Ischemic Stroke

Snapshot

• A 60-year-old woman is immediately brought to the emergency department due to slurred speech and right arm and leg weakness. The patient was eating breakfast with her husband prior to developing these symptoms. Her husband denies his wife having any head trauma or recent surgeries. It has been one hour since her symptoms began. Medical history is significant for hypertension and type II diabetes mellitus. On physical exam, the patient can comprehend but speech is impaired. There is 0/5 strength in both right upper and lower extremities. Non-constrast computerized tomography (CT) of the head does not show any intracranial bleeds. After further evaluation, she was started on intravenous tPA.

Introduction

• Clinical definition
  • a sudden loss of blood supply to an area of the brain leading to
    • a neurologic deficit
      • the deficit depends on which area of the brain is affected
• Epidemiology
  • incidence
    • 3rd leading cause of death in the United States
  • risk factors 
    • hypertension
    • diabetes
    • smoking
    • atrial fibrillation  
    • mechanical valves
    • valvular abnormalities
    • patent foramen ovale 
    • significant decreased ejection fraction
    • hypercoagulable state
    • family history
    • prior history of
      • stroke
      • vascular disease
• Pathogenesis
  • ↓ blood supply to a region of the brain for enough time to result in infarcted (liquefactive necrosis) cerebral tissue
    • the most vulnerable to ischemic hypoxia is the
      • hippocampus 
        • Specifically, CA1 pyramidal neurons of the hippocampus 
    • after 5 minutes, irreversible neuronal damage occurs
    • causes of this ↓ blood supply include
      • embolic infarction
        • a clot (typically) from one region of the body travels in the blood stream and occludes a vessel supplying the brain
        • consider in cases of sudden neurologic deficit
          • maximal neurologic deficit occurs at onset
        • large vessel infarcts are commoly due to an embolism
      • thrombotic infarction
        • a clot is locally formed in the wall of the blood vessel usually
          • where an atherosclerotic plaque is found
        • typically has a stuttering course

Large vs. Small Vessel Infarcts
Type	Comments
Large vessel	Occlusion of the major blood vessels such as themiddle cerebral arteryOcclusion is most often caused by emboli
Small vessel	Occlusion of the small penetrating arteries that supply the deep cerebral structures such asbasal gangliathalamusinternal capsuleSometimes called lacunar infarcts

Ischemic Stroke Syndromes

Ischemic Stroke Syndromes
Anterior Circulation Stroke	Findings
Middle cerebral artery (MCA) stroke	Symptoms contralateral weakness and sensory loss in theface and upper limbhemineglect if the non-dominant hemisphere is involvedaphasiaBroca’s aphasia if the superior division of the MCA is involved in the dominant hemisphereWernicke’s aphasia if the inferior division of the MCA is involved in the dominant hemispheremay also result in a right superior quadrant visual field defectLesion localizationmotor and sensory cortices distributed by theMCAWernicke’s or Broca’s area
Anterior cerebral artery (ACA) stroke	Symptomscontralateral weakness and sensory loss in thelower extremity Lesion localizationmotor and sensory cortices supplied by theACA
Lenticulostriate artery stroke	Symptomscontralateral weakness and sensory loss in theface and body in the absence ofcortical signs (e.g., neglect)Commentsa common site of lacunar infarcts secondary to chronic hypertension leading tolipohyalinosis
Posterior Circulation Stroke	Findings
Medial medullary (Dejerine) syndrome	Secondary to occlusion of theparamedian branches of the anterior spinal artery and/or vertebral arterySymptomstriadipsilateral hypoglossal palsycontralateral hemiparesiscontralateral lemniscal sensory loss (e.g., proprioception)Lesion localizationlateral corticospinal tractcaudal medullamedial lemniscus
Lateral medullary (Wallenberg) syndrome	Secondary to occlusion of theposterior inferior cerebellar artery (PICA) orvertebral arterySymptomsdysphagiahoarsness↓ gag reflex vertigo↓ pain and temperature sensation of theipsilateral facecontralateral bodyHorner’s syndromeataxiaLesion localizationlateral medulla involving thenucleus ambiguusvestibular nucleilateral spinothalamic tractspinal trigeminal nucleussympathetic fibersinferior cerebellar peduncle
Lateral pontine syndrome	Secondary toanterior inferior cerebellar artery Symptomsfacial paralysis↓ salivation, lacrimation, and taste from the anterior tongue (2/3rd)vertigo↓ pain and temperature sensation of theipsilateral facecontralateral bodyipsilateral Horner’sataxiaLesion localizationLateral pons involving thefacial nucleusvestibular nucleispinothalamic tractspinal trigeminal nucleussympathetic fibersmiddle and inferior cerebellar peduncle
Locked-in syndrome	Secondary to occlusion of thebasilar artery Symptomsquadraplegiabulbar manifestationsable to perform vertical eye movementspreserved conciousnessLesion localizationventral pons, lower midbrain, and medulla affecting thecorticospinal and corticobulbar tractsoculomotor nerve nucleiparamedian pontine reticular formation
Posterior cerebral artery (PCA) occlusion	Symptomscontralateral hemianopsia with macular sparingLesion localizationoccipital lobe
Weber syndrome	Secondary to occlusion of thepeduncular perforating branches of the posterior cerebral arterySymptomsipsilateral ptosisipsilateral oculomotor palsycontralateral hemiparesisLesion localizationventral midbrain involving thecerebral peduncles that contain thecorticospinal and corticobulbar tractsoculomotor fibers

Presentation

• Symptoms
  • dependent on which area of the brain is involved
    • review chart above
• Physical exam
  • dependent on which area of the brain is involved
• review chart above

Imaging

• Computerized tomography (CT)
  • indications
    • a non-contrast head CT should be performed in patients presenting with symptoms concerning for stroke and
      • to exclude intracerebral hemorrhage
    • CT angiography should be performed to assess for a thrombus and to evaluate the carotid and vertebral neck arteries
• Magnetic resonance imaging (MRI)
  • indications
• MRI/MRA can aid in assessing infarct volume for further management

Studies

• Labs
  • complete blood count
  • basal metabolic panel
  • prothrombin time
  • partial thromboplastin time
  • cardiac enzymes
• Histology

Histology
Time after Ischemic Event	Histologic findings
12-24 hours	Red neuronthe cytoplasm is eosinophilicthe nuclei is pyknoticcell body shrinkageloss of Nissl substance
1-3 days	Tissue necrosisNeutrophillic infiltration
3-5 days	Macrophage (microglial) infiltration
1-2 weeks	Reactive gliosisVascular proliferation
> 2 weeks	Glial scar

Differential

• Transient ischemic attack
  • key distinguishing factors 
    • no evidence of infarction on brain imaging
    • symptoms are transient and completely resolve after the event
    • major risk factor for ischemic stroke in the future
  • treatment 
    • lifestyle modification and medical treatment (aspirin, statins, antihypertensives, and glycemic control) to reduce future ischemic stroke risk 
• Hemorrhagic stroke

Treatment

• Medical
  • intravenous tPA
    • indication
      • used in patients presenting with
        • stroke symptoms, excluded to have an intracranial hemorrhage, and time since symptom onset is within the last 3-4.5 hours
• Operative
  • mechanical thrombectomy
    • indication
      • used in patients presenting with
        • stroke symptoms, excluded to have an intracerebral hemorrhage, and a proximal large artery occlusion involving the anterior circulation whether or not the patient received tPA
• time since symptom onset within the last 8 hours

Complications

• Intracerebral hemorrhage
• Seizures
• Aspiration pneumoniae