COVID-19-associated stroke

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

Synonyms and keywords: COVID-19, SARS-CoV-2, stroke, CT scan, cerebrovascular disease, TPA, alteplase

Overview

Cerebral hemorrhage or cerebral ischemia disrupts cerebral perfusion and can lead to an acute neurologic condition, called stroke. Cerebrovascular complications have been reported in severe Coronavirus Disease 2019 (COVID-19). However, neurological complications are not very common in rapidly spreading COVID-19 which is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The presenting complaints in majority of stroke patients reported in different studies were respiratory complaints (shortness of breath, cough) and non-specific constitutional symptoms such as fever, malaise, etc., and stroke developed later in the course of the disease. This is thought to be due to COVID-19-associated coagulopathy. However, there are few case reports and studies that have mentioned specific neurological presenting complaints such as altered mental status, limb weakness, and aphasia. Various non-pulmonary features are being reported as the COVID-19 understanding is unfolding with the spike of cases and continuously rising number of cases globally.

To view general COVID-19 section, click here.

Historical Perspective

• Stroke was first recognized by Hippocrates, in the fourth century BC, almost 2,400 years ago, and it was reffered to as Apoplexy, a Greek medical literature term, which means 'struk down by violence'. Later, renaissance anatomists, in mid-16th century A.D., explained the pathophysiology of stroke, differentiating the causes as bleeding or blockage of A cerebral artery.
• Mao et al., in his study, first reported neurological symptoms in COVID-19 patients hospitalized in Wuhan, China from January 16, 2020, to February 19, 2020. Neurological symptoms were reported in 78 patients out of 214 COVID-19 positive hospitalized patients with COVID-19 in Wuhan, China. The stroke patients reported specifically were 14. In this study, patients with cardiovascular risk factors who presented with severe systemic symptoms were at higher risk of stroke.
• Yaghi et al. retrospectively examined stroke patients admitted across different locations of NYU Langone hospital in New York. In this study, the incidence of 0.9% was observed in laboratory confirmed COVID-19 positive patients included in this study. Stroke diagnosis was proved by imaging, and cryptogenic stroke was seen in most of these patients. The mortality was much higher in stroke patients who were COVID-19 positive.

To view historical perspective of COVID-19 section, click here.

Classification

• There is no specific classification established for 'Stroke in COVID-19 patients'.
• It is same as the general classification of stroke.

• Stroke can be classified into
  • Ischemic stroke: This can be due to
    • Thrombosis (Large vessel or Small vessel thrombosis)
    • Embolism
    • Systemic hypoperfusion
    • Cryptogenic (unknown origin)
  • Hemorrhagic stroke: This can be due to
    • Intracerebral hemorrhage
    • Subarachnoid hemorrhage
    • Subdural Hemorrhage
    • Epidural hemorrhage

To view classification of COVID-19 section, click here.

Pathophysiology

• The exact pathophysiology of stroke in COVID-19 is not fully understood.
• However, it is thought that stroke in COVID-19 could be due to one of the following pathophysiologies
  • Sepsis induced coagulopathy:
    • Sepsis induced coagulopathy in COVID-19 patients is thought to be contributing to microthromobosis.
    • This is supported by elevation of D-dimer and C-reactive protein, which are hypercoagulability and inflammatory markers, in COVID-19 positive patients.
  • The angiotensin-converting enzyme II:
    • (ACEII) receptors are also present on the vascular endothelial cells and neural cells in the brain .
    • These receptors expressed in the brain are responsible for sympathoadrenal system regulation, and vascular autoregulation.
    • When the virus binds to these receptors, this vascular autoregulation is hampered and can lead to elevated blood pressure, eventually leading to rupture of the cerebral vessels and intracranial hemorrhage.
    • It does so by altering the balance of renin-angiotensin system which likely triggers endothelium dysfunction, organ damage, which eventually results in stroke.
  • Viral neurotropism and neuroinvasion
    • Viral Neurotropism and Neuroinvasion is another possible pathogenic mechanism for cerebrovascular accidents in COVID-19 patients.
    • The coronaviruses usually cause mild respiratory illness, but the beta coronavirues are known to have a role in nervous system involvement.
    • The Novel coronavirus “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)” is a beta coronavirus, similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV).
    • It,therefore, has an infection mechanism and potential to invade the nervous system, similar to SARS-Cov and MERS-Cov. The detection of the virus in the cells of the brain on autopsy (neural and capillary endothelial cells), and viral presence in the cerebrospinal fluid of the encephalitis patient infected with SARS-Cov-2 supports the neuro-invasiveness of the virus.
    • The two possible routes are retrograde axonal transport (via nasal cavity) or hematogenous spread (via blood brain barrier endothelial cells). Once the virus reaches the brain, it attaches to the ACE II receptors.
  • Direct entry into brain tissues:
    • Direct entry into brain tissues from cribriform plate to brain. This is one of the proposed mechanism as COVID-19 positive patients also presented with anosmia and hyposmia which possibly occurs due to viral effect on olfactory bulb, which is in close proximity to cribriform plate

• Further investigations should be done to better understand the mechanism of Stroke in patients with COVID-19.

To view pathophysiology COVID-19 section, click here.

Causes

• Coronavirus disease 2019 (COVID-19) associated stroke is caused by SARS-CoV-2.
• To view causes of COVID-19 section, click here.

Differentiating COVID-19-associated stroke from other Diseases

• For further information about the differential diagnosis, click here.
• To view the differential diagnosis of COVID-19, click here.

Epidemiology and Demographics

• The case fatality rate of cerebrovascular accidents is 41.7 deaths per 100, 000 population. The mortality in patients with COVID-19 associated stroke is higher.

• The incidence of stroke in COVID-19 varies significantly depending on the study population. The prevalence of COVID-19-associated stroke varies in different studies.

Prevalence of stroke in patients with COVID-19

Date of publication	Country	Author	Number of patients	Severe infection	Neurological symptoms	Acute Cerebrovascular disease	Ischemic/Hemorrhagic Stroke
April 10, 2020	Wuhan, China	Mao et al.	214	88 patients (41.1%), Mean age-58.2 years	78 patients (36.4%)	5 among severe [5.7%] infection group vs 1 [0.8%]) in non-severe group	Ischemic-4, Hemorrhagic-1
May 29, 2020	Wuhan, China	Qin et al. (Retrospective cohort study)	1875	461 severe on admission		50 patients ie. 15 among severe and 35 among mild on admission (Median age-70 years), 30 males and 20 females	Ischemic-90%, Hemorrhagic-10%
May 20, 2020	New York	Yaghi et al. (Retrospective cohort study)	3556		Stroke at the time of admission-14/32 (43.8%), eventually developed stroke during hospitalization-18 (56.2%)	32 patients (0.9%)	Ischemic stroke- 32
April 28, 2020	New York city	Oxley et al.	5				Large vessel stroke-5, Mean age-<50 years
July 12, 2020	New York	Valderrama et al.	1 (52-year old male)				Ischemic stroke
Prevalence of COVID-19-associated stroke varies in different studies

• The incidence of stroke in hospitalized COVID-19 patients is reported to be 0.9–2%.majority of them being ischemic subtype. The mortality in COVID-19 positive stroke patients is reported to be 39%.

• The ischemic stroke prevalence in COVID-19 patients is 1.6%.

• A New York study published in May reported that the proportion of these strokes seem to be higher in younger men. Most of these strokes are large vessel ischemic strokes and are catastrophic.

• In a retrospective observational case series of six stroke patients in a hospital in Italy, with lab confirmed COVID-19, the median age reported was 69 years. Ischemic stroke subtype was seen in 4 patients(67%) as compared to hemorrhagic which was only seen in 2 patients (33%). Vascular risk factors were seen in 5/6 patients, which included diabetes mellitus, arterial hypertension

• In a single center retrospective study conducted in Wuhan by Qin C. et al. which included 1875 laboratory-confirmed COVID-19 patients from january 27th, 2020, to March 5th, 2020, 50 patients had history of stroke. The median age of this study group was 63 years, with stroke patients relatively older(70 years) when compared to non-stroke patients (62 years).

• Stroke is one of the neurological manifestations in patients with severe infection. There is limited information on COVID-19 patients with stroke who survived.

To view epidemiology and demographics of COVID-19 section, click here.

Risk Factors

• According to one of the study conducted in New York, Stroke in COVID-19 infected patients is seen in relatively young patients as compared to with non COVID-19 patients.

• A study by Mao et. al. reported COVID-19 associated stroke in seen in critically patients. The patients who developed stroke were older population with comorbidities like diabetes, hypertension, etc.

• However, due to disparities in the stroke prevalence in different studies, no clear association has been established.

To view risk factors of COVID-19 section, click here.

Screening

• There is insufficient evidence to recommend routine screening for stroke in COVID-19 patients. However, if the patient presents with stroke, COVID-19 screening should be done.

To view screening of COVID-19 section, click here.

Natural History, Complications, and Prognosis

• Prognosis is generally poor for COVID-19 patients with stroke. A study reported a high proportion of these patients were admitted to the Intensive Care Unit(ICU) and required mechanical ventilation. The mortality of COVID-19 patients with stroke was much higher when compared to COVID-19 patients with no history of stroke.

To view natural history, complications and prognosis of COVID-19 section, click here.

Diagnosis

• Diagnosis of stroke associated to COVID-19 is based on history of symptoms development, physical examination, imaging findings, plus a positive COVID-19 test.
• There are no standard criteria for the evaluation of stroke associated to COVID-19.
• General management protocols for COVID-19-associated stroke should be established so that brain imaging can be realized as prompt as possible in patients who may be candidates for IV fibrinolysis or mechanical thrombectomy or both.
• The current diagnostic approach for stroke associated to COVID-19 is the same as for people with non-COVID infection.

Diagnostic Study of Choice

• Non-contrast CT Scan of the brain within 20 minutes of arrival to the emergency department is the diagnostic test of choice for stroke in patients with COVID-19 infection.
• MRI may detect smaller lesions with certainty if required, once the hemorrhagic stroke is excluded by non-contrast CT Scan.
• In a patient who presents with neurological symptoms, RT-PCR for SARS-CoV-2 should be done as well.

History and Symptoms

• The extent of damage and symptoms which may result from stroke associated to COVID-19 highly depends on the site of infarction, the blood vessels involved, and the presence of other risk factors.

• The majority of patients with COVID-19-associated stroke initially presented with respiratory symptoms (e.g. cough, shortness of breath etc) and constitutional features. These patients developed cerebrovascular signs and symptoms later in the course of disease.
• The following table summarizes the signs and symptoms found in 5 patients with COVID-19 infection that later acquiered a stroke:

Patient no.	Onset of neurologic symptoms	Age and Gender	Neurologic Signs & Symptoms
1	On Admission	73-year old, Male	Respiratory distress, fever, and altered mental status
2	On Admission	83-year old, Female	Fever, slurring of speech, facial droop, and reduced oral intake
3	On Admission	80-year old female	Left sided weakness, altered mental status, one week history of frequent falls
4	On Admission	88-year old, Female	An 15 minute episode of weakness and numbness of right arm and word finding difficulty
5	On Admission	58-year old, Male	Dense Right-sided weakness and acute onset aphasia
Reported cases of patients with COVID-19 infection and symptoms suggestive of stroke.

Most common symptoms

• Cough
• Dyspnea
• Fever
• Altered mental status

Less common symptoms

• Aphasia
• Motor impairmant
• Sensory impairmant
• Slurred speech
• Facial droop
• Frequent falls
• Reduced oral intake

Physical Examination

• The physical examination findings in stroke associated to COVID-19 will highly depend on the site of infarction, the blood vessels involved, and the presence of other risk factors.
  

Physical examination of patients with stroke depending on vessel involved

Vessel involved	Physical examination
Anterior cerebral artery	Decreased motor strength- contralateral lower limb Absent or decreased sensations-contralateral lower limb Increased reflexes-contralateral lower limb Babinski's reflex positive Constructional and dressing apraxia-hemineglect Transcortical motor aphasia(non fluent) Mutism Contralateral grasp and sucking reflex Memory impairment Confabulation
Middle cerebral artery Most common site of infarction	Decreased motor strength-contralateral arm and face Absent or decreased sensations-contralateral left arm and face Increased deep tendon reflexes - contralateral arm Babinski's sign positive Contralateral Hemineglect Broca's aphasia Wernicke's aphasia Contralateral visual field defect
Posterior cerebral artery	Contralateral visual field defects Complex hallucinations Prosopagnosia Unable to remember names-Nominal aphasia Acalculia and agraphia -Gerstmann syndrome Memory deficit Hemisensory loss Contralateral hemiparesis Thalamic pain syndrome Hemiballismus Occulomotor nerve palsy Intention tremors Alexia without agraphia
Vertebrobasilar artery	Midbrain Weber syndrome Contralateral decreased motor strength Deviation of eye downwards and outwards-ipsilateral 3rd nerve palsy
	Medulla Lateral medullary syndrome Impaired gag reflex Uvula deviated to the opposite side of lesion Ptosis Miosis Enophthalmos Ipsilateral impaired pain, touch and temperature sensation on the upper half of the face Contralateral decreased motor strength and sensory loss Romberg's sign Medial medullary syndrome Deviation of the tongue to the side of the lesion-hypoglossal nerve Contralateral decreased motor strength Contralateral loss of position sense, vibration and two point discrimination
	Pons Inability to close eyes Deviation of angle of mouth Facial muscle weakness-Facial nerve Loss of taste and sensation on the anterior two thirds of the tongue Affected eye deviation inwardsand down-Abducent nerve Locked-in syndrome
	Cerebellum Vertigo Romberg's sign positive Intension tremors Dysdiadochokinesia Dysarthria

• The use of stroke scales helps to measure the degree of neurological impairment, ease communication, may help select patients candidates for fibrinolytic or mechanical therapy, permits the evaluation of changing clinical status, and identifies those patients at higher risk for complications (eg. intracerebral hemorrhage).
• The National Institutes of Health Stroke Scale (NIHSS) is a tool used to measure the neurologic impairment caused by a stroke in a quantitative manner. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0.

National Institutes of Health Stroke Scale (NIHSS)

Tested item	Title	Response and score
1A	Level of consciousness	0—Alert
		1—Drowsy
		2—Obtunded
		3—Coma/unresponsive
1B	Orientation questions (2)	0—Answers both correctly
		1—Answers 1 correctly
		2—Answers neither correctly
2	Gaze	0—Normal horizontal movements
		1—Partial gaze palsy
		2—Complete gaze palsy
3	Visual fields	0—No visual field defect
		1—Partial hemianopia
		2—Complete hemianopia
		3—Bilateral hemianopia
4	Facial movement	0—Normal
		1—Minor facial weakness
		2—Partial facial weakness
		3—Complete unilateral palsy
5	Motor function (arm) a. Left b. Right	0—No drift
		1—Drift before 10 s
		2—Falls before 10 s
		3—No effort against gravity
		4—No movement
6	Motor function (leg) a. Left b. Right	0—No drift
		1—Drift before 5 s
		2—Falls before 5 s
		3—No effort against gravity
		4—No movement
7	Limb ataxia	0—No ataxia
		1—Ataxia in 1 limb
		2—Ataxia in 2 limbs
8	Sensory	0—No sensory loss
		1—Mild sensory loss
		2—Severe sensory loss
9	Language	0—Norma
		1—Mild aphasia
		2—Severe aphasia
		3—Mute or global aphasia
10	Articulation of words	0—Norma
		1—Mild dysarthria
		2—Severe dysarthria
11	Extinction or inattention	0—Absent
		1—Mild loss (1 sensory modality lost)
		2—Severe loss (2 modalities lost)
Adapted from Lyden et al., 1994 American Heart Association, Inc.

• The pre-stroke Modified Rankin Score (mRS) is an estimated score used to assess the patient’s pre-stroke level of function. An estimated mRS should be abstracted from current medical record documentation about the patient’s ability to perform activities of daily living prior to the hospitalization for the acute ischemic stroke event.

Alberta stroke program early CT score (ASPECTS)

Area affected		Score
Subganglionic Nuclei:	M1 - Frontal operculum	1
	M2 - Anterior temporal lobe	1
	M3 - Posterior temporal lobe	1
Supraganglionic Nuclei:	M4  - Anterior MCA	1
	M5  - Lateral MCA	1
	M6  - Posterior MCA	1
Basal Ganglia:	C - Caudate	1
	L - Lentiform Nucleus	1
	I - Insula	1
	IC - Internal Capsule	1
Adapted from The University of Calgary ASPECT score in Accute stroke, 2020

• Alberta stroke program early CT score (ASPECTS) is a 10 point quantitative score used to asses early ischemic changes in patients suspected of having acute large vessel anterior circulation occlusion.

Pre-Stroke Modified Rankin Score (mRS)

Score	Item tested
0	The patient had no residual symptoms.
1	The patient had no significant disability; able to carry out all activities.
2	The patient had slight disability; unable to carry out all activities but able to look after self without daily help.
3	The patient had moderate disability; requiring some external help but able to walk without the assistance of another individual.
4	The patient had moderately severe disability; unable to walk or attend to bodily functions without assistance of another individual.
5	The patient had severe disability; bedridden, incontinent, requires continuous care.
6	Unable to determine (UTD) from the medical record documentation.
Adapted from Specifications Manual for Joint Commission National Quality Measures, 2018

Laboratory Findings

• Patients with stroke associated to COVID-19 will have a positive test for COVID-19 confirmed either through molecular tests, nucleic acid amplification test, or serological testing.

• Serum glucose assessment is the only lab study that should proceed IV alteplase initiation, this should be over 50 mg/dL for its administration.
• Coagulation studies and complete blood count should be delayed until after IV alteplase initiation unless there is suspicion for a coagulopathy disorder.
• Troponin should be assessed in patients presenting with ischemic stroke.
• In patirents 20 years or older and not on lipid-lowering therapy, baseline measurement of plasma lipid profile is effective in estimating atherosclerotic cardiovascular disease (ASCVD); after that, plasma lipid profile should be measured every 4 to 12 weeks after statin initiation.

Ultrasound

• Echocardiography may be necessary in patients with ischemic stroke to identify and prevent secondary causes of stroke such as structural changes, atrial fibrillation, valvular heart disease and atherosclerosis.
• Carotid ultrasound should be performed in all patients with ischemic stroke to assess for narrowing of carotids and decrease recurrence of thromboembolic events.

X-ray

• Head x-rays can help rule out foreign metal objects in the head before performing an MRI, detect skull fractures, and identify intracranial calcifications that may serve as hallmarks for brain structural changes in countries with poor access to more specific imaging tests.
• There is no evidence of usefulness of chest x-ray in the acute setting of stroke.

CT scan

• Non-contrasted CT scan of the head should should always be performed before initiating IV alteplase.
• Once hemorragic stroke is excluded, CT scan with contrast should be realized in patients with no history of renal disease without measuring creatinine concentration, taking into account that both COVID-19 infection and stroke increase the risk for renal impairment per se.
• CT angiography of the brain may be needed in patients to make a decision for mechanical thrombectomy.
• CT angiography's contrast can increase the risk of acute kidney injury in patients with COVID-19 infection.
• CT perfusion should be done in patients who present within 24 hours of the initiation of symptoms.
• Concurrent CT scan of the head and chest may be ordered at the same time in patients with COVID-19 infection.
• CT angiography of the extracranial carotid and vertebral arteries, in addition to the intracranial circulation,is recommended in patients who are potential candidates for mechanical thrombectomy.

MRI

• MRI of the head before IV alteplase administration to exclude microbleeds is not recommended.
• Multimodal MRI of the head should be done in patients who present within 24 hours of the initiation of symptoms.
• In patients who wake up with clinical symptoms of stroke of unknown onset (more than 3 hours?), an MRI with diffusion-positive FLAIR may be useful for selecting those who can benefit from IV alteplase administration.

Electrocardiogram

• Baseline electrocardiographic assessment is recommended in patients with stroke to help determine the follingow:
  • Underlying cause for ischemic stroke such as embolic source in atrial fibrillation, ongoing myocardial ischemia, chronic myocardial injury and valvular abnormalities.
  • ECG monitoring in first 24 hours may help determine the new onset or paroxysmal atrial fibrillation.
  • May determine cardiac complications of acute ischemic stroke such as myocardial ischemia or arrythmias.

• To view diagnosis of COVID-19 section, click here.

Treatment

Early assesment

• The initial assesment goals of ischemic stroke may include the following:

1) Airway 2) Breathing 3) Circulation

1) O2 administration at SpO2<94% 2) Ventilatory assisstance is provided to patients who have difficulty breathting 3) IV fluids or vasopressors are given to maintain hemodynamic stability

Early Diagnosis

History and PE 1) Help assess the severity of neurological deficit 2) Give clue to the underlying cause 3) Determine the site of infarction

Initial diagnostic tests 1) Noncontrast brain CT or brain MRI 2) Blood glucose 3) Oxygen saturation 4) Serum electrolytes/renal function tests 5) Complete blood count, including platelet count 6) Markers of cardiac ischemia 7) Prothrombin time/INR 8) Activated partial thromboplastin time 9) ECG

Early assessment of ischemic stroke

Reperfusion therapy

Medical r-tPA in eligible patients within 3-4.5 hours of onset of symptoms

Surgical

Symptomatic relief

1) Fever 2) Headache 3) Shortness of breath

Prognosis

1)NIHSS scoring 2)Glassgow coma scale

Medical therapy

• The reported cases of treatment for COVID-19-associated stroke have followed the same guidelines as patients with no COVID-19 infection. The following recommendations are mainly based on the current guidelines of management for stroke of the AHA 2019.
• IV alteplase is always preferred over mechanical thrombectomy when there are no contraindications.
• The usefulness of anticoagulants such as thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) is not well established in the acute setting of stroke.
• The use of thrombolysis via ultrasound waves concomitant to IV fibrinolysis is not recommended.
• High-intensity statin therapy should be initiated in patients younger than 75 with clinical ASCVD, to achieving a reduction in LDL-C levels of at least 50%.
• In patients older than 75 years of age with clinical ASCVD, it is reasonable to initiate moderate or high-intensity statin therapy after reviewing adverse effects and drug interactions.
• Risk and beneffits should be discussed before initiation of statin therapy to weight ASCVD risk reduction against the potential for statin-associated side effects.
• Continuation of statin therapy during the acute period of ischemic stroke is reasonable among patients already taking statins.

Summarized management of ischemic stroke

Medical treatment	Drug class	Recommendations
		Acute	Long-Term
Reperfusion therapy	Tissue plasminogen activator (t-PA)	Recommended within 3-4.5 hours of onset of ischemic stroke in eligible patients by guidelines and systematic reviews	None
Antithrombotic agents	Antiplatelet agents	Oral administration of aspirin (initial dose is 325 mg) is recommended within 24 to 48 hours after stroke onset in most patients Aspirin is contraindicated in patients with ischemic stroke within 24 hours of t-PA administration DAPT therapy (aspirin and clopidogrel) is recommended for 90 days in patients with symptomatic intracranial large artery disease	Long term therapy with clopidogrel or aspirin extended release dipyridamole may be used for secondary prevention of non cardioembolic stroke
	Anticoagulants	Parenteral or oral anticoagulation is not recommended within 48 hours of onset of ischemic stroke	Oral anticoagulants may be used for secondary prevention of ischemic stroke in patients with atrial fibrillation or other cardioembolic disease
Antilipid therapy	Statins	Among patients already taking statins at the time of onset of ischemic stroke, continuation of statin therapy during the acute period is reasonable	Long term management of ischemic stroke with high intensity statins may be recommended for patients with atherosclerotic disease Patients who cannot tolerate high intensity dose, medium or low intensity statins may prove beneficial
Antihypertensive therapy	Intravenous antihypertensives (Labetolol, nitroprusside)	Used to control high blood pressure in patients with BP>185/110 mmHg before starting t-PA	Long term oral antihypertensives may be used after 24 hours of ischemic stroke in patients having history of hypertension
	Oral antihypertensive therapy	Recommended after 24 hours in patient having hypertension	Long term oral antihypertensives may be used after 24 hours of ischemic stroke in patients having history of hypertension
Antihyperglycemic agents	Insulin	May be used to control blood glucose between range of 140-180 mg/dl since hyperglycemia is associated with worst outcome in patients with acute ischemic stroke	Long term oral antidiabetic may be used for secondary prevention of ischmeic stroke in patients with diabetes mellitus

Alteplase

• IV alteplase is recommended for selected patients who can be treated within 3-4.5 hours of ischemic stroke symptom onset or patient last known well or at baseline state.
• The dose of IV alteplase is 0.9 mg/kg (maximum dose 90 mg) over 60 min, with 10% of the dose given as a bolus over 1 min.
• IV alteplase should be initiated as soon as possible, having been demonstrated better outcomes the sooner is administered.
• Hyperglycemia should be treated during the first 24 hours after ischemic stroke, to achieve values of 140 to 180 mg/dL.
• IV alteplase may cause bleeding and angioedema.
• Glycoprotein IIb/IIIa inhibitors (tirofiban, apiximab, eptifibatide) should not be coadministered with IV alteplase.
• IV alteplase may be used in patients under warfarin if the INR is lower than 1.7.
• IV alteplase should not be administered to patients who have received a full dose of low-molecular-weight heparin within the previous 24 hours (including prophylactic doses).
• Blood pressure should be sustained lower than 180/105 mmHg the first 24 hours after IV alteplase administration. Intensive lowering has been shown to be safe.
• In case of intracranial bleeding due to alteplase administration, alteplase should be suspended, blood draws should be taken (CBC, coagulation studies), tranexamic acid should be administered (1000 mg IV infused over 10 min), and a subsecuent non-contratested CT scan of the head taken.
• The use of IV alteplase should be used cautiously in patients who undergone a major surgery in the past 2 weeks.
• IV alteplase for ischemic stroke is contraindicated in patients with a severe head trauma or subarachnoid hemorrage in the preceding 3 months.

Tenecteplase

• Tenecteplase may be useful in patients with minor neurological impairment.
• The dose of tenecteplase is a single IV bolus of 0.25-mg/kg (maximum 25 mg).

Antiplatelet therapy

• Administration of aspirin is recommended in patients with AIS within 24 to 48 hours after onset. For those treated with IV alteplase, aspirin administration is generally delayed until 24 hours later.
• The dose of aspirin is usually between 160-300mg daily.
• IV aspirin administration within 90 minutes after the start of IV alteplase is associated with symptomatic intracranial hemorrhage, for which co administration is discouraged but benefits should be assessed in each individual case.
• Dual antiplatelet therapy with aspirin and clopidogrel (75 mg/d, with a loading dose of 600mg) may be started within 24 hours after symptom onset and continued for 21 days in patients with no cardioembolic ischemic stroke.
• Aspirin should not substitute IV alteplase or mechanical thrombectomy in patients eligible for these therapies.

Surgery

• The usefulness of emergency carotid endarterectomy, carotid angioplasty and stenting in the absence of an intracranial clot is not well established.

Mechanical thrombectomy with a stent retriever

• Mechanical thrombectomy with stent retrievers is recommended over intra arterial fibrinolysis as first-line therapy.
• Mechanical thrombectomy may be useful in selected patients with up to 24 hours of initiation of stroke.
• In patients who undergo mechanical thrombectomy,blood pressure should be maintained below 180/105 mmHg during and for 24 hours after the procedure.

• Patients should receive mechanical thrombectomy with a stent retriever if they meet all the following criteria:
  1. Prestroke mRS score of 0 to 1
  2. Causative occlusion of the internal carotid artery or MCA segment 1 (M1)
  3. Age ≥18 years
  4. NIHSS score of ≥6
  5. ASPECTS of ≥6; and
  6. Treatment can be initiated within 6 hours of symptom onset

Aspiration thrombectomy

• Aspiration thrombectomy has not been shown to be inferior to stent retriever.

• Direct aspiration thrombectomy as first-pass mechanical thrombectomy is recommended as noninferior to stent retriever for patients who meet all the following criteria:
  1. Prestroke mRS score of 0 to 1;
  2. Causative occlusion of the internal carotid artery or M1;
  3. Age ≥18 years;
  4. NIHSS score of ≥6;
  5. ASPECTS ≥6; and
  6. Treatment initiation within 6 hours of symptom onset.

Intra arterial fibrinolysis

• Intra-arterial fibrinolysis may be initiated within 6 hours of stroke onset in selected patients in whom IV alteplase is contraindicated.

Other aspects of management

• Volume expansors are not recommended in ischemic stroke.
• The best head positioning after stroke is not well established.

• Supplemental oxygen and mechanical ventilation support should be provided when necessary to maintain oxygen saturation higher than 93%.

• Sources of hyperthermia (>38°C) should be identified and treated with antipyretics in patients with stroke.
• Hypoglycemia (<60 mg/dL) should be treated in the acute setting in patients with ischemic stroke.
• Blood pressure ≥220/120 in patients who did not receive TPA should be treated within the first 48 to 72 hours after the onset of ischemic stroke.
• Enteral feeding should be started within 7 days of admission after an acute stroke when there is no contraindications.
• Psychological screening is always recommended to exclude poststroke depression.
• Early rehabilitation in patients with stroke is adviced.

Primary Prevention

• There is currently no vaccine to prevent COVID-19. The best way to prevent infection is to avoid being exposed to this virus.
• COVID-19 increases the probability of developing ischemic stroke, but there are several measures that can decrease the risk of stroke, among them:
• Smoking cessation
• Lowering blood pressure
• Decreasing alcohol intake
• Exercise
• Treatment of atrial fibrillation
• Weight loss
• Procedures such as carotid endarterectomy or carotid angioplasty when necessary

Secondary Prevention

• Smoking cessation should be highly encouraged in patients who suffered from stroke, behavioral interventions and nicotine replacement may be necessary.

To view treatment of COVID-19 section, click here.

References

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