Vascular Diseases of the brain and spinal cord
Brain and spinal cord can be affected by various vascular conditions:
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Ischemic stroke
Intracranial or spinal hemorrhage
o Epidural
o Subdural
o Subarachnoid
o Intraparenchymal (intracerebral) (hematomyelia)
o Intraventricular
Cerebral venous sinus thrombosis (CVST)
Vascular malformations (ex: AVM)
Vasculopathies (ex: vasculitis and RCVS)
Stroke refers to clinical scenarios of patient “struck” by sudden onset neuro deficit localizable to the brain (or
rarely the spinal cord). Includes ischemic stroke and intracerebral hemorrhage (ICH/IPH). Although SAH is
sometimes included as a cause of stroke, its clinical presentation and management are distinct from ischemic
stroke and ICH/IPH.
Ischemic stroke and ICH both p/w sudden-onset focal neuro deficits; however, ICH typically is accompanied by
HA, N/V, depressed LOC d/t mass effect.
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Goals for acute ischemic stroke:
o Decrease thrombosis
 Thrombolysis (TNK, mechanical thrombectomy)
 Anti-Plt (aspirin)
 Anticoagulation (heparin)
o Allow autoregulation of BP
 Restore/maintain tissue perfusion
Goals for acute ICH:
o Stop bleeding
 Reversal of AC
 Administration of clotting factors
o Reduce BP
 Reduce risk of hematoma expansion
Supportive care for stroke and ICH:
o ECG
o Swallow eval
o Glucose control
o Euthermia
o Tx of seizures if they occur
o Eval for elevated ICP
o Early mobilization
o VTE ppx (mechanical immediately; ex: SCDs)
o PT/OT/SLP
TIA refers to transient stroke-like sx that resolve completely w/o evidence of infarction on MRI. Sx can last
minutes to an hour. Those that last longer often have evidence of infarction on DWI even if sx completely resolve.
The risk of subsequent stroke after TIA is estimated by ABCD2 score:
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Age
Blood pressure
Clinical sx of TIA
Diabetes
Duration of of TIA sx
Diseases of arterial cerebral vasculature that can lead to ischemic stroke:
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Atherosclerosis and thromboembolic disease of arteries
o Thrombosis – local formation of clot
 Main cause is atherosclerosis
 RF for atherosclerosis – HTN, DM, HLD, smoking
o Embolism – passage of material from a more proximal source to a more distal location
 May arise from heart, aortic arch, cervical vessels (carotids or verts), or venous circulation
if PFO (paradoxical embolism).
 Rare causes: air embolism, fat embolism, amniotic fluid embolism.
Lipohyalinosis of small penetrating arteries (small vessel disease)
o Chronic HTN leads to wall thickening of small penetrating arteries, predisposing patient to lacunar
infarcts in deep subcortical regions (ex: internal capsule or thalamus) or the anterior pons.
Sometimes referred to as lacunar infarcts.
Carotid or vertebral artery dissection (cervical vessels)
o Common cause of stroke in younger patients
o Causes include: head/neck trauma, chiropractic manipulation, collagen disorders (Ehlers-Danlos,
fibromuscular dysplasia, etc).
o Can present as stroke or TIA
o Can also present w/ local sx (ex: neck pain, headache, lower CN palsies (9-12), Horner’s
o CTA – flame-shaped appearance
o T1-weighted fat saturation MRI – crescentic intramural hematoma
Cerebral vasospasm (ex: RCVS or 2/2 SAH)
o Local irritation – SAH, meningitis
o Failure of cerebral autoregulation – PRES, eclampsia, post-partum angiopathy
o Drugs (and RCVS) – marijuana, coke, SSRIs, sympathomimetic cold meds
Vascular compression by external mass
o Neck tumors, etc
Vasculopathy (ex: vasculitits, radiation induced, moyamoya)
o Radiation-induced vasculopathy
o RCVS (reversible cerebral vasoconstriction syndrome)
o Moyamoya
o Cerebral AD arteriopathy w/ subcortical infarcts and leukoencephalopathy (CADASIL)
o Cerebral AR arteriopathy w/ subcortical infarcts and leukoencephalopathy (CARASIL)
o Vasculitis
Cardiac disease processes can lead to ischemic stroke:
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A Fib
Valvular disease (or mechanical valve)
LV failure w/ dilated LV
MI
Infective endocarditis (w/ septic embolization)
Nonbacterial thrombotic endocarditis (marantic endocarditis: rheum or malignancy)
Cardiac tumors
PFO
Cardiac arrest w/ hypoxic-ischemic injury
Hematologic disease processes can lead to ischemic stroke:
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Hypercoagulable states
o Inherited – factor V Leiden, Prothrombin gene, protein C or S def, antithrombin III def
o Acquired – antiphospholipid Abs, malignancy, DIC
Sickle Cell Anemia
Hyperviscosity – polycythemia vera, Waldenstrom’s macroglobulinemia
Intravascular lymphoma
Initial eval of “stroke” patient:
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Exclude potential “mimics” such as:
o Seizure
o Postictal state and/or Todd’s paralysis
o Migraine
o Unwitnessed head trauma
o Hypoglycemia
o Other acute metabolic abnormalities
 Although metabolic derangements often p/w global neuro deficits, focal findings can
occur ISO Hyperglycemia
o Intoxication
o Psych
o MI (if pt p/w acute LUE and/or face sensory sx)
Order (initially):
o VS monitoring STAT
o ECG STAT
o CTH w/o con STAT
o POC blood glucose, Cr, PT/INR STAT
o Coag panel (PT/INR, etc)
o Troponin
o CMP
o CBC
o UTox
o UA w/ micro
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CTA H/N – assess for LVO
 Note: guidelines recommend that contrast studies should not be delayed while awaiting
serum Cr if patient has no history of renal disease.
o CTP – assess for tissue that is ischemic but not yet infarcted (ischemic Penumbra), which is
potentially salvageable w/ early reperfusion if mechanical thrombectomy is performed.
Neuroimaging findings in Acute Ischemic Stroke
o CTH
 Hypodensity caused by ischemic stroke may take up to 12 hours to show
 Subtle acute findings related to vessel occlusion or early ischemia:
 Hyperdense vessel (c/f clot and/or slow flow)
 Blurring of gray-white junction (or sulcal effacement)
 Hypodensity of insular ribbon (in MCA strokes)
 Note: early parenchymal hypodensity may be more easily visible by changing the
window setting to 30-30.
 NOTE: If the imaging does not reveal an alternative explanation for patients acute sx
onset (bleed, trauma, mass, etc) and you have strong s/f acute ischemic stroke as the
primary cause of their debilitating sx, and they are w/in the window (4.5 hr), the patient
can be considered for thrombolytic therapy (TNK) if no other contraindications.
o MRI
 DWI and ADC sequences can demonstrate ischemic stroke w/in less than an hour after
the onset; therefore, MRI is more sensitive than CT in acute setting. Stroke appears:
 DWI – BRIGHT
 ADC – DARK
 Note: false negatives can occur w/ posterior fossa strokes, small strokes, or MRI
that was obtained very early after sx onset.
 FLAIR sequences demonstrate ischemic strokes after 6 hours from onset.
 Therefore, if stroke is visible on Diffusion sequences (ADC/DWI) but NOT yet on
FLAIR, assume the stroke is less than 6 hours from onset.
o Post-Constrast CTH and MRI
 Can demonstrate enhancement ISO subacute strokes (~ 1 wk – 1 mo)
 Subacute strokes typically conform to a vascular territory and usually demonstrate no or
minimal surrounding edema or mass effect, therefore differentiating them from tumors.
Likewise, on repeat imaging, one would likely see encephalomalacia (vol loss) w/ stroke.
Initial Treatment of Acute Ischemic Stroke:
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Goals of treatment of acute ischemic stroke:
o Restoration of brain perfusion
 Thrombolysis (ex: TNK if w/in 4.5 hr from LKW)
 Thrombectomy
 Consider permissive HTN (BP autoregulation) if not a candidate
WAKE-UP trial (2018)
o If patient p/w unknown LKW (ex: awakening w/ stroke deficits, wake up strokes, unknown LKW),
can obtain MRI brain STAT.
 If there is DWI evidence of stroke but NO FLAIR evidence of stroke, it is safe to assume
that the stroke has occurred w/in the past 6 hours.
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Patients w/ wake-up stroke or unknown LKW w/ DWI (+) but FLAIR (-) strokes on MRI appear to
benefit from thrombolysis (ex: TNK)
Contraindications for TNK
o BP > 185/110
o Coagulopathy (intrinsic or d/t AC)
 INR > 1.7
 PT > 15 sec
 Plt < 100,00
 On AC (ex: apixaban, dabigatran, edoxaban, rivaroxaban) w/in 48 hr
 Prior ICH
 Recent major surgery or trauma (w/in 14 days)
 Recent systemic (ex: GI) hemorrhage (w/in 21 days)
 Recent stroke (w/in 3 months)
 Recent trauma to head (w/in 3 months)
 Aortic dissection
 Endocarditis
Avoiding complications s/p thrombolysis
o Close monitoring (q2hr neurochecks) for s/sx ICH
o BP < 180/105
o Repeat CTH w/in 24 hrs
o NO AC/AP for at least 24 hrs
If ICH develops:
o NO AC/AP
o Strict BP control; SBP < 180
o Coagulopathy addressed w/ cryoprecipitate or ant-fibrinolytic agents (aminocaproic acid or
tranexammic acid)
o Notify Neurology attending ASAP
o Consider NSGY consult
o Consider ICU consult
o Many other actions, but these are very important
Rare post-tPA complication is orolingual angioedema
o Typically unilateral (on side of deficits; c/l to infarcted region). Patients on ACE-inhibitors are at
higher risk. If severe, may require steroids, diphenhydramine, ranitidine or famotidine, ICU
consult, intubation.
Mechanical Thrombectomy:
o Cath-based procedure using stent retriever or aspiration device to extract clot if LVO present
o Window: 6-24 hours from LKW
 Up to 24 hours from LKW in patients who have demonstrable salvageable tissue at risk
(ischmic but not yet infarcted; penumbra) based on DEFUSE 3 and DAWN trials.
 DEFUSE 3 trial (2018) – showed benefit of mechanical thrombectomy over
medical therapy b/w 6-16 hr in patients w/ NIHSS > 6 and mismatch b/w ischemic
core and penumbra based on automated image analysis
 DAWN trial (2018) – showed benefit b/w 6-24 hr in patients w/ NIHSS > 10 and
mismatch b/w clinical severity and infarct volume on neuroimaging.
 Posterior circulation thrombectomy information is scarce, but can be considered up to 1224 hr after onset of stroke in the posterior circulation, in some cases.
o Risks:
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 Groin hematoma at insertion site
 Arterial dissection
 Intracerebral hemorrhage (low risk)
 Embolism
 Death
Permissive HTN (BP autoreg) and Induced HTN:
o Elevated BP ISO acute ischemic stroke is a physiologic response to improve perfusion through
collateral vessels.
o It is recommended that the BP be allowed to autoregulate (aka: permissive HTN) up to 220/110 if
thrombolytic therapy is not given or up to 180/105 if thrombolysis is given, as tolerated for the
first 24 hours after ischemic stroke.
o Some patients w/ LVO (ex: occlusion of ICA or prox MCA, etc) may have worsening of sx when
their BP decreases too low. Therefore, it may be necessary to provide agents such as
phenylephrine to maintain the patients BP above threshold.
AP and AC
o All patients w/ acute ischemic stroke who do not receive thrombolytics should receive aspirin
w/in 48 hours.
 IST and CAST trials (1997, 2000) – showed that aspirin w/in 48hr after acute ischemic
stroke reduced risk of second in-hospital stroke and increased survival to discharge, in
spite of small increased risk of ICH.
o In patients who receive thrombolytics, aspirin is generally initiated 24 hours after this if there is
no thrombolytic-related hemorrhage
o CHANCE and POINT trials (2013, 2018) – patients w/ minor strokes (who are not on AC for AFib)
benefit from a short course (21 days) of DAPT (clopidogrel 75mg + aspirin 81mg daily) to prevent
early recurrent ischemic stroke in the first 90 days out.
o The only time that acute anticoagulation (ex: heparin) is considered at time of stroke is if the
stroke is due to venous sinus thrombosis.
 Note, that some practitioners have considered AC for strokes in the following scenarios,
but studies to support this practice is scarce:
 Acute basilar artery thrombosis
 Artery to artery embolism from carotid stenosis while awaiting carotid
endarterectomy (TOAST trial)
 Acute cervical artery dissection (carotid or vertebral)
o CADISS trial (2015) – suggested that there is NO difference in outcome
between patients tx w/ AP vs AC
 Cardioembolism from AFib
o Especially if the stroke occurred in a patient w/ known hx of AFib who has
been off of AC or is subtherapeutically anticoagulated.
o Note: this is a risk-benefits situation.
o Note: AC is recommended for long-term secondary stroke prevention in
patients w/ stroke caused by AFib. When to reinitiate is the tricky part.
Surgical Interventions
o For large strokes of the Cerebellum or large MCA territory strokes, cerebral edema may raise
intracranial pressure, putting the patient at risk for herniation.
o Consider physical changes, hyperosmolar therapy, craniectomy, decompression
Good national reference:
o AHA/ASA Guidelines for Early Management of Patients w/ Acute Ischemic Stroke
Uncovering the Etiology of Ischemic Stroke:
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Screen for modifiable risk factors:
o HTN
o DM
o HLD
o Smoking
o Excessive alcohol use and/or drug use
Assess intracranial and cervical vasculature:
o MRA (TOF MRA may exaggerate degree of stenosis compared to CTA and Doppler)
o CTA
o Digital subtraction angiography
o Doppler ultrasound (carotids)
Assess the heart:
o ECG
o Telemetry
o TTE w/ bubble study
o ZioPatch (14-30 days)
Additional Studies to Consider:
o Implantable cardiac monitor (CRYSTAL AF study, 2014)
o DVT of b/l LE + MRV of pelvis (if PFO on TTE)
 May-Thurner syndrome – iliac vein thrombosis d/t compression of L common iliac vein by
the R common iliac artery
o Coag studies
 Antiphospholipid Abs (anti-cardiolipin, lupus anticoag, beta-2 glycoprotein Ab)
 Genetic mutations (protein C or S def, antithrombin III def, factor V leiden, prothrombin)
o Malignancy screening w/ PET scan or CT C/A/P
o LP if c/f vasculopathy
o TEE
o Blood Cx if c/f infectious endocarditis
Secondary Ischemic Stroke Prevention:
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No smoking/drugs/excessive alcohol
BP control; SBP goal < 130
HLD tx w/ statin and exercise; LDL goal < 70
Glucose control; A1c goal < 6.5
Antiplatelet agents (ex: aspirin, clopidogrel, ticagrelor) if not on anticoagulation
Management of AFib w/ rate control and anticoagulation (ex: apixaban)
Consider carotid endarterectomy or carotid artery stenting (if symptomatic severe stenosis)
Consider anticoagulation in patients w/ hypercoagulable state
Anti-platelets for secondary stroke prevention:
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MATCH 2004; CHARISMA 2006; SPS3 2012 – combined treatment w/ aspirin and clopidogrel is not more
effective than either alone in LONG-TERM secondary stroke prevention, and bleeding risk is increased
compared to either alone.
CHANCE 2013; POINT 2018 – use of aspirin and clopidogrel together is beneficial compared to aspirin
alone when used for the first 21 days following TIA or small ischemic stroke in preventing recurrent stroke
in the SHORT-TERM.
THALES 2020 – combination of ticagrelor and aspirin for 30 days after mild/moderate stroke (NIHSS 5) or
TIA also improves short term outcomes (at 30 days) compared to aspirin alone, though higher rates of
severe bleeding occur w/ ticagrelor and aspirin compared to aspirin alone.
SAMMPRIS – maximal medical therapy (included 90 days of aspirin and clopidogrel) was superior to
stenting for secondary stroke prevention in patients with stroke due to symptomatic intracranial stenosis;
however, there was no comparision of DAPT to antiplatelet monotherapy.
Anti-coagulation for secondary stroke prevention:
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If AFib is dx, anticoagulation w/ warfarin or a novel oral anticoag (apixaban, rivaraoxaban, dabigatran,
edoxaban) is indicated for secondary stroke prevention unless there is a strong contraindication; in such
patients an antiplatelet agent is used.
Use of novel oral anticoagulants for secondary prevention after an embolic stroke of undetermined
source (ESUS) has shown no benefit beyond aspiin and increased bleeding risk compared to aspirin
(NAVIGATE ESUS, 2018, RESPECT ESUS, 2019)
Other scenarios that AC may be warranted for secondary ischemic stroke prevention:
o Hypercoagulable states
 Genetic – protein C or S def, Antithrombin III def
 Acquired – antiphospholipid antibodies, malignancy
o Low cardiac EF d/t cardiomyopathy
 More benefit for primary stroke prevention (WARCEF trial of warfarin)
o Left ventricular thrombus
o Venous sinus thrombosis stroke
Many providers wait 2-4 weeks from time of an ischemic stroke before initiating anticoagulation if the size
of the stroke is large, in order to lower the risk of hemorrhagic conversion of the stroke.
Secondary Stroke Prevention in patients w/ Carotid Artery Stenosis:
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Symptomatic carotid stenosis refers to Stroke or TIA ipsilateral to stenosis