Lit Matters 3: NINDS: t-PA for acute ischemic stroke + Lit Matters 4: PECARN - Pediatric Head Injury Algorithm

Alteplase for acute ischemic stroke offers a modest functional benefit when given early, but that benefit is inseparable from a real intracranial hemorrhage risk. PECARN remains the benchmark pediatric head injury rule, identifying children at very low risk of clinically important traumatic brain injury and helping avoid unnecessary CT radiation.

Alteplase for Acute Ischemic Stroke

• Landmark treatment window: NINDS established that IV alteplase can improve 3-month functional outcomes when used within 3 hours of clearly defined ischemic stroke onset, anchoring modern reperfusion care.
• Functional benefit signal: The clearest effect was a 12% absolute increase in minimal or no disability at 3 months, while the 24-hour neurologic endpoint was not convincingly different.
• Hemorrhage tradeoff: Symptomatic intracranial hemorrhage rose in the first 36 hours with alteplase, reinforcing that thrombolysis is a benefit-harm decision rather than an uncomplicated win.
• Trial fragility concern: The study was methodologically rigorous but carried a fragility index of 3, one reason alteplase split emergency medicine and neurology for years. We get into that controversy in the episode.
• Eligibility discipline: Baseline noncontrast head CT excluding hemorrhage, a measurable NIHSS deficit, and blood pressure below 185/110 were central gatekeepers for treatment in the original trial.

PECARN Pediatric Head Injury Algorithm

• Clinically important TBI target: PECARN was built to predict clinically important traumatic brain injury, defined by outcomes that matter: neurosurgery, prolonged intubation, death, or a significant admission with CT findings.
• Age-specific decision rules: The rule uses separate predictor sets for children younger than 2 years and those 2 years or older, a key reason it performs better than one-size-fits-all head injury tools.
• Low-risk rule performance: In children under 2, the validated low-risk rule had 100% sensitivity and 100% negative predictive value for clinically important TBI, with no missed neurosurgical cases.
• Older child validation: For children 2 years and older, the low-risk rule reached 96.8% sensitivity and 99.95% negative predictive value; the rare misses did not require neurosurgery.
• CT reduction rationale: Only 0.9% of the cohort had clinically important TBI, yet more than a third underwent CT, making PECARN especially valuable for avoiding radiation in minor blunt head trauma. We walk through the bedside use of that distinction in the chapter.