What are the current stroke guidelines for acute assessment (including NIH Stroke Scale), eligibility for intravenous alteplase and mechanical thrombectomy, management of intracerebral hemorrhage, and secondary prevention strategies?

Recent Stroke Guidelines: Acute Assessment, Treatment, and Prevention

Acute Stroke Assessment

All patients with suspected acute ischemic stroke should undergo immediate neurological assessment using the NIH Stroke Scale (NIHSS), which quantifies stroke severity and guides treatment decisions. 1

• The NIHSS is an 11-item scale that evaluates level of consciousness, visual fields, extraocular movements, facial palsy, motor strength, ataxia, sensory loss, language, dysarthria, and neglect. 1
• A shortened 8-item version (NIHSS-8) demonstrates 97.5% sensitivity and 96.9% specificity compared to the full scale, making it suitable for rapid emergency department triage when time is critical. 2
• Stroke severity rating scales should be applied to all stroke and TIA patients during initial evaluation. 1
• Patients with NIHSS ≥6 or any disabling deficit warrant immediate evaluation for large-vessel occlusion and potential endovascular therapy. 1

Immediate Imaging Protocol

Non-contrast CT of the head is the only mandatory imaging before administering IV alteplase and must be performed within 25 minutes of hospital arrival to exclude intracranial hemorrhage. 1, 3

• The CT scan must also assess for early ischemic changes using the Alberta Stroke Program Early CT Score (ASPECTS); changes involving >1/3 of the middle cerebral artery territory contraindicate thrombolysis. 1, 3
• For patients with suspected large-vessel occlusion (NIHSS ≥6, cortical signs, severe deficit), obtain CT angiography from the aortic arch to the vertex immediately after the non-contrast CT—but do not delay IV alteplase for this imaging. 1, 3
• CT perfusion is not required for patients presenting within 6 hours and should only be obtained for: (1) unknown time of onset (wake-up stroke), (2) presentation >6 hours with confirmed large-vessel occlusion being considered for thrombectomy, or (3) extended-window thrombolysis evaluation. 1, 3

Intravenous Alteplase Eligibility and Administration

Standard Dosing Protocol

Administer IV alteplase at 0.9 mg/kg (maximum 90 mg total) with 10% given as an IV bolus over exactly 1 minute, followed by the remaining 90% infused over 60 minutes. 1, 3, 4

• This dosing applies to all eligible patients regardless of age, stroke severity, or body weight. 3, 4
• The maximum dose cap of 90 mg should be maintained even for patients >100 kg, as higher absolute doses increase symptomatic intracerebral hemorrhage risk (2.6% vs 1.7%) and mortality without improving outcomes. 5
• Lower doses (0.6 mg/kg) are not recommended, as the ENCHANTED trial failed to demonstrate non-inferiority for the primary outcome of death or disability, despite fewer hemorrhages. 6

Time Windows and Eligibility Criteria

0–3 Hour Window (Broadest Eligibility)

All patients meeting basic inclusion criteria should receive IV alteplase within 3 hours of symptom onset, regardless of age >80 years, stroke severity (NIHSS >25), or current single/dual antiplatelet therapy. 1, 3

• Treatment within 1.5 hours yields an odds ratio of 2.81 for favorable outcome (modified Rankin Scale 0-1) compared to placebo. 3
• The absolute benefit is 12% (39% vs 26% achieving minimal/no disability), corresponding to a number-needed-to-treat of 8.3. 3
• Each 15-minute delay in treatment exponentially reduces the probability of favorable outcome—door-to-needle time should be <60 minutes in ≥50% of patients. 3, 7

3–4.5 Hour Extended Window (ECASS III Criteria)

Patients presenting between 3 and 4.5 hours may receive alteplase if they meet ECASS III criteria, which impose four additional exclusions beyond the 0-3 hour window. 1, 3

• Additional exclusions for the 3-4.5 hour window: age >80 years, any oral anticoagulant use (regardless of INR), NIHSS >25, or combined history of diabetes and prior stroke. 1, 3
• The odds ratio for favorable outcome versus placebo in this window is 1.40 (95% CI 1.05–1.85). 3

Beyond 4.5 Hours (Imaging-Selected Patients)

For patients with unknown onset time (e.g., wake-up stroke) or presenting >4.5 hours, alteplase may be considered if DWI-FLAIR mismatch is present on MRI, indicating symptom onset likely <4.5 hours ago. 1, 3

• The WAKE-UP trial demonstrated that DWI-FLAIR mismatch-selected patients had significantly higher rates of favorable outcome (53.3% vs 41.8%; adjusted OR 1.61,95% CI 1.06–2.36). 1, 3
• However, parenchymal hemorrhage type 2 risk was higher (4% vs 0.4%), though confidence intervals were wide due to early trial termination. 1, 3
• A pilot study (SAIL ON) showed feasibility and potential safety of treating wake-up stroke patients within 4.5 hours of awakening using non-contrast CT alone, with no symptomatic hemorrhages in 20 patients, but this requires validation in larger trials. 8

Mandatory Pre-Treatment Requirements

Three requirements must be met before initiating alteplase: (1) non-contrast CT excluding hemorrhage, (2) blood pressure <185/110 mmHg, and (3) bedside glucose >50 mg/dL (>2.7 mmol/L). 1, 3, 4

• Do not wait for complete laboratory panels (CBC, INR, PTT, creatinine) before administering alteplase unless there is clinical suspicion of coagulopathy or thrombocytopenia. 3, 7
• Blood pressure must be maintained <180/105 mmHg for 24 hours after alteplase infusion. 1, 3, 7
• Use labetalol or nicardipine to achieve blood pressure targets before and after thrombolysis. 3, 7

Absolute Contraindications

Absolute contraindications to IV alteplase include: 1, 3

• Intracranial hemorrhage on initial CT scan
• Platelet count <100,000/mm³
• INR >1.7 or aPTT >40 seconds
• History of any prior intracranial hemorrhage
• Ischemic stroke or severe head trauma within the preceding 3 months
• Intracranial or intraspinal surgery within 3 months
• Clinical presentation suggesting subarachnoid hemorrhage
• Gastrointestinal malignancy or bleeding within 21 days

Relative Contraindications and Special Scenarios

Several clinical scenarios require individualized risk-benefit assessment but are not absolute contraindications: 1, 3

• Warfarin use with INR ≤1.7: Alteplase may be reasonable (Class IIb). 1, 3
• Seizure at stroke onset: Alteplase is reasonable if residual deficits are clearly stroke-related (Class IIa). 1, 3
• Small unruptured intracranial aneurysm (<10 mm): Alteplase is reasonable and probably recommended (Class IIa). 1
• Giant unruptured aneurysm (≥10 mm): Usefulness and risk are uncertain (Class IIb). 1
• Cerebral microbleeds (CMBs) 1-10 on MRI: Alteplase is reasonable (Class IIa). 1
• High CMB burden (>10): Treatment may be associated with increased hemorrhage risk; may be reasonable if potential benefit is substantial (Class IIb). 1
• Recent myocardial infarction (within 3 months): Alteplase is reasonable if the MI was non-STEMI or STEMI involving right/inferior myocardium (Class IIa); may be reasonable for left anterior STEMI (Class IIb). 1
• Concurrent acute MI and stroke: Treat with stroke-dose alteplase followed by percutaneous coronary intervention if indicated (Class IIa). 1

Mechanical Thrombectomy for Large-Vessel Occlusion

Indications and Patient Selection (0-6 Hour Window)

Mechanical thrombectomy with stent retrievers is the standard of care for anterior circulation large-vessel occlusions (internal carotid artery, M1 segment of MCA, or proximal M2 divisions) presenting within 6 hours of symptom onset. 1, 3

• Eligibility criteria for the 0-6 hour window: 1
  • Pre-stroke modified Rankin Scale 0-1 (functionally independent)
  • NIHSS ≥6 (though lower scores may be considered for disabling deficits)
  • ASPECTS ≥6 on non-contrast CT or small ischemic core on CT perfusion
  • Age ≥18 years (no upper age limit, though advanced age affects prognosis)
• Administer IV alteplase to all eligible patients even when mechanical thrombectomy is planned—do not delay thrombolysis to assess thrombectomy eligibility, and do not wait to evaluate the response to IV alteplase before proceeding to catheter angiography. 1, 3, 7
• The combination of IV alteplase plus thrombectomy achieves recanalization rates of 72-88% with modern stent retrievers, compared to near-zero with IV therapy alone for high clot burden. 3, 7
• The number-needed-to-treat with thrombectomy for one additional good outcome is approximately 3-4 patients. 3
• Symptomatic intracerebral hemorrhage rates are similar between thrombectomy (4.4%) and control (4.3%) groups. 3

Extended Window Selection (6-24 Hours)

For patients presenting 6-24 hours after last known well with anterior circulation large-vessel occlusion, use advanced imaging (CT perfusion or diffusion-weighted MRI) to identify candidates with small ischemic core and large penumbra. 1, 3

• DAWN trial criteria (6-24 hours): 1
  • NIHSS ≥10 and ischemic core 0-21 mL (if age >80 years) or 0-31 mL (if age <80 years), OR
  • NIHSS ≥20 and ischemic core 31 to <51 mL (if age <80 years)
• DEFUSE-3 criteria (6-16 hours): 1
  • Ischemic core volume <70 mL
  • Mismatch ratio ≥1.8
  • Mismatch volume ≥15 mL
• Moderate-to-good pial collateral filling on CTA or evidence of CTP mismatch predict better response to thrombectomy. 1

Technical Goals and Monitoring

The technical goal of mechanical thrombectomy is achieving modified Thrombolysis in Cerebral Infarction (mTICI) grade 2b/3 reperfusion, with groin puncture initiated within 6 hours of symptom onset for early-window patients. 1, 7

• Door-to-groin puncture time should be minimized, as every 30-minute delay decreases the chance of good functional outcome by 8-14%. 7
• Posterior circulation occlusions (basilar artery, P1, P2 segments) should be considered for thrombectomy depending on symptom severity, patient factors, and operator expertise. 1

Intracerebral Hemorrhage Management

For patients with acute intracerebral hemorrhage (ICH) and hypertension, initiate antihypertensive therapy immediately upon hospital arrival with a target systolic blood pressure <140 mmHg achieved within 1 hour. 1

• The proportion of ICH patients achieving adequate blood pressure control (<140 mmHg systolic) in the first 24 hours is a key performance metric. 1
• For patients with anticoagulation-related ICH, administer adequate anticoagulation reversal treatment immediately upon hospital arrival. 1
• Time from hospital arrival to administration of reversal agents is a critical quality indicator. 1
• Patients with large hemispheric infarction who are eligible should be treated with decompressive hemicraniectomy. 1

Post-Thrombolysis Monitoring and Management

After alteplase administration, perform neurological assessment and vital signs every 15 minutes during and for 2 hours after infusion, then every 30 minutes for 6 hours, then hourly for 16 hours. 3, 7

• If severe headache, acute hypertension, nausea, or vomiting occur, stop the infusion immediately and obtain an emergent CT scan. 3
• Symptomatic intracerebral hemorrhage occurs in 2.4-6.4% of alteplase-treated patients. 3, 7
• Avoid all antiplatelet agents and anticoagulants for 24 hours after alteplase; obtain a follow-up CT scan at 24 hours before initiating these agents. 3, 7
• Delay placement of nasogastric tubes, indwelling bladder catheters, and intra-arterial pressure catheters until after the 24-hour monitoring period. 3
• Maintain oxygen saturation ≥94% with supplemental oxygen. 3, 7
• Treat fever >38°C with antipyretics. 7
• Initiate continuous cardiac monitoring for at least 24 hours to detect arrhythmias. 7

Secondary Prevention Strategies

Antiplatelet Therapy

Initiate aspirin 160-300 mg within 24-48 hours of stroke onset for all ischemic stroke patients not receiving anticoagulation; after alteplase, delay aspirin for at least 24 hours. 3

• For minor stroke (NIHSS ≤3 for clopidogrel or NIHSS ≤5 for ticagrelor) or high-risk TIA (ABCD² ≥4), initiate dual antiplatelet therapy (aspirin plus clopidogrel or aspirin plus ticagrelor) within 24 hours of symptom onset. 1
• Dual antiplatelet therapy should be continued for 21-90 days, then transitioned to single-agent therapy. 1

Anticoagulation for Atrial Fibrillation

All stroke or TIA patients with atrial fibrillation should receive oral anticoagulation unless contraindicated. 1

• Direct oral anticoagulants (DOACs) are preferred over warfarin for most patients with non-valvular atrial fibrillation. 1
• The proportion of atrial fibrillation patients receiving oral anticoagulation is a key performance metric. 1

Vascular Imaging and Intervention

All stroke or TIA patients should undergo complete brain and extracranial/intracranial vascular imaging within 48 hours of symptom onset. 1

• Patients with severe ipsilateral internal carotid artery stenosis (70-99%) should undergo carotid endarterectomy within 14 days of symptom onset. 1
• For symptomatic carotid stenosis 50-69%, endarterectomy is recommended for selected patients. 1

Cardiac Monitoring and Patent Foramen Ovale

All stroke or TIA patients should receive at least 24 hours of cardiac monitoring to detect paroxysmal atrial fibrillation. 1

• Extended cardiac monitoring (30-day event monitors or implantable loop recorders) should be considered for cryptogenic stroke. 1
• Cryptogenic stroke patients with patent foramen ovale (PFO), aged 18-60 years, should be assessed by a neurocardiology team or combined cardiology-neurology consultation; PFO closure should be offered to appropriate candidates. 1

Risk Factor Management

All stroke and TIA patients require comprehensive cardiovascular risk factor modification: 1

• Blood pressure: Assess and treat all patients; target <130/80 mmHg for most patients
• Lipids: Achieve LDL-cholesterol <1.8 mmol/L (70 mg/dL) with high-intensity statin therapy
• Diabetes: Target HbA1c ≤7% for patients with diabetes
• Lifestyle modifications:
  • Engage in low-to-moderate intensity aerobic activity for ≥10 minutes, 4 days per week
  • Reduce sodium intake to <2000 mg daily
  • Limit alcohol to ≤2 drinks daily for men, ≤1 drink daily for women
  • Provide smoking cessation counseling to all active smokers
• Body weight: Estimate BMI at the time of the event and provide weight management counseling

Acute Stroke Unit Care and Rehabilitation

All stroke patients should be admitted to a dedicated acute stroke unit with specialized nursing care, continuous monitoring, and early mobilization protocols. 1

• Patients should be screened or assessed for swallowing deficits before any oral intake. 1
• Aspirin 160-300 mg should be administered within the first 48 hours (after the 24-hour post-thrombolysis period if applicable). 1
• All patients should receive DVT prophylaxis with intermittent pneumatic compression devices or subcutaneous heparin/LMWH if immobile. 1
• Early mobilization should begin as soon as safely possible, with time from stroke onset to first mobilization tracked as a performance metric. 1
• Patients should receive education about stroke, warning signs, and risk factor modification before discharge. 1

Discharge Planning and Follow-Up

Before discharge, establish a comprehensive health and social care plan with the patient and family, ensure a safe home environment, and confirm caregivers have adequate support. 1

• Patients with disabilities after stroke should be followed up within 72 hours by specialist stroke rehabilitation teams. 1
• Those with ongoing rehabilitation goals or difficulty performing activities of daily living require continued access to specialized stroke services. 1
• Implement a planned transition from structured in-hospital aerobic exercise to self-directed physical activity at home or in the community. 1
• Review health and social care needs of stroke survivors and their caregivers at 6 months and annually thereafter, including those in care homes. 1

Critical Pitfalls to Avoid

• Do not withhold alteplase from patients >80 years old presenting within 0-3 hours; age is only an exclusion in the 3-4.5 hour window. 1, 3
• Do not exclude patients with NIHSS >25 from alteplase in the 0-3 hour window; severe stroke is not a contraindication when treatment is early. 1, 3, 4
• Do not delay IV thrombolysis to obtain or interpret CTA for thrombectomy evaluation; administer alteplase first, then proceed with vascular imaging. 1, 3, 7
• Do not wait for complete laboratory panels beyond bedside glucose before initiating alteplase; each minute of delay worsens outcomes. 3, 7
• Do not obtain CT perfusion for patients presenting within 6 hours without large-vessel occlusion; it provides no actionable information and only delays treatment. 1, 3
• Do not wait to assess the response to IV alteplase before proceeding to mechanical thrombectomy; proceed directly to angiography when large-vessel occlusion is confirmed. 1, 3, 7
• Do not apply myocardial infarction alteplase dosing (accelerated regimen) to stroke patients; always use the stroke-specific 0.9 mg/kg protocol. 3, 4