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A 62-year-old man with a history of hypertension, type 2 diabetes mellitus, and atrial fibrillation is brought to the emergency department by his family. He was last seen well 90 minutes ago. On arrival he is confused, has right-sided hemiplegia, and right facial droop. His BP is 195/108 mmHg, HR 88 bpm and irregular, SpO2 96% on air. He is on warfarin for AF but his INR on arrival is 1.3.

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QUESTION 1

What is the most likely diagnosis and how would you confirm it?

ANSWER:

The most likely diagnosis is acute ischemic stroke. The sudden-onset focal neurological deficit — right hemiplegia and facial droop — with a clear time of onset and a background of AF (a major cardioembolic risk factor) makes this the leading diagnosis.

Confirmation requires:

• Urgent non-contrast CT head to exclude haemorrhage and detect early ischaemic changes. CT is the first-line imaging modality as it is widely available and fast.
• NIHSS score to quantify neurological deficit and guide reperfusion decisions.
• CT angiography (or MR angiography) to identify large vessel occlusion if mechanical thrombectomy is being considered — this should not delay IV thrombolysis if otherwise indicated.
• MRI DWI is more sensitive for early infarct and can identify penumbral tissue but should not delay treatment.
• Blood glucose must be checked immediately, as hypoglycaemia can mimic stroke.
• 12-lead ECG, FBC, coagulation screen, renal function, and troponin.

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QUESTION 2

What are the goals of initial emergency management?

ANSWER:

Three overarching goals govern initial management:

1. Physical stabilisation (ABC): Protect the airway in patients with altered sensorium or bulbar dysfunction — intubation may be necessary to prevent aspiration. Correct hypoxaemia with supplemental oxygen; do not give oxygen to non-hypoxaemic patients. Treat hypotension aggressively with fluids and vasopressors as it worsens ischaemic injury. Hypertension should not be treated unless BP >185/110 mmHg and thrombolysis is planned.
2. Prevention of secondary neurological injury: Maintain euthermia, euglycaemia, and normocapnia (hypercarbia causes cerebral vasodilation and worsens ICP). Treat seizures promptly — prophylactic antiepileptics are not recommended.
3. Timely reperfusion: Determine as quickly as possible whether the patient is a candidate for IV thrombolysis and/or mechanical thrombectomy. Time is brain.

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QUESTION 3

Is this patient a candidate for IV thrombolysis? Walk through your decision-making.

ANSWER:

Step-by-step assessment:

Inclusion criteria — all must be met:

• Symptom onset within 4.5 hours — YES (90 minutes)
• Age ≥18 years — YES
• Measurable persistent neurological deficit — YES (hemiplegia, facial droop)
• BP controlled to <185/110 mmHg before administration — needs treatment first
• Blood glucose >50 mg/dL — must confirm

Absolute contraindications — must exclude:

• CT evidence of ICH or extensive hypoattenuation — pending imaging
• Ischaemic stroke within 3 months — must verify history
• History of ICH — must verify
• Intracranial/intraspinal surgery within 3 months — must verify
• Aortic arch dissection — must exclude clinically
• Infective endocarditis — no clinical features
• Intra-axial intracranial neoplasm — pending imaging
• GI malignancy or GI bleed within 21 days — must verify
• Platelets <100,000/mm³, INR >1.7, aPTT >40 sec, PT >15 sec — INR is 1.3, which is acceptable; await full coagulation screen
• Therapeutic LMWH within 24 hours — must verify
• Direct thrombin inhibitor or factor Xa inhibitor use — must verify

Additional exclusion criteria for the 3–4.5 hour window: This patient presented at 90 minutes, so he is within the 0–3 hour window. The additional ECASS-3 exclusion criteria (age >80, prior stroke + diabetes, NIHSS >25, OAC use with any PT elevation, multilobar infarction) apply only if onset were in the 3–4.5 hour window.

Conclusion: Assuming imaging excludes haemorrhage and contraindications are not present, this patient is eligible for IV thrombolysis. BP must be brought below 185/110 mmHg before administration.

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QUESTION 4

How do you manage the blood pressure in this patient?

ANSWER:

Pre-thrombolysis (BP is currently 195/108 mmHg):

The target is BP <185/110 mmHg before giving rtPA.

Options:

• Labetalol 10–20 mg IV over 1–2 minutes; or
• Nicardipine 5 mg/h IV, titrate up by 2.5 mg/h every 5–15 minutes to a maximum of 15 mg/h; or
• Clevidipine 1–2 mg/h IV, doubling every 2–5 minutes to a maximum of 21 mg/h.

If BP cannot be brought to or below 185/110 mmHg, rtPA must not be administered.

During and post-thrombolysis:

Monitor BP every 15 minutes for 2 hours from start of infusion, then every 30 minutes for 6 hours, then hourly for the next 16 hours.

If SBP >180–230 mmHg or DBP >105–120 mmHg post-infusion: give labetalol 10 mg IV followed by infusion at 2–8 mg/min, or nicardipine as above. If DBP >140 mmHg and not controlled, consider IV sodium nitroprusside (0.5 mcg/kg/min).

Important: Nitrates should be avoided as they tend to increase ICP.

If thrombolysis is not given: BP can be allowed to remain elevated (permissive hypertension) as it supports collateral perfusion to the ischaemic penumbra. Treatment is only initiated if BP >220/120 mmHg, and then with a 10–15% reduction as the target.

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QUESTION 5

Describe the administration of IV alteplase and the monitoring protocol.

ANSWER:

Dose: 0.9 mg/kg of actual body weight, maximum dose 90 mg.

• 10% of the total dose given as a slow IV bolus over 1 minute.
• Remaining 90% infused over 60 minutes.

Alternative — Tenecteplase: 0.25 mg/kg as a single IV bolus, maximum 25 mg. Easier dosing reduces door-to-needle time. AHA/ASA recommends tenecteplase only as a bridging agent before mechanical thrombectomy in large vessel occlusion — not as a routine substitute for alteplase in all-comers.

Monitoring during and after infusion:

• BP and neurological assessment every 15 minutes during infusion and for 2 hours after.
• Then every 30 minutes for 6 hours, then hourly until 24 hours.
• If the patient develops sudden severe headache, acute hypertension, nausea, vomiting, or neurological worsening — stop the infusion immediately and obtain urgent non-contrast CT head.

Post-thrombolysis precautions:

• Avoid anticoagulants and antiplatelets for at least 24 hours.
• Avoid invasive procedures (arterial lines, urinary catheters, NG tubes) for at least 24 hours if clinically safe.
• Obtain follow-up CT or MRI at 24 hours before restarting anticoagulation or antiplatelet therapy.

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QUESTION 6

What are the major complications of IV thrombolysis and how do you manage symptomatic intracranial haemorrhage?

ANSWER:

Major complications:

• Symptomatic intracranial haemorrhage (sICH) — occurs in approximately 6–7% of patients; 50% of these will not survive.
• Systemic bleeding.
• Angioedema — a dreaded complication; can cause airway compromise.
• Seizures.
• Distal embolisation.
• Transient hypotension.

Management of sICH occurring within 36 hours of alteplase:

1. Stop the alteplase/tenecteplase infusion immediately.
2. Send urgent bloods: FBC, PT (INR), aPTT, fibrinogen, and group and cross-match.
3. Emergent non-contrast CT head.
4. Cryoprecipitate: 10 units IV over 10–30 min. Give additional dose if fibrinogen <200 mg/dL.
5. Tranexamic acid 1000 mg IV over 10 minutes OR epsilon-aminocaproic acid 4–5 g over 1 hour, followed by 1 g IV until bleeding is controlled.
6. Neurosurgery and haematology consultations.
7. Supportive: BP management, ICP control, maintain CPP, normothermia, euglycaemia.

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QUESTION 7

Is this patient a candidate for mechanical thrombectomy? What is the evidence base?

ANSWER:

Indication: Mechanical thrombectomy is indicated in patients with large artery occlusion in the proximal anterior circulation (distal ICA, M1, M2 of MCA, A1/A2 of ACA). Given this patient’s clinical syndrome and AF, a proximal MCA occlusion is likely and CT angiography should be obtained urgently.

Prerequisites:

• Neuroimaging evidence of small infarct core and exclusion of haemorrhage.
• Angiographic evidence of proximal large artery occlusion.
• Persistent disabling neurological deficit.
• No significant pre-stroke disability (mRS ≤1).
• Facilities and expertise available.
• Femoral puncture achievable within 24 hours of last known neurological baseline.

Time windows and trials:

Within 6 hours: Supported by five landmark RCTs — MR CLEAN, SWIFT PRIME, REVASCAT, EXTEND-IA, and ESCAPE — all published in 2015, demonstrating superior outcomes with second-generation stent retrievers over standard IV thrombolysis alone.

6–24 hours: The DAWN trial (deficit–infarct mismatch) and DEFUSE 3 trial (perfusion imaging selection up to 16 hours) demonstrated benefit in late-window mechanical thrombectomy in carefully selected patients.

Key principle: Thrombectomy, if indicated, should proceed as early as possible and should not wait for the response to IV rtPA.

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QUESTION 8

What is the role of antiplatelet therapy in acute ischaemic stroke?

ANSWER:

• All patients with ischaemic stroke who are not receiving thrombolysis should receive aspirin 325 mg (loading dose) within 24–48 hours of onset, followed by 100–150 mg daily.
• In patients receiving IV thrombolysis, aspirin should be delayed by 24 hours (pending 24-hour CT scan showing no haemorrhage).
• GP IIb/IIIa inhibitors (e.g., abciximab) are potentially harmful and increase the risk of ICH — should not be used.

Dual antiplatelet therapy (DAPT):

• The CHANCE trial showed that aspirin + clopidogrel for 21 days in minor non-cardioembolic stroke (NIHSS ≤3) reduced early recurrent stroke without increasing major bleeding.
• The POINT trial showed that DAPT reduced major ischaemic events but nearly doubled major bleeding risk at 90 days.
• Current recommendation: DAPT (aspirin + clopidogrel) initiated within 24 hours of onset and continued for 21 days is appropriate in patients with minor non-cardioembolic ischaemic stroke (NIHSS ≤3) who did not receive IV alteplase.
• DAPT should be avoided in patients at high bleeding risk.

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QUESTION 9

Two days later, the patient deteriorates suddenly. GCS falls to 10/15 with unequal pupils sluggishly reacting to light. He is also noted to have a new tonic-clonic seizure. What are the differential diagnoses for this deterioration?

ANSWER:

• Progression of the ischaemic infarct with midline shift (malignant MCA syndrome).
• Haemorrhagic transformation of the ischaemic infarct.
• Recurrent ischaemic stroke.
• Cerebral oedema causing mass effect and transtentorial herniation.
• Post-ictal state or ongoing subclinical seizure activity.
• Metabolic derangements: hypo/hypernatraemia, hypoglycaemia, hyperglycaemia, uraemia, hyperammonaemia, hypercalcaemia.
• Sepsis (particularly aspiration pneumonia, UTI — both common in stroke patients).
• Drug effects/sedative accumulation.

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QUESTION 10

CT brain shows extensive right MCA territory infarction with midline shift consistent with malignant MCA syndrome. How do you manage this patient and what is the role of decompressive craniectomy?

ANSWER:

Immediate medical management:

• Intubate and ventilate. Maintain normocapnia (PaCO₂ 35–40 mmHg). Avoid hypercapnia.
• Head-end elevation to 30–45 degrees.
• Osmotherapy: mannitol or hypertonic saline as a bridging measure — beneficial effects are transient.
• ICP monitoring and CSF drainage (EVD if hydrocephalus or to guide therapy).
• Maintain cerebral perfusion pressure (CPP = MAP – ICP).
• Achieve euvolaemia, euglycaemia (target serum glucose <200 mg/dL), and euthermia.
• Initiate antiepileptics for ongoing seizures (no role for prophylaxis in the absence of seizures).
• Multidisciplinary input: neurology, neurosurgery, neurointensive care.
• Frequent sodium monitoring — rapid sodium changes risk cerebral oedema.

Decompressive craniectomy (DHC):

Malignant MCA syndrome is defined by:

• MCA territory infarction >50% on CT.
• Perfusion deficit >66% on CT.
• Infarct volume >82 mL within 6 hours on MRI, or >145 mL within 14 hours.

DHC reduces ICP by increasing cranial compliance, prevents transtentorial herniation, and may improve penumbral perfusion.

Evidence:

• DESTINY (2007): DHC in ages 18–60; 30-day mortality significantly reduced; functional outcome at 6 months not significantly different.
• DECIMAL (2007): Ages 18–55; mortality significantly lower with DHC; favourable functional outcome (mRS ≤3) not significantly different, but outcomes better with the broader threshold of mRS ≤4.
• HAMLET (2009): DHC within 4 days; mortality significantly lower; no significant difference in good vs. poor outcome (mRS) at 1 year. Meta-analysis of all three trials confirmed reduction in case fatality and unfavourable outcomes.
• DESTINY II (2011): Patients ≥61 years; DHC within 48 hours still reduced mortality but surviving patients had none with mRS 0–2 — all survivors had significant disability.

Current recommendation:

• DHC should be considered in patients below 60 years of age and performed within 48 hours of stroke onset.
• It should not be performed in patients >60 years as survivors have substantially increased disability.
• Informed discussion with the family about the quality of survival is essential before proceeding.

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QUESTION 11

What are the indications for ICU admission in a stroke patient?

ANSWER:

• Altered sensorium or brainstem dysfunction requiring airway protection.
• Respiratory compromise (aspiration pneumonia, respiratory failure requiring mechanical ventilation).
• Severe bradyarrhythmia or tachyarrhythmia.
• Severe hypo- or hypertension requiring continuous infusions.
• Signs of raised ICP or refractory seizures.
• High-risk lesions:
  • Basilar artery occlusion / brainstem infarction.
  • Large hemispheric infarction, especially in younger patients.
  • Large territorial cerebellar infarction susceptible to oedema and obstructive hydrocephalus.
• Patients receiving IV thrombolytics requiring close monitoring when a stroke unit bed is not available.

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QUESTION 12 — EXAMINER PUSH (landmark trials summary)

Name the key trials and their primary findings relevant to ischaemic stroke management.

ANSWER:

Trial	Topic	Key finding
NINDS (1995)	IV tPA <3 hours	Despite increased sICH, functional outcomes at 3 months significantly better in tPA group. NIHSS at 24 hours not significantly different.
ECASS-3 (2008)	IV tPA 3–4.5 hours	IV thrombolysis up to 4.5 hours beneficial; additional exclusion criteria apply (age >80, prior stroke + diabetes, NIHSS >25, OAC use)
WAKE-UP (2018)	Unknown-onset stroke	DWI–FLAIR mismatch can identify patients within 3-hour equivalent window; tPA improved outcomes by 11.5%
EXTEND (2019)	tPA 4.5–9 hours	Perfusion–core mismatch on RAPID software identifies late-window tPA candidates
MR CLEAN, SWIFT PRIME, REVASCAT, EXTEND-IA, ESCAPE (all 2015)	Mechanical thrombectomy <6 hours	All demonstrated superiority of thrombectomy + standard care over standard care alone for proximal large vessel occlusion
DAWN (2018)	Thrombectomy 6–24 hours	Deficit–infarct mismatch identifies patients benefitting from late thrombectomy
DEFUSE 3 (2018)	Thrombectomy 6–16 hours	Perfusion imaging selection identifies late-window thrombectomy candidates
CHANCE (2013)	DAPT in minor stroke	Aspirin + clopidogrel for 21 days reduces early recurrence without increasing major bleeding
POINT (2018)	DAPT at 90 days	DAPT reduces ischaemic events but nearly doubles major bleeding at 90 days
DESTINY / DECIMAL / HAMLET (2007–2009)	DHC for malignant MCA	Mortality reduced; functional outcomes not significantly improved in mRS ≤3; age <60 and <48 hours is critical
DESTINY II (2011)	DHC in >60 years	Mortality reduced but no survivors achieved mRS 0–2; proceed with caution
ELAN (2023)	Early DOAC in AF-related stroke	Early DOAC (<48 hours in minor/moderate stroke) showed non-significant trend of benefit without increased sICH

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Sources: Case-based Review in Critical Care Medicine (2nd ed.); ICU Protocols Vol. 1; Key Trials in Intensive Care Medicine — Passing the Final FFICM (Ali & Kondratowicz, 2024, CRC Press); Clinical Cases in Critical Care (Myers & Samuels, 2022, Wiley-Blackwell).