Stroke

Stroke Thrombolysis

⏱️ Time is brain! Acute ischaemic stroke is a medical emergency. IV thrombolysis should be given as fast and as safely as possible in eligible patients, and mechanical thrombectomy should be pursued urgently when indicated.

🧠 Core Principle

• Exclude intracranial haemorrhage urgently with brain imaging.
• If the patient is eligible, give IV thrombolysis within 4.5 hours of symptom onset / last known well.
• Do not delay transfer for thrombectomy while waiting to see the effect of thrombolysis.
• Selected patients with wake-up stroke or presentation beyond 4.5 hours may still be eligible if advanced imaging shows salvageable brain tissue.

✅ Current Thrombolytic Drugs

• Tenecteplase is now a NICE-recommended option for acute ischaemic stroke.
• Alteplase remains an option.
• In practice, local stroke services usually use the least expensive suitable option in line with NICE guidance.

💉 Drug Protocols

• Tenecteplase
  • 0.25 mg/kg IV bolus (maximum 25 mg)
  • Given as a single IV bolus over about 5–10 seconds
  • Much simpler logistically than alteplase
• Alteplase
  • 0.9 mg/kg (maximum 90 mg)
  • 10% of the total dose as an initial IV bolus
  • 90% infused over 60 minutes

🧾 Who Should Be Considered for IV Thrombolysis?

• Clinical diagnosis of acute ischaemic stroke causing a disabling neurological deficit
• Intracranial haemorrhage excluded on urgent imaging
• Treatment can start within 4.5 hours of symptom onset / last known well
• Given within a well-organised stroke service with trained staff, imaging, monitoring, and re-imaging available

🕒 Extended / Imaging-Selected Thrombolysis

• Selected patients may be considered for alteplase when:
  • treatment can start between 4.5 and 9 hours from known onset, or
  • they have wake-up stroke and treatment can start within 9 hours of the midpoint of sleep, or
  • MRI shows DWI–FLAIR mismatch suggesting salvageable tissue
• This depends on local imaging capability and stroke specialist assessment.

🚫 Major Contraindications / Reasons Not to Thrombolyse

• Intracranial haemorrhage on imaging
• Clinical suspicion of subarachnoid haemorrhage, even if CT is initially normal
• Blood pressure >185/110 mmHg despite treatment
• Current major bleeding or very high bleeding risk
• Recent major surgery / major trauma / significant invasive procedure where bleeding risk is unacceptable
• Known coagulation abnormality or anticoagulant effect that is unsafe for thrombolysis
• Very low platelets or major uncontrolled metabolic abnormality mimicking stroke
• Stroke mimic or another diagnosis judged more likely than acute ischaemic stroke

⚠️ Important Practical Points

• Age alone is not a reason to withhold thrombolysis.
• Stroke severity alone is not an absolute exclusion.
• Minor symptoms may still justify treatment if the deficit is disabling (for example aphasia, hemianopia, severe hand weakness, disabling ataxia).
• Seizure at onset is not an absolute exclusion if persistent deficits are thought to be due to stroke rather than purely post-ictal change.
• Posterior circulation stroke can be thrombolysed if otherwise eligible.

🖥️ Imaging Checklist

• Non-contrast CT head immediately if the patient may be eligible for reperfusion therapy
• If thrombectomy may be indicated, perform CT angiography after the non-contrast CT
• Add CT perfusion (or MR equivalent) if thrombectomy may be indicated beyond 6 hours or in wake-up stroke
• Large established infarction reduces the benefit and increases the risk of reperfusion therapy
• Note: A hyperdense artery sign supports large vessel occlusion and is not a contraindication to thrombolysis

🧪 Key Bedside / Lab Checks Before Thrombolysis

• Capillary blood glucose - exclude hypoglycaemia as a mimic
• Platelet count if thrombocytopenia is suspected
• Coagulation tests if anticoagulation or bleeding disorder is possible
• Weight for drug dosing
• Blood pressure
• NIHSS and pre-stroke modified Rankin score

🫀 Blood Pressure Management

• Before thrombolysis: reduce BP to <185/110 mmHg if otherwise eligible
• Monitor closely during and after treatment
• Persistent severe hypertension after treatment increases the risk of haemorrhagic transformation

🧲 Mechanical Thrombectomy

• Offer thrombectomy as soon as possible and within 6 hours for:
  • acute ischaemic stroke
  • proximal anterior circulation large-vessel occlusion
  • usually with pre-stroke mRS <3 and NIHSS >5
• Offer thrombectomy up to 24 hours in selected patients with:
  • proximal anterior circulation occlusion
  • favourable advanced imaging showing salvageable tissue
• Consider thrombectomy up to 24 hours in selected posterior circulation occlusions as well.
• If eligible for thrombectomy and thrombolysis, give IV thrombolysis first unless contraindicated.

📋 First 24 Hours After IV Thrombolysis

• Close neurological and haemodynamic monitoring
• Avoid unnecessary invasive procedures if possible
• No antiplatelet or anticoagulant therapy in the first 24 hours
• Repeat brain imaging before starting antiplatelet therapy
• Start antiplatelet treatment after 24 hours once significant haemorrhage has been excluded

⚠️ Complications

• Symptomatic intracranial haemorrhage - suspect if headache, vomiting, acute hypertension, reduced consciousness, or worsening neurological deficit
• Orolingual angioedema, particularly with alteplase and especially in patients on ACE inhibitors
• Systemic bleeding
• Reperfusion injury / haemorrhagic transformation

🚨 If Deterioration Occurs During or After Thrombolysis

• Stop the infusion if alteplase is still running
• Urgent senior stroke / neurology review
• Repeat urgent brain imaging
• Manage airway, breathing, circulation, and blood pressure
• Follow local haemorrhage-reversal / complication protocols immediately

📖 Cases - Stroke Reperfusion Therapy

• Case 1 - Classic anterior circulation stroke 🧠: A 68-year-old man presents 90 minutes after onset with right hemiparesis and expressive dysphasia. CT head shows no haemorrhage. Diagnosis: acute ischaemic stroke within the standard reperfusion window. Management: IV thrombolysis plus stroke unit care.
• Case 2 - Posterior circulation stroke 🚨: A 55-year-old woman presents with sudden vertigo, vomiting, diplopia, and ataxia. CTA shows basilar artery occlusion. Management: IV thrombolysis if eligible and urgent transfer for mechanical thrombectomy.
• Case 3 - Wake-up stroke 🕒: A 72-year-old man wakes with left hemiparesis. Advanced imaging shows a small infarct core and salvageable tissue. Diagnosis: imaging-selected wake-up stroke. Management: consider reperfusion therapy according to local hyperacute stroke protocol and imaging findings.

Teaching Point 🩺:
Modern acute ischaemic stroke care is about rapid reperfusion. Use non-contrast CT to exclude haemorrhage, add CTA when thrombectomy may be needed, and use advanced imaging for selected late-presenting or wake-up strokes. 💉 Tenecteplase is now a NICE-recommended thrombolytic option within 4.5 hours, while alteplase remains an option. 🧲 Large-vessel occlusion should trigger urgent assessment for mechanical thrombectomy.

📚 References

• NICE TA990 – Tenecteplase for treating acute ischaemic stroke (2024)
• NICE NG128 – Stroke and TIA in over 16s: diagnosis and initial management
• National Clinical Guideline for Stroke (UK and Ireland, 2023)
• Tenecteplase (Metalyse 25 mg) SmPC
• Alteplase (Actilyse) SmPC

Stroke - General Management

🧠 Introduction

Foster Kennedy Syndrome is a rare neurological disorder defined by a striking combination of findings - optic atrophy in one eye and papilloedema in the other. It reflects both local compressive damage and raised intracranial pressure (ICP), classically from a frontal lobe or olfactory groove tumour such as a meningioma.

📚 Key Pathophysiology

• 👁️ Ipsilateral optic atrophy: Direct compression of the optic nerve by the mass leads to loss of axons and pallor of the optic disc on the same side as the lesion.
• 👁️ Contralateral papilloedema: Raised intracranial pressure causes venous congestion and swelling of the optic disc in the opposite eye, where the optic nerve is not compressed.
• 🧩 The combination is diagnostic - one disc pale (atrophic) and one swollen (oedematous).

🎯 Common Causes

• Olfactory groove meningioma - the classic cause; the tumour compresses the ipsilateral optic nerve and elevates intracranial pressure.
• Medial sphenoid wing meningioma - second most common location.
• Less commonly: frontal lobe glioma, craniopharyngioma, aneurysm, or metastatic lesion.

👀 Clinical Features

• Progressive unilateral visual loss (from optic atrophy).
• Contralateral visual blurring or headaches from raised ICP.
• Anosmia (loss of smell) if olfactory nerve compressed.
• Headache, nausea, and vomiting due to increased ICP.
• On fundoscopy:
  • Atrophic disc (pale, flat) on the side of the tumour.
  • Papilloedema (swollen disc margins, hyperaemia, blurred edges) on the opposite side.

🔎 Investigations

• Ophthalmic Assessment:
  • Fundoscopy - confirm optic atrophy vs papilloedema pattern.
  • Visual acuity and visual field testing (commonly central scotoma or field constriction).
• Imaging:
  • MRI brain with contrast - gold standard for defining mass lesion and relation to optic nerves.
  • CT scan - useful for identifying calcification or hyperostosis (typical in meningioma).
• ICP Assessment:
  • Indirectly via clinical and imaging markers (ventricular dilation, peritumoural oedema).
  • Formal ICP monitoring only if diagnosis unclear or perioperative guidance required.
• Neurological Examination: Evaluate cranial nerves I–VI, motor and sensory function, and higher cortical signs to localise lesion.

🧩 Differential Diagnosis

• Pseudo–Foster Kennedy Syndrome: Sequential optic neuritis or bilateral papilloedema with optic atrophy in one eye following chronic raised ICP (without a mass).
• Anterior ischaemic optic neuropathy or optic nerve glioma may mimic the appearance.

🩺 Management

• 🎯 Definitive Treatment – Neurosurgical:
  • Surgical resection of the meningioma (often via transcranial or endoscopic approach) to relieve compression and restore CSF dynamics.
  • Goal: decompress optic apparatus and reduce ICP.
  • Postoperative radiotherapy may be considered for residual tumour.
• 🧴 ICP Control (Pre- and Peri-operative):
  • Mannitol and dexamethasone to reduce oedema.
  • Optimise positioning (head elevated 30°), maintain normocapnia and euvolaemia.
• 📅 Follow-up and Monitoring:
  • Regular neuro-ophthalmologic review to monitor visual fields and disc changes.
  • Postoperative MRI scans to detect recurrence or residual tumour.
  • Long-term rehabilitation for persistent visual loss or olfactory deficits.

💡 Teaching Points

• Foster Kennedy Syndrome = optic atrophy + papilloedema = think frontal meningioma.
• Always exclude a mass lesion before assuming benign raised ICP (idiopathic intracranial hypertension).
• “Pseudo–Foster Kennedy” describes a similar optic appearance but without a space-occupying lesion.
• Early recognition allows curative surgery before irreversible optic damage occurs.

🧩 Summary: Foster Kennedy Syndrome is a distinct neuro-ophthalmological sign complex signalling a frontal intracranial mass. Multidisciplinary management involving neurology, neurosurgery, and ophthalmology is vital for preserving vision and preventing recurrence.

Ischaemic Stroke

📖 About

• Sudden onset focal neurological deficit due to reduced cerebral blood flow → infarction.
• ~80% of all strokes are ischaemic (rest haemorrhagic).
• Stroke includes brain, spinal cord, and retinal ischaemia (WHO definition).
• Diagnosis increasingly based on imaging (CT/MRI DWI) rather than just time.

🔎 Trial of Org 10172 in Acute Stroke Treatment (TOAST)

• Large-artery atherosclerosis
• Cardioembolism
• Small-vessel occlusion (lacunar)
• Other determined aetiology
• Undetermined aetiology (cryptogenic)

🧠 Causes

• Large Arterial Thrombosis: Atherosclerosis of ICA/MCA/PCA, plaque rupture, distal embolisation.
• Embolism: AF, endocarditis, LV thrombus post-MI, mitral stenosis, atrial myxoma, paradoxical embolus (PFO), aortic arch plaque, dissection.
• Small vessel disease: Lipohyalinosis → lacunar strokes (<15 mm) in internal capsule, basal ganglia, thalamus, pons.
• Venous thrombosis: Sinus thrombosis with secondary venous infarction ± haemorrhage.
• Low flow: Hypotension/shock → watershed infarcts.
• Cryptogenic: No clear cause despite work-up.

⚠️ General Risk Factors

• Hypertension, diabetes, hyperlipidaemia, smoking, age
• Arterial dissection (trauma, fibromuscular dysplasia, Marfan/Ehlers-Danlos)
• Vasculitis (GCA, PAN, Behçet’s, lupus)
• Prothrombotic states (Factor V Leiden, Protein C/S deficiency, antiphospholipid, malignancy)
• Migraine with aura, OCP/oestrogens

🩻 Investigations

• Bloods: FBC, U&E, LFT, glucose, lipids, ESR/CRP.
• ECG (AF, MI, LVH, cardiomyopathy).
• CXR (exclude cardiopulmonary causes, but don’t delay CT).
• CT Head (urgent): exclude haemorrhage. Early signs: dense MCA sign, loss of insular ribbon, grey-white loss.
• MRI DWI: more sensitive, esp. for small/early infarcts.
• Further tests (senior decision): carotid Doppler, echocardiogram, Holter (AF), vasculitis/thrombophilia screen in young.

🧾 Clinical Syndromes

• MCA: Contralateral hemiplegia (face/arm > leg), hemisensory loss, homonymous hemianopia, aphasia (dominant), neglect (non-dominant).
• ACA: Leg > arm weakness, urinary incontinence, apathy/abulia, primitive reflexes.
• Vertebrobasilar: CN palsies, contralateral weakness, sensory loss, ataxia, Horner’s syndrome.
• Lacunar: Pure motor, pure sensory, dysarthria-clumsy hand, ataxic hemiparesis.

💊 Management

• Thrombolysis: Alteplase if onset <4.5 hrs, NIHSS 4–25, CT excludes haemorrhage.
• Mechanical thrombectomy: Consider if large vessel occlusion (MCA/ICA, ≤6 hrs; up to 24 hrs in selected).
• Antiplatelet: Aspirin 300 mg OD x2 weeks then clopidogrel 75 mg OD long term. (Dual therapy not routine except in minor stroke/TIA, short course).
• Anticoagulation (AF): Start between 3–14 days depending on infarct size (TIA day 1, small stroke day 3, moderate day 6, large stroke ≥2 wks).
• BP control: Avoid acute lowering unless BP >220/120 or candidate for thrombolysis (<185/110).
• Lipids: Atorvastatin 80 mg after 48 hrs (unless contraindicated).
• Glucose: Keep 4–11 mmol/L. Avoid hypoglycaemia.
• Fluids/Nutrition: Swallow screen. NG feeding if unsafe swallow. IV fluids if nil orally.
• Oxygen: Only if sats <95%.
• VTE prophylaxis: Intermittent compression stockings. LMWH only if high-risk immobile.
• Surgery: Hemicraniectomy for malignant MCA infarct in <60 yrs.
• Carotid endarterectomy: If symptomatic carotid stenosis >70% and mild/moderate stroke.
• Rehab: Early supported discharge, MDT therapy essential.

📚 Key Classification: TOAST

• Large-artery atherosclerosis
• Cardioembolism
• Small vessel occlusion
• Other determined
• Undetermined (cryptogenic)

Mechanical Thrombectomy for Ischaemic Stroke

🧠 Mechanical thrombectomy is a life-saving endovascular procedure used to remove large clots from cerebral arteries in acute ischaemic stroke. ⚡ It has revolutionized stroke care by rapidly restoring blood flow, improving survival, and reducing long-term disability when performed promptly.

📖 About

• Definition: Endovascular removal of intracranial clots in large vessel occlusion (LVO) stroke.
• History: Modern thrombectomy emerged in 2015 with stent retrievers & aspiration catheters after multiple landmark RCTs.
• Purpose: Rapid recanalization → salvage brain tissue → improve functional outcome.

📑 Evidence & Number Needed to Treat (NNT)

• Landmark RCTs:
  • MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, EXTEND-IA → all showed clear benefit over IV thrombolysis alone.
• Meta-analyses: Confirm thrombectomy is superior to medical therapy alone for LVO strokes.
• NNT:
  • ~2–3 to achieve functional independence (mRS 0–2 at 90 days).
  • ~6–10 to prevent one death.
• Guidelines: AHA, ESO & NICE endorse thrombectomy for eligible patients.

🧾 Pre-Thrombectomy Assessment

• Clinical: NIHSS to quantify deficit severity (higher scores suggest LVO).
• Imaging:
  • NCCT: exclude haemorrhage.
  • CTA: confirm large vessel occlusion.
  • CTP/MR perfusion: assess penumbra vs infarct core.
• Labs: FBC, coagulation profile, renal function (contrast safety), glucose.
• Eligibility:
  • Time window: ≤6h (up to 24h in selected patients by perfusion imaging).
  • LVO: ICA, MCA (M1/M2), basilar artery.
  • Adequate salvageable brain tissue.
  • No major contraindications (extensive infarct, severe comorbidity).

🎯 Indications

• Acute ischaemic stroke with confirmed LVO.
• Within time window (6–24h depending on imaging).
• Favourable penumbra-to-core ratio on perfusion studies.

🛠️ Devices

• Stent Retrievers: Solitaire, Trevo → ensnare clot & pull it out.
• Aspiration Catheters: ADAPT → suction clot out.
• Combined Techniques: Stent retriever + aspiration (Solumbra approach).

⚙️ Procedure

• Access: Usually femoral artery → navigate catheter to clot.
• Retrieval: Deploy retriever/aspiration → remove clot (multiple passes if needed).
• Verification: Angiography confirms recanalization (TICI 2b–3 = success).
• Closure: Sheath removal & haemostasis.

⚠️ Complications

• Intracranial haemorrhage (ICH).
• Vessel injury: dissection or perforation.
• Distal embolization of clot fragments.
• Access site haematoma/AV fistula.
• Reperfusion injury.
• Contrast nephropathy (rare).

📈 Outcomes

• Recanalization success in >80–90% with modern devices.
• Significant functional improvement (mRS 0–2 at 90 days in 45–60%).
• Mortality reduction compared to IV thrombolysis alone.
• “Time is brain”: benefit falls with delay.

🩺 Post-Procedure Care

• ICU/HDU monitoring for neuro status & haemodynamics.
• Follow-up CT/MRI to assess reperfusion & exclude haemorrhage.
• Early rehabilitation: physio, OT, speech therapy.
• Secondary prevention: antiplatelet/anticoagulation as indicated.

🚀 Recent Advances

• Better imaging → extended treatment windows (DAWN, DEFUSE 3 trials).
• Next-gen aspiration catheters with improved suction.
• Trials of posterior circulation thrombectomy (basilar artery occlusion).

✅ Conclusion

Mechanical thrombectomy is now gold standard therapy for eligible LVO strokes. Success depends on rapid recognition, efficient pathways, expert intervention, and careful post-stroke care. Each minute saved → better neurological recovery.

📚 References

• Goyal M, Menon BK, et al. Lancet 2016;387:1723–31.
• Albers GW, Marks MP, et al. NEJM 2018;378:708–18.
• NINDS – Mechanical Thrombectomy
• World Stroke Organization – Guidelines