Ischemic stroke resident survival guide: Difference between revisions

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==Definitions==
==Overview==
===Ischemic Stroke===  
[[Ischemic stroke]] is defined as an episode of neurological dysfunction caused by focal cerebral, spinal, or retinal infarction. Infarction of the [[central nervous system]] serves as the main pathogenetic mechanism implicated in the etiology of ischemic stroke.  CNS Infarction refers to [[brain]], [[spinal cord]], or retinal cell death attributable to ischemia, based on:
Ischemic stroke is defined as an episode of neurological dysfunction caused by focal cerebral, spinal, or retinal infarction.
 
====CNS Infarction====
CNS infarction is brain, spinal cord, or retinal cell death attributable to ischemia, based on:


1. Pathological, imaging, or other objective evidence of cerebral, spinal cord, or retinal focal ischemic injury in a defined vascular distribution; or
1. Pathological, imaging, or other objective evidence of cerebral, spinal cord, or retinal focal ischemic injury in a defined vascular distribution; or
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====Time of Onset====  
====Time of Onset====  
Time of onset is defined as when the patient was last awake and symptom-free or known to be “normal".<ref name="Jauch-2013">{{Cite journal  | last1 = Jauch | first1 = EC.| last2 = Saver | first2 = JL. | last3 = Adams | first3 = HP. | last4 = Bruno | first4 = A. | last5 = Connors | first5 = JJ. | last6 = Demaerschalk | first6 = BM. | last7 = Khatri | first7 = P.| last8 = McMullan | first8 = PW. | last9 = Qureshi | first9 = AI. | title = Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. | journal = Stroke | volume = 44 | issue = 3 | pages = 870-947 | month = Mar | year = 2013 | doi = 10.1161/STR.0b013e318284056a | PMID = 23370205 }}</ref>
Time of onset is defined as when the patient was last awake and symptom-free or known to be “normal".<ref name="Jauch-2013">{{Cite journal  | last1 = Jauch | first1 = EC.| last2 = Saver | first2 = JL. | last3 = Adams | first3 = HP. | last4 = Bruno | first4 = A. | last5 = Connors | first5 = JJ. | last6 = Demaerschalk | first6 = BM. | last7 = Khatri | first7 = P.| last8 = McMullan | first8 = PW. | last9 = Qureshi | first9 = AI. | title = Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. | journal = Stroke | volume = 44 | issue = 3 | pages = 870-947 | month = Mar | year = 2013 | doi = 10.1161/STR.0b013e318284056a | PMID = 23370205 }}</ref>
==Causes==
==Causes==
===Life Threatening Causes===
===Life Threatening Causes===
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{{familytree | | | | | | | | | | | | | G01 | | | | | G02 | | | | | |!| | | |G01=[[Ischemic stroke resident survival guide#Exclusion Criteria for IV Recombinant TPA Treatment|Eligibility criteria for IV rTPA]] (see below)|G02=Consider rTPA after reviewing the additional exclusion criteria for this category (see below)}}
{{familytree | | | | | | | | | | | | | |!| | | | | | |!| | | | | | |!| |}}
{{familytree | | | | | | | | | | | | | |!| | | | | | |!| | | | | | |!| |}}
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{{familytree | | | | | H01 | | | | | | | | | | H02 | |!| | | | | | |!| | | |H01=Eligible|H02=Not eligible}}
{{familytree | | | | | H01 | | | | | | | | | | H02 | |!| | | | | | |!| | | |H01=Eligible|H02=Not eligible}}
{{familytree | |,|-|-|-|^|-|-|-|.| | | | | | | |`|-|-|+|-|-|-|-|-| M01 | |M01=[[Stroke resident survival guide#Management of Blood Pressure|Blood Pressure Management]]<br><br>Treat fever with IV antipyretics ([[acetaminophen]])}}
{{familytree | |,|-|-|-|^|-|-|-|.| | | | | | | |`|-|-|+|-|-|-|-|-| M01 | |M01=[[Ischemic stroke resident survival guide#Management of Blood Pressure|Blood Pressure Management]]<br><br>Treat fever with IV antipyretics ([[acetaminophen]])}}
{{familytree | I01 | | | | | | I02 | | | | | | | | | |!| ||I01='''BP≤180/110'''|I02='''BP≥180/110'''}}
{{familytree | I01 | | | | | | I02 | | | | | | | | | |!| ||I01='''BP≤180/110'''|I02='''BP≥180/110'''}}
{{familytree | |!| | | | | | | |!| | | | | | | | | | |!| |}}
{{familytree | |!| | | | | | | |!| | | | | | | | | | |!| |}}
{{familytree | J01 | | | | | | JO2 | | | | | | | | | |!| |J01=IV rTPA 0.9 mg/kg (maximum of 90 mg).  Give the first 10% as IV bolus over 1 minute, then give the remaining as IV infusion over 1 hour|JO2=Ensure BP<180/110 mmHg before initiating rTPA (see [[Stroke resident survival guide#Management of Blood Pressure|Blood Pressure Management]])}}
{{familytree | J01 | | | | | | JO2 | | | | | | | | | |!| |J01=IV rTPA 0.9 mg/kg (maximum of 90 mg).  Give the first 10% as IV bolus over 1 minute, then give the remaining as IV infusion over 1 hour|JO2=Ensure BP<180/110 mmHg before initiating rTPA (see [[Ischemic stroke resident survival guide#Management of Blood Pressure|Blood Pressure Management]])}}
{{familytree | |`|-|-|-|-|-|-|-|+|-|-|-|-|-|-|-|-|-|-|'| |}}
{{familytree | |`|-|-|-|-|-|-|-|+|-|-|-|-|-|-|-|-|-|-|'| |}}
{{familytree | | | | | | | | | K01 | |K01=Admit ICU (for BP monitoring + bleeding complications)<br><br>Hourly vitals and neurocheck<br>Aspiration precautions}}
{{familytree | | | | | | | | | K01 | |K01=Admit ICU (for BP monitoring + bleeding complications)<br><br>Hourly vitals and neurocheck<br>Aspiration precautions}}
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{{familytree | | | | | |!| ||}}
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{{familytree | |,|-|-|-|+|-|-|-|v|-|-|-|.| | | | | | |}}
{{familytree | N01 | | N02 | | N03 | | N04 | | |N01='''<u>Specific measures</u>'''<br>'''ASA''' 325 mg (if no contraindication)<br>'''Statins'''<br>'''DVT prophylaxis'''|N02='''<u>General measures</u>'''<br>PT/OT evaluation<br>Speech and swallow evaluation|N03='''<u>Investigate the etiology</u>'''<br>MRA/CTA/carotid duplex, venous doppler USS, echocardiography<br><u>'''Ages 18-45 years'''</u><br>Proteins C & S assay, [[antithrombin III|antithrombin III assay]], [[factor V Leiden mutation]], [[prothrombin mutation]], [[lupus anticoagulant]], [[anti-cardiolipin antibodies]]), [[hemoglobin electrophoresis]], [[VDRL]], [[toxicology screen]], [[CSF analysis]], [[holter monitor|holter monitoring]]|N04='''Manage Complications'''}}
{{familytree | N01 | | N02 | | N03 | | N04 | | |N01=<div style="float: left; text-align: left; line-height: 150% ">'''Specific measures:'''<br> '''ASA''' 325 mg (if no contraindication)<br> '''Statins'''<br>'''DVT prophylaxis'''</div>|N02=<div style="float: left; text-align: left; line-height: 150% ">'''General measures:'''<br>❑ Frequent vitals and neurochecks<br>❑ Cardiac monitoring (to screen for afib)<br>❑ Optimal BP control<br>❑ Airway and ventilatory support (in ↓consciousness)<br>❑ Supplemental O<sub>2</sub> (if SaO<sub>2</sub> <94%)<br>❑ Maintain normothermia (T <38<sup>o</sup>C)<br>❑ Maintain normovolemia - IV normal saline<br>❑ Achieve normoglycemia (SG 90 - 140 mg/dL)<br>❑ ‡ Patient positioning<br>❑ Early mobilization after 24 - 48 hours of less severely affected patients<br>PT/OT evaluation<br>Speech and swallow evaluation</div>|N03=<div style="float: left; text-align: left; line-height: 150% ">'''Investigate the etiology:'''<br>MRA/CTA/carotid duplex<br>❑ Venous doppler USS<br>❑ Echocardiography<br><br>'''Ages 18-45 years:'''<br>Proteins C & S assay<br>❑ [[antithrombin III|Antithrombin III assay]]<br>❑ [[Factor V Leiden mutation]]<br>❑ [[Prothrombin mutation]]<br>❑ [[Lupus anticoagulant]]<br>❑ [[Anti-cardiolipin antibodies]]<br>❑ [[Hemoglobin electrophoresis]]<br>❑ [[VDRL]]<br>❑ [[Toxicology screen]]<br>❑ [[CSF analysis]]<br>❑ [[holter monitor|Holter monitoring]]</div>|N04='''Manage Complications'''}}
{{familytree | | | | | | | | | | | |,|-|^|-|.| | | | |}}
{{familytree | | | | | | | | | | | |,|-|^|-|.| | | | |}}
{{familytree | | | | | | | | | | | X01 | | X02 | | |X01='''<u>Hemorrhagic Infarction'''</u><br>Continue with present management|X02='''TPA-Induced Parenchymal Hemorrhage'''}}
{{familytree | | | | | | | | | | | X01 | | X02 | | |X01='''<u>Hemorrhagic Infarction'''</u><br>Continue with present management|X02='''TPA-Induced Parenchymal Hemorrhage'''}}
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{{familytree | | | | | | | | | | | | | | | Q01 | |Q01=Consult to Neurosurgery<br>'''Consider repeat CT to assess hemorrhage size'''}}
{{familytree | | | | | | | | | | | | | | | Q01 | |Q01=Consult to Neurosurgery<br>'''Consider repeat CT to assess hemorrhage size'''}}
{{familytree/end}}
{{familytree/end}}
‡ '''Patient positioning:'''
* Supine position is preferred if there is no risk of elevated ICP or aspiration.
* Nurse at 15 - 30 degrees head-of-bed elevation if there is risk of elevated ICP, aspiration or cardiopulmonary compromise.
* Prevent pressure sores - frequent turning.


==Management of Blood Pressure==
==Management of Blood Pressure==
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* Order a follow-up CT/MRI before commencement of antiplatelets.
* Order a follow-up CT/MRI before commencement of antiplatelets.
* Give ASA 325 mg within 24 to 48 hours to most patients (except if contraindicated).
* Give ASA 325 mg within 24 to 48 hours to most patients (except if contraindicated).
* Strict blood pressure monitoring for the first 24 hours, especially if rTPA was administered - every 15 minutes for 2 hours, then every 30 mins for 6 hours, and every hour for the next 16 hours.
* Strict blood pressure monitoring for the first 24 hours, especially if rTPA was administered - every '''15 minutes''' for 2 hours, then every '''30 mins''' for 6 hours, and every '''hour''' for the next 16 hours.


==Don'ts==
==Don'ts==

Latest revision as of 18:44, 11 March 2014

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ayokunle Olubaniyi, M.B,B.S [2]

Overview

Ischemic stroke is defined as an episode of neurological dysfunction caused by focal cerebral, spinal, or retinal infarction. Infarction of the central nervous system serves as the main pathogenetic mechanism implicated in the etiology of ischemic stroke. CNS Infarction refers to brain, spinal cord, or retinal cell death attributable to ischemia, based on:

1. Pathological, imaging, or other objective evidence of cerebral, spinal cord, or retinal focal ischemic injury in a defined vascular distribution; or

2. Clinical evidence of cerebral, spinal cord, or retinal focal ischemic injury based on symptoms persisting ≥24 hours or until death, and other etiologies excluded.

CNS infarction also include:

  • Hemorrhagic infarction ("hemorrhagic transformation of infarction", "hemorrhagic conversion of infarction")[1] - This may occur spontaneously or due to antithrombotic or thrombolytic treatment. They generally lack a mass effect, and are managed according to ischemic stroke recommendations. There are two types:
Type I - petechiae of blood along the margins of the infarction.
Type II - confluent petechiae within the infarction but without a space-occupying effect.

Time of Onset

Time of onset is defined as when the patient was last awake and symptom-free or known to be “normal".[2]

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

  • All the causes of stroke are life-threatening.

Common Causes

Ischemic Stroke

Management

Within the First 24 Hours

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Acute Ischemic Stroke
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Time of Onset
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
<3 hours
 
 
 
 
3 - 4.5 hours
 
 
 
 
>4.5 hours
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria for IV rTPA (see below)
 
 
 
 
Consider rTPA after reviewing the additional exclusion criteria for this category (see below)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligible
 
 
 
 
 
 
 
 
 
Not eligible
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood Pressure Management

Treat fever with IV antipyretics (acetaminophen)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BP≤180/110
 
 
 
 
 
BP≥180/110
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IV rTPA 0.9 mg/kg (maximum of 90 mg). Give the first 10% as IV bolus over 1 minute, then give the remaining as IV infusion over 1 hour
 
 
 
 
 
Ensure BP<180/110 mmHg before initiating rTPA (see Blood Pressure Management)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Admit ICU (for BP monitoring + bleeding complications)

Hourly vitals and neurocheck
Aspiration precautions
 

After 24 Hours

 
 
 
 
After 24 hours post rTPA or no rTPA
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Follow-up head CT/MRI before commencing antiplatelets to r/o secondary hemorrhage
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Specific measures:
ASA 325 mg (if no contraindication)
Statins
DVT prophylaxis
 
General measures:
❑ Frequent vitals and neurochecks
❑ Cardiac monitoring (to screen for afib)
❑ Optimal BP control
❑ Airway and ventilatory support (in ↓consciousness)
❑ Supplemental O2 (if SaO2 <94%)
❑ Maintain normothermia (T <38oC)
❑ Maintain normovolemia - IV normal saline
❑ Achieve normoglycemia (SG 90 - 140 mg/dL)
❑ ‡ Patient positioning
❑ Early mobilization after 24 - 48 hours of less severely affected patients
❑ PT/OT evaluation
❑ Speech and swallow evaluation
 
Investigate the etiology:
❑ MRA/CTA/carotid duplex
❑ Venous doppler USS
❑ Echocardiography

Ages 18-45 years:
❑ Proteins C & S assay
Antithrombin III assay
Factor V Leiden mutation
Prothrombin mutation
Lupus anticoagulant
Anti-cardiolipin antibodies
Hemoglobin electrophoresis
VDRL
Toxicology screen
CSF analysis
Holter monitoring
 
Manage Complications
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hemorrhagic Infarction
Continue with present management
 
TPA-Induced Parenchymal Hemorrhage
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TPA Reversal
Give Cryoprecipitate (1-2 U/10 Kg)
Plus
Platelet transfusion (titrate according to follow-up labs)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Consult to Neurosurgery
Consider repeat CT to assess hemorrhage size
 


Patient positioning:

  • Supine position is preferred if there is no risk of elevated ICP or aspiration.
  • Nurse at 15 - 30 degrees head-of-bed elevation if there is risk of elevated ICP, aspiration or cardiopulmonary compromise.
  • Prevent pressure sores - frequent turning.

Management of Blood Pressure

 
 
 
 
 
 
 
 
Blood Pressure Management
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review Exclusion Criteria for IV rTPA Administration
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligible
 
 
 
 
 
 
 
Not eligible
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Before treatment
 
 
 
During/After treatment
 
BP <220/120 mmHg
 
 
 
BP >220/120 mmHg
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BP>185/110 mm Hg
Labetalol 10–20 mg IV over 1–2 minutes, may repeat 1 time; or nicardipine 5 mg/h IV infusion; titrate up by 2.5 mg/h every 5–15 minutes, maximum 15 mg/h; when desired BP reached, adjust to maintain proper BP limits; or other agents (hydralazine,enalaprilat, e.t.c.) may be considered when appropriate
 
 
 
 
 
 
 
 
Observe unless evidence of end-organ damage is present (e.g., acute myocardial infarction, aortic dissection, pulmonary edema, hypertensive encephalopathy)

Conservative management - treat fever, pain, headaches, nausea, vomiting
 
 
 
Labetalol 10–20 mg IV over 1–2 minutes, may repeat or double every 10 minutes (maximum dose of 300 mg); or nicardipine 5 mg/h IV infusion; titrate up by 2.5 mg/h every 5–15 minutes, maximum 15 mg/h
Aim at 15% reduction during the first 24 hours after stroke onset
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SBP>180–230 mm Hg
or
DBP >105–120 mm Hg
 
 
 
 
 
BP not controlled
or
DBP >140 mm Hg
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Labetalol 10 mg IV
followed by continuous IV infusion 2–8 mg/min;
or nicardipine 5 mg/h IV, titrate up to desired effect by
2.5 mg/h every 5–15 minutes, maximum 15 mg/h
 
 
 
 
 
Sodium nitroprusside 0.5 mcg/kg/min
IV infusion as initial dose, then
titrate to desired blood pressure
 
 

All algorithms are based on recommendations from AHA/ASA for the early management of patients with acute ischemic stroke (2013)


Exclusion Criteria for IV Recombinant TPA Treatment

Less than 3 hours of onset

  • Significant head trauma or prior stroke in previous 3 months
  • Symptoms suggest subarachnoid hemorrhage
  • Arterial puncture at noncompressible site in previous 7 days
  • History of previous intracranial hemorrhage
  • Intracranial neoplasm, arteriovenous malformation, or aneurysm
  • Recent intracranial or intraspinal surgery
  • Elevated blood pressure (systolic >185 mm Hg or diastolic >110 mm Hg)
  • Active internal bleeding
  • Acute bleeding diathesis, including but not limited to
  • Platelet count <100,000/mm³
  • Heparin received within 48 hours, resulting in abnormally elevated aPTT greater than the upper limit of normal
  • Current use of anticoagulant with INR >1.7 or PT >15 seconds
  • Current use of direct thrombin inhibitors or direct factor Xa inhibitors with elevated sensitive laboratory tests (such as aPTT, INR, platelet count, and

ECT; TT; or appropriate factor Xa activity assays)

  • Blood glucose concentration <50 mg/dL (2.7 mmol/L)
  • CT demonstrates multilobar infarction (hypodensity >1/3 cerebral hemisphere)

Relative exclusion criteria

  • Only minor or rapidly improving stroke symptoms (clearing spontaneously)
  • Pregnancy
  • Seizure at onset with postictal residual neurological impairments
  • Major surgery or serious trauma within previous 14 days
  • Recent gastrointestinal or urinary tract hemorrhage (within previous 21 days)
  • Recent acute myocardial infarction (within previous 3 months)

Between 3 and 4.5 hours of onset

  • Aged >80 years
  • Severe stroke (NIHSS>25)
  • Taking an oral anticoagulant regardless of INR
  • History of both diabetes and prior ischemic stroke

Dos

  • Obtain a brief history, including time of onset, time of arrival at the ED, and medications (especially anticoagulants).
  • Rule out conditions mimicking stroke (i.e., Seizures, syncope, migraine with aura, hypoglycemia, hypertensive encephalopathy, Wernicke encephalopathy, CNS abscess, CNS tumor, drug toxicity (lithium, phenytoin, carbamazepine)
  • Review the criteria for the administration of IV rTPA to determine the patient's eligibilty status.
  • Order a limited number of investigation during the initial emergency evaluation. Only the estimation of blood glucose should precede the administration of IV rTPA.
  • Cardiac monitoring for at least the first 24 hours to screen for atrial fibrillation.
  • Ensure blood pressure of ≤180/110 mmHg before initiating IV rTPA, and maintain it below 180/105 mmHg for at least the first 24 hours post-IV rTPA.
  • Order a follow-up CT/MRI before commencement of antiplatelets.
  • Give ASA 325 mg within 24 to 48 hours to most patients (except if contraindicated).
  • Strict blood pressure monitoring for the first 24 hours, especially if rTPA was administered - every 15 minutes for 2 hours, then every 30 mins for 6 hours, and every hour for the next 16 hours.

Don'ts

  • Do not treat hypertension except the blood pressure is >220/120 mmHg, and not until CT/MRI have been performed.
  • Do not initiate anticoagulation treatment within the first 24 hours.
  • Do not commence oral administration of medications before speech and swallow evaluation.
  • Do not delay sending the patient to CT for any reason.

References

  1. Trouillas, P.; von Kummer, R. (2006). "Classification and pathogenesis of cerebral hemorrhages after thrombolysis in ischemic stroke". Stroke. 37 (2): 556–61. doi:10.1161/01.STR.0000196942.84707.71. PMID 16397182. Unknown parameter |month= ignored (help)
  2. Jauch, EC.; Saver, JL.; Adams, HP.; Bruno, A.; Connors, JJ.; Demaerschalk, BM.; Khatri, P.; McMullan, PW.; Qureshi, AI. (2013). "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. 44 (3): 870–947. doi:10.1161/STR.0b013e318284056a. PMID 23370205. Unknown parameter |month= ignored (help)

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