Stroke Recognition and Management

Ischemic mechanisms (TOAST framework)

• Large-artery atherosclerosis: plaque at the carotid bifurcation, vertebral origin, or intracranial vessels causes artery-to-artery embolism or low-flow watershed infarction; amaurosis fugax and carotid bruit point here.
• Cardioembolism: atrial fibrillation is the prototype (stasis in the left atrial appendage); also recent anterior MI with mural thrombus, dilated cardiomyopathy, mechanical valves, infective endocarditis (septic emboli, may cause mycotic aneurysm), and paradoxical embolism through a PFO in a young patient with DVT.
• Small-vessel (lacunar) disease: chronic hypertension and diabetes drive lipohyalinosis of penetrating lenticulostriate, thalamoperforator, and pontine branches, producing subcortical infarcts without cortical signs.
• Cryptogenic/ESUS: no source found after standard workup; prompts prolonged rhythm monitoring for occult AF.
• Other determined causes: cervical artery dissection (neck trauma, chiropractic manipulation, Marfan/Ehlers-Danlos — think young patient with neck pain plus Horner syndrome), sickle cell disease, vasculitis, hypercoagulable states (antiphospholipid syndrome), moyamoya, and stimulant use.

Hemorrhagic mechanisms

• Hypertensive intracerebral hemorrhage: rupture of Charcot-Bouchard microaneurysms, classically basal ganglia/putamen, thalamus, pons, cerebellum.
• Cerebral amyloid angiopathy: recurrent lobar hemorrhage in the elderly.
• Structural/iatrogenic: AVM, saccular aneurysm rupture (SAH), anticoagulants and thrombolytics.

Ischemic Stroke (87% of cases)

• Arterial occlusion and hypoperfusion: Thrombus or embolus blocks cerebral vessel, causing immediate cessation of blood flow to downstream territory; neurons depend almost exclusively on oxidative metabolism and cannot tolerate ischemia beyond 3-10 minutes
• Core vs. penumbra concept: The ischemic core represents irreversibly damaged tissue (infarction), while the penumbra is hypoperfused but still viable tissue at risk of infarction; reperfusion therapy's goal is salvaging penumbral tissue before it becomes core
• Excitotoxicity cascade: Ischemia causes failure of ATP-dependent Na+/K+-ATPase, leading to cellular depolarization, calcium influx, glutamate release, and activation of NMDA receptors; excessive intracellular calcium triggers caspase activation and apoptosis
• Inflammatory response: Ischemic tissue triggers microglia activation, cytokine release (TNF-α, IL-1), and leukocyte infiltration, causing secondary damage hours to days after initial insult
• Blood-brain barrier disruption: Ischemia damages tight junctions and endothelial cells, increasing permeability and promoting vasogenic edema, particularly during reperfusion

Hemorrhagic Stroke

• Direct tissue damage: Extravasated blood causes mass effect, increased intracranial pressure, and direct neuronal injury from blood products
• Secondary injury mechanisms: Iron and thrombin released from clot trigger inflammation, oxidative stress, and microglial activation; hemoglobin breakdown products (bilirubin, heme) are directly toxic to neurons
• Hematoma expansion: Active bleeding continues in the first few hours after symptom onset; aggressive blood pressure management is critical to minimize expansion

• Sudden focal neurological deficits: Face drooping, arm weakness, speech difficulty (classic "FAST" signs); deficits appear suddenly without prodrome, distinguishing stroke from gradual processes
• Motor deficits with typical distribution: Contralateral hemiparesis (arm and leg) from motor cortex or internal capsule involvement; facial drooping is often ipsilateral to lesion when involving motor nucleus in brainstem
• Sensory loss: Contralateral sensory loss (sharp/dull discrimination and proprioception) indicating thalamic or cortical involvement
• Visual disturbances: Homonymous hemianopia (occipital lobe), monocular vision loss (amaurosis fugax suggests carotid disease), diplopia (brainstem or cranial nerve involvement)
• Language disorders: Expressive aphasia (Broca's area, non-fluent) vs. receptive aphasia (Wernicke's area, fluent but nonsensical); expressive aphasia preserves comprehension while receptive spares production
• Neglect and coordination: Unilateral neglect (right parietal stroke), ataxia and dysmetria (cerebellar stroke), gait abnormalities
• Brainstem stroke red flags: Bilateral symptoms, cranial nerve involvement with contralateral motor findings ("crossed syndromes"), locked-in syndrome, respiratory compromise
• Hemorrhagic stroke presentations: Often more severe headache than ischemic stroke, nausea/vomiting from increased ICP, declining level of consciousness, rapid neurological deterioration
• Seizures: Present in 5-10% of acute ischemic strokes; hemorrhagic strokes have higher seizure risk (10-20%), especially with lobar or large volume bleeds

• NIH Stroke Scale (NIHSS): Standardized 11-item assessment scoring 0-42; higher scores correlate with larger infarcts and worse outcomes; essential for communication and research but should NOT delay imaging or treatment initiation
• Non-contrast head CT (gold standard initial imaging): Performed emergently to rule out hemorrhagic stroke before thrombolytic therapy; sensitivity ~90% for acute blood; CT may appear normal in first 6-12 hours of acute ischemic stroke (false reassurance—proceed with treatment if clinical suspicion is high)
• CT perfusion (CTP) and CT angiography (CTA): CTA identifies arterial occlusions and can help select thrombectomy candidates; CTP demonstrates perfusion deficits showing core/penumbra mismatch; increasingly used for extended window patient selection (6-24 hours)
• MRI with DWI/ADC: Diffusion-weighted imaging (DWI) shows restricted diffusion in ischemic tissue within minutes (appears bright/hyperintense), more sensitive than CT for acute ischemia; ADC (apparent diffusion coefficient) confirms true restriction; FLAIR shows subacute changes; MRI is gold standard but may delay treatment if not immediately available
• Serum labs: Glucose (hyperglycemia worsens outcome), platelets, coagulation studies, troponin, renal function; these should not delay imaging
• ECG: Identifies atrial fibrillation, acute MI, or other sources of cardioembolism
• Modified Rankin Scale (mRS) and TOAST classification: mRS (0-6) used for outcome assessment; TOAST (Trial of Org 10172 in Acute Stroke Treatment) classifies stroke etiology (large vessel disease, cardioembolism, small vessel, undetermined)
• Imaging interpretation pitfalls: Hypodensity in early ischemic stroke may be subtle (loss of gray-white differentiation, obscuration of insular ribbon); hemorrhagic conversion appears as new hyperdensity on follow-up imaging

ACUTE ISCHEMIC STROKE - Time-Dependent Management

• IV alteplase (tissue plasminogen activator) - FIRST-LINE within 4.5 hours: Dose 0.9 mg/kg (maximum 90 mg); give 10% as bolus over 1 minute, remainder over 60 minutes; number needed to treat (NNT) = 9 to prevent one adverse outcome when given within 3 hours; benefit decreases significantly after 3 hours but still measurable through 4.5 hours; established by NINDS rt-PA Stroke Study
• Inclusion criteria: Confirmed acute ischemic stroke by CT, age 18-80 (guideline suggests benefit extends to 80+), symptom onset <4.5 hours (last known normal time used)
• Key exclusion criteria: Recent surgery/trauma, bleeding history, INR >1.7, platelets <100,000, uncontrolled hypertension (>185/110 acceptable if controlled with medications), current anticoagulation use
• Hemorrhagic transformation risk: 6-7% symptomatic in clinical trials; higher risk with older age, large infarcts, and diabetes

• Mechanical thrombectomy - SECOND-LINE for large vessel occlusion (LVO): Superior to IV thrombolytics alone for proximal artery occlusions (ICA, M1 MCA); multiple randomized controlled trials (MR CLEAN, EXTEND-IA, ESCAPE) demonstrated NNT = 3-4; dramatically expanded treatment window
• Standard window: 6-24 hours with favorable imaging (penumbral mismatch on CTP/MRI or minimal core infarct)
• Technique: Mechanical catheter-based recanalization using aspiration or stent retrievers; MERCI/Penumbra devices most commonly used
• Indications for thrombectomy: NIHSS ≥6, proximal occlusion on imaging (ICA, M1, M2 MCA), ASPECTS score ≥6 (Alberta Stroke Program Early CT Score predicting good outcome potential)
• Relative contraindications: Severe coagulopathy,

Treatment-related emergencies

• Symptomatic hemorrhagic transformation after alteplase (emergency): plasmin-mediated fibrinolysis in reperfused, blood-brain-barrier–damaged tissue; signaled by acute neurologic decline, new headache, vomiting, or an abrupt BP surge during or after infusion. Stop the infusion, obtain STAT non-contrast CT, send fibrinogen/coagulation studies, and give cryoprecipitate (or fibrinogen concentrate) with an antifibrinolytic such as tranexamic acid, per AHA/ASA; consult neurosurgery.
• Orolingual angioedema (airway emergency): bradykinin accumulation from plasmin activation, markedly more common in patients on ACE inhibitors; typically contralateral tongue/lip swelling. Prepare for difficult airway; treat with antihistamines, corticosteroids, and epinephrine if progressive.
• Reperfusion/procedural injury: thrombectomy can cause vessel perforation, dissection, distal embolization to a new territory, or contrast nephropathy.

Complications of the infarct itself

• Malignant MCA edema (emergency): cytotoxic then vasogenic edema peaking roughly 2–5 days, most common in young patients with large hemispheric infarcts and little brain atrophy; heralded by declining consciousness, pupillary asymmetry, and midline shift. AHA/ASA supports decompressive hemicraniectomy in selected patients.
• Cerebellar infarct with swelling (emergency): fourth-ventricle compression causes obstructive hydrocephalus and brainstem compression; suboccipital decompression ± external ventricular drain.
• Hemorrhagic stroke sequelae: hematoma expansion in the first hours, intraventricular extension with hydrocephalus, seizures, and — after aneurysmal SAH — delayed cerebral ischemia from vasospasm around days 3–14 (nimodipine is standard prophylaxis) plus hyponatremia from SIADH or cerebral salt wasting.
• Aspiration pneumonia: impaired swallow and cough; AHA/ASA mandates a bedside dysphagia screen before any oral intake, including medications.
• Venous thromboembolism: immobility; intermittent pneumatic compression is recommended.
• Cardiac and systemic: neurogenic stunned myocardium/*takotsubo*, arrhythmias, troponin elevation, UTI, pressure ulcers.
• Late: post-stroke depression, spasticity and contractures, central post-stroke pain, epilepsy, vascular cognitive impairment, and recurrent stroke.

• Check a fingerstick glucose before anything else: hypoglycemia is the classic stroke mimic and is instantly reversible. Other mimics examiners plant: Todd paralysis after a seizure, hemiplegic migraine, and conversion disorder.
• The single best next step in a suspected acute stroke is non-contrast head CT: it exists to exclude hemorrhage before thrombolysis, not to "confirm" ischemia — an entirely normal CT in the first hours does not argue against stroke.
• Blood pressure targets differ by plan: per AHA/ASA, before and for 24 hours after thrombolysis keep BP below roughly 185/110 and 180/105 respectively; if no reperfusion therapy is given, permissive hypertension is allowed unless BP is extreme, because dropping it collapses collateral flow to the penumbra. The classic distractor is aggressively normalizing BP in an untreated ischemic stroke.
• Antiplatelets are withheld for 24 hours after alteplase (repeat imaging first). For a minor non-cardioembolic stroke or high-risk TIA not given lysis, AHA/ASA endorses short-course dual antiplatelet therapy (aspirin plus clopidogrel) begun early and then narrowed to monotherapy.
• Atrial fibrillation means anticoagulation, not aspirin, for secondary prevention; timing of initiation is deferred based on infarct size and hemorrhage risk. Anticoagulation intensity is guided by CHA₂DS₂-VASc per the ACC/AHA/HRS atrial fibrillation guideline.
• Lacunar syndromes have no cortical signs: pure motor hemiparesis (posterior limb of internal capsule), pure sensory stroke (VPL thalamus), ataxic hemiparesis, and dysarthria–clumsy hand. Aphasia, neglect, or gaze deviation means a cortical/large-vessel event and should trigger vessel imaging.
• Symptomatic high-grade carotid stenosis ipsilateral to the deficit warrants revascularization (carotid endarterectomy in most candidates), and AHA/ASA favors performing it early rather than months later.
• Wake-up stroke is not automatically excluded: the clock starts at last known well, but advanced imaging (perfusion mismatch or DWI–FLAIR mismatch) can still identify treatable patients. Also give high-intensity statin therapy to essentially all ischemic stroke patients.