Basic Science Clinical
Vascular Headache Epilepsy Immunology Movement Neuromuscular Dementia Other Topics Neurosurgery
Clinical
Vascular
12 notes available
1 Last Minute Review 2 Cerebrovascular Anatomy 3 Stroke Syndromes 4 Acute Stroke Management 5 Stroke Workup 6 Secondary Prevention 7 Intracerebral Hemorrhage 8 SAH & Aneurysms 9 SDH & EDH 10 Venous Thrombosis 11 Vascular Malformations 12 Special Vascular Topics
Clinical › Vascular

Stroke Syndromes

Ischemic Stroke: Pathophysiology & Clinical Syndromes

What Do You Need to Know?

  • Definitions of ischemic stroke, CNS infarction, and TIA (tissue-based vs. time-based)
  • Cerebral blood flow thresholds, ischemic penumbra, and the ischemic cascade
  • Modifiable and non-modifiable stroke risk factors
  • CHA2DS2-VASc scoring and anticoagulation indications
  • TOAST classification and ischemic stroke subtypes
  • Clinical stroke syndromes by vascular territory (ICA, MCA, ACA, PCA)
  • Aphasia types, localization, and distinguishing features
  • Classic lacunar syndromes and their anatomical correlates
  • Brainstem stroke syndromes (medullary, pontine, midbrain)
  • TIA risk stratification and the ABCD2 score
Definitions
  • Ischemic stroke: Episode of neurological dysfunction caused by focal cerebral, spinal, or retinal infarction
  • CNS infarction: Cell death attributable to ischemia, based on pathological/imaging evidence of focal ischemic injury in a defined vascular distribution, OR clinical evidence persisting ≥24 hours
  • TIA: Transient neurological dysfunction from focal ischemia without acute infarction on imaging
💎 Board Pearl

Up to 1/3 of patients with symptoms <24 hours have infarction on imaging. Modern TIA definition is tissue-based (no infarction), NOT time-based. DWI-positive = stroke, even if symptoms resolved.

Epidemiology
  • ~795,000 new or recurrent strokes per year in the US
  • 5th leading cause of death and leading cause of long-term disability
  • 87% ischemic, 13% hemorrhagic (10% ICH, 3% SAH)

Ischemic Stroke Subtypes by Frequency

  • Cardioembolism: 30% (most common ischemic subtype)
  • Large-vessel atherosclerosis: 20%
  • Small-vessel disease (lacunar): 20%
  • Cryptogenic: ~27%
  • Other determined: 3%
Pathophysiology of Ischemic Stroke

Cerebral Blood Flow Thresholds

  • Normal CBF: 50 cc/100g/min
  • ~20 cc/100g/min: EEG changes; neurons still viable
  • <10 cc/100g/min: Irreversible neuronal death

The Ischemic Penumbra

  • Core (CBF <10): Irreversible infarction within minutes
  • Penumbra (CBF 10–20): Electrically silent but structurally intact — SALVAGEABLE tissue — target of reperfusion therapy
  • Without reperfusion, penumbra progressively converts to core over hours

Ischemic Cascade

  • 30 seconds: Metabolism altered → 1 minute: Neuronal function ceases → 5 minutes: Chain of events leading to infarction
  • Energy failure → loss of ion homeostasis → glutamate excitotoxicity (NMDA/AMPA) → Ca2+ overload → free radicals → apoptosis/necrosis

Pathological Evolution of Infarction

  • 6–24 hours: Coagulation necrosis — “red neurons” (eosinophilic neuronal shrinkage), polymorphonucleocytes around vessels
  • 3–4 days: Edematous swelling, red cell extravasation
  • 72–96 hours: Liquefaction — macrophage invasion; “glitter cells” (lipid-laden macrophages)
  • Weeks–months: Astrocyte hypertrophy then hyperplasia; macrophages clear debris at ~1 cc/month
💎 Board Pearl

Penumbra (CBF 10–20) = target of reperfusion. “Time is brain” — ~1.9 million neurons die per minute during LVO. “Red neurons” = hallmark of acute ischemic injury on pathology.

Stroke Risk Factors

Non-Modifiable

  • Age: Strongest determinant; risk rises exponentially >65
  • Sex: Males higher risk (women have more deaths due to longer lifespan)
  • Race: African American > Hispanic > Caucasian for extracranial disease; Asian populations have higher intracranial stenosis

Modifiable

  • Hypertension: Most important modifiable risk factor — 4x increased risk
  • Atrial fibrillation: Nonvalvular AF = 5% per year stroke risk; valvular AF = 17x higher risk
  • Diabetes: 1.8–6.0 relative risk
  • Hyperlipidemia: 1.5 RR; treat with statins for atherosclerotic disease
  • Smoking: 1.9x risk; cessation reduces risk by 50% in 1 year, to baseline by 5 years
  • Carotid stenosis: Asymptomatic ≥70% = ~2%/year risk; symptomatic ≥70% = ~24.5% in 2 years

CHA2DS2-VASc Score

Factor Points
Congestive heart failure1
Hypertension1
Age 65–741
Age ≥752
Diabetes mellitus1
Stroke/TIA history2
Vascular disease (PAD, MI, aortic plaque)1
Female Sex1
  • 0 points: Low risk → aspirin or nothing
  • 1 point: Consider anticoagulation
  • ≥2 points: Anticoagulation recommended
💎 Board Pearl

HTN is the #1 modifiable risk factor (4x risk). CHA2DS2-VASc ≥2 = anticoagulate. Age ≥75 and prior stroke/TIA each get 2 points (highest weighted). Smoking cessation cuts risk 50% in 1 year.

TOAST Classification
Category Criteria Typical Features
1. Large-artery atherosclerosis≥50% stenosis or occlusionCortical or subcortical infarct >1.5cm; ipsilateral atherosclerosis
2. CardioembolismIdentified cardiac sourceAF, mechanical valve, MI, LV thrombus, IE; often cortical, may be multiterritory
3. Small-vessel (lacunar)Classic lacunar syndrome + <1.5cm subcortical infarctPure motor, pure sensory, sensorimotor, ataxic hemiparesis, clumsy-hand-dysarthria
4. Other determinedRare cause identifiedDissection, vasculitis, hypercoagulable states
5. CryptogenicNo etiology despite workup~27% of ischemic strokes; consider ESUS
💎 Board Pearl

Lacunar = <1.5cm subcortical + classic syndrome. Large-artery = ≥50% stenosis + cortical/large subcortical infarct. If both large-artery and cardiac source are present, classify as cryptogenic.

Clinical Stroke Syndromes

ICA Stroke

  • Often presents as MCA ± ACA territory (depending on collaterals)
  • Key clue: Ipsilateral monocular blindness (amaurosis fugax/CRAO) + contralateral hemiparesis = ICA
  • Carotid T occlusion: Dense contralateral hemiplegia, gaze deviation, aphasia/neglect, hemianopia

MCA Stroke

  • M1 stem: Dense contralateral hemiplegia (face, arm, leg) + hemianesthesia + HH + gaze deviation toward lesion + global aphasia (L) or anosognosia/neglect (R)
  • Superior division: Face & arm >> leg weakness + Broca’s aphasia (dominant)
  • Inferior division: Minimal weakness + Wernicke’s aphasia (dominant) or neglect (non-dominant) + superior quadrantanopia/HH
  • Gerstmann syndrome (dominant angular gyrus): Finger agnosia + acalculia + right-left disorientation + agraphia

ACA Stroke

  • Contralateral leg >> arm/face weakness and sensory loss
  • Urinary incontinence, abulia, alien limb, grasp reflex
  • Bilateral ACA: Paraplegia, akinetic mutism, frontal personality changes

PCA Stroke

  • Cortical: Contralateral homonymous hemianopia (macular sparing possible); alexia without agraphia (L PCA + splenium); prosopagnosia (bilateral)
  • Bilateral PCA: Cortical blindness → Anton syndrome (denial of blindness); Balint syndrome (oculomotor apraxia + optic ataxia + simultanagnosia)
  • Thalamic (Dejerine-Roussy): Deep sensory loss → delayed thalamic pain with hyperpathia and athetotic posturing

Aphasia Quick Reference

Type Comprehension Fluency Repetition
Broca’sNormalImpairedImpaired
Wernicke’sImpairedNormal (fluent)Impaired
ConductionNormalNormalImpaired
Transcortical motorNormalImpairedNormal
Transcortical sensoryImpairedNormalNormal
GlobalImpairedImpairedImpaired
💎 Board Pearl

Transcortical aphasias = PRESERVED repetition (perisylvian area intact, infarct in border zone). Conduction aphasia = IMPAIRED repetition only (arcuate fasciculus). Anton = cortical blindness + denial. Gerstmann = dominant angular gyrus.

Lacunar Stroke Syndromes

Lacunar infarcts are <15mm, from small penetrating end-artery occlusion. Pathology: lipohyalinosis or microatherosclerosis, primarily from hypertension.

Syndrome Location Features
Pure motor hemiparesisPosterior limb IC, corona radiata, ponsFace, arm, leg weakness (equal); NO sensory/visual/cortical signs
Pure sensory strokeVPL/VPM thalamusNumbness/paresthesias face, arm, leg; NO weakness
Sensorimotor strokeThalamus + posterior limb ICHemiparesis + hemisensory loss
Ataxic hemiparesisPons, IC, deep grey nucleiWeakness + ipsilateral ataxia (out of proportion to weakness)
Dysarthria-clumsy handAnterior limb IC, genu, ponsFacial weakness, dysarthria, dysphagia + hand clumsiness
💎 Board Pearl

Lacunar strokes have NO cortical signs (no aphasia, neglect, hemianopia, gaze deviation). If cortical signs are present, it’s NOT lacunar. Pure motor hemiparesis is the most common. HTN is the strongest risk factor.

Brainstem Stroke Syndromes

Key principle: “Crossed findings” = ipsilateral cranial nerve deficit + contralateral motor/sensory deficit = brainstem localization.

Medullary Syndromes

Syndrome Artery Key Features
Lateral medullary (Wallenberg)PICA / vertebralVertigo, nystagmus; ipsilateral face pain/temp loss (descending V); contralateral body pain/temp loss (spinothalamic); dysphagia, hoarseness (nucleus ambiguus); ipsilateral Horner’s; ipsilateral ataxia
Medial medullaryAnterior spinalContralateral hemiparesis (pyramid) + contralateral dorsal column loss + ipsilateral tongue weakness (CN XII) — tongue deviates toward lesion
Hemimedullary (Babinski-Nageotte)VertebralCombined medial + lateral medullary syndromes

Pontine Syndromes

Syndrome Artery Key Features
Lateral inferior pontineAICAIpsilateral CN VII + CN VIII (hearing loss, vertigo) + ataxia + contralateral pain/temp loss
Millard-GublerParamedian basilarIpsilateral CN VI + CN VII + contralateral hemiplegia
Locked-in syndromeBasilar (ventral pons)Quadriplegia + anarthria; preserved consciousness and vertical eye movements only

Midbrain Syndromes

Syndrome Location Key Features
WeberCerebral peduncleIpsilateral CN III + contralateral hemiplegia
ClaudeTegmentum (red nucleus)Ipsilateral CN III + contralateral cerebellar ataxia and tremor
BenediktTegmentum + baseIpsilateral CN III + contralateral hemiplegia + tremor/chorea (red nucleus)
ParinaudDorsal midbrainParalysis of upward gaze + convergence-retraction nystagmus + light-near dissociation + lid retraction (Collier sign)
💎 Board Pearl

Weber = CN III + contra hemiplegia (most tested midbrain syndrome). Wallenberg = most tested brainstem syndrome overall. Locked-in = bilateral ventral pons; patient is CONSCIOUS — do not confuse with coma. AICA = the one with hearing loss.

TIA & ABCD2 Score
  • Stroke risk after TIA: ~4% at 2 days, ~9% at 90 days — TIA is a medical emergency
  • Workup: brain MRI, CTA/MRA, cardiac monitoring, echo
  • CHANCE trial: Dual antiplatelet (aspirin + clopidogrel) for 21 days after high-risk TIA or minor stroke → reduced recurrent stroke risk

ABCD2 Score

Factor Criteria Points
Age>60 years1
Blood pressure>140/901
ClinicalUnilateral weakness2
Speech impairment without weakness1
Duration10–59 min1
≥60 min2
DiabetesPresent1
  • Score 0–3: Low risk (~3% at 90 days)
  • Score 4–5: Moderate risk (~10%)
  • Score 6–7: High risk (~18%) → urgent inpatient workup
💎 Board Pearl

TIA = medical emergency (~4% stroke risk within 2 days). ABCD2 ≥4 = urgent workup. CHANCE: dual antiplatelet (ASA + clopidogrel) for 21 days after high-risk TIA/minor stroke. DWI-positive = stroke by definition, not TIA.

High-Yield Localization Clues
  • Cortical signs (aphasia, neglect, hemianopia) = NOT lacunar — think large vessel or cardioembolic
  • Face/arm > leg = MCA; Leg > arm = ACA; Isolated hemianopia = PCA
  • Crossed findings (ipsilateral CN + contralateral body) = brainstem
  • Ipsilateral monocular vision loss + contralateral hemiparesis = ICA
  • Multiterritory infarcts = think cardioembolic source

References

  1. Adams HP Jr, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke (TOAST). Stroke. 1993;24(1):35-41.
  2. Caplan LR. Caplan’s Stroke: A Clinical Approach. 5th ed. Cambridge University Press; 2016.
  3. Sacco RL, Kasner SE, Broderick JP, et al. An updated definition of stroke for the 21st century (AHA/ASA). Stroke. 2013;44(7):2064-2089.
  4. Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack (CHANCE). N Engl J Med. 2013;369(1):11-19.
  5. Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet. 2007;369(9558):283-292.