EMC’s “Ep 208 Paradigm Shift in Ischemic Stroke Management Part 1: Disabling Strokes”

Today, I review, link to, and excerpt from Emergency Medicine Cases‘ Ep 208 Paradigm Shift in Ischemic Stroke Management Part 1: Disabling Strokes.*

*Helman, A. Himmel, W. Lin, K. A Paradigm Shift in Ischemic Stroke Management Part 1: Disabling Strokes. Emergency Medicine Cases. October, 2025. https://emergencymedicinecases.com/ischemic-stroke-management-disabling-strokes. Accessed November 10, 2025

All that follows is from the above outstanding resource.

Ep 208 Paradigm Shift in Ischemic Stroke Management Part 1: Disabling Strokes

We are amidst a paradigm shift in the emergency management of acute ischemic stroke. The traditional way of categorizing ischemic strokes as ‘minor’ vs ‘major’ is no longer relevant to what we do in the ED. It’s now about ‘disabling’ vs ‘non-disabling’ strokes. And this is no small change. This categorization dictates urgency of ED work-up and treatments, imaging choices, treatment decisions and goals of care. In this Part 1 or our 2-part main episodes EM Cases podcast series on management of ischemic stroke with Dr. Walter Himmel and Dr. Katie Lin, we answer questions like: How can we best rapidly determine if an ischemic stroke is disabling or non-disabling at the bedside? In what ways are ‘wake up strokes’ managed uniquely and what’s the latest thinking on their pathophysiology? How should we best prioritize imaging depending on timing, geography and resources? How do we best predict large vessel occlusion amenable to endovascular therapy (EVT) at the bedside? How can we efficiently establish goals of care at the bedside to inform our emergency decision making around strokes? Which is better for thrombolysis in ischemic stroke – Tenecteplase or Alteplase? How have contraindications to IV thrombolysis changed over the last decade? When should we consider bridge therapy with EVT after IV thrombolysis? What are 4 key items the ED physician should have ready for the stroke neurologist on the first call? and many more…

Podcast: Play in new window

 Download (Duration: 1:36:12 — 88.1MB)

Podcast production, sound design & editing by Anton Helman; Voice editing by Braedon Paul

Written Summary and blog post by Anton Helman October, 2025

Major vs Minor Stroke – An impractical categorization of stroke

The historical “major (NIHSS ≥5) vs minor (NIHSS  <5)” dichotomy is convenient for research stratification but problematic clinically: so-called “minor” presentations (e.g., isolated aphasia, dense hemianopia, disabling distal limb weakness of the dominant hand) frequently carry marked functional morbidity and should not be excluded from reperfusion solely on the basis of a low NIHSS. The contemporary approach reframes categorization around disability and patient-centred outcomes rather than an arbitrary score threshold.

NIHSS is a descriptor, not a decision tool. A low score can still be functionally catastrophic and should not exclude reperfusion.

Pitfall: One pitfall in the decision to employ IV thrombolytics and/or endovascular therapy (EVT) is to assume that a minor stroke (NIHSS <5) is not eligible for such therapies. Many patients who have an NIHSS <5 have disabling stroke that do fulfill criteria for these aggressive, time dependent therapies.

Major vs Minor Stroke – An impractical categorization of stroke

The historical “major (NIHSS ≥5) vs minor (NIHSS  <5)” dichotomy is convenient for research stratification but problematic clinically: so-called “minor” presentations (e.g., isolated aphasia, dense hemianopia, disabling distal limb weakness of the dominant hand) frequently carry marked functional morbidity and should not be excluded from reperfusion solely on the basis of a low NIHSS. The contemporary approach reframes categorization around disability and patient-centred outcomes rather than an arbitrary score threshold.

NIHSS is a descriptor, not a decision tool. A low score can still be functionally catastrophic and should not exclude reperfusion.

Pitfall: One pitfall in the decision to employ IV thrombolytics and/or endovascular therapy (EVT) is to assume that a minor stroke (NIHSS <5) is not eligible for such therapies. Many patients who have an NIHSS <5 have disabling stroke that do fulfill criteria for these aggressive, time dependent therapies.

Disabling vs Non-disabling – The practical categorization of ischemic stroke

Reframe the first decision point as disabling vs non-disabling. A structured conversation around values helps determine whether a deficit is “disabling” for this patient. At the bedside, determine whether the deficit is disabling for this patient—i.e., likely to compromise independent living, employment, or meaningful communication. Cortical signs (aphasia/dysphasia, neglect, gaze deviation, hemianopia) combined with significant motor deficits imply a high pretest probability of large-vessel occlusion (LVO) and generally warrant aggressive reperfusion pathways when imaging and contraindication screening align with benefit. [Emphasis added] A patient-centred frame improves both selection for reperfusion and shared decision-making. Classify the presentation as disabling when it threatens independence or meaningful quality of life (speech/language, vision, ambulation, dominant-hand function, or level of consciousness), and nondisabling when deficits are unlikely to impact these domains if untreated. This “disability” lens operationalizes risk-benefit conversations around things patients value (home, work, communication), rather than a numerical threshold.

• Core principle: Focuses on deficits that disrupt independence and meaningful activities, e.g., speech, vision, motor, consciousness.

• Features typically considered disabling:

  • Speech: Major speech deficit (severe aphasia or dysarthria compromising functional communication)

  • Motor: Dense motor loss (especially dominant hand/arm, profound leg weakness)

  • Vison: Amaurosis fugax, cortical blindness, dense hemianopia.

  • Consciousness/Brainstem: depressed level of consciousness, locked-in syndrome from basilar occlusion.

• Patient and family context:

  • What is disabling varies with occupation, age, lifestyle.

  • Shared decision-making is vital for subtle deficits.

• Implementation: ED teams must weigh patient’s premorbid status, functional demands, and goals of care.

Bedside script (shared decision-making): “There are time-sensitive treatments that can help, but they carry bleeding risks (~3–5% symptomatic ICH with IV thrombolysis).* Given your deficits and what matters to you, are these risks acceptable to try to preserve speech/hand/ambulation?”

Below is Dr. Lin’s basic ischemic stroke algorithm based on the ‘disabling’ vs ‘non-disabling’ categorizations of stroke to be used as a framework for these 2 EM Cases episodes on ED management of ischemic stroke.

The Importance of Time Windows in Disabling Ischemic Stroke Management

• 0–4.5 h: May be eligible for IV thrombolysis (per local protocol); a subset also proceeds to EVT when CTA confirms large vessel occlusion (LVO) – see ‘bridge therapy’ below.
• 4.5–6 h: IV thrombolysis generally excluded; EVT remains indicated when CTA demonstrates large vessel occlusion (LVO)—no additional imaging beyond CTA is required for selection in this interval.
• 6–24 h (late window): Selection hinges on advanced imaging beyond CTA to demonstrate a small infarct core with a robust penumbra (e.g., favorable CTP, multiphase CTA collaterals, or MRI mismatch).

The Significance of ‘Last Seen Normal’ in Ischemic Stroke Management

• Definition: Last time patient was at neurologic baseline (not just symptom onset).
• Utility: Determines upper time boundary for treatment eligibility.
• Application: Especially critical in unwitnessed and “wake-up” strokes.
• Acute therapies: IV thrombolysis usually offered up to 4.5 hours, EVT up to 24 hours, all measured from “last seen normal.”
• Evidence: Late window trials (DAWN, DEFUSE3) justify aggressive intervention ≤24 hours with favorable imaging.

“Last seen normal” (LSN) anchors onset time when symptoms are unwitnessed; however, LSN should not be conflated with tissue viability. Patients presenting close to 24 h from LSN may still be candidates for late-window endovascular therapy (EVT) if imaging reveals a small infarct core with a substantial penumbra. Practically, LSN documents chronology; selection for therapy is driven by imaging-demonstrated salvageable tissue.

“Wake Up” Strokes – Where urgent imaging is paramount

A wake up stroke occurs when precise onset is unknown, but “last seen normal” is when patient went to sleep. Most wake-up strokes occur just before awakening due to physiologic changes (cortisol/BP spikes), a time at which there is likely to be more salvagable tissue that can be saved by EVT than if the time of the stroke occurred upon falling asleep. Imaging may be more likely to reveal salvageable tissue, making many wake-up stroke patients candidates for EVT. Many patients treated in the extended (≤24 h) reperfusion window in landmark thrombectomy trials (Dawn, Extended IA, Diffuse 3) were wake-up strokes; physiology (diurnal BP/cortisol surge) suggests many such events occur shortly before waking. Unknown onset should trigger, not throttle, reperfusion work-up. Do not exclude patients from EVT on time grounds for wake up strokes; instead, expedite imaging for all suspected wake-up strokes.

Pitfall: Do not exclude wake up stroke patients from EVT on time grounds alone; instead, expedite imaging for all suspected wake-up strokes, as many of these strokes occur close to the time of awakening.

Treat wake up strokes as time-critical like any stroke: Non-contrast CT to exclude hemorrhage + CTA head/neck to assess for LVO; add advanced imaging (CTP, multiphase CTA, or MRI DWI–FLAIR mismatch) when beyond standard IV thrombolysis windows or onset is uncertain. Consider IV thrombolytics (TNK or tPA per local protocol) when advanced imaging shows salvageable tissue (e.g., DWI–FLAIR mismatch or favorable CTP profile) and there are no contraindications. If CTA shows LVO, proceed down your EVT pathway. In unknown/late windows, use CTP/multiphase CTA/MRI to confirm a small core with salvageable penumbra. Bridging lysis is still reasonable when eligible (anatomy may preclude rapid catheter access, and early recanalization can occur while mobilizing the suite).

Bottom line: Wake-up strokes are imaging emergencies. Use vascular and perfusion/collateral imaging to identify candidates for IV thrombolysis and/or EVT, and keep decisions anchored to disability and salvageable tissue, not the clock. Wake-up strokes have an a priori higher probability of treatment eligibility than witnessed late-window strokes because the true ischemic duration may be short. The systems error is deprioritizing these patients as “too late.” Instead, prioritize expedited imaging (non-contrast CT to exclude hemorrhage; CTA head/neck to define occlusion; and—when beyond standard IV thrombolysis windows—advanced imaging such as CTP, multiphase CTA, or MRI for core-penumbra or DWI–FLAIR mismatch). Unknown onset should trigger, not throttle, reperfusion work-up.

Clinical Determination of Large Vessel Occlusion – The scores are not reliable!

Look for dramatic arm weakness plus cortical signs (aphasia/dysphasia, neglect, gaze deviation, hemianopia). This constellation implies high LVO probability → CTA ASAP to determine eligability for EVT and rapid transfer if needed. Clinical LVO tools (e.g., VAN, ACT-FAST (see blelow), Cincinnati, LAMS) are reasonably sensitive (~80–90%) for pre-imaging triage, but lack specificity; when a disabling cortical syndrome is present, pursue vascular imaging even if a scale is “negative”.

Pitfall: A “negative” FAST or VAN or Cincinnati score does not rule out a LVO stroke that may be eligable for EVT. Prioritize CTA for any disabling focal deficit whenever feasible.

Establishing Goals of Care and Determining Premorbid Status in Ischemic Stroke Management

Acute stroke decisions are time-critical; pair rapid medical assessment with a focused values discussion:

Dr. Lin’s 4 part approach to establishing goals of care:

1. Signpost the urgency/time-sensitivity and importance of the conversation.
2. Summarize what’s happening and the options (IV Thrombolysis/EVT or not), including best/worst-case outcomes and bleeding risk for both options.
3. Align recommendations with what matters most to the patient (include 1. home independence, 2. return to work, 3. acceptable long term disability).
4. Give your simplified recommendation.

Two-question premorbid screen:

1. Where does the patient live? (independent home vs assisted vs long-term care)
2. How do they mobilize? (independent vs aid vs bed-bound)
   This rapidly informs whether aggressive therapy aligns with baseline quality of life.

Rapid, structured values clarification should occur in parallel with medical work-up. Discuss realistic best-/worst-case outcomes, bleeding risk, and likelihood of returning to independent living, home residence, and work—factors that most influence stroke survivors and families.

Systemic Thrombolytics in Ischemic Stroke Management

Indications for IV Thrombolysis in Ischemic Stroke Management

1. Age: 18 years or older.
2. Disabling: Symptoms suggestive of an acute ischemic stroke that are deemed to be disabling, regardless of whether there has been some early improvement. Disabling symptoms are specifically referenced as an inclusion criterion (e.g., aphasia, dominant‐hand weakness, dense hemianopia, etc.). When in doubt, our experts advise erring on the side of treating if the patient is in window, has no contraindications, and the deficit is disabling — a normal CTA does not rule out eligibility.
3. Time Window: Ability to initiate treatment within 4.5 hours from the time the patient was last seen normal. Unknown onset / wake-up stroke: still consider IVT if imaging selection and local stroke protocol support it; wake-up patients are often more likely to be treatable—expedite imaging rather than exclude on the basis of the clock.
4. Plain CT Head: Diagnostic imaging (typically non-contrast CT) ruling out intracranial hemorrhage.
5. Absence of Contraindications: Absence of absolute exclusion criteria, including but not limited to: recent head trauma, previous intracerebral hemorrhage, active internal bleeding, recent major surgery, or severe uncontrolled hypertension. Blood pressure can be made safe for lysis: Able to reduce/maintain BP to <180/110 before thrombolysis and <180/105 after; avoid hypotension. Note that age >80 and prior stroke + diabetes are no longer absolute exclusions; warfarin acceptable if INR <1.7; UFH off ≥4 h with normal PTT; LMWH >24 h; DOACs >48 h; untreated intracranial AVM remains a contraindication; judgment required for recent GI/GU bleeding and intracranial tumors (e.g., meningioma generally acceptable).

Pitfall: A common pitfall is assuming that a normal CTA deems the patient ineligible for IV thrombolysis. It is age of patient, disability, time and absence of thrombolysis contraindications that dictates eligibility for IV thrombolysis, not the findings on CTA.

The Evidence for Systemic Thrombolytics in Ischemic Stroke Management

• Most evidence supports admin ≤4.5hr from onset (window opened from 3hr in 2008 to 4.5hr)
• Improves functional outcome (modified Rankin score, NNT ~7 for good outcome if given promptly)
• Best results ≤90min; efficacy diminishes with time but remains present ≤4.5hr
• Risks:
  • Symptomatic intracerebral hemorrhage 3–5%
• Door-to-needle:
  • Goal is ≤30–60 minutes

Tenectaplase (TNK) vs Alteplase (tPA) – Which one is better?

• Tenecteplase (TNK):

• • FDA approved (2025) and guideline-recommended
  • Single-bolus dosing simplifies workflow/logistics (versus continuous 1hr infusion for TPA)
  • May reduce dosing errors, improve EMS and transport process

Multiple trials—including the Canadian ACT-QUICKR—support non-inferiority of tenecteplase (TNK) to alteplase (tPA) for functional outcomes, with signals toward superior reperfusion and a favorable safety profile in some cohorts. Logistics strongly favor TNK: single-bolus administration is thought to reduce dosing errors and simplify interfacility transfer when bridging to EVT.

Given at least non-inferior efficacy and pragmatic advantages, many systems are transitioning to TNK as first-line IV thrombolytic where available; agent selection remains protocol-dependent and should be harmonized with regional stroke pathways.

Contraindications to IV Thrombolytics in Ischemic Stroke Management Update 2025

• Absolute contraindications:

• • Active major bleeding, intracranial mass (mets, AV malformations), recent neurosurgery, uncontrolled hypertension (>185/110 prior to administration)
  • Known coagulopathy (platelets <100,000, INR ≥1.7)

• Relative contraindications—more liberal than before:

• • Minor GI/GU bleeds, age >80, prior stroke/diabetes no longer strict, but risk remains increased
  • DOACs: Must be held ≥48hr, LMWH ≥24hr
  • Oral anticoagulants: INR <1.7 required

Contraindications to IV Thrombolytics in Ischemic Stroke Management Update 2025

• Absolute contraindications:

• • Active major bleeding, intracranial mass (mets, AV malformations), recent neurosurgery, uncontrolled hypertension (>185/110 prior to administration)
  • Known coagulopathy (platelets <100,000, INR ≥1.7)

• Relative contraindications—more liberal than before:

• • Minor GI/GU bleeds, age >80, prior stroke/diabetes no longer strict, but risk remains increased
  • DOACs: Must be held ≥48hr, LMWH ≥24hr
  • Oral anticoagulants: INR <1.7 required

Updates to contraindication to IV Thrombolytics for Stroke 2025

• Age >80 y: no longer a contraindication.
• Prior stroke + diabetes: no longer a contraindication.
• Warfarin: acceptable if INR <1.7.
• UFH infusion: off ≥4 h and normal PTT.
• LMWH (e.g., enoxaparin, fragmin): wait 24 h since last dose.
• DOACs: (local protocols vary; many require ~48 h if normal renal function—confirm regionally).
• Eye surgery: recent corneal and lens surgery are generally not a contraindication while retinal surgery is a contraindcation
• Small unruptured aneurysm (<10 mm) and meningioma not absolute contraindications; untreated AVM remains a contraindication; recent retinal surgery may be a concern.

These updates align TNK with historical alteplase criteria; always confirm the dynamic local checklist at the bedside.