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Stroke (Cerebrovascular Ischemic Infarct)

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Stroke (Cerebrovascular Ischemic Infarct)

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Stroke

Overview

Overview

Here, we will develop a working knowledge of the evaluation and management of stroke (cerebral infarction). Note that we'll only address cerebral infarction, here (not spinal cord or peripheral nerve infarctions).

The first thing we need to address is what a stroke actually is, so start a table and let's provide a simple definition.

Definition of Stroke (& TIA)

Stroke & TIA

  • Both stroke and TIA (transient ischemic attack) involve focal neurological symptoms from a lack of cerebral perfusion (adequate blood flow).

Stroke

  • Stroke refers to an insult that produces permanent brain injury (even if the person fully recovers from the stroke deficits).

TIA (transient ischemic attack)

  • TIA is a transient phenomena that gets better on its own within 24 hours, without an MRI finding of stroke.
    Historically TIAs were treated less aggressively but now we lump them together in how we handle their diagnostic work-up and management, so the distinction is functionally unimportant.

Stroke Classifications

Next, let's address how we distinguish ischemic and hemorrhagic strokes -- this distinction is crucial to our evaluation and management.

Ischemic vs Hemorrhagic Strokes

  • Indicate that, very simply, an ischemic stroke is a non-bleeding stroke and a hemorrhagic stroke is a bleeding stroke (a "brain bleed").
  • Write-out that roughly 85% of strokes are ischemic whereas 15% are hemorrhagic.

Petechial hemorrhages & Hemorrhagic conversion

  • Two potentially confusing entities are petechial hemorrhages and hemorrhagic conversion.
  • Roughly one-third (30 - 40%) of ischemic strokes will have some degree of bleeding (what we call petechial hemorrhagic changes). Think of these as bruising in the area of stroke injury. With any issue injury, tiny vessels can be damaged that will produce blood spots.
  • This is different than hemorrhagic conversion of an ischemic stroke. Hemorrhagic conversion is a stroke that starts out as an ischemic, non-bleeding stroke, but then develops secondary significant bleeding.

Embolic vs Thrombotic Infarcts

As far as the causes of ischemic stroke go, there are two key types:

  • Embolic (when a clot travels from the body and becomes lodged in the brain).
  • Thrombotic (when a clot forms within the brain vessel, itself).

Ischemic Stroke Classifications

We can further classify ischemic strokes as:

  • Cardioembolic [~ 25% of ischemic strokes], which is when a clot travels from the heart into the brain.
    • For instance, a cardiac embolus from atrial fibrillation.
  • Lacunar (small vessel disease), [~ 25% of ischemic strokes]. These small vessel clots can occur from lipohyalinosis (gradual clogging of the vessel from cardiovascular disease), atheromatous disease (atherosclerotic plaque), or an embolism that becomes lodged deep in the brain.
    • Think of a deep perforator infarct within the basal ganglia.
  • Watershed strokes, which refers to hypoperfusion (low flow) in the borderzone between arterial territories. This is an important, underreported phenomenon that occurs in the setting of low blood flow (from low blood pressure or blood loss). It has a specific pattern of affecting the proximal upper and lower extremities.
  • Cryptogenic [~ 33% of ischemic strokes], which means no identifiable cause can be determined.
  • Miscellaneous, which we can use to remember:

Hemorrhagic Strokes

We address hemorrhagic strokes elsewhere but briefly indicate that they can involve:

  • Intracerebral hematoma, meaning within the brain tissue, such as (most commonly) the basal ganglia or a cerebral lobe, or other areas including (notably) the thalamus, pons, or cerebellum.
  • Extracerebral/intracranial hemorrhages, which are bleeds outside of the brain tissue but still within the skull (within the cranial vault). These are, primarily:

Stroke Patterns

If we know the stroke is ischemic, we want to try to use the history and exam to figure out the location.

So, let's walk through some common, key stroke syndrome pattens. As we do, let's build our Circle of Willis, which is a core to understanding stroke syndromes.

Diagram of the Circle of Willis

Cerebral Angiography of the Circle of Willis

Anterior Circulation

First, let's draw the anterior circulation, which is the internal carotid arterial system.

ICA

MCA

  • Indicate that Left MCA strokes will notably produce aphasia (language dysfunction), right facial droop and weakness and numbness that is more prominent in the right upper extremity than the extremity. The MCA covers the lateral two-thirds of the brain, which maps to the face and arm, primarily, (less-so the leg).
  • Right MCA strokes produce hemineglect, left facial droop, and (again), weakness and numbness that is more prominent in the left upper extremity than the lower extremity.

ACA

  • ACA strokes most notably produce contralateral lower extremity weakness (the ACA covers the medial one-third of the brain -- the leg maps to the convexity and inner portion of the brain), as well as certain apraxias.
    • An apraxia is the inability to perform a task that you have the sensorimotor capability to complete, in essence it's a sequencing issue. You have the ability to do each step in brushing your teeth but you can't put them all together to make sense of the task.

MCA Perforators

  • Show deep perforators off the MCA.
  • Indicate that there are numerous forms of subcortical: deep perforator infarction, including those that produce motor deficits (notably from the basal ganglia and internal capsule), and those that produce sensory deficits (notably from the thalamus -- these include somatosensory (what we feel) and also visuosensory (visual perception).

Posterior Circulation

Next, let's address the posterior circulation territory (from the vertebral arteries).

Vertebral arteries

PCA

  • Indicate that PCA territory strokes cause contralateral vision loss (vision maps to the back one-third of the brain) and they also often cause confusion. These strokes are easy to miss because visual fields may be the only deficit (and visual fields can be particularly hard to examine in confused patients).

Basilar Artery

PICA

Lastly include the posterior inferior cerebellar arteries (PICAs). PICA infarct produces Wallenberg syndrome (posterolateral medullary infarction) which produces ataxia (imbalance), sensory deficits, but, notably, there is preserved power. There are also various cranial nerve injuries along with Horner's syndrome, and, oddly hiccups.

Connecting Vessels

Emergency Stroke Therapies

Now, we are ready to consider steps in stroke management. First, let's dive in on emergency stroke therapies -- things we do to reverse the stroke. We have at our disposal IV thrombolytics (currently, tPA and TNK), which are "clot busting drugs" and endovascular therapies (thrombectomy, mechanical clot removal)

Thrombolytics: tPA (tissue plasminogen activator, altepase) and TNK (tenecteplase)

Initially, there were an extensive number of absolute contraindications to thrombolytics. Over time, we've backed off on these precautions, which means there is a ton of contradicting information in the literature about absolute vs relative contraindications.

See the following calculator regarding contraindications to tpa in ischemic stroke.

In general, it'll come down to the neurologist to decide whether or not IV thrombolytics are safe to give but it's helpful to know have some quick tips to understanding the decision-making behind whether or not to administer thrombolytics:

Select Key Parameters

Time Since Last Normal

  • The time since last normal (since stroke onset) must be less than 4.5 hours (it's less than 3 hours in 80 year-olds).
  • Wake-Up Strokes need to be treated within 4.5 hours of recognition AND if meet certain MRI of Brain criteria.

The following are some select absolute contraindications (not a complete list):

  • Active bleeding
  • Arterial puncture at a non-compressible site
  • Stroke within the past 3 months
  • History of intracranial hemorrhage
  • Recent major surgery
  • Anticoagulation
  • Ongoing SBP > 185 or DBP > 110 with aggressive treatment, because of increased bleeding risk.
  • If the patient is still symptomatic with blood glucose less than 50 mg/dL, there is too much risk the blood sugar is the cause of the symptoms to give thrombolytic. Pay attention that a fingerstick accucheck glucose can be inaccurate and an actual blood-draw is more reliable in cases where there accucheck doesn't match your expectations.

For further details see: - See American Heart Association Guidelines

Bleeding Risk

  • Indicate that there is an 7% risk of converting an ischemic stroke to a hemorrhagic stroke with thrombolytics.

endovascular therapy (thrombectomy)

Basic Criteria

In regards to endovascular therapy (thrombectomy), the basic criteria are the patient has a large vessel occlusion and there should be evidence of a sizable ischemic penumbra (amount of tissue at risk).

Ischemic Penumbra

The ischemic penumbra refers to tissue that is being starved of blood but is not yet completely infarcted (completely dead).

Select Parameters

Just like with thrombolytics, however, there are many factors that ultimately come into play in making the decision of whether or not to intervene. This factors include (but are not limited to): where the clot is (whether is in a proximal portion of the artery or a more distal branch), generally anterior circulation clots are more amenable to thrombectomy than posterior, the ischemic penumbra size, and time since onset of symptoms, as well as the degree of infarcted tissue.

Diagnostic Work-up

Now, let's move on to stroke management, which is primarily about further (secondary) stroke prevention.
We'll divide this section into essentials of diagnostic work-up and the basics of therapies to prevent stroke.

Routine Work-Up

A routine diagnostic work-up generally includes the following

Brain Imaging

  • A nonconstrast head CT, most importantly to help distinguish ischemic from hemorrhagic stroke.
  • An MRI of the Brain – which, is ideal to get, but not necessary for stroke management, despite how widely we rely on it.

Carotid Imaging

  • Imaging for carotid stenosis in anterior circulation strokes (CTA, MRA, carotid ultrasound).
  • Generally, CTA is preferred.
  • As a simple rule, only symptomatic high-grade carotid stenosis, should absolutely be intervened on (via carotid endarterectomy or carotid stent).
    • Symptomatic high-grade stenosis means narrowing of 70% or greater in a vessel that has produced a TIA or stroke.
    • Note that an occluded vessel (if there is 100% stenosis) should not be intervened on. The finding of an occluded vessel should make you cautious about blood pressure lowering. These patients are reliant on the remaining, open vessels to perfuse the territory the occluded vessel no longer can cover.

Echocardiography

  • Transthoracic Echocardiogram (TTE) in all-comers to look for a cardiac etiology for stroke (thrombus, atrial myxoma, etc…), and to assess for patent foramen ovale in cryptogenic stroke.
  • And the option for transesophageal echocardiogram (TEE) in suspected endocarditis or in cryptogenic stroke.
  • Note that there is a calculator to determine the risk/benefit of PFO closure but as a general rule, it is only advisable in young patients with no substantial stroke risk factors. See: Risk of Paradoxical Embolism (RoPE) Calculator

Telemetry Monitoring

  • In-hospital telemetry monitoring for atrial fibrillation.
  • 30-day event monitoring, post discharge, if you want to be more aggressive with monitoring.

Bloodwork

  • HgbA1C to look for occult diabetes mellitus
  • Lipid panel to especially assess the LDL (low density lipid) level.

Advanced Diagnostic Work-up

Select considerations include (but are not limited to)

Hypercoagulability

  • Assessment for a hypercoagulable state with coagulopathy labs with/without a malignancy w/u (such as a CT of chest/abdomen/pelvis).

Arterial Dissection

  • Arterial dissection w/u with CTA or MRA of Head & Neck.

Stroke Prevention

In terms of stroke prevention therapies, briefly:

Antithrombotics & Anticoagulants

Antithrombotics

  • Antithrombotic agents include a standard post-stroke regimen of aspirin + clopidogrel for 90 days then clopidogrel alone (you'll see variations on this regimen).

Anticoagulants

  • Anticoagulation for various reasons, including atrial fibrillation, but also basilar stenosis, or hypercoagulability (antiphospholipid syndrome).
  • Nonvalvular atrial fibrillation can be treated with direct oral anticoagulants (apixaban, rivaroxaban, etc…). As a general rule, patients with atrial fibrillation are at a five-fold increased risk of stroke.
  • The CHA2DS2-VASc calculator can be used to determine anticoagulation benefit in patients with atrial fibrillation.

Additional Treatments

Additional treatments include, but are not limited to:

Blood Pressure

  • There should be permissive hypertension early-on, when cerebral autoregulation is impaired. During this time, patients are reliant on good perfusion to feed the ischemic penumbra.
  • Over time, there should be cautious control: this is highly person-dependent and requires close consideration about each patient's stroke mechanism and situation, so no blanket rules should be applied, especially in early stroke management when cerebral autoregulation is impaired).

Cholesterol Management

  • High-dose statin therapy (eg, initially atorvastatin 80 mg/day).

Tobacco cessation & lifestyle modifications

  • Tobacco cessation and other lifestyle modifications (reasonable exercise and diet (Mediterranean diet is often recommended).

Obstructive sleep apnea

  • Obstructive sleep apnea evaluation and management (often overlooked).

Board Review

Getting ready for boards? Review these concise, bulleted high yield reviews for your exam.

USMLE & COMLEX-USA

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Clinical Practice Questions





References

"2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association." Accessed December 7, 2023. https://doi.org/10.1161/STR.0000000000000375.

"Acute Ischaemic Stroke: Recent Advances in Reperfusion Treatment | European Heart Journal | Oxford Academic." Accessed December 7, 2023. https://academic.oup.com/eurheartj/article/44/14/1205/6881118.

"Acute Ischemic Stroke | NEJM." Accessed December 7, 2023. https://www.nejm.org/doi/10.1056/NEJMcp1917030.

"Advances in Acute Stroke Treatment 2020 | Stroke." Accessed December 7, 2023. https://www.ahajournals.org/doi/10.1161/STROKEAHA.120.033744.

"Endovascular Therapy for Acute Stroke with a Large Ischemic Region | NEJM." Accessed December 7, 2023. https://www.nejm.org/doi/full/10.1056/nejmoa2118191.

Fisher, Marc, and Sean I. Savitz. "Pharmacological Brain Cytoprotection in Acute Ischaemic Stroke - Renewed Hope in the Reperfusion Era." Nature Reviews. Neurology 18, no. 4 (April 2022): 193–202. https://doi.org/10.1038/s41582-021-00605-6.

———. "Pharmacological Brain Cytoprotection in Acute Ischaemic Stroke — Renewed Hope in the Reperfusion Era." Nature Reviews Neurology 18, no. 4 (April 2022): 193–202. https://doi.org/10.1038/s41582-021-00605-6.

Grefkes, Christian, and Gereon R. Fink. "Recovery from Stroke: Current Concepts and Future Perspectives." Neurological Research and Practice 2, no. 1 (June 16, 2020): 17. https://doi.org/10.1186/s42466-020-00060-6.

Gu, Hong-Qiu, Chun-Juan Wang, Xin Yang, Xing-Quan Zhao, Yi-Long Wang, Li-Ping Liu, Yong Jiang, Hao Li, Yong-Jun Wang, and Zi-Xiao Li. "Clinical Characteristics, in-Hospital Management, and Outcomes of Patients with in-Hospital vs. Community-Onset Ischaemic Stroke: A Hospital-Based Cohort Study." The Lancet Regional Health – Western Pacific 38 (September 1, 2023). https://doi.org/10.1016/j.lanwpc.2023.100890.

Hurd, Mason Daniel, Isha Goel, Yasuyuki Sakai, and Yuji Teramura. "Current Status of Ischemic Stroke Treatment: From Thrombolysis to Potential Regenerative Medicine." Regenerative Therapy 18 (December 1, 2021): 408–17. https://doi.org/10.1016/j.reth.2021.09.009.

Kleindorfer, Dawn O., Amytis Towfighi, Seemant Chaturvedi, Kevin M. Cockroft, Jose Gutierrez, Debbie Lombardi-Hill, Hooman Kamel, et al. "2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association." Stroke 52, no. 7 (July 2021): e364–467. https://doi.org/10.1161/STR.0000000000000375.

Kuriakose, Diji, and Zhicheng Xiao. "Pathophysiology and Treatment of Stroke: Present Status and Future Perspectives." International Journal of Molecular Sciences 21, no. 20 (October 15, 2020): 7609. https://doi.org/10.3390/ijms21207609.

Liaw, Nicholas, and David Liebeskind. "Emerging Therapies in Acute Ischemic Stroke." F1000Research 9 (June 5, 2020): F1000 Faculty Rev-546. https://doi.org/10.12688/f1000research.21100.1.

Rossi, Rosanna, Seán Fitzgerald, Sara Molina, Oana Madalina Mereuta, Andrew Douglas, Abhay Pandit, Andreia M. Silva Santos, et al. "The Administration of rtPA before Mechanical Thrombectomy in Acute Ischemic Stroke Patients Is Associated with a Significant Reduction of the Retrieved Clot Area but It Does Not Influence Revascularization Outcome." Journal of Thrombosis and Thrombolysis 51, no. 2 (February 2021): 545–51. https://doi.org/10.1007/s11239-020-02279-1.

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