotic disturbance in astrocytes due to ammonia Mild case: symmetric T1

McKinney et all AJNR 2010 hyperintensity in globus pallidus Rovira et all AJNR 2008

Hepatic encephalopathy Cortical and deep gray matter Creutzfeldt‐Jakob disease

• Transmissible and fatal neurodegenerative disease caused by a misfolded prion protein • Sporadic, familiar and acquired (iatrogenic and variant) forms • Patients present with a rapidly progressive • Involvement of the basal ganglia (symmetric)

Case courtesy: Fabricio Goncalvez • Involvement of the cortex (symmetric or assymetric) Severe case: T2 hyperintensity and restricted diffusion • DWI is more sensitive than FLAIR orT2WI in the cortex (especially the cingulate gyri and insula), • Decreased ADC McKinney et all AJNR 2010 Wada R, Kucharczyk W. Neuroimag Clin 2008 basal ganglia, and thalami Rovira et all AJNR 2008 Boulter TJ, Schaeffer PW. Seminars in Radiology 2014

Creutzfeldt‐Jakob disease Deep gray matter Perforating vessel infarction

Carbon monoxide poisoning

Osmotic demyelination syndrome

Vigabatrin toxicity

Nonketotic hyperglycemia Sporadic CJD • EEG with period sharp wave complexes • 14‐3‐3 protein positive in CSF • sCJD has not pulvinar and hockey stick signs seen in vCJD Radiology Assistant.com

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Deep gray matter Carbon monoxide poisoning Carbon monoxide poisoning

Basal ganglia, thalami

Restricted diffusion GP Severe Cerebral cortex and wm Mild T2 hyperintense GP Corpus callosum • Delayed encephalopathy : – Bilateral confluent periventricular white matterT2 hyperintensity – Areas of restricted diffusion • Restricted diffusion – Acute phase : cytotoxic edema – Delayed phase: demyelination

Deep gray matter Osmotic demyelination syndrome Osmotic demyelination syndrome

• Due to rapid correction of hyponatremia • Can be seen with malnourishment, chronic alcoholism, hyperosmolar conditions, liver transplant • Patients typically present with pseudobulbar palsy and spastic quadriplegia

Osmotic demyelination • Pontine lesion : centrally located and spares the corticospinal tracts syndrome • Extrapontine lesions : thalamus, basal ganglia, lateral geniculate body and cerebellar white matter Central pontine Extrapontine • T2 hyperintensity may lag up to 2 weeks

Osmotic demyelination syndrome White matter

Ischemic White Matter Disease

Metronidazole toxicity

Metrotexate toxicity Howard SA, RadioGraphics Heroin induced leukoencephalopathy

• Restricted diffusion appears within the first 24 hours and Multiple sclerosis may persist up to 3 weeks Infectious cerebritis and abscess

Howard SA et all. RadioGraphics 2009 thelancet.com

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White matter Multiple sclerosis Multiple sclerosis

• Inflammatory demyelinating disorder • Can present with sudden acute deficits similar to acute stroke • Acute demyelinating lesions (2‐7 days) may show transient restricted diffusion • Cytotoxic edema : Excitotoxic injury to oligodendrocytes, Differentiating factors: myelin sheaths and axons • Typical MRI • Multiple periventricular, deep and juxtacorticalT2/FLAIR hyperintense lesions • Combination of clinical features and short‐term follow‐up imaging

Multiple sclerosis Scattered punctate foci Central embolism

Small vessel disease

Diffuse axonal injury Multiple sclerosis Fat embolism

Differentiating factors: Metastases • Typical MRI • Multiple periventricular, deep and juxtacorticalT2/FLAIR hyperintense lesions • Combination of clinical features and short‐term follow‐up imaging

Scattered punctate foci Diffuse axonal injury Diffuse axonal injury

• Disruption of axons • Caused by rapid deceleration or rotational forces • Severe head trauma • Multiple foci of restricted diffusion and/or hemorrhage • Located at gray‐white matter interface and along the cerebral • Restricted diffusion for days to weeks white matter fiber tracts, corpus callosum and brainstem • Differentiating features: – Nonvascular distributions and sparing of cortex – Presence of early hemorrhage – Clinical context of head trauma

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Scattered punctate foci Fat embolism Fat embolism

• Secondary to spread of fat globules that reach the systemic circulation and lung • Setting of a recent long bone fracture or orthopedic procedure • Can also occur following pulmonary contusion, cardiac surgery or liposuction • Patients present with – Changes in the respiratory pattern – Neurologic deficits – Petechial rash • Not a clear known mechanism, toxic intermediaries proposed

Endothelial injury and microhemorrhages • Punctate foci of restricted diffusion in white and gray matter • Multiple hypointense foci on SWI Kamalian S et all. Applied Radiology, 2015 Boulter TJ,Schaeffer PW, Seminars in Radiology 2014

Scattered punctate foci Metastases Metastases

• Highly cellular metastases (small cell lung carcinoma) – Can show restricted diffusion Differentiating factors – May be confused with subacute central embolic infarcts • Vasogenic edema • Features favoring metastases • Ring‐pattern enhancement – Presence of vasogenic edema surrounding the larger lesions • Additional sites of disease – Ring‐pattern enhancement • Absence of large infarcts – Additional sites of disease due to more proximal emboli – Absence of large infarcts due to more proximal emboli

Boulter TJ,Schaeffer PW, Seminars in Radiology 2014

Border zone pattern Border zone pattern Border zone infarction PRES Severe carotid stenosis,Moya Moya, RCVS • Posterior reversible encephalopathy syndrome • Loss of vascular autoregulation and capillary leakage leads to Posterior reversible encephalopathy vasogenic edema syndrome (PRES) • Clinical presents with headaches, cortical visual symptoms, seizures, and confusion Cerebral hyperperfusion syndrome • Triggered by – Hypertension – Eclampsia/ pre‐eclampsia – Critical medical illness – Immunosuppressants Manga et all. Radiographics 2011 Petrovic, Radiol Clin N Am ,2011 Radiology Assistant.com

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PRES Stroke Mimics

• Introduction • Topographic distribution patterns • Imaging approach in stroke mimics • T2‐FLAIR hyperintensity with elevated diffusion • Take home messages • Bilateral occipital and parietal lobes • Borderzone distribution between the anterior and middle cerebral arteries • Restricted diffusion in 10–25% patients • Intraparenchymal hemorrhage in 15% of cases

Approach to MRI and CT in Stroke Approach to MRI and CT in Stroke Mimics Mimics

Regional grey and Cortical and deep Regional grey and Cortical and deep Deep grey matter Deep grey matter white matter gray matter white matter gray matter

Large artery Hypoxic‐ischemic Perforating vessel territory infarct encephalopathy infarction

White matter Scattered foci Border zone White matter Scattered foci Border zone pattern pattern Ischemic White Central embolism Border zone Matter Disease infarction

Approach to MRI and CT in Stroke Approach to MRI and CT in Stroke Mimics Mimics

Regional grey and Cortical and deep Regional grey and Cortical and deep Deep grey matter Deep grey matter white matter gray matter white matter gray matter

Large artery Hypoxic‐ischemic Perforating vessel Large artery Hypoxic‐ischemic Perforating vessel territory infarct encephalopathy infarction territory infarct encephalopathy infarction Seizures Migraine Wernicke’s encephalopathy Carbon monoxide poisoning Brain tumors Osmotic myelinolysis Herpes simplex encephalitis Hepatic encephalopathy Hypoglicemia Vigabatrin toxicity Transient global amnesia Creutzfeldt‐Jakob disease MELAS Nonketotic hyperglycemia Venous infarctions Eastern equine encephalitis White matter Scattered foci Border zone White matter Scattered foci Border zone pattern pattern Ischemic White Ischemic White Central embolism Border zone Central embolism Border zone Matter Disease infarction Matter Disease infarction Metronidazole toxicity Diffuse axonal injury Metrotexate toxicity Posterior reversible Heroin induced leukoencephalopathy Fat emboli encephalopathy syndrome (PRES) Multiple sclerosis Cerebral hyperperfusion syndrome Infectious cerebritis and abscess Metastases

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Stroke Mimics Take home messages

• Up to 30% of suspected strokes are stroke mimics • Introduction • Most frequent causes of stroke mimics are: • Topographic distribution patterns – Seizures, sepsis, toxic/metabolic, space occupying lesions, syncope • Imaging approach in stroke mimics • Inaccurate Dx can lead to unnecessary administration of • Take home messages thrombolytic therapy or delays in appropriate therapy

Take home messages

• Review the clinical records of the patients • Have an adequate knowledge of the vascular territories and evolution of images on stroke • Remember there are different causes of diffusion restriction • Always keep alternate diagnoses in mind when you are looking at the images • Use a careful pattern based approach

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