Lacunar Stroke

Overview and Recommendations

Background

● Lacunar stroke (or lacunar infarct) is de ned as a stroke caused by occlusion of small vessels in the
brain.
⚬ Infarcts result in a small cavity, or lacune, which typically ranges from 3 mm to < 15 mm.

● Acute symptomatic lacunar infarcts are predominantly found in primary sensory and motor pathways,
explaining their stroke presentation.

● Reported prevalence of lacunar stroke is approximately 25% of all ischemic strokes; with a higher
incidence of lacunar stroke among African-American and Hispanic persons.

● Lacunar infarcts are accepted as a sign of intrinsic disease of the small vessel, however, they may also
be caused by nonsmall vessel mechanisms such as arteriolosclerosis of parent large vessel and
embolism.

● Not all lacunar strokes are due to small vessel disease; 10%-15% of acute lacunar infarcts are reported
to be caused by embolism.

● Risk factors are similar to other ischemic strokes: hypertension, diabetes, smoking, older age, heart
disease, hypercholesterolemia, metabolic syndrome.

● There are multiple classic clinical presentations of lacunar stroke that re ect the most common lesion
locations.
⚬ Pure motor stroke, also called pure motor hemiparesis, is the most frequent presentation.

– It accounts for 50%-66% of all lacunar infarcts.

– It is characterized by weakness of similar severity a ecting face, arm, and leg.
– The most common lesion locations for this syndrome include posterior limb of internal capsule,
corona radiata, mesencephalon, and medulla oblongata.
⚬ Pure sensory stroke

– Hemianesthesia that may involve face, arm, and leg equally, or may be incomplete.
– Lesions located in the lateral nucleus of thalamus, or thalamocortical projections, a ect areas of
the body separated from una ected areas along a median line which bisects nose, tongue, and
anus.
– The lesions are typically located in lateral nucleus of thalamus, thalamocortical projections, or
sensory pathways of brainstem, however, lesions may extend to internal capsule.
⚬ Sensorimotor stroke is characterized by overall or partial defects of both motor and sensory
(hemiparesis) function.
– Lesion locations include internal capsule (posterior or anterior limb), thalamus, and corona
radiata.
⚬ Ataxic hemiparesis is characterized by hemiparesis with associated cerebellar syndrome on the
same side.
– Lesion locations include foot of pons or posterior arm of internal capsule, corona radiata,
thalamus, cerebellum, frontal cortex, or lenticular nucleus
 ⚬ Clumsy hand-dysarthria syndrome is characterized by moderate-to-severe dysarthria and ataxia of
the hand.
– Lesion locations include foot of pons or anterior arm of internal capsule.

● Lacunar stroke may be complicated by deterioration after initial stroke assessment, with long-term
consequences, including vascular cognitive impairment or vascular dementia, or pseudobulbar
syndrome.

Evaluation

● Use prehospital and emergency room evaluation similar to other acute ischemic strokes and follow
published guidelines (Strong recommendation). See Stroke (acute management).

● Base the diagnosis of lacunar stroke on the clinical presentation in combination with imaging (Strong
recommendation).
⚬ Neuroimaging is used to con rm the presence of lacunar infarct/cause of stroke; See
Neuroimaging for acute stroke for details.
⚬ Magnetic resonance imaging (MRI) of head without contrast, or MRI with and without contrast,
including di usion-weighted imaging (DWI) is the most appropriate imaging technique after acute
management.

● Obtain electrocardiogram, but if hemodynamically stable, defer until after determination of acute
therapy, including assessment for thrombolytic or endovascular therapy (Strong recommendation).

● Order blood work for electrolytes, glucose, hematology/complete blood count (CBC), coagulation
studies (INR/activated partial thromboplastin time [aPTT]), renal function (creatinine level/estimated
glomerular ltration rate [GFR]), and troponin (Strong recommendation).

● Evaluate swallowing before initiating any oral intake to reduce risk of aspiration and pneumonia
(Strong recommendation) .

Management

● An acute treatment regimen speci c to lacunar stroke (due to small vessel disease [SVD]) is not
currently available.

● Patients should be admitted to a stroke unit and treated according to current stroke guidelines
(Strong recommendation). See Stroke (acute management) for further information.

● Use thrombolysis in appropriate candidates (Strong recommendation). See Thrombolytics for acute
stroke

● Take into account the presence of SVD during treatment, speci cally with regard to

⚬ Thrombolytic therapy

– Although evidence on management strategies for speci c stroke subtypes is limited,

thrombolytic therapy appears to improve neurological outcomes in patients with acute lacunar
stroke.
– Leukoaraiosis prior to treatment with thrombolytics may increase risk of symptomatic
intracerebral hemorrhage and poor functional outcome in patients with acute ischemic stroke.
⚬ Antiplatelet therapy for secondary prevention
Antiplatelet monotherapy may reduce risk of recurrent stroke in patients with lacunar stroke.
 – The addition of clopidogrel to aspirin does not decrease stroke recurrence and increases
–
mortality and hemorrhage in patients with symptomatic lacunar infarct.
⚬ Use of anticoagulation

– Anticoagulants have higher risk of death and symptomatic intracranial hemorrhage than
antiplatelet agents in acute ischemic stroke.
– SVD is not an absolute contraindication to anticoagulant use.

● See Treatment in Stroke (acute management) for details of overall acute stroke treatment.

● There is insu cient evidence regarding the utility of carotid endarterectomy in patients with lacunar
stroke in the distribution of the carotid stenosis.

● Avoid any oral intake until after swallowing screen (Strong recommendation).

● Mobilize less severely a ected patients early (Strong recommendation) to reduce risk for pneumonia,
deep vein thrombosis, pulmonary embolism, and pressure ulcers.

● All patients with acute stroke should be assessed by rehabilitation professionals, ideally within 48
hours of hospital admission (Strong recommendation).

● Patients with lacunar stroke should be treated for secondary prevention of recurrent stroke
consistent with published guidelines.
⚬ Initiate or continue high-intensity statin as rst-line therapy in patients ≤ 75 years old with clinical
atherosclerotic cardiovascular disease, unless contraindicated (Strong recommendation); see
Primary prevention of stroke for more details.
⚬ Antiplatelet agents recommended over anticoagulation (Strong recommendation); see Antiplatelet
Therapy for Secondary Prevention of Stroke or Transient Ischemic Attack for more details.

● The prognosis for lacunar stroke is generally good, especially in patients ≤ 50 years old. Neurologic
de cits generally improve within the rst few weeks after lacunar stroke. Up to 94% of lacunar stroke
patients are reported to be self-su cient at 6 months.

Related Summaries

● Stroke (acute management)

● Transient ischemic attack (TIA)

General Information

Description

● lacunar stroke (or lacunar infarct) is de ned as stroke caused by occlusion of small vessels in the

brain 1 , 2
⚬ infarcts are generally rounded, ovoid, or tubular in shape, and < 20 mm in axial diameter
⚬ infarcts result in a small cavity, or lacune, which typically ranges from > 3 mm to < 15 mm

● acute symptomatic lacunar infarcts are predominantly found in primary sensory and motor pathways,

explaining stroke presentation 2

● lacunar infarcts are accepted as a sign of small vessel disease; however, they may also be caused by

non-small vessel disease mechanisms 1

Also called

● lacunar infarct

● cerebral small vessel disease

● small vessel disease

● small artery disease

Definitions

● small vessel disease is de ned broadly as any pathological process which a ects the small vessels of

the brain, including small arteries, arterioles, small veins, and capillaries 1
⚬ parenchyma lesions thought to be caused by vessel changes have become synonymous with small
vessel disease due to the fact that small vessels cannot currently be seen in vivo
⚬ only the ischemic component of the pathological process (lacunar infarcts and white matter
lesions) is de ned, misleadingly, as small vessel disease

● arteriolosclerosis, lipohyalinosis, and brinoid necrosis refer to di use, intrinsic disease of small

arterioles and have varying degrees of severity 2

⚬ small arterioles de ned as vessels with diameter 40-200 mcm
⚬ disease process thought to result largely from hypertension

Types

● pure motor stroke, also called pure motor hemiparesis 3

⚬ most frequent presentation; reported to account for 50%-66% of all lacunar infarcts
⚬ characterized by weakness of similar severity a ecting face, arm, and leg
⚬ most common locations of lesion include posterior limb of internal capsule, corona radiata,
mesencephalon, and medulla oblongata

● pure sensory stroke 3

⚬ lesion typically located in lateral nucleus of thalamus, thalamocortical projections, or sensory

pathways of brainstem, however, may extend to internal capsule
⚬ includes complete (involvement extending throughout 50% of the body) and incomplete
hemisensory syndromes
⚬ in the case of lesions located in the lateral nucleus of thalamus or thalamocortical projections,
a ected areas are separated from una ected areas along a median line which bisects nose,
tongue, and anus (as opposed to lesions in other sensory areas)

● sensorimotor stroke 3

⚬ characterized by overall or partial defects of both motor and sensory (hemiparesis) function
⚬ lesion locations include internal capsule (posterior or anterior limb), thalamus, and corona radiata
(Front Neurol Neurosci 2012;30:94 )
● ataxic hemiparesis 3

⚬ characterized by hemiparesis with associated cerebellar syndrome on the same side

⚬ lesion locations include foot of pons or posterior arm of internal capsule, corona radiata, thalamus,
cerebellum, frontal cortex, or lenticular nucleus

● clumsy hand-dysarthria syndrome 3

⚬ characterized by moderate-to-severe dysarthria and ataxia of the hand

⚬ may have associated central facial paresis, homolateral hyperre exia with Babinski signs
⚬ lesion locations include foot of pons or anterior arm of internal capsule

Epidemiology

Who is most affected

● older patients with hypertension or diabetes 1 , 2 , 3

STUDY
● SUMMARY
higher incidence of lacunar stroke among African-American and Hispanic persons

COHORT STUDY: Circulation 2005 Mar 15;111(10):1327 | Full Text

Details
⚬ based on population-based cohort study
⚬ 714 patients ≥ 20 years old with rst ischemic stroke between 1993 and 1997 from Northern
Manhattan Study (NOMAS) were analyzed
– 29% were non-Hispanic white Americans, 22% were African-Americans, and 49% were Hispanic
– patients were excluded for transient ischemic attack without subsequent stroke or for history of
stroke
⚬ age-adjusted incidence of lacunar stroke

– 40 per 100,000 in African-Americans

– 31 per 100,000 in Hispanics
– 13 per 100,000 in non-Hispanic white Americans

⚬ Reference - Circulation 2005 Mar 15;111(10):1327 full-text

STUDY
● SUMMARY
lacunar stroke present as an incidental finding in 5.7% of brain magnetic resonance imaging
(MRI) in patients ≥ 55 years old

COHORT STUDY: N Engl J Med 2007 Nov 1;357(18):1821 | Full Text

Details
⚬ based on population-based cohort study
⚬ 2,000 patients (mean age 63 years) from Rotterdam Study with high-resolution structural brain MRI
available were evaluated for brain abnormalities
⚬ 2 experienced neuroradiologists reviewed all incidental ndings discovered by trained reviewers
⚬ 7.2% had asymptomatic brain infarction

– lacunar infarction 5.6%

– cortical infarction 2.0%
 ⚬ Reference - N Engl J Med 2007 Nov 1;357(18):1821 full-text , commentary can be found in N
Engl J Med 2008 Feb 21;358(8):853 , J Radiol 2008 Apr;89(4):457

Incidence/Prevalence

● reported prevalence of lacunar stroke approximately 25% among all ischemic strokes (J Neurol 2014
Feb;261(2):405 )

● small vessel disease is common and reported to account for approximately one- fth of all strokes

worldwide 2

● 25% reported prevalence of lacunar strokes among white patients with ischemic stroke 2

● crude annual incidence for rst-ever lacunar stroke 33 per 100,000 in Italy 1994-1998 based on 491
patients with lacunar stroke (Neurology 2006 May 9;66(9):1335 )

● lacunar stroke accounts for about 37% of ischemic strokes in Thailand (J Stroke 2014 Jan;16(1):1 full-
text )

● 5.6% prevalence of asymptomatic lacunar infarct (112 cases) in brain magnetic resonance imaging
(MRI) of 2,000 persons > 45 years old in the Netherlands (N Engl J Med 2007 Nov 1;357(18):1821 full-
text ), commentary can be found in N Engl J Med 2008 Feb 21;358(8):853

● see Stroke (acute management) for information on overall Incidence/Prevalence

Likely risk factors

● hypertension 1 , 2 , 3

● diabetes 1 , 2 , 3

● smoking 2 , 3

● older age 1 , 3

● heart disease 3

● hypercholesterolemia 2

● insulinemia 3

STUDY
● SUMMARY
metabolic syndrome, increased insulin resistance, higher waist-to-hip ratio, and elevated
triglycerides each associated with increased risk of lacunar infarct

COHORT STUDY: Stroke 2015 Nov;46(11):3131 | Full Text

Details
⚬ based on cohort study
 ⚬ 934 black patients aged 45-64 years from Atherosclerosis Risk in Communities Study (ARIC) who
had cerebral magnetic resonance imaging (MRI) were enrolled in Brain MRI Ancillary Study 10 years
later
⚬ 34.8% had metabolic syndrome
⚬ incident lacunar infarct (3-20 mm) occurred in 14.8% with metabolic syndrome vs. 8.5% without (p <
0.05)
⚬ increased risk of incident lacunar infarct associated with

– metabolic syndrome (adjusted odds ratio [OR] 1.98, 95% CI 1.28-3.05)

– higher insulin resistance score (adjusted OR 1.33 per 1-standard deviation increase, 95% CI 1.05-
1.68)
– increased waist-to-hip ratio (adjusted OR 1.3 per 1-standard deviation increase, 95% CI 1.03-
1.65)
– elevated triglycerides (adjusted OR 1.24 per 1-standard deviation increase, 95% CI 1.04-1.47)

⚬ patients with metabolic syndrome had increased prevalence of diabetes mellitus and coronary
heart disease
⚬ Reference - Stroke 2015 Nov;46(11):3131 full-text

STUDY
● SUMMARY
higher serum levels of fatty acids associated with increased risk of lacunar infarction

CASE-CONTROL STUDY: Stroke 2002 Aug;33(8):2086

Details
⚬ based on nested case-control study
⚬ 7,450 Japanese adults aged 40-85 years who participated in cardiovascular risk surveys from 1984
to 1989 or 1989 to 1992 had frozen serum samples analyzed
⚬ 197 incident strokes occurred through 1998 (lacunar stroke in 48.2%)
⚬ 197 patients with stroke were compared to 591 patients without stroke
⚬ 1 standard deviation-increase in saturated fatty acids (4% increase) associated with

– lacunar infarction (adjusted OR 1.44, 95% CI 1.03-2.01)

– ischemic stroke (adjusted OR 1.35, 95% CI 1.01-1.79)
– stroke of any type (adjusted OR 1.13, 95% CI 1.05-1.65)

⚬ Reference - Stroke 2002 Aug;33(8):2086

● see also Risk factors for stroke or transient ischemic attack

Possible risk factors

● elevated homocysteine 2

● male sex 3

STUDY
● SUMMARY
African-Americans appear to have increased risk of lacunar stroke compared to white persons

COHORT STUDY: Stroke 2006 Oct;37(10):2493

Details
⚬ based on prospective cohort study
 ⚬ 14,448 adults aged 45-64 years (between 1987 and 1989) were followed for mean 13.4 years

– 74.6% were non-Hispanic white Americans and 25.4% were African-Americans

– patients with history of stroke or transient ischemic attack were excluded

⚬ 531 incident ischemic strokes occurred

⚬ incidence per 1,000 person-years comparing non-Hispanic white Americans vs. African-Americans

– lacunar stroke 1.38 vs. 0.27

– nonlacunar stroke 2.41 vs. 1.44
– cardioembolic stroke 0.83 vs. 0.42

⚬ in multivariate analysis, African-American race associated with increased risk of lacunar stroke
(adjusted relative risk [RR] 2.98, 95% CI 1.87-4.76)
⚬ no signi cant di erences in nonlacunar or cardioembolic stroke in multivariate analysis
⚬ Reference - Stroke 2006 Oct;37(10):2493

● see also Risk factors for stroke or transient ischemic attack

Associated conditions

● cerebral ischemic changes, such as 1 , 2

⚬ white matter lesions

⚬ microinfarcts

Etiology and Pathogenesis

Causes

● age or vascular risk-factor-related small vessel disease (arteriolosclerosis), such as 1 , 2 , 3

⚬ lipohyalinosis
⚬ microatheroma
⚬ microaneurysms
⚬ segmental arterial disorganization
⚬ brinoid necrosis

● 10%-15% of acute lacunar infarcts reported to be caused by embolism 2

● proximal embolic source reported to be more common with basal ganglia lesions compared to

centrum semiovale lesions 2

● lacunar stroke caused by radiation-induced intracranial arteriopathy in case report (Eur J Neurol 2007
Aug;14(8):937 )

Pathogenesis

● exact mechanism unknown, however microatheroma thought to contribute to vessel wall changes

and damage 2

● lacunar lesions thought to result from 1 , 2 , 3

⚬ loss of smooth muscle cells, endothelial failure, lumen restriction, and vessel wall thickening due to
small vessel disease which causes chronic hypoperfusion of white matter and loss of
 autoregulation
⚬ acute, severe ischemia results in focal complete necrosis (pan-necrosis) in gray or white matter
(lacunar infarct)

● possible outcomes resulting from lacunar lesion, include 2

⚬ appearance of cavity, or lacunae, in deep gray structures or in white matter areas (usual outcome)
⚬ complete disappearance of lesion
⚬ existence of long-term lesion as noncavitated white matter hyperintensity

History and Physical

Clinical presentation

● clinical presentation may include any of the following 2

⚬ sudden-onset stroke symptoms or syndromes

⚬ mild neurological symptoms and signs
⚬ physical disabilities

● multiple lacunar strokes may cause

⚬ dementia
⚬ pseudobulbar a ect
⚬ cognitive de cits

● lacunar stroke presents di erently due to lesion location and size; "classical" presentations include 3

Table 1. Lacunar Syndromes

Syndrom A ected Areas Signs and Symptoms Lesion

e Location

Pure Face, leg, or arm on Complete or partial ⚬ Posterior

motor one side of the body palsy limb of
stroke internal
(Hemisen capsule
sory ⚬ Corona
syndrom radiata
e) ⚬ Mesencephal
on
⚬ Medulla
oblongata
Syndrom A ected Areas Signs and Symptoms Lesion
e Location

Pure ⚬ Face, limbs, scalp, ⚬ Numbness and/or ⚬ Thalamus

sensory neck, trunk, and paresthesia (such as ⚬ Sensory
stroke genitals burning, prickling, or pathways of
(complete) straining sensations) brainstem
⚬ Face, arm, ngers, ⚬ Sensory involvement ⚬ May extend
and leg with bisects body along a to internal
intraoral and median line capsule
perioral ⚬ Rare presentation
localization on one (Dejerine-Roussy
side only syndrome) includes
(incomplete) mild contralateral
⚬ Face, ngers, and hemiparesis, severe
foot (incomplete) hemianesthesia,
⚬ Shoulders, jaw, hemiataxia, tactile
and ngers or leg amnesia, and painful
(incomplete) hyperesthesia

Sensorim Entire side of body Hemiparesthesia with ⚬ Internal

otor (overall) or some of complete or partial capsule
stroke one side (partial) pyramidal syndrome (posterior or
anterior
limb)
⚬ Thalamus
⚬ Corona
radiata
 Syndrom A ected Areas Signs and Symptoms Lesion
e Location

Ataxic Predominantly ⚬ Hemiparesis or ⚬ Foot of pons

hemipare a ects leg corticospinal signs ⚬ Posterior
sis (sometimes arm) (weakness, arm of
ipsilateral to lesion hyperre exia, and/or internal
Babinski sign), capsule
nystagmus, and/or ⚬ Corona
dysarthria radiata
⚬ May be associated ⚬ Thalamus
with hemiataxia- ⚬ Cerebellum
hemihypoesthesia, ⚬ Frontal
painful ataxia, and cortex
hypoesthetic ataxic ⚬ Lenticular
hemiparesis nucleus

Dysarthri Face, hand ⚬ Moderate-to-severe ⚬ Foot of pons

a with dysarthria, central ⚬ Anterior arm
motor facial paresis, of internal
impedim Babinkski sign and capsule
ent of motor delay
hand ⚬ Abnormal weakness
("clumsy (hyposthenia) of the
hand hand, and
syndrom sometimes leg,
e") highly excitable
re exes on a ected
side, and/or
extended sole of foot
⚬ May initially involve
vomiting, disturbed
balance, and coma

References - Clin Exp Hypertens 2006 Apr-May;28(3-4):205 , Front Neurol Neurosci 2012;30:94
.

History

Chief concern (CC)

● most common presenting symptoms of ischemic stroke 3

⚬ hemiparesis
 ⚬ di culty with speech (dysarthria)

● other symptoms may include 3

⚬ burning, prickling, or straining sensations (paresthesia)

⚬ numbness of face, limbs, scalp, neck, trunk, and/or genitals
⚬ weakness of arm, leg, face, and/or hand
⚬ loss of sensation on one side (hemianesthesia)
⚬ ataxia or hemiataxia
⚬ tactile amnesia
⚬ excessive physical sensitivity, particularly of skin (hyperesthesia)
⚬ reduction of physical sensitivity on one side (hemihypoesthesia)
⚬ disturbed balance

History of present illness (HPI)

● time of symptom onset is important for administration of thrombolytic or endovascular therapy 4

⚬ time of stroke onset is when patients were at their previous baseline or symptom-free state
⚬ if patient cannot give this information, time of onset is when patient was last awake and symptom
free or known to be "normal"
⚬ if patient had neurological symptoms that resolved, time of symptom onset begins anew
⚬ eligibility criteria for thrombolytic or endovascular therapy include 5

– no intracerebral hemorrhage on imaging

– ability to treat within 4.5 hours of onset for thrombolytic (CSBPR Evidence Level A) and within 24
hours for endovascular therapy
⚬ see Thrombolytics for acute stroke and Endovascular therapy for acute stroke for additional
information

● if symptoms are transient, may be transient ischemic attack (TIA) rather than stroke

● ask about other history including 4

⚬ risk factors for arteriosclerosis and cardiac disease

⚬ history of

– drug use disorder

– migraine
– seizure
– infection
– trauma
– pregnancy

STUDY
● SUMMARY
history and physical suggests possible stroke

SYSTEMATIC REVIEW: JAMA 2005 May 18;293(19):2391

Details
⚬ based on systematic review of 14 studies using neuroimaging as reference standard with 5,484
patients
⚬ presence of acute facial paralysis, arm drift, or abnormal speech predicts stroke
 – positive likelihood ratio 5.5 if any of these 3 ndings
– negative likelihood ratio 0.39 if none of these 3 ndings

⚬ symptoms associated with vascular event (stroke or transient ischemic attack) are sudden change
in speech, visual loss, diplopia, numbness or tingling, paralysis or weakness, and nonorthostatic
dizziness
⚬ Reference - JAMA 2005 May 18;293(19):2391

STUDY
● SUMMARY
findings predictive of stroke

Stroke 2006 Mar;37(3):769

Details
⚬ based on 350 presentations by 336 patients with suspected stroke in urban teaching hospital
⚬ 69% episodes had nal diagnosis of stroke
⚬ factors predictive of stroke included

– exact time of onset

– de nite focal symptoms
– abnormal vascular ndings
– presence of neurological signs
– ability to lateralize signs to left or right side of brain
– ability to determine clinical stroke subclassi cation

⚬ ndings predictive of mimic (not stroke)

– cognitive impairment
– abnormal signs in other (nonneurologic) systems

⚬ Reference - Stroke 2006 Mar;37(3):769

Medication history

● ask about current use of antiplatelet agent or anticoagulation (including time of last dose of
anticoagulant) as may be contraindication to thrombolytic therapy

● ask about any other medication usage 5

● if suspected intracerebral hemorrhage, ask about anticoagulant therapy (CSBPR Evidence Level A) 5

Physical

General physical

● conduct clinical assessment immediately to establish diagnosis, rule out stroke mimics, determine
eligibility for thrombolytic or endovascular therapy, and develop plans for further care (CSBPR
Evidence Level B) 5

● initial assessment at emergency department should include 4 , 5

⚬ vital signs (CSBPR Evidence Level B)

– heart rate and rhythm

– blood pressure
– temperature
 – oxygen saturation
– hydration status

⚬ neurological examination to determine focal neurological de cits and assess severity (AHA/ASA
Class I, Level B; CSBPR Evidence Level B) - use standardized scale such as National Institutes of
Health Stroke Scale (NIHSS) or Canadian Neurological Scale (CNS)
– see DynaMed calculator for National Institutes of Health Stroke Scale (NIHSS)

⚬ assessment for presence of seizure activity (CSBPR Evidence Level B)

● assess for clinical signs of elevated intracranial pressure and, if present, suspect intracerebral

hemorrhage (CSBPR Evidence Level B) 5

⚬ clinical presentation of elevated intracranial pressure includes nausea and vomiting, altered level
of consciousness, and papilledema

● assess nutritional and hydration status as early as possible, ideally on same day as admission (CSBPR
Evidence Level B) (Int J Stroke 2016 Feb;11(2):239 )

STUDY
● SUMMARY
some bedside findings may help distinguish hemorrhagic from ischemic stroke, though
diagnostic certainty requires neuroimaging

SYSTEMATIC REVIEW: JAMA 2010 Jun 9;303(22):2280

Details
⚬ based on systematic review
⚬ systematic review of 19 prospective studies of accuracy of clinical exam compared with accepted
diagnostic standards (computed tomography [CT] or autopsy) for distinguishing hemorrhagic and
ischemic stroke in 6,438 adults
⚬ 24% had hemorrhagic stroke
⚬ ndings associated with probability of hemorrhagic stroke
– coma (likelihood ratio [LR] 6.2, 95% CI 3.2-12)
– neck sti ness (LR 5, 95% CI 1.9-12.8)
– seizures accompanying neurologic de cit (LR 4.7, 95% CI 1.6-14)
– diastolic blood pressure > 110 mm Hg (LR 4.3, 95% CI 1.4-14)
– vomiting (LR 3, 95% CI 1.7-5.5)
– headache (LR 2.9, 95% CI 1.7-4.8)
– Siriraj score > 1 (LR 5.7, 95% CI 4.4-7.4)

⚬ ndings associated with decreased probability of hemorrhagic stroke

– cervical bruit (LR 0.12, 95% CI 0.03-0.47)
– prior transient ischemic attack (TIA) (LR 0.34, 95% CI 0.18-0.65)
– Siriraj score < -1 (LR 0.29, 95% CI 0.23-0.37)

⚬ Reference - JAMA 2010 Jun 9;303(22):2280

STUDY
● SUMMARY
presence of pure motor syndrome might indicate lacunar infarct, however specificity too low for
diagnosis without imaging DynaMed Level 2

DIAGNOSTIC COHORT STUDY: J Stroke Cerebrovasc Dis 2014 Sep;23(8):2085

 Details
⚬ based on diagnostic cohort study without blinding of reference standard
⚬ 86 patients (mean age 69 years) with acute lacunar syndrome who were admitted to stroke unit
were evaluated for lacunar infarct with CT plus di usion-weighted imaging (DWI) (reference
standard) within 1 week of presentation
– 59.3% had pure motor syndrome, 31.4% had sensorimotor syndrome, 5.8% had pure sensory
syndrome, 2.3% had dysarthria-clumsy hand syndrome, and 1.2% had ataxic hemiparesis
– exclusion criteria were TIA and intracerebral hemorrhage

⚬ acute ischemic lesions were de ned as lacunar infarcts if < 15 mm and located subcortically or in
the brainstem
⚬ 65.1% had lacunar infarct on magnetic resonance imaging (MRI)
⚬ for diagnosis of lacunar infarct

– pure motor syndrome had

● sensitivity 68%
● speci city 57%
● positive predictive value 75%
● negative predictive value 49%

– sensorimotor syndrome had

● sensitivity 23%
● speci city 53%
● positive predictive value 48%
● negative predictive value 27%

⚬ analyses were not performed to assess diagnostic accuracy of pure sensory syndrome, dysarthria-
clumsy hand syndrome, or ataxic hemiparesis due small sample sizes
⚬ Reference - J Stroke Cerebrovasc Dis 2014 Sep;23(8):2085

Skin

● skin may show evidence predisposing to stroke, such as 4

⚬ purpura (may suggest coagulopathy)

⚬ petechia (may suggest platelet disorders)
⚬ signs of trauma
⚬ embolic lesions

– Janeway lesions - macular, blanching, painless, violaceous lesions on palms and soles
– Osler nodes - painful, violaceous nodules on pulp of ngers and toes

HEENT

● assess for 3

⚬ facial paresis
⚬ nystagmus
⚬ diplopia
⚬ anisocoria (unequal pupil size) (Acta Neurol Scand Suppl 2013;(196):52 )

● look for signs of trauma or seizure activity, such as contusions or tongue lacerations 4

Cardiac
● identify possible comorbidities, such as 4

⚬ hypertension
⚬ heart disease
⚬ arrhythmia (particularly, atrial brillation or utter)

Extremities

● assess for 3 , 4

⚬ weakness of arm, leg, and hand

⚬ numbness
⚬ burning, prickling, or straining sensations (paresthesia)
⚬ hyperre exia and/or Babinkski sign
⚬ loss of sensation on one side (hemianesthesia)
⚬ excessive physical sensitivity, particularly of skin (hyperesthesia)
⚬ reduction of physical sensitivity on one side (hemihypoesthesia)
⚬ evidence of distal emboli in extremities, such as Osler nodes

Neuro

● most common physical ndings include 3

⚬ hemiparesis or ataxia
⚬ speech disturbance (dysphasia or dysarthria)
⚬ focal weakness of arm, leg, face, and/or hand
⚬ focal numbness of face, limbs, scalp, neck, trunk, and/or genitals
⚬ burning, prickling, or straining sensations (paresthesia)
⚬ loss of sensation on one side (hemianesthesia)
⚬ ataxia or hemiataxia
⚬ excessive physical sensitivity, particularly of skin (hyperesthesia)
⚬ reduction of physical sensitivity on one side (hemihypoesthesia)
⚬ tactile amnesia
⚬ disturbed balance

● common clinical manifestations of stroke not found in lacunar stroke include 3

⚬ aphasia
⚬ apraxia
⚬ agnosia
⚬ memory disturbance
⚬ neglect phenomenon (patient neglecting sensations or objects contralateral to stroke side)
⚬ visual de cits
⚬ deterioration of higher function
⚬ loss of consciousness
⚬ convulsions

● neurologic exam should use formal stroke scale (AHA/ASA Class I, Level B-NR; CSBPR Evidence Level B)
to determine focal neurological de cits and for diagnostic and prognostic classi cation of stroke
severity 4 , 5 , 6
⚬ see DynaMed calculator for National Institutes of Health Stroke Scale (NIHSS)
⚬ Canadian Neurological Scale (CNS) is also an option
Diagnosis

Making the diagnosis

● lacunar stroke diagnosis should be based on

⚬ clinical presentation

– common manifestations of acute neurologic dysfunction include di culty with speech

(dysarthria or aphasia) or hemiparesis 3
– other symptoms may include numbness of face, limbs, scalp, neck, trunk, and/or genitals, and

weakness of arm, leg, face, and/or hand 3

⚬ neuroimaging

– used to con rm presence of lacunar infarct/cause of stroke

– magnetic resonance imaging (MRI) of head, with or without contrast, including di usion-
weighted imaging (DWI) is most appropriate imaging technique (AAN Level A; AHA/ASA Class I,
Level A; EFNS Level A, Class I)

● National Institutes of Health Stroke Scale (NIHSS) may help with diagnostic and prognostic

classi cation of stroke severity (AHA/ASA Class I, Level B) 4

● see DynaMed calculator for National Institutes of Health Stroke Scale (NIHSS)

Differential diagnosis

● stroke mimics may include 4

⚬ complicated or basilar-type migraine

⚬ seizure or postictal state (Todd paralysis)
⚬ brain tumor
⚬ toxic-metabolic disturbances (hypoglycemia most common)
⚬ systemic infection (including meningitis and encephalitis)
⚬ syncope, presyncope, or hypotension
⚬ acute confusional state
⚬ dizziness

– isolated symptom of dizziness not usually stroke

– vertigo from stroke usually associated with nystagmus or other cerebellar or brainstem signs

⚬ functional or medically unexplained physical symptoms

⚬ dementia

● di erential diagnosis also includes

⚬ hypertensive encephalopathy 4

⚬ transient ischemic attack (TIA)

⚬ diseases associated with increased blood-brain barrier permeability, including 1 , 2

– Alzheimer dementia
– multiple sclerosis
– sporadic and hereditary amyloid angiopathy

⚬ venous collagenosis 1

⚬ genetic or inherited small vessel diseases (SVDs) distinct from cerebral amyloid angiopathy, such

as 1
 – Fabry disease
– cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
(CADASIL)
– mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome)
– hereditary endotheliopathy with retinopathy, nephropathy, and stroke
– hereditary cerebroretinal vasculopathy
– hereditary multi-infarct dementia of the Swedish type
– SVDs caused by COL4A1 mutations

⚬ in ammatory and immunologically mediated SVDs, such as 1

– granulomatosis with polyangiitis

– Churg-Strauss syndrome
– microscopic polyangiitis
– Henoch-Schonlein purpura
– cryoglobulinemic vasculitis
– cutaneous leukocytoclastic angiitis
– primary angiitis of central nervous system (CNS)
– Sneddon syndrome
– nervous system vasculitis secondary to infections
– nervous system vasculitis associated with connective tissue disorders, such as

● systemic lupus erythematosus (SLE)

● Sjogren syndrome
● rheumatoid vasculitis
● scleroderma
● dermatomyositis

⚬ other SVDs, such as 1

– postradiation angiopathy
– nonamyloid microvessel degeneration in Alzheimer disease

Testing overview

● see Testing overview in Stroke (acute management) for details on tests to be performed immediately
in all suspected acute stroke patients

● in patients with suspected lacunar stroke

⚬ perform neuroimaging

– most appropriate imaging technique is magnetic resonance imaging (MRI) of head, with or
without contrast, including di usion-weighted imaging (DWI) (AAN Level A; AHA/ASA Class I,
Level A; EFNS Level A, Class I)
● MRI displays ≥ 70% of recent lacunar infarcts and should be used for diagnosis of lacunar
stroke
● MRI may be more sensitive than computed tomography (CT) for ischemic stroke
DynaMed Level 2 , but CT adequate for emergency management decisions in most cases

● MRI may have low speci city; about one-third of asymptomatic elderly have infarct-like
lesions on MRI
– Canadian guidelines recommend all patients with suspected acute stroke within acute stroke
treatment time windows must have immediate noncontrast CT brain imaging, and vascular
imaging with CTA including extracranial and intracranial arteries to guide hyperacute care
(CSBPR Evidence Level A)
 ● CT scan and clinical presentation are not reliable for di erentiation between lacunar and
nonlacunar stroke
● noncontrast CT may detect lacunar infarct but sensitivity too low to rule out lacunar infarct
as cause of stroke even with additional CT angiography and CT perfusion imaging
DynaMed Level 2

– other vascular imaging may include computed tomographic angiography (CTA), magnetic
resonance angiography (MRA), carotid ultrasound, or transcranial Doppler (EFNS Level B, Class
II)
⚬ electrocardiogram (ECG) - baseline ECG recommended, but should not delay IV tissue plasminogen

activator (t-PA) (AHA/ASA Class I, Level B) 4

Clinical prediction rules

● emergency medical services personnel should use standardized acute stroke out-of-hospital

screening tool such as (AHA/ASA Class I, Level B; CSBPR Evidence Level B) 4 , 5

⚬ Los Angeles Prehospital Stroke Screen PDF (LAPSS)
⚬ Cincinnati Prehospital Stroke Scale PDF (CPSS)
⚬ if positive

– direct all actions toward moving to ambulance and beginning transport

– any treatments not immediately required, such as IVs, should be performed en route to hospital

● see Stroke (acute management) for additional information on prediction rules

⚬ prehospital prediction
⚬ emergency department prediction
⚬ predicting ischemic vs. hemorrhagic stroke

Blood tests

● blood glucose measurement is the only assessment required to precede IV alteplase initiation in all

patients (AHA/ASA Class I, Level B-R) 6

● order blood work for (CSBPR Evidence Level B) 5

⚬ electrolytes
⚬ glucose
⚬ hematology/complete blood count (CBC)
⚬ coagulation (INR/activated partial thromboplastin time [aPTT])
⚬ renal function (creatinine level/estimated glomerular ltration rate [GFR])
⚬ troponin

● in selected patients, consider 4

⚬ pregnancy test
⚬ hepatic function tests
⚬ thrombin time and/or ecarin clotting time, factor Xa activity assays (if patient taking direct
thrombin inhibitor or direct factor Xa inhibitor)
⚬ toxicology screen
⚬ blood alcohol level
⚬ arterial blood gas (if hypoxemia suspected)
● see Blood tests in Stroke (acute management) for additional information

Imaging studies

● neuroimaging needed for determining eligibility for thrombolytic therapy (tissue-type plasminogen
activator [t-PA])
⚬ computed tomography (CT) or magnetic resonance imaging (MRI) needed to rule out intracerebral
hemorrhage which is absolute contraindication to t-PA (AHA/ASA Class I, Level A)
⚬ frank hypodensity on CT (or hyperintensity on MRI) of > one-third of middle cerebral artery
territory is contraindication to t-PA (AHA/ASA Class I, Level A)
⚬ early ischemic changes (other than frank hypodensity) in > one-third of middle cerebral artery
territory may be associated with increased mortality with t-PA DynaMed Level 2 but evidence
inconsistent and early ischemic changes no longer considered contraindication to t-PA (AHA/ASA
Class I, Level A; EFNS GCPP, Class IV)

● vascular imaging

⚬ noninvasive intracranial vascular study is strongly recommended during initial imaging evaluation
of acute stroke patient if mechanical thrombectomy is considered for management but should not
delay IV brinolysis if indicated (AHA/ASA Class I, Level A)
⚬ Canadian guidelines recommend vascular imaging with CT angiography (CTA) (including
extracranial and intracranial arteries) along with noncontrast brain CT for all patients with
suspected acute stroke (CSBPR Evidence Level A)

● most appropriate imaging studies for evaluating focal neurologic de cits or suspected stroke are

⚬ magnetic resonance imaging (MRI) of head without contrast, or MRI with and without contrast,
including di usion-weighted imaging (DWI) (AAN Level A; AHA/ASA Class I, Level A; EFNS Level A,
Class I)
– MRI displays ≥ 70% of recent lacunar infarcts and should be used for diagnosis of lacunar stroke
– MRI may be more sensitive than CT for ischemic stroke DynaMed Level 2 , but CT adequate for
emergency management decisions in most cases
– MRI may have low speci city; about one-third asymptomatic elderly have infarct-like lesions on
MRI
⚬ computed tomography (CT) of head without contrast (AHA/ASA Class I, Level A; EFNS Level B, Class
II; CSBPR Evidence Level B), is test of choice for subarachnoid hemorrhage (EFNS Level A, Class I)

● beyond the acute stroke treatment time window, transcranial Doppler (TCD) useful for diagnosis of
intracranial stenosis or occlusion (EFNS Level B, Class II)

● see Neuroimaging for acute stroke for details

● MRI displays interrelated features of small vessel disease (SVD) 1 , 2 , 3 , 4

⚬ standard MRI sequences (T1-weighted, T2-weighted, and uid-attenuated inversion recovery

[FLAIR])
– diagnostic ability is superior to CT but less sensitive than advanced MRI for acute infarct
– acute lacunar infarct appears as

● reduced signal on T1-weighted MRI

● increased signal on T2- weighted imaging
● increased signal on FLAIR
features that may be identi ed by standard MRI include
 – ● acute lacunar (or small subcortical) infarcts or hemorrhages
● lacunes (or uid- lled cavities) thought to represent old infarcts, including clinically silent
ones
● white matter hyperintensities (or small deep gray matter hyperintensities, mostly clinically
silent) - more common and extensive in acute lacunar stroke than in other stroke subtypes
● visible perivascular spaces, which suggest active in ammation in increased numbers
● microbleeds
● brain atrophy

⚬ advanced MRI sequence (DWI)

– DWI is most helpful imaging technique for diagnosis of acute lacunar infarct
– acute lacunar infarct appears as increased signal on di usion-weighted imaging
– features of advanced MRI may include

● microinfarcts
● altered white matter integrity
● disrupted axonal connections
● increased brain water content
● altered myelination
● secondary focal thinning of cortical gray matter

– 28%-94% of acute lacunar infarcts con rmed by di usion-weighted MRI progress to lacunes
(depending on de nition of cavitation), but not all lesions cavitate
● some lesions ultimately disappear (even large acute lacunar infarcts)
● some lesions remain long-term as noncavitated white matter hyperintensities

⚬ presence of white matter hyperintensities and lacunes, thought to be more likely if lacunar stroke
is caused by lipohyalinosis or arteriolosclerosis
⚬ perfusion abnormality more often associated with lacunar stroke caused by proximal perforating
arteriolar atheroma

● CT can be used to identify infarcts, however CT has lower accuracy than MRI and thus is not a reliable

imaging modality for di erentiation between lacunar and nonlacunar stroke 2

⚬ CT has been shown to display around 50% of recent lacunar infarcts
⚬ infarcts appear as areas of low attenuation

STUDY
⚬ SUMMARY
noncontrast CT may detect lacunar infarct but sensitivity too low to rule out lacunar infarct
as cause of stroke even with additional CT angiography and CT perfusion imaging
DynaMed Level 2

DIAGNOSTIC COHORT STUDY: AJNR Am J Neuroradiol 2015 Jun;36(6):1069 | Full Text

Details
– based on retrospective diagnostic cohort study without clear blinding of reference standard
results
– 88 patients (median age 73 years) with stroke and classic lacunar syndrome who presented to
stroke center ≤ 4.5 hours from symptom onset had CT scans at admission and follow-up MRI
● all patients had noncontrast CT (NCCT), CTA, and CT perfusion (CTP) performed
● images were reviewed incrementally in 3 sessions (NCCT only, NCCT/CTA, and
NCCT/CTA/CTP) by 2 readers blinded to clinical information but aware of study nature
 – diagnostic con dence was assessed on 6-point scale with 1 point de ning "de nitely present"
and 6 points de ning "de nitely absent" lacunar infarct
– lacunar infarction identi ed in 67% using di usion-weighted MRI/apparent di usion coe cient
(ADC) (reference standard)
– for detection of lacunar infarct

● CT imaging (with con dence cuto 2 points)

⚬ NCCT plus CTA plus CTP had sensitivity 42.4% and speci city 91.9%
⚬ NCCT plus CTA had sensitivity 26.3% and speci city 95.3%
⚬ NCCT only had sensitivity 9.3% and speci city 91.9%

● CT imaging (with con dence cuto 5 points)

⚬ NCCT plus CTA plus CTP had sensitivity 55.9% and speci city 83.3%
⚬ NCCT plus CTA had sensitivity 51.7% and speci city 78.2%
⚬ NCCT only had sensitivity 40.7% and speci city 70.5%

– Reference - AJNR Am J Neuroradiol 2015 Jun;36(6):1069 full-text

–
DynaMed Commentary

CTP and magnetic resonance perfusion are now considered the standard of care for the
selection of patients for endovascular thrombectomy from 6 to 24 hours after the time of
the last known normal (see DAWN and DEFUSE 3 trials in Endovascular therapy for acute
stroke for more details).

● usefulness of chest x-rays in hyperacute stroke setting (in absence of evidence of acute pulmonary,
cardiac, or pulmonary vascular disease) is unclear; if obtaining x-ray do not unnecessarily delay
administration of IV alteplase (AHA/ASA Class IIb, Level B-NR) 6

Electrocardiography (ECG)

● obtain electrocardiogram, but if hemodynamically stable, defer until after determination of acute
therapy including assessment for thrombolytic or endovascular therapy (AHA/ASA Class I, Level B;
CSBPR Evidence Level B) 4 , 5

● baseline ECG assessment recommended in patients presenting with acute ischemic stroke, but do not

delay initiation of IV alteplase (AHA/ASA Class I, Level B-NR) 6

⚬ if ischemic stroke or transient ischemic attack, also assess (with additional ECG after initial
assessment if appropriate), baseline cardiac rhythm or evidence of structural heart disease such as
previous myocardial infarction or left ventricular hypertrophy (CSBPR Evidence Level C)

● monitor cardiac rhythm for at least rst 24 hours to screen for arrhythmias (AHA/ASA Class I, Level

B) 4

● consider recommending prolonged cardiac monitoring to assess for paroxysmal atrial brillation if
cardioembolic mechanism suspected and no evidence of atrial brillation on 24-48 hour ECG
monitoring 5

● see Electrocardiography (ECG) in Stroke (acute management) for additional information

Cerebrospinal fluid (CSF) analysis

● most patients with stroke do not need examination of CSF 4

● if new, severe acute headache that raises suspicion of subarachnoid hemorrhage (SAH) 5

⚬ lumbar puncture for CSF analysis not necessary if normal imaging as assessed by neuroradiologist
with third-generation or higher computed tomography (CT) scan within 6 hours of headache
(CSBPR Evidence Level B)
⚬ lumbar puncture for CSF analysis should be performed if high clinical suspicion of SAH and

– neuroradiologist not available to interpret third-generation or higher CT scan (CSBPR Evidence

Level C)
– CT scan not interpreted by experienced radiologist
– normal reading on second- or lower-generation CT scan
– CT scan performed ≥ 6 hours after headache onset
– patient has altered consciousness

⚬ if ≥ 12 hours after headache onset, xanthochromia evaluation may be more sensitive than other
analyses (CSBPR Evidence Level B)

● also examine CSF if strong suspicion for acute central nervous system infection 4

Other diagnostic testing

● all patients with stroke should have swallowing evaluated before initiating any oral intake to reduce
risk of aspiration and pneumonia (AHA/ASA Class I, Level B; CSBPR Evidence Level B; SIGN Grade C)

● see Swallowing dysfunction after stroke for details

Management

Management overview

● treatment regimen speci c to lacunar stroke (due to small vessel disease [SVD]) is not currently

available 1

● patients should be admitted to a stroke unit and treated according to current stroke guidelines 1

● see Stroke (acute management)

● presence of SVD should be taken into account during treatment, speci cally with regard to 1

⚬ thrombolytic therapy

– follow standard protocol for acute thrombolytic therapy - see Thrombolytics for acute stroke
– thrombolytic therapy appears to improve stroke symptoms but also increases risk of
asymptomatic hemorrhage in patients with acute lacunar stroke DynaMed Level 2

– presence of leukoaraiosis prior to treatment with thrombolytics may increase risk of

symptomatic intracerebral hemorrhage and poor functional outcome in patients with acute
ischemic stroke DynaMed Level 2

⚬ antiplatelet therapy
 – antiplatelet monotherapy may reduce risk of recurrent stroke in patients with lacunar stroke
DynaMed Level 2

– addition of clopidogrel to aspirin does not decrease stroke recurrence and increases mortality
and hemorrhage in patients with symptomatic lacunar infarct DynaMed Level 1

– elevated high-sensitivity C-reactive protein associated with increased risk of recurrent ischemic
stroke in patients with previous lacunar stroke receiving antiplatelet therapy DynaMed Level 2

⚬ anticoagulation

– anticoagulants have higher risk of death and symptomatic intracranial hemorrhage than
antiplatelet agents in acute ischemic stroke DynaMed Level 1

– though SVD is not an absolute contraindication to anticoagulant use, lower doses should be
used when possible as SVD increases risk of bleeding

● see Treatment in Stroke (acute management) for details

Diet

● avoid any oral intake until after swallowing screen (CSBPR Evidence Level B) 5

● swallowing function

⚬ impaired swallowing common after stroke (especially brainstem stroke) and can result in poor
nutrition and dehydration
⚬ all patients with stroke should have swallowing evaluated before initiating any oral intake to
reduce risk of aspiration and pneumonia (AHA/ASA Class I, Level B; CSBPR Evidence Level B; SIGN
Grade C)
⚬ patients who cannot take food and uids orally should receive nasogastric, nasoduodenal, or
percutaneous endoscopic gastrostomy (PEG) feedings to maintain hydration and nutrition while
having e orts to restore swallowing (AHA/ASA Class I, Level B); reasonable to prefer nasogastric
tube feeding over PEG tube feeding until 2-3 weeks after stroke onset (AHA/ASA Class IIa, Level B)
⚬ for patients with dysphagia, it is reasonable to initially use nasogastric feeding tubes in early phase
of stroke (starting within rst 7 days) and to place percutaneous gastronomy tubes in patients with
longer anticipated inability to swallow safely (> 2-3 weeks) (AHA/ASA Class IIa, Level C-EO)
⚬ insu cient evidence to assess therapies (including PEG feedings) for dysphagia on reduction of risk
of pneumonia or death in patients with acute stroke; aspiration pneumonia may be common
complication in patients with percutaneous endoscopic gastrostomy tube after stroke
⚬ see Swallowing dysfunction after stroke for details

● nutritional supplements not routinely needed (AHA/ASA Class III, Level B) 4

● see Diet in Stroke (acute management) for details

Activity

● early mobilization recommended for less severely a ected patients (AHA/ASA Class I, Level C) to

reduce risk for pneumonia, deep vein thrombosis, pulmonary embolism, and pressure ulcers 4

● mobilization should be started 24-48 hours after stroke onset if no contraindications (CSBPR Evidence
Level B)
⚬ contraindications include

– arterial puncture
 – unstable medical condition
– low oxygen saturation
– lower limb injury

⚬ mobilization within 24 hours of stroke onset may be reasonable for some patients; use clinical
judgement (CSBPR Evidence Level C)
⚬ Reference - Int J Stroke 2016 Feb;11(2):239

● see Activity in Stroke (acute management) for details

Medications

● treatment should be according to current stroke guidelines, however medication regimen should take
into account presence of small vessel disease (SVD), speci cally with regard to use of thrombolytics,
antiplatelet therapy, and anticoagulants 1

● See Stroke (acute management) for details on treatment with

⚬ thrombolytics
⚬ antiplatelet therapy
⚬ antihypertensives
⚬ anticoagulants
⚬ statins
⚬ oxygen
⚬ antipyretics
⚬ antibiotics
⚬ insulin
⚬ anticonvulsants

● thrombolytic therapy

STUDY
⚬ SUMMARY
thrombolytic therapy given ≤ 4.5 hours after onset of stroke appears to improve neurological
outcomes with acute lacunar stroke DynaMed Level 2

COHORT STUDY: J Neurol 2014 Feb;261(2):405

Details
– based on cohort study
– 537 patients with acute lacunar stroke from 2004 to 2011 who had thrombolytic therapy or
standard care were analyzed
● 12.8% had thrombolytic therapy (recombinant tissue plasminogen activator [rt-PA])
● rt-PA was given ≤ 4.5 hours after onset

– severity of stroke was assessed with National Institutes of Health Stroke Scale (NIHSS)
– clinical lacunar syndrome at baseline in 73.9% with thrombolytic therapy vs. 88% with standard
care (p = 0.003)
– comparing thrombolytic therapy vs. standard care

● clinical improvement (≥ 4 points on NIHSS) in 31.9% vs. 7.7% (p < 0.001, NNT 5)
● median initial NIHSS score 5 points vs. 3 points (p < 0.001)
● asymptomatic hemorrhagic transformation in 11.6% vs. 1.9% (p = 0.001, NNH 10)

– no signi cant di erences in overall complications or functional de cit at 3 months

 – Reference - J Neurol 2014 Feb;261(2):405

STUDY
⚬ SUMMARY
leukoaraiosis prior to treatment with thrombolytics may increase risk of symptomatic
intracerebral hemorrhage and poor functional outcome in patients with acute ischemic stroke

SYSTEMATIC REVIEW: Neurology 2017 Feb 14;88(7):638 | Full Text

Details
– based on systematic review of retrospective cohort studies
– systematic review of 15 retrospective cohort studies evaluating thrombolysis (IV or intra-arterial)
in 6,967 patients with acute ischemic stroke
● thrombolysis included IV recombinant tissue plasminogen activator (IV rt-PA) in 13 studies,
intra-arterial rt-PA or urokinase in 4 studies, endovascular treatment in 2 studies, and
mechanical thrombectomy in 2 studies
● all patients had pretreatment imaging available (computed tomography [CT] in 10 studies
and magnetic resonance imaging [MRI] in 6 studies)
– leukoaraiosis present on imaging was rated according to severity using

● Fazekas and Schmidt scale

● van Swieten scale

– mean symptomatic intracerebral hemorrhage rate ranged from 10.2% in patients with
moderate-to-severe leukoaraiosis to 4% for patients with mild-to-no leukoaraiosis
– increased risk of symptomatic intracerebral hemorrhage following thrombolysis associated with

● any leukoaraiosis (relative risk [RR] 1.65, 95% CI 1.26-2.16) in analysis of 10 studies with 5,551
patients
● moderate-to-severe leukoaraiosis (RR 2.4, 95% CI 1.83-3.14) in analysis of 8 studies with 4,192
patients
– poor functional outcome (modi ed Rankin Scale [mRS] score ≥ 2 at 3 months) following
thrombolysis associated with
● any leukoaraiosis (RR 1.3, 95% CI 1.19-1.42) in analysis of 8 studies with 3,401 patients
● moderate-to-severe leukoaraiosis (RR 1.31, 95% CI 1.22-1.42) in analysis of 6 studies with
3,659 patients
– Reference - Neurology 2017 Feb 14;88(7):638 full-text
– see Thrombolytics for acute stroke for details

● antiplatelet therapy

⚬ oral administration of aspirin (initial dose 325 mg) 24-48 hours after stroke onset is recommended

for most patients (AHA/ASA Class I, Level A) 4

STUDY
⚬ SUMMARY
anticoagulants have higher risk of death and symptomatic intracranial hemorrhage than
antiplatelet agents in acute ischemic stroke DynaMed Level 1

COCHRANE REVIEW: Cochrane Database Syst Rev 2002;(4):CD003242

Details
– based on Cochrane review
 – systematic review of 4 randomized trials comparing anticoagulants (unfractionated heparin
[UFH] or low-molecular-weight heparin) vs. antiplatelet agents (aspirin) in 16,558 patients with
acute ischemic stroke
– no signi cant di erences in death or dependency (odds ratio 1.07, 95% CI 0.98-1.15)
– harms with anticoagulants include increased risk for death (NNH 50, 95% CI 33-in nity) and
symptomatic intracranial hemorrhage
– bene t limited to reduced symptomatic deep venous thrombosis at 14 days (NNT 100, 95% CI
33-in nity)
– subgroup analysis suggested addition of low-dose UFH to aspirin was associated with

● marginally signi cant reduction in any recurrent stroke (odds ratio 0.75, 95% CI 0.56-1.03)
● marginally signi cant reduction in death at 14 days (odds ratio 0.84, 95% CI 0.69-1.01) but not
signi cant at end of follow-up
– Reference - Cochrane Database Syst Rev 2002;(4):CD003242 , commentary can be found in
ACP J Club 2003 Jul-Aug;139(1):5 , Cochrane for Clinicians summary can be found in Am Fam
Physician 2003 Oct 1;68(7):1307 full-text
– See Anticoagulation therapy for acute stroke for details

STUDY
⚬ SUMMARY
antiplatelet monotherapy may reduce risk of recurrent stroke in patients with lacunar stroke
DynaMed Level 2

SYSTEMATIC REVIEW: Stroke 2015 Apr;46(4):1014

Details
– based on systematic review limited by clinical heterogeneity
– systematic review of 17 randomized trials evaluating antiplatelet therapy for secondary stroke
prevention in 42,234 patients with lacunar stroke
– heterogeneity in antiplatelet therapies limited overall analysis
– follow-up ranged from 1 month to 3.5 years
– comparing antiplatelet monotherapy (ticlopidine, aspirin, dipyridamole, cilostazol) to placebo

● antiplatelet monotherapy associated with

⚬ reduction in any stroke in analysis of 2 trials with 2,215 patients

– risk ratio (RR) 0.77 (95% CI 0.62-0.97)

– NNT 18-223 with any stroke in 15% of placebo group

⚬ reduction in ischemic stroke in analysis of 2 trials with 858 patients

– RR 0.48 (95% CI 0.3-0.78)

– NNT 13-42 with ischemic stroke in 11% of placebo group

● no signi cant di erences in composite outcome of any stroke, myocardial infarction, and
death in analysis of 2 trials with 8,204 patients
– comparative e cacy evaluated only in single trials
● signi cant reduction in any stroke reported only for

⚬ cilostazol vs. aspirin (stroke in 6.8% vs. 9.7%, p = 0.03, NNT 35) in 1 trial with 1,743 patients
⚬ addition of dipyridamole to aspirin (stroke in 7.9% vs. 11.5% with aspirin alone, p = 0.03,
NNT 28) in 1 trial with 3,020 patients
● no signi cant di erence in any stroke comparing

⚬ dipyridamole vs. aspirin in 1 trial with 1,260 patients

 ⚬ dipyridamole plus aspirin vs. clopidogrel in 1 trial with 10,578 patients
⚬ clopidogrel plus aspirin vs. aspirin alone in 1 trial with 3,020 patients (summarized below)
⚬ cilostazol plus aspirin vs. aspirin alone in 1 trial with 203 patients
⚬ ticlopidine vs. aspirin in 1 trial with 1,221 patients

– Reference - Stroke 2015 Apr;46(4):1014 , commentary can be found in Ann Intern Med 2015
Aug 18;163(4):JC6

STUDY
⚬ SUMMARY
addition of clopidogrel to aspirin does not decrease stroke recurrence and increases mortality
and hemorrhage in patients with symptomatic lacunar infarct DynaMed Level 1

RANDOMIZED TRIAL: N Engl J Med 2012 Aug 30;367(9):817 | Full Text

Details
– based on randomized trial
– 3,020 patients (mean age 63 years) with recent symptomatic lacunar infarct randomized to
clopidogrel hydrogen sulfate 75 mg/day vs. placebo and followed for mean 3.4 years
– all patients received aspirin 325 mg/day
– trial terminated after second planned interim analysis following prespeci ed stopping rule due
to futility and evidence of harm (increased mortality with dual antiplatelet therapy)
– 16% did not complete trial, all patients included in analyses
– comparing clopidogrel vs. placebo

● ischemic stroke in 2% per year vs. 2.4% per year (not signi cant)
● intracranial hemorrhage in 0.42% per year vs. 0.25% per year (not signi cant)
● disabling or fatal stroke in 0.84% per year vs. 0.78% per year (not signi cant)
● all-cause mortality 2.1% per year vs. 1.4% per year (p = 0.004, NNH 143/year)
● major hemorrhage in 2.1% per year vs. 1.1% per year (p < 0.001, NNH 100/year)

– 71% of 187 classi able recurrent ischemic strokes were lacunar strokes
– Reference - SPS3 trial (N Engl J Med 2012 Aug 30;367(9):817 full-text ), commentary can be
found in Ann Intern Med 2012 Dec 18;157(12):JC6
– addition of clopidogrel to aspirin for symptomatic lacunar infarct associated with
increased mortality in patients with ischemic heart disease or
normotension/prehypertension
DynaMed Level 2

● based on secondary analysis of SPS3 trial

● all patients were included in analyses
● 80% had hypertension, 37% had diabetes mellitus, and 10% had ischemic heart disease at
baseline
● comparing clopidogrel plus aspirin to aspirin alone

⚬ clopidogrel plus aspirin associated with increased mortality in patients with

– ischemic heart disease (adjusted hazard ratio [HR] 2.7, 95% CI 1.8-4.1)
– normotension/prehypertension (adjusted HR 2.5, 95% CI 1.5-4)

⚬ no signi cant di erence in mortality in patients with hypertension

● baseline factors associated with signi cantly increased mortality regardless of antiplatelet
therapy included diabetes mellitus, decreased body mass index, history of hypertension,
 increased systolic blood pressure (SBP), older age, hemoglobin < 13 g/dL (2.017 mmol/L), and
decreased glomerular ltration rate
● nonfatal major hemorrhage during trial associated with increased mortality regardless of
antiplatelet therapy (adjusted HR 4.5, 95% CI 3.1-6.6)
● Reference - Stroke 2014 Oct;45(10):2989

⚬ American Geriatrics Society (AGS) Beers Criteria recommends (in patients ≥ 65 years old) avoiding
ticlopidine due to availability of safer and e ective alternatives (AGS Strong recommendation,
Moderate quality evidence) (J Am Geriatr Soc 2015 Nov;63(11):2227 ), commentary can be found
in J Am Geriatr Soc 2016 Apr;64(4):920

STUDY
● SUMMARY
B vitamin supplementation might slow progression of white matter hyperintensities (WMH) in
patients with recent stroke or transient ischemic attack (TIA) and evidence of severe cerebral
small vessel disease DynaMed Level 3

Stroke 2012 Dec;43(12):3266

Details
⚬ based on nonclinical outcome from post hoc subgroup analysis of VITATOPS trial
⚬ 359 patients (mean age 64 years) who were randomized to B vitamins (2 mg folic acid, 25 mg
vitamin B6, and 0.5 mg vitamin B12) vs. placebo after stroke or TIA were analyzed after 2 years
– 77.5% had ischemic stroke, 2% had hemorrhagic stroke, and 20.5% had TIA
– all patients included in analysis had MRI performed at baseline and at 2-year follow-up

⚬ images were evaluated for WMHs and rated (0 = absent, 1 = punctate, 2 = early con uent, and 3 =
con uent)
⚬ at baseline, 100 patients (27.9%) had severe cerebral small vessel disease (de ned as deep WMH
score ≥ 2 and with lacunes)
⚬ comparing B vitamins vs. placebo at 2 years among patients with severe cerebral vessel disease

– median WMH volume increase 0.3 cm3 vs. 1.7 cm3 (p = 0.039)

– incident lacunes in 16.6% vs. 10.8% (not signi cant)

⚬ no signi cant di erences in WMH volume change or incidence of lacunes in analysis of patients
without severe cerebral vessel disease
⚬ Reference - Stroke 2012 Dec;43(12):3266

Surgery and procedures

STUDY
● SUMMARY
carotid endarterectomy may reduce risk of additional stroke in patients with lacunar stroke

SYSTEMATIC REVIEW: QJM 2002 May;95(5):313

Details
⚬ based on systematic review without assessment of trial quality
⚬ systematic review identi ed 5 trials in which carotid endarterectomy was used in treatment of
stroke
⚬ subgroup analysis identi ed 1 trial (NASCET) with enough patients treated for lacunar stroke to
perform subgroup analysis, but outcome had borderline statistical signi cance
 ⚬ in NASCET trial

– 2,226 patients with moderate carotid stenosis and transient ischemic attack (TIA) or
nondisabling stroke on ipsilateral side of stenosis within 180 days strati ed by degree of
stenosis (50%-69% or < 50%) and randomized to carotid endarterectomy vs. medical care alone
– in subgroup of 210 patients with probable lacunar infarction (lacunar syndrome plus congruous
computed tomography [CT] lesions), ipsilateral stroke within 3-year follow-up occurred in 16.5%
treated with carotid endarterectomy vs. 26.5% treated with medical care alone (not signi cant)
⚬ Reference - QJM 2002 May;95(5):313

Consultation and referral

● Canadian Stroke Best Practices Advisory Committee (CSBPR) recommendations

⚬ all patients with acute stroke should be assessed by rehabilitation professionals (CSBPR Evidence
Level A), ideally within 48 hours of hospital admission (CSBPR Evidence Level C)
⚬ if abnormal swallowing screen, refer to speech language pathologist, occupational therapist, and/
or dietitian for detailed assessment of swallowing, nutrition, and hydration status (CSBPR Evidence
Level C)
⚬ if concerns over nutrition, hydration, dysphagia, or comorbidities that may a ect nutrition, refer to
dietician
– to meet nutrition and hydration needs (while supporting food texture/ uid consistency
alterations recommended by speech language pathologist or other specialist) (CSBPR Evidence
Level B)
– for enteral nutrition support if necessary; decision for enteral nutrition should be made as early
as possible in collaboration with patient, family, decision-makers, and interprofessional team
(CSBPR Evidence Level B)
⚬ Reference - Int J Stroke 2016 Feb;11(2):239
⚬ See Consultation and referral in Stroke (acute management) for details

Other management

Secondary prevention

STUDY
● SUMMARY
systolic blood pressure (SBP) target < 130 mm Hg might not decrease risk of recurrent stroke
compared to target 130-149 mm Hg in patients with lacunar stroke DynaMed Level 2

RANDOMIZED TRIAL: Lancet 2013 Aug 10;382(9891):507 | Full Text

Details
⚬ based on randomized trial with inadequate statistical power
⚬ 3,020 patients (mean age 63 years) with lacunar stroke within past 6 months were randomized to
SBP target < 130 mm Hg (lower) vs. 130-149 mm Hg (higher)
– patients also randomized to aspirin 325 mg plus clopidogrel hydrogen sulfate 75 mg/day vs.
aspirin 325 mg alone (results not reported)
– patients receiving antihypertensive medications at baseline were allowed to continue use during
trial
⚬ mean follow-up 3.7 years
⚬ SBP target achieved in 65% of lower target group and 75% of higher target group
 ⚬ power calculation based on expected 3-year recurrence rate of 21% in higher target group and risk
reduction of 25% in lower target group (observed rates were signi cantly lower than expected)
⚬ annual outcome rates comparing lower SBP target vs. higher SBP target

– any recurrent stroke 2.25% vs. 2.77% (p = 0.08)

– intracerebral hemorrhage 0.11% vs. 0.29% (p = 0.03)
– disabling or fatal stroke 0.72% vs. 0.89% (not signi cant)
– all-cause death 1.8% vs. 1.74% (not signi cant)

⚬ Reference - SPS3 trial (Lancet 2013 Aug 10;382(9891):507 full-text ) and protocol Int J Stroke
2011 Apr;6(2):164 full-text , correction can be found in Lancet 2013 Aug 10;382(9891):506,
editorial can be found in Lancet 2013 Aug 10;382(9891):482 , commentary can be found in Lancet
2014 Feb 8;383(9916):512

STUDY
● SUMMARY
SBP target < 130 mm Hg may increase rapid renal function decline in first year compared to SBP
target 130-149 mm Hg in patients with prior lacunar stroke and relatively preserved kidney
function DynaMed Level 3

RANDOMIZED TRIAL: Circulation 2016 Feb 9;133(6):584 | Full Text

Details
⚬ based on nonclinical outcome from post hoc secondary analysis of SPS3 trial
⚬ 2,610 patients (86%) with prior lacunar stroke who were randomized to SBP target < 130 mm Hg
(lower) vs. 130-149 mm Hg (higher) were assessed
⚬ 84% had preserved renal function (de ned as estimated glomerular ltration rate [GFR] ≥ 60
mL/minute/1.73 m2) at baseline
⚬ rapid renal function decline de ned as estimated GFR decline > 30%
⚬ comparing lower SBP target vs. higher SBP target

– rapid renal function decline at 1 year in 11% vs. 8% (p < 0.05, NNH 33)
– rapid renal function decline at 1-5 years in 8% vs. 8% (not signi cant)

⚬ Reference - Circulation 2016 Feb 9;133(6):584 full-text , editorial can be found in Circulation
2016 Feb 9;133(6):552 , commentary can be found in Circulation 2016 Jul 26;134(4):e24

Follow-up

● control hypertension and diabetes (important chronically but not on presentation) 3

● Scottish Intercollegiate Guidelines Network (SIGN) recommendations

⚬ patients with mild or moderate stroke should be able to access early supported discharge services
with stroke specialist as well as conventional inpatient services (SIGN Grade A)
⚬ early discharge teams should be multidisciplinary and include nursing, medical, physical therapy,
speech and language therapy, and occupational therapy sta (SIGN Grade B)
⚬ Reference - SIGN national clinical guideline on stroke (rehabilitation, prevention and management
of complications, and discharge planning) (SIGN 2010 Jun PDF )
⚬ see Follow-up in Stroke (acute management) for details

Complications and Prognosis

Complications
● vascular dementia 2 , 3

● pseudobulbar syndrome 3

● deterioration after initial stroke assessment is common and can be due to 4

⚬ stroke progression
⚬ brain edema
⚬ recurrent ischemia
⚬ hemorrhage

STUDY
● SUMMARY
thrombolysis associated with symptomatic intracerebral hemorrhage (ICH) in 6.8% of patients
with ischemic stroke but only 1.5% of patients with lacunar stroke

COHORT STUDY: Int J Stroke 2013 Oct;8 Suppl A100:45

SYSTEMATIC REVIEW: JAMA Neurol 2016 Jun 1;73(6):675
SYSTEMATIC REVIEW: Neurology 2015 Sep 15;85(11):927 | Full Text

Details
⚬ based on cohort study
⚬ 11,503 patients with ischemic stroke identi ed in Registry of Canadian Stroke Network between
2003 and 2008 were analyzed
⚬ 43.8% had partial anterior circulation stroke, 24.9% had posterior circulation stroke, 19.1% had
lacunar stroke, and total anterior circulation stroke
⚬ among 1,630 patients (14.2%) who received thrombolysis, intracerebral hemorrhage occurred in

– 12.5% with ischemic stroke (symptomatic hemorrhage [de ned as increase ≥ 4 on NIHSS ] in
6.8%)
– 2.1% with lacunar stroke (symptomatic hemorrhage in 1.5%)

⚬ in multivariate analysis, thrombolysis associated with increased likelihood of

– good outcome (modi ed Rankin Scale [MRS] score 0-2) in patients with

● ischemic stroke (risk ratio [RR] 1.49, 95% CI 1.38-1.61)

● lacunar stroke (RR 1.84, 95% CI 1.59-2.13)

– discharge home in patients with

● ischemic stroke (RR 1.29, 95% CI 1.2-1.4)

● lacunar stroke (RR 1.38, 95% CI 1.19-1.6)

– no signi cant di erence in 90-day mortality

⚬ Reference - Int J Stroke 2013 Oct;8 Suppl A100:45

STUDY
– SUMMARY

Details
presence of cerebral microbleeds prior to thrombolysis associated with increased risk of
symptomatic intracerebral hemorrhage (ICH) after thrombolysis in patients with acute
ischemic stroke
● based on 2 systematic reviews of observational studies
● systematic review of 9 studies evaluating association between cerebral microbleeds prior to
treatment and symptomatic intracerebral hemorrhage in 2,479 patients with acute ischemic
 stroke treated with IV alteplase
⚬ increased risk of symptomatic intracerebral hemorrhage after IV thrombolysis with

– ≥ 1 cerebral microbleed compared to none (risk ratio [RR] 2.36, 95% CI 1.21-4.61) in
analysis of 9 studies with 2,479 patients
– > 10 cerebral microbleeds compared to ≤ 10 microbleeds (RR 12.10, 95% CI 4.36-33.57)
in analysis of 5 studies with 1,808 patients
– > 10 cerebral microbleeds compared to 1-10 microbleeds (RR 7.01, 95% CI 3.2-15.38) in
analysis of 5 studies with 358 patients
⚬ Reference - JAMA Neurol 2016 Jun 1;73(6):675

● systematic review of 10 cohort studies (5 prospective and 5 retrospective studies) evaluating

association between cerebral microbleeds on magnetic resonance imaging prior to
thrombolysis and risk of symptomatic ICH in 2,028 patients with acute ischemic stroke
⚬ thrombolysis regimens included IV tissue plasminogen activator (tPA) (7 studies) or
recombinant tPA (3 studies), intra-arterial urokinase (2 studies) or tPA (1 study),
endovascular therapy (1 study), or mechanical thrombectomy during intra-arterial
thrombolysis (1 study)
⚬ upper limit of time to treatment ranged from 3 to 7 hours in 7 studies (not speci ed in 3
studies)
⚬ 23.3% of patients had cerebral microbleeds before thrombolysis, and 5% had
symptomatic ICH after thrombolysis
⚬ compared to no cerebral microbleeds, presence of any cerebral microbleeds associated
with increased risk of symptomatic ICH
– after any thrombolysis regimen (odds ratio 2.26, 95% CI 1.46-3.49) in analysis of all
studies
– after IV tPA (odds ratio 2.87, 95% CI 1.76-4.69) in analysis of 8 studies with 1,704
patients
⚬ Reference - Neurology 2015 Sep 15;85(11):927 full-text , editorial can be found in
Neurology 2015 Sep 15;85(11):925

● seizures reported in < 10% patients after ischemic infarction, but may have increased incidence after

hemorrhagic transformation 4

● long-term complications include 3

⚬ poststroke depression
⚬ fatigue
⚬ see also

– Swallowing dysfunction after stroke

– Long-term management of stroke
– Stroke rehabilitation in adults

● see Complications in Stroke (acute management) for details on other potential complications of stroke

Prognosis

● prognosis generally good, especially in patients ≤ 50 years old 3

⚬ prognosis of lacunar stroke reported to be better than other vascular disturbances

 ⚬ better prognosis associated with partial motor or sensory syndromes compared to complete
syndrome

● neurologic de cits generally improve within the rst few weeks 3

⚬ 94% reported to be self-su cient at 6 months

⚬ rapid fatigue may impact quality of life making prognosis slightly worse in patients with
supratentorial lacunar infarct

● 1-year risk of recurrence approximately 10% with static risk thereafter 3

● poor prognosis after lacunar infarct thought to be associated with 2 , 3

⚬ stroke caused by proximal perforating arteriolar atheroma

⚬ initially severe stroke
⚬ gross alterations of biochemical parameters, especially blood glucose
⚬ low or excessively high blood pressure (BP)
⚬ transient ischemic attacks (TIAs) preceding stroke
⚬ diabetes
⚬ coronary artery disease
⚬ neuroimaging results, including

– early appearance of hypodensity at lesion site

– large lesion size
– occlusion of median cerebral artery
– presence of edema

STUDY
● SUMMARY
previous symptomatic lacunar stroke or TIA, diabetes, black race, and male sex may each
increase risk of symptomatic ischemic stroke DynaMed Level 2

RANDOMIZED TRIAL: J Stroke Cerebrovasc Dis 2014 Apr;23(4):618 | Full Text

Details
⚬ based on cohort analysis of data from randomized trial
⚬ 3,020 patients (mean age 63 years) with lacunar stroke from SPS3 trial were analyzed according to
recurrence
⚬ patients with recent or remote cortical infarct, large subcortical infarct, prior intracerebral
hemorrhage, or Rankin Scale score ≥ 4 were excluded
⚬ 8% (243 patients) had recurrent ischemic stroke over mean 3.7-year (range 0-8.6 year) follow-up
(recurrent lacunar stroke in 56% of patients with recurrent ischemic stroke)
⚬ increased risk of recurrent ischemic stroke associated with

– prior symptomatic lacunar stroke or TIA (hazard ratio [HR] 2.2, 95% CI 1.6-2.9)
– diabetes (HR 2, 95% CI 1.5-2.5)
– black race (HR 1.7, 95% CI 1.3-2.3)
– male sex (HR 1.5, 95% CI 1.1-1.9)

⚬ Reference - J Stroke Cerebrovasc Dis 2014 Apr;23(4):618 full-text

STUDY
● SUMMARY
compared to nonlacunar ischemic stroke, lacunar stroke associated with reduced mortality risk
for up to 1 year following stroke and reduced risk of recurrence at 1 month following stroke

SYSTEMATIC REVIEW: Brain 2005 Nov;128(Pt 11):2507 | Full Text

Details
⚬ based on systematic review of observational studies
⚬ systematic review of 27 cohort studies evaluating risk of death and stroke recurrence in 4,940
patients with lacunar stroke and 10,426 patients with nonlacunar ischemic stroke
⚬ mortality

– among patients with lacunar stroke, 1-month mortality ranged from 0% to 2% and death within
1-12 months in 8%
– among patients with nonlacunar ischemic stroke, 1-month mortality ranged from 10% to 20%
and death within 1-12 months in 20%
⚬ compared to lacunar stroke, nonlacunar ischemic stroke associated with

– increased risk of mortality

● at 1 month (pooled odds ratio [OR] 3.81, 95% CI 2.77-5.23) in analysis of 7 studies with 2,638
patients
● within 1-12 months (pooled OR 2.32, 95% CI 1.74-3.08) in analysis of 7 studies with 2,334
patients
– increased risk of recurrence at 1 month (pooled OR 2.11, 95% CI 1.20-3.69) in analysis of 6
studies with 2,137 patients
– no signi cant di erence in risk of recurrence within 1-12 months in analysis of 6 studies with
1,665 patients
⚬ in subgroup analysis, increased risk of lacunar recurrence associated with lacunar event at baseline
compared to non-lacunar event at baseline (relative risk 2.24, 95% CI 1.3-3.85) in analysis of 3
studies with 396 patients, results limited by signi cant heterogeneity
⚬ Reference - Brain 2005 Nov;128(Pt 11):2507 full-text

STUDY
● SUMMARY
systolic blood pressure variability > 17.5 mm Hg may increase risk of all-cause mortality in
patients with recent lacunar infarct DynaMed Level 2

COHORT STUDY: Eur J Neurol 2014 Feb;21(2):319

Details
⚬ based on prospective cohort study
⚬ 281 patients (mean age 70 years) with lacunar infarct ≤ 14 days prior admitted to stroke unit in
Chinese hospital from 2004 to 2008 were followed for mean 78 months
– at discharge, 82% were prescribed antihypertensives (1 agent in 52%, 2 agents in 31%, and ≥ 3
agents in 17%)
– 74% had hypertension at baseline

⚬ patients had BP assessed every 3-4 months during follow-up outpatient visits (mean 12 visits) and
blood pressure variability (BPV) was determined by standard deviations of systolic (SBP) and
diastolic blood pressure (DBP) across clinic visits
– mean SBP was 142 mm Hg and mean DBP was 74 mm Hg
– mean systolic blood pressure variability was 16 mm Hg and mean diastolic blood pressure
variability was 8 mm Hg
 ⚬ patients were strati ed into tertiles according to systolic blood pressure variability (< 13 mm Hg, 13-
17.5 mm Hg, and > 17.5 mm Hg)
⚬ 23% (65 patients) died

– 31% due to cardiovascular causes

– 14% due to recurrent stroke
– 7% due to acute coronary syndrome

⚬ compared to systolic blood pressure variability < 13 mm Hg, systolic blood pressure variability >
17.5 mm Hg associated with increased risk of
– all-cause mortality (adjusted hazard ratio 1.97, 95% CI 1.02-3.8)
– cardiovascular mortality (adjusted hazard ratio 7.64, 95% CI 1.65-35.41)

⚬ no signi cant di erences in

– death due to recurrent stroke or acute coronary syndrome associated with systolic blood
pressure variability
– all-cause mortality, cardiovascular mortality, or death due to recurrent stroke or acute coronary
syndrome associated with diastolic blood pressure variability
⚬ Reference - Eur J Neurol 2014 Feb;21(2):319

STUDY
● SUMMARY
in patients with prior lacunar stroke, combination of diabetes mellitus and metabolic syndrome
associated with increased risk of recurrent stroke

RANDOMIZED TRIAL: Neurology 2015 Sep 15;85(11):935 | Full Text

Details
⚬ based on cohort analysis of data from randomized trial
⚬ 2,999 patients with recent symptomatic, magnetic resonance image-con rmed lacunar stroke from
SPS3 trial were followed for median of 3.8 years
⚬ 25% had metabolic syndrome without diabetes mellitus, 6% had diabetes mellitus without
metabolic syndrome, and 32% had metabolic syndrome that included mellitus
⚬ 274 recurrent strokes occurred during follow-up, including 240 ischemic (56% lacunar) and 34
hemorrhagic
⚬ compared to no metabolic syndrome or diabetes, concurrent metabolic syndrome and diabetes
associated with increased risk of
– any recurrent stroke (hazard ratio 1.7, 95% CI 1.3–2.3)
– recurrent lacunar stroke (hazard ratio 2.4, 95% CI 1.5–3.7)

⚬ no signi cant di erences in recurrent stroke outcomes comparing no metabolic syndrome or

diabetes to metabolic syndrome alone or to diabetes alone
⚬ original randomization to single vs. dual antiplatelet therapy and di erent blood pressure targets
did not in uence risk of recurrent stroke in any metabolic syndrome/diabetes group
⚬ Reference - Neurology 2015 Sep 15;85(11):935 full-text

STUDY
● SUMMARY
elevated high-sensitivity C-reactive protein (hsCRP) associated with increased risk of recurrent
ischemic stroke in patients with previous lacunar stroke receiving antiplatelet therapy
DynaMed Level 2

RANDOMIZED TRIAL: Stroke 2014 Mar;45(3):707 | Full Text

 Details
⚬ based on cohort analysis of data from randomized trial
⚬ 1,244 patients (mean age 63 years) with lacunar stroke from SPS3 trial were analyzed
⚬ all patients received aspirin with or without clopidogrel
⚬ median hsCRP level 2.16 mg/L (20.57 nmol/L)
⚬ prevalence of recurrent ischemic stroke 7% (of which 54% were lacunar)
⚬ compared to lowest quartile of hsCRP (≤ 0.93 mg/L [8.86 nmol/L]), highest quartile of hsCRP (> 4.86
mg/L [46.29 nmol/L]) associated with increased risk of recurrent ischemic stroke (hazard ratio 2.5,
95% CI 1.3-5)
⚬ no signi cant di erence in e ect of hsCRP on risk comparing aspirin vs. aspirin plus clopidogrel
⚬ Reference - Stroke 2014 Mar;45(3):707 full-text

● cognitive decline and dementia onset 1 , 2

STUDY
⚬ SUMMARY
mild cognitive impairment or dementia occurs in about 37% of patients after lacunar stroke

SYSTEMATIC REVIEW: J Neurol Neurosurg Psychiatry 2013 Aug;84(8):893 | Full Text

Details
– based on systematic review
– systematic review of 24 observational studies assessing cognitive impairment after lacunar or
cortical ischemic stroke in 7,575 patients
– cognitive assessment rst month after stroke in 4 studies, 3 months to 1 year in 12 studies, 1-4
years in 8 studies
– 6,478 patients included in analysis of cognitive impairment, including 2,222 patients (35%) with
lacunar stroke
– prevalence of mild cognitive impairment or dementia after lacunar stroke was 29%
– cognitive impairment outcomes after rst or recurrent lacunar stroke in patients without
baseline cognitive de cits (all results limited by signi cant heterogeneity)
● incidence of dementia 12% (95% CI 6%-18%) in analysis of 6 studies with 397 patients
● incidence of mild cognitive impairment or dementia 37% (95% CI 23%-53%) in analysis of 4
studies with 275 patients
– Reference - J Neurol Neurosurg Psychiatry 2013 Aug;84(8):893 full-text

STUDY
⚬ SUMMARY
≥ 1 lacunae in thalamus associated with decrease in cognitive function on Mini Mental Status
Exam (MMSE)

COHORT STUDY: J Neurol Neurosurg Psychiatry 2009 May;80(5):478

Details
– based on cohort study
– 633 patients (mean age 74 years) with white matter hyperintensities (WMHs) on magnetic
resonance imaging (MRI) (of any degree) and no or mild disability as assessed by the
Instrumental Activities of Daily Living (IADL) scale were analyzed
● patients were evaluated in stroke units and various clinics due to mild memory loss, minor
focal cerebrovascular events, minor motor disturbances, or nonspeci c reasons (with WMH
 as incidental nding)
● MRI was performed at initial presentation and WMHs and lacunes were graded according to
Fazekas Scale (grade 1: punctate, grade 2: early con uent, or grade 3: con uent)
– all patients had neuropsychological evaluation using MMSE with higher score indicating better
performance
– 47% patients had ≥ 1 lacunar infarct with total of 958 lacunar infarcts identi ed
– locations of lunar infarcts in percent of 633 patients

● lobar white matter in 27%

⚬ frontal in 20%
⚬ parieto-occipital in 11%
⚬ temporal in 5%

● infratentorial in 12%
● basal ganglia in 31%

⚬ caudate nucleus in 8%
⚬ putamen and pallidum in 17%
⚬ internal capsule in 5%
⚬ thalamus in 12%
⚬ external capsule in 6%

– ≥ 1 lacunae in thalamus associated with lower scores on

● MMSE (p = 0.043)
● speed and motor control assessed by z-score (p = 0.006)
● executive function assessed by z-score (p = 0.022)

– ≥ 1 lacunae in putamen/pallidum associated with lower memory z -score (p = 0.038)

– no signi cant di erences in cognitive function (assessed by MMSE) associated with presence of
lacunes in caudate nucleus, internal capsule, lobar white matter, putamen/pallidum, or external
capsule
– Reference - J Neurol Neurosurg Psychiatry 2009 May;80(5):478

STUDY
⚬ SUMMARY
elevated pulsatility index of middle cerebral artery associated with cognitive deficiency in
patients with acute lacunar infarct

COHORT STUDY: J Neuroimaging 2016 Jul;26(4):431

Details
– based on prospective cohort study
– 113 patients (mean age 70 years) with acute clinical lacunar syndrome who were admitted to
stroke unit were evaluated for lacunar infarct with Doppler ultrasound of intracranial arteries,
including assessment of pulsatility index of middle cerebral artery
– cognitive function was assessed by MMSE, clock drawing test, and trail making tests A and B
between days 2 and 5
● clock drawing test assesses visuospatial and executive functioning with results deemed
correct or incorrect
● trail making tests A and B require patients to connect numbered dots in a timed environment
(test A assesses psychomotor speed and test B assesses executive functioning); more time
spent indicates a cognitive de ciency
– 75.2% had acute lacunar infarct and 24.3% had ≥ 1 nonlacunar infarct
 – mean pulsatility index of middle cerebral artery was 1.46
– among patients with lacunar infarct, elevated pulsatility index of middle cerebral artery was
associated with cognitive de ciency in adjusted analyses, including
● lower score on MMSE (p = 0.02)
● increased time spent on trail making test A (p = 0.013)
● increased time spent on trail making test B (p = 0.047)

– no signi cant di erence in results of clock drawing test associated with elevated pulsatility index
– Reference - J Neuroimaging 2016 Jul;26(4):431

Prevention and Screening

Prevention

● see Primary prevention of stroke for information on primary prevention

● interventions for secondary prevention of stroke, after ischemic stroke or transient ischemic attack
(TIA)
⚬ risk factor reduction strategies include

– moderate-to-vigorous aerobic physical activity for an average of 40 minutes 3-4 times/week

(AHA/ASA Class IIa, Level C)
– statins

● initiate or continue high-intensity statin as rst-line therapy in patients ≤ 75 years old with
clinical atherosclerotic cardiovascular disease (AHA/ASA Class I, Level A)
● use statins with intensive lipid-lowering e ects to reduce risk of stroke and cardiovascular
events in patients with ischemic stroke or TIA of presumed atherosclerotic origin and either
⚬ low-density lipoprotein cholesterol level ≥ 100 mg/dL with or without evidence of other
atherosclerotic cardiovascular disease (AHA/ASA Class I, Level B)
⚬ low-density lipoprotein cholesterol level < 100 mg/dL even if no other evidence of
atherosclerotic cardiovascular disease (AHA/ASA Class I, Level C)
● patients with ischemic stroke or TIA and other comorbid atherosclerotic cardiovascular
disease should be managed according to 2013 ACC/AHA cholesterol guidelines PDF
(AHA/ASA Class I, Level A)
● statins reduce subsequent cerebrovascular events in adults with history of stroke or TIA
(level 1 [likely reliable] evidence )
– blood pressure reduction

● treat previously untreated patients with blood pressure ≥ 140 mm Hg systolic or ≥ 90 mm Hg

diastolic (AHA/ASA Class I, Level B) and previously treated patients with known hypertension
(AHA/ASA Class I, Level A)
● target blood pressure level should be individualized, but reasonable goal is systolic pressure
< 140 mm Hg and diastolic pressure < 90 mm Hg (AHA/ASA Class IIa, Level B), or systolic
blood pressure < 130 mm Hg in patients with recent lacunar stroke (AHA/ASA Class IIb, Level
B)
● calcium channel blockers more e ective than beta blockers and similar to angiotensin-
converting enzyme (ACE) inhibitors and diuretics in preventing stroke in patients with
hypertension (level 1 [likely reliable] evidence )
● optimal medication for patients with history of stroke or TIA unclear, but evidence suggests
diuretics or combination of diuretics plus ACE inhibitors are useful (AHA/ASA Class I, Level A)
 ● antihypertensive medications may reduce risk of adverse cardiovascular events in patients
without hypertension but with history of cardiovascular disease or diabetes (level 2 [mid-
level] evidence )
– smoking cessation (AHA/ASA Class I, Level C)
– avoiding heavy alcohol use (AHA/ASA Class I, Level C)

⚬ following noncardioembolic stroke or TIA - antiplatelet agents recommended over anticoagulation

(ACCP Grade 1B; AHA/ASA Class I, Level A; CSBPR Evidence Level A)
– options include

● combination of aspirin 25 mg plus extended-release dipyridamole 200 mg twice daily

(Aggrenox, Asasantin) (AHA/ASA Class I, Level B; CSBPR Evidence Level A)
● aspirin with suggested dose ranges including 75-100 mg once daily (ACCP), 50-325 mg/day
(AHA/ASA Class I, Level A), and 81-325 mg/day (CSBPR Evidence Level A)
● clopidogrel (Plavix) 75 mg once daily (AHA/ASA Class IIa, Level B; CSBPR Evidence Level A)
● cilostazol (Pletal) 100 mg twice daily (ACCP); FDA approved only for intermittent claudication

– clopidogrel or combination aspirin plus extended-release dipyridamole suggested over aspirin

alone (ACCP Grade 2B) or cilostazol (ACCP Grade 2C)
– combination of aspirin plus clopidogrel

● not usually recommended for long-term secondary prevention of stroke (AHA/ASA Class III,
Level A; CSBPR Evidence Level A) due to increased risk of life-threatening or major bleeding
(level 1 [likely reliable] evidence )
● might be considered if initiated ≤ 24 hours after minor ischemic stroke or TIA and continued
for 90 days (AHA/ASA Class IIb, Level B)
– tri usal (A en, Disgren, Grendis, Tri ux) also has evidence to support use (level 2 [mid-level]
evidence )
– anticoagulation appears to increase adverse events without increased bene ts compared to
aspirin in patients with nonembolic stroke or TIA (level 2 [mid-level] evidence )
⚬ following cardioembolic stroke or TIA (atrial brillation), oral anticoagulation recommended (ACCP
Grade 1A; ACC/AHA Class I, Level A; ESC Class I, Level B; CCS Strong recommendation, High-quality
evidence)
– in patients with atrial brillation and prior stroke or TIA, anticoagulants reduce risk of stroke
compared to placebo (level 1 [likely reliable] evidence ) or antiplatelet therapy (level 2 [mid-
level] evidence )
– some guidelines recommend newer anticoagulants over warfarin (ACCP Grade 2B; ESC Class I,
Level A; CCS Conditional recommendation, High-quality evidence); compared to warfarin
● dabigatran (Pradaxa) 150 mg twice daily further reduces risk for stroke with similar bleeding
risk (level 1 [likely reliable] evidence ) and possibly higher incidence of myocardial
infarction (level 2 [mid-level] evidence ) and nonbleeding upper gastrointestinal adverse
events (level 2 [mid-level] evidence ); lower doses (110 mg twice daily in Europe, 75 mg
twice daily in United States) used if moderate renal impairment or higher bleeding risk
● rivaroxaban (Xarelto) 20 mg once daily (15 mg if creatinine clearance 30-49 mL/minute) may
be as e ective for preventing stroke or systemic embolism in patients with nonvalvular atrial
brillation (level 2 [mid-level] evidence )
● apixaban (Eliquis) 5 mg twice daily associated with reduced risk of stroke and major bleeding
and might reduce risk of mortality (level 2 [mid-level] evidence )
– warfarin recommended over new oral anticoagulants for patients with any of (ACC/AHA Class I,
Level B; CCS Strong recommendation, Moderate-quality evidence)
 ● mechanical prosthetic valve
● rheumatic mitral stenosis
● estimated glomerular ltration rate (GFR) of 15-30 mL/minute/1.73 meters2

– with contraindications to anticoagulant therapy, consider combination of aspirin plus

clopidogrel over aspirin alone if low risk of bleeding (AHA/ASA Class IIb, Level B; ACCP Grade 2B)
⚬ for details on secondary prevention of stroke, see

– Secondary Prevention of Stroke or Transient Ischemic Attack

– Antiplatelet Therapy for Secondary Prevention of Stroke or Transient Ischemic Attack

Guidelines and Resources

Guidelines

United States guidelines

● American Heart Association/American Stroke Association (AHA/ASA)

⚬ AHA/ASA 2019 update to the 2018 guidelines for the early management of acute ischemic stroke
can be found in Stroke 2019 Dec;50(12):e344 , correction can be found in Stroke 2019
Dec;50(12):e440
⚬ AHA/ASA statement on scienti c rationale for the inclusion and exclusion criteria for intravenous
alteplase in acute ischemic stroke can be found in Stroke 2016 Feb;47(2):581 , correction can be
found in Stroke 2016 Nov;47(11):e262
⚬ AHA/ASA scienti c statement on management of stroke in neonates and children can be found in
Stroke 2019 Mar;50(3):e51
⚬ AHA/ASA scienti c statement on prevention of stroke in patients with silent cerebrovascular
disease can be found in Stroke 2017 Feb;48(2):e44
⚬ AHA/ASA scienti c statement on telemedicine quality and outcomes in stroke can be found in
Stroke 2017 Jan;48(1):e3
⚬ AHA/ASA statement on updated de nition of stroke for the 21st century can be found in Stroke
2013 Jul;44(7):2064

● American Geriatrics Society (AGS) 2019 Beers Criteria for potentially inappropriate medication use in
older adults can be found in J Am Geriatr Soc 2019 Apr;67(4):674 , commentary can be found in J
Urol 2019 Sep;202(3):438

● expert consensus statement on diagnosis of subcortical small vessel disease can be found in J Cereb
Blood Flow Metab 2016 Jan;36(1):6 full-text

United Kingdom guidelines

● Royal College of Physicians (RCP) national clinical guideline on stroke can be found at RCP 2016 Oct 3
PDF

● Scottish Intercollegiate Guidelines Network (SIGN) national clinical guideline on stroke (rehabilitation,
prevention and management of complications, and discharge planning) can be found at SIGN 2010
Jun PDF

Canadian guidelines

● Canadian Stroke Best Practice Recommendations (CSBPR) guidelines

 ⚬ CSBPR guidelines on acute inpatient stroke care can be found in Int J Stroke 2016 Feb;11(2):239

⚬ CSBPR guidelines on hyperacute stroke care can be found in Int J Stroke 2015 Aug;10(6):924

European guidelines

● European Academy of Neurology (EAN) guideline on diagnosis and therapy of monogenic cerebral
small-vessel diseases can be found in Eur J Neurol 2020 Mar 20 early online

● European Federation of Neurological Societies (EFNS) guideline on use of imaging in cerebrovascular

disease can be found at EFNS 2011 PDF

● Finnish Medical Society Duodecim/Finnish Neurological Society current care summary on cerebral
infarction (stroke) can be found at Duodecim 2016 Jan [Finnish]

Asian guidelines

● Indian expert working group clinical guidelines on stroke management can be found in Ann Indian
Acad Neurol 2011 Jul;14(Suppl 1):S82 full-text

Review articles

● review can be found in Clin Sci (Lond) 2017 Jun 1;131(12):1191

● review can be found in Stroke Vasc Neurol 2016 Sep;1(3):83 full-text

● review can be found in J Stroke 2015 Jan;17(1):2 full-text

● reviews of prevention and management of cerebral small vessel disease can be found in

⚬ J Stroke 2015 May;17(2):111 full-text

⚬ Int J Stroke 2015 Jun;10(4):469 full-text

● review of long-term prognosis after lacunar infarction can be found in Lancet Neurol 2003
Apr;2(4):238

● review of thrombolysis in acute stroke patients with cerebral small vessel disease can be found in
Cerebrovasc Dis 2014;37(1):5 full-text

● review of the blood-brain barrier in lacunar stroke, leukoaraiosis, and dementia can be found in
Stroke 2003 Mar;34(3):806 , editorial can be found in Stroke 2003 Mar;34(3):806

● review of cerebral small vessel disease and Alzheimer disease can be found in Clin Interv Aging
2015;10:1695 full-text

● case report of cerebellar ischemic stroke can be found in N Engl J Med 2013 Oct 31;369(18):1736 ,
correction can be found in N Engl J Med 2014 Jan 2;370(1):93

● case report of lacunar pontine infarction in 65-year-old man with eight-and-a-half syndrome can be
found in J Stroke Cerebrovasc Dis 2014 Sep;23(8):e389

MEDLINE search
● to search MEDLINE for (Lacunar stroke) with targeted search (Clinical Queries), click therapy ,
diagnosis , or prognosis

Patient Information

● handout on ischemic stroke from EBSCO Health Library

● handout on ischemic stroke from American Heart Association

● handout on ischemic stroke from Internet Stroke Center

ICD Codes

ICD-10 codes

● I63.3 cerebral infarction due to thrombosis of cerebral arteries

● I63.4 cerebral infarction due to embolism of cerebral arteries

● I63.5 cerebral infarction due to unspeci ed occlusion or stenosis of cerebral arteries

● I63.6 cerebral infarction due to cerebral venous thrombosis, nonpyogenic

● I63.8 other cerebral infarction

● I63.9 cerebral infarction, unspeci ed

● I67.2 cerebral atherosclerosis

● I67.8 other speci ed cerebrovascular diseases

● I67.9 cerebrovascular disease, unspeci ed

● G46 vascular syndromes of brain in cerebrovascular diseases

⚬ G46.5 pure motor lacunar syndrome

⚬ G46.6 pure sensory lacunar syndrome
⚬ G46.7 other lacunar syndromes

References

General references used

1. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic
challenges. Lancet Neurol. 2010 Jul;9(7):689-701

2. Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights
from neuroimaging. Lancet Neurol. 2013 May;12(5):483-97 full-text , commentary can be found in
Lancet Neurol 2013 Aug;12(8):735

3. Lastilla M. Lacunar infarct. Clin Exp Hypertens. 2006 Apr-May;28(3-4):205-15

4. Jauch EC, Saver JL, Adams HP Jr, et al; American Heart Association Stroke Council., Council on
Cardiovascular Nursing., Council on Peripheral Vascular Disease., Council on Clinical Cardiology.
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.
2013 Mar;44(3):870-947

5. Casaubon LK, Boulanger JM, Blacquiere D, et al; Heart and Stroke Foundation of Canada Canadian
Stroke Best Practices Advisory Committee. Canadian Stroke Best Practice Recommendations:
Hyperacute Stroke Care Guidelines, Update 2015. Int J Stroke. 2015 Aug;10(6):924-40

6. Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association Stroke Council. 2018
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.
2018 Mar;49(3):e46-e110 , corrections can be found in Stroke 2018 Mar;49(3):e138 , Stroke 2018
Jun;49(6):e233

Recommendation grading systems used

● European Society of Cardiology (ESC) grading system for recommendations

⚬ classes of recommendations

– Class I - evidence and/or general agreement that given treatment or procedure is bene cial,
useful, and e ective
– Class II - con icting evidence and/or divergence of opinion about usefulness/e cacy of given
treatment or procedure
● Class IIa - weight of evidence/opinion in favor of usefulness/e cacy
● Class IIb - usefulness/e cacy less well-established by evidence/opinion
– Class III - evidence or general agreement that given treatment or procedure is not
useful/e ective, and in some cases may be harmful
⚬ levels of evidence

– Level A - data derived from multiple randomized clinical trials or meta-analyses

– Level B - data derived from single randomized trial or large nonrandomized studies
– Level C - consensus of opinion of experts and/or small studies, retrospective studies, registries

⚬ References

– ESC guideline on diagnosis and management of acute pulmonary embolism (Eur Heart J 2014
Nov 14;35(43):3033 full-text ), corrections can be found in Eur Heart J 2015 Oct
14;36(39):2642 and Eur Heart J 2015 Oct 14;36(39):2666, commentary can be found in Rev Esp
Cardiol (Engl Ed) 2015 Jan;68(1):10
– ESC guideline on management of atrial brillation (Eur J Cardiothorac Surg 2016 Nov;50(5):e1

full-text )

● Canadian Cardiovascular Society (CCS) grading system for recommendations

⚬ strength of recommendation

– Strong
– Conditional (weak)

⚬ quality of evidence

– High - future research unlikely to change con dence in estimate of e ect; multiple well-
designed, well-conducted clinical trials
 – Moderate - further research likely to have important impact on con dence in estimate of e ect
and may change estimate; limited clinical trials, inconsistency of results, or study limitations
– Low - further research very likely to have signi cant impact on estimate of e ect and is likely to
change estimate; small number of clinical studies or cohort observations
– Very Low - estimate of e ect is very uncertain; case studies or consensus opinion

⚬ References

– CCS atrial brillation guidelines 2010: rate and rhythm management (Can J Cardiol 2011 Jan-
Feb;27(1):47 , Can J Cardiol 2011 Jan-Feb;27(1):27 )
– CCS focused 2012 update of atrial brillation guidelines: recommendations for stroke
prevention and rate/rhythm control (Can J Cardiol 2012 Mar-Apr;28(2):125 )
– CCS focused 2014 update of atrial brillation guidelines: management of atrial brillation (Can J
Cardiol 2014 Oct;30(10):1114 )
– CCS focused 2016 update on atrial brillation guidelines: management of atrial brillation (Can J
Cardiol 2016 Oct;32(10):1170 )

● American College of Chest Physicians (ACCP) grades

⚬ Grade 1 - strong recommendation based on clear risk/bene t balance

⚬ Grade 2 - weak recommendation based on unclear or close risk/bene t balance
⚬ Grade A - high-quality evidence based on consistent evidence from randomized trials without
important limitations or exceptionally strong evidence from observational studies
⚬ Grade B - moderate-quality evidence based on randomized trials with important limitations
(inconsistent results, methodologic aws, indirect or imprecise results) or very strong evidence
from observational studies
⚬ Grade C - low- or very low-quality evidence based on evidence for ≥ 1 critical outcome from
observational studies, case series, or randomized trials with serious aws or indirect evidence
⚬ Reference - ACCP evidence-based clinical practice guideline on methodology for development of
antithrombotic therapy and prevention of thrombosis (Chest 2012 Feb;141(2 Suppl):53S full-text
), commentary can be found in Chest 2013 Apr;143(4):1190

● Scottish Intercollegiate Guidelines Network (SIGN) grading system for recommendations

⚬ grades of recommendations

– Grade A

● ≥ 1 meta-analysis, systematic review, or randomized controlled trial (RCT) that is rated as

1++, and directly applicable to the target population, or
● a body of evidence consisting principally of studies rated as 1+, directly applicable to the
target population and demonstrating overall consistency of results
– Grade B

● a body of evidence that includes studies rated as 2++, directly applicable to the target
population and demonstrating overall consistency of results, or
● extrapolated evidence from studies rated as 1++ or 1+

– Grade C

● a body of evidence that includes studies rated as 2+, directly applicable to the target
population and demonstrating overall consistency of results, or
● extrapolated evidence from studies rated as 2++

– Grade D

● evidence level 3 or 4, or
● extrapolated evidence from studies rated as 2+
 – Good Practice Point - recommended best practice based on clinical experience of guideline
development group
⚬ levels of evidence

– 1++ - high-quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias

– 1+ - well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias
– 1- - meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias

– 2++

● high-quality systematic reviews of case-control or cohort studies

● high-quality case-control or cohort studies with a very low risk of confounding or bias and a
high probability that the relationship is causal
– 2+ - well-conducted case-control or cohort studies with a low risk of confounding or bias and a
moderate probability that the relationship is causal
– 2- - case-control or cohort studies with a high risk of confounding or bias and a signi cant risk
that the relationship is not causal
– 3 - nonanalytical studies (for example, case reports, case series)
– 4 - expert opinion

⚬ Reference - SIGN national clinical guideline on management of patients with stroke: identi cation
and management of dysphagia (SIGN 2010 Jun PDF )

● American Academy of Neurology (AAN) grading system for recommendations

⚬ grades of recommendation

– Level A - e ective, ine ective, or harmful; requires ≥ 2 consistent Class I studies

– Level B - probably e ective, ine ective, or harmful; requires ≥ 1 Class I study or 2 consistent
Class II studies
– Level C - possibly e ective, ine ective, or harmful; requires ≥ 1 Class II study or 2 consistent
Class III studies
– Level U - inadequate or con icting data

⚬ classi cations of evidence for diagnostic tests

– Class I

● cohort study with prospective data collection of broad spectrum of persons with suspected
condition which uses reference standard for case de nition
● test is objective or interpreted and performed without information on clinical status of
patient
● results allow calculation of measures of diagnostic accuracy

– Class II

● case-control study of broad spectrum of persons with suspected condition which uses
reference standard compared to broad spectrum of controls OR
● cohort study of broad spectrum of persons with suspected condition with data collected
retrospectively
● test is objective or interpreted and performed without information on disease status
● results allow calculation of measures of diagnostic accuracy

– Class III

● case control or cohort study with persons with condition or controls of narrow spectrum;
condition established by reference standard
● test and reference standard are objective or interpreted and performed by di erent
observers
 ● results allow calculation of measures of diagnostic accuracy

– Class IV - studies not meeting Class I-III criteria; consensus, expert opinion, or case report

⚬ Reference - AAN guideline on the role of di usion and perfusion magnetic resonance imaging for
diagnosis of acute ischemic stroke (Neurology 2010 Jul 13;75(2):177 full-text )

● American Heart Association/American Stroke Association (AHA/ASA) grading system for

recommendations
⚬ classi cations of recommendations

– Class I - procedure or treatment should be performed or administered

– Class IIa - reasonable to perform procedure or administer treatment, but additional studies with
focused objectives needed
– Class IIb - procedure or treatment may be considered; additional studies with broad objectives
needed, additional registry data would be useful
– Class III - procedure or treatment should not be performed or administered because it is not
helpful or may be harmful
● Class III ratings may be subclassi ed as Class III No Bene t or Class III Harm

⚬ levels of evidence

– Level A - data derived from multiple randomized clinical trials or meta-analyses

– Level B - data derived from single randomized trial or nonrandomized studies
– Level C - only expert opinion, case studies, or standard of care

⚬ References

– AHA/ASA guideline on early management of adults with ischemic stroke (Stroke 2013
Mar;44(3):870 )
– AHA/ASA guidelines on prevention of stroke in patients with stroke or transient ischemic attack
(Stroke 2014 Jul;45(7):2160 )
– AHA/ASA guidelines for primary prevention of stroke (Stroke 2011 Feb;42(2):517 )

● American Heart Association/American Stroke Association (AHA/ASA) 2018 grading system for
recommendations
⚬ classi cations of recommendations

– Class I - procedure or treatment should be performed or administered

– Class IIa - reasonable to perform procedure or administer treatment, but additional studies with
focused objectives needed
– Class IIb - procedure or treatment may be considered; additional studies with broad objectives
needed, additional registry data would be useful
– Class III - procedure or treatment should not be performed or administered because it is not
helpful or may be harmful
● Class III ratings may be subclassi ed as Class III No Bene t or Class III Harm

⚬ levels of evidence

– Level A - high-quality evidence from > 1 randomized controlled trial or meta-analysis of high-
quality randomized controlled trials
– Level B-R - moderate-quality evidence from ≥ 1 randomized controlled trial or meta-analysis of
moderate-quality randomized controlled trials
– Level B-NR - moderate-quality evidence from ≥ 1 well-designed nonrandomized trial,
observational studies, or registry studies, or meta-analysis of such studies
 – Level C-LD - randomized or nonrandomized studies with methodological limitations or meta-
analyses of such studies
– Level C-EO - consensus of expert opinion based on clinical experience

⚬ Reference - ASA/AHA 2018 guideline on early management of patients with acute ischemic stroke
(Stroke 2018 Mar;49(3):e46 ), corrections can be found in Stroke 2018 Mar;49(3):e138 , Stroke
2018 Jun;49(6):e233

● American College of Cardiology/American Heart Association (ACC/AHA) grading system for guidelines

⚬ classi cations of recommendations

– Class I - procedure or treatment should be performed or administered

– Class IIa - reasonable to perform procedure or administer treatment, but additional studies with
focused objectives needed
– Class IIb - procedure or treatment may be considered; additional studies with broad objectives
needed, additional registry data would be useful
– Class III - procedure or treatment should not be performed or administered because it is not
helpful or may be harmful
● Class III ratings may be subclassi ed as Class III No Bene t or Class III Harm

⚬ levels of evidence

– Level A - data derived from multiple randomized clinical trials or meta-analyses

– Level B - data derived from single randomized trial or nonrandomized studies
– Level C - only expert opinion, case studies, or standard of care

⚬ References

– AHA/ACC/HRS guideline on management of patients with atrial brillation (J Am Coll Cardiol

2014 Dec 2;64(21):e1 )
– AHA/American Stroke Association (AHA/ASA) guidelines on secondary prevention of stroke in
patients with paroxysmal or permanent atrial brillation (Stroke 2014 Jul;45(7):2160 PDF )
– ACC/AHA/Heart Rate Society (HRS) 2011 focused update on management of patients with atrial
brillation (Circulation 2011 Jan 4;123(1):104 full-text )
– ACC/AHA/European Society of Cardiology (ESC) 2006 guidelines for management of patients
with atrial brillation (Circulation 2006 Aug 15;114(7):e257 full-text ), correction can be
found in Circulation. 2007 Aug 7;116(6):e138

● Canadian Stroke Best Practice Recommendations (CSBPR) levels of evidence

⚬ Evidence Level A

– meta-analysis of randomized controlled trials or consistent ndings from ≥ 2 randomized trials

– desirable e ects clearly outweigh undesirable e ects or vice versa

⚬ Evidence Level B

– single randomized controlled trial or consistent ndings from ≥ 2 well-designed nonrandomized

and/or uncontrolled trials, and large observational studies
– desirable e ects outweigh or are closely balanced with undesirable e ects or vice versa

⚬ Evidence Level C

– writing group consensus and/or supported by limited research evidence

– desirable e ects outweigh or are closely balanced with undesirable e ects or vice versa

⚬ Reference - CSBPR Overview and Methodology (CSBPR 2014 PDF )

● European Federation of Neurological Societies (EFNS) levels of recommendations

 ⚬ levels of recommendation

– Level A - established as useful/predictive or not useful/predictive; requires at least 1 convincing

Class I study or at least 2 consistent, convincing Class II studies
– Level B - established as probably useful/predictive or not useful/predictive; requires at least 1
convincing Class II study or overwhelming Class III evidence
– Level C - established as possibly useful/predictive or not useful/predictive; requires at least 2
convincing Class III studies
– GCPP - good clinical practice point, supported primarily by expert opinion

⚬ evidence classi cation

– Class I - prospective study in broad spectrum of persons with suspected condition, using 'gold
standard' for case de nition, where test is applied in blinded evaluation, and enabling
assessment of appropriate tests of diagnostic accuracy
– Class II - prospective study of narrow spectrum of persons with suspected condition, or well-
designed retrospective study of broad spectrum of persons with established condition (by 'gold
standard') compared with broad spectrum of controls, where test is applied in blinded
evaluation, and enabling assessment of appropriate tests of diagnostic accuracy
– Class III - retrospective study where either persons with established condition or controls are of
narrow spectrum, and where test is applied in blinded evaluation
– Class IV - test not applied in blinded evaluation OR evidence provided by expert opinion alone
or in descriptive case series (without controls)
⚬ Reference - EFNS guideline on use of imaging in cerebrovascular disease (EFNS 2011 PDF )

● American Geriatrics Society (AGS) Beers Criteria grading system for recommendations

⚬ strength of recommendation

– Strong - bene ts clearly outweigh harms, adverse events, and risks, or harms, adverse events,
and risks clearly outweigh bene ts
– Weak - bene ts may not outweigh harms, adverse events, and risks
– Insu cient - evidence inadequate to determine net harms, adverse events, and risks
⚬ quality of evidence

– High - evidence includes consistent results from well-designed, well-conducted studies in

representative populations that directly assess e ects on health outcomes, based on either
● ≥ 2 consistent, higher-quality randomized controlled trials
● multiple, consistent observational studies with no signi cant methodological aws showing
large e ects
– Moderate - evidence su cient to determine risks of adverse outcomes
● strength of evidence limited by any of

⚬ number, quality, size, or consistency of included studies

⚬ generalizability to routine practice
⚬ indirect nature of evidence on health outcomes

● based on any of

⚬ ≥ 1 higher-quality trial with > 100 participants

⚬ ≥ 2 higher-quality trials with some inconsistency
⚬ ≥ 2 consistent, lower-quality trials
⚬ multiple, consistent observational studies with no signi cant methodological aws
showing at least moderate e ects
– Low - evidence insu cient to assess harms or risks in health outcomes due to any of
 ● limited number or power of studies
● large and unexplained inconsistency between higher-quality studies
● important aws in study design or conduct
● gaps in chain of evidence
● lack of information on important health outcomes

⚬ Reference - AGS 2015 updated Beers Criteria for potentially inappropriate medication use in older
adults (J Am Geriatr Soc 2015 Nov;63(11):2227 ), commentary can be found in J Am Geriatr Soc
2016 Apr;64(4):920

Synthesized Recommendation Grading System for DynaMed Content

● The DynaMed Team systematically monitors clinical evidence to continuously provide a synthesis of
the most valid relevant evidence to support clinical decision-making (see 7-Step Evidence-Based
Methodology ).

● Guideline recommendations summarized in the body of a DynaMed topic are provided with the
recommendation grading system used in the original guideline(s), and allow users to quickly see
where guidelines agree and where guidelines di er from each other and from the current evidence.

● In DynaMed content, we synthesize the current evidence, current guidelines from leading authorities,
and clinical expertise to provide recommendations to support clinical decision-making in the Overview
& Recommendations section.

● We use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to

classify synthesized recommendations as Strong or Weak.
⚬ Strong recommendations are used when, based on the available evidence, clinicians (without
con icts of interest) consistently have a high degree of con dence that the desirable consequences
(health bene ts, decreased costs and burdens) outweigh the undesirable consequences (harms,
costs, burdens).
⚬ Weak recommendations are used when, based on the available evidence, clinicians believe that
desirable and undesirable consequences are nely balanced, or appreciable uncertainty exists
about the magnitude of expected consequences (bene ts and harms). Weak recommendations are
used when clinicians disagree in judgments of relative bene t and harm, or have limited
con dence in their judgments. Weak recommendations are also used when the range of patient
values and preferences suggests that informed patients are likely to make di erent choices.

● DynaMed synthesized recommendations (in the Overview & Recommendations section) are
determined with a systematic methodology:
⚬ Recommendations are initially drafted by clinical editors (including ≥ 1 with methodological
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and harms, and the recommendations from guidelines.
⚬ Recommendations are phrased to match the strength of recommendation. Strong
recommendations use "should do" phrasing, or phrasing implying an expectation to perform the
recommended action for most patients. Weak recommendations use "consider" or "suggested"
phrasing.
⚬ Recommendations are explicitly labeled as Strong recommendations or Weak
recommendations when a quali ed group has explicitly deliberated on making such a
recommendation. Group deliberation may occur during guideline development. When group
deliberation occurs through DynaMed Team-initiated groups:
 – Clinical questions will be formulated using the PICO (Population, Intervention, Comparison,
Outcome) framework for all outcomes of interest speci c to the recommendation to be
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have su cient clinical expertise for the subject(s) pertinent to the recommendation,
methodological expertise for the evidence being considered, and experience with guideline
development.
– All recommendation panel members must disclose any potential con icts of interest
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signi cant con ict exists for the recommendation in question.
– Panel members will make Strong recommendations if and only if there is consistent
agreement in a high con dence in the likelihood that desirable consequences outweigh
undesirable consequences across the majority of expected patient values and preferences.
Panel members will make Weak recommendations if there is limited con dence (or
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⚬ Recommendations are veri ed by ≥ 1 editor with methodological expertise, not involved in
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⚬ Recommendations are published only after consensus is established with agreement in phrasing
and strength of recommendation by all editors.
⚬ If consensus cannot be reached then the recommendation can be published with a notation of
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⚬ If recommendations are questioned during peer review or post publication by a quali ed
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DynaMed Editorial Process

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● All editorial team members and reviewers have declared that they have no nancial or other
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Special acknowledgements

● DynaMed topics are written and edited through the collaborative e orts of the above individuals.
Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medical practice.
 Recommendations Editors are actively involved in development and/or evaluation of guidelines.

● Editorial Team role de nitions

Topic Editors de ne the scope and focus of each topic by formulating a set of clinical
questions and suggesting important guidelines, clinical trials, and other data to be
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● DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T115834, Lacunar
Stroke; [updated 2018 Nov 30, cited place cited date here]. Available from
https://www.dynamed.com/topics/dmp~AN~T115834. Registration and login required.

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