Stroke

Introduction

• Annual stroke death rate in US dropped 35.8% from 2000 to 2010
• 77% of strokes are primary and 23% recurrent
• Ischaemic stroke 87% vs. haemorrhage 13%
  • Thrombotic
  • Embolic
  • Hypoperfusion
  • Intracerebral haemorrhage 10%
  • Non-traumatic SAH 3%

Anterior and posterior circulations

Clinical presentation

• History
  • Onset – Sudden (embolic or haemorrhagic) vs. waxing/waning (thrombotic/hypoperfusive)
  • Time of onset = time last seen without symptoms
  • Risk factors for thrombus – HTN, smoking, DM, coronary disease
  • Risk factors for embolism – AF, valve replacement, recent MI
  • Transient deficits in same vascular distribution suggests thrombotic/hypoperfusive vs. transient deficits in different vascular distributions suggests embolic
  • Exclude stroke mimics
  • Then if stroke mimics excluded, identify indications and contraindications to thrombolysis/ECR

Ischaemic stroke

Stroke symptoms

• Traditional
  • Sudden numbness/weakness of face/arm/leg – especially unilateral (more common in men)
  • Sudden altered mental status (more common in women)
  • Sudden aphasia
  • Sudden memory deficit or spatial orientation/perceptual difficulties
  • Sudden visual defect or diplopia (more common in men)
  • Sudden dizziness, gait disturbance or ataxia (more common in men)
  • Sudden severe headache (most common symptom of posterior stroke)

Stroke symptoms

• Non-traditional
  • Loss of consciousness or syncope (vertebrobasilar insufficiency)
  • Generalised weakness (more common in women)
  • Shortness of breath
  • Sudden pain in face, chest, arms or legs
  • Seizure
  • Falls or accidents
  • Sudden hiccups
  • Sudden nausea
  • Sudden fatigue
  • Sudden palpitations
  • Altered mental status

Stroke mimics

• Seizures/Todd’s paresis
• Syncope
• Meningitis/encephalitis
• Complicated migraine
• Brain neoplasm/abscess
• Epidural/subdural haematoma
• Subarachnoid haemorrhage
• Hypoglycaemia
• Hyponatraemia
• Hypertensive encephalopathy
• Hyperosmotic coma
• Wernicke’s encephalopathy – triad of ataxia, ophthalmoplegia and confusion
• Labyrinthitis
• Drug toxicity (lithium, phenytoin, carbamazepine)
• Bell’s palsy
• Meniere’s disease
• MS
• Conversion disorder

Examination

• ABC priority to scanner
• Fever should prompt investigation for infection
  • CNS infection or consequence of stroke e.g. aspiration/UTI
  • Look for meningismus, Janeway lesions, Osler nodes, murmurs
• Check for bleeding diatheses e.g. purpura/petechiae
• Fundoscopy may reveal papilloedema (mass lesion, cerebral vein thrombosis, hypertensive crisis or pre-retinal haemorrhage – Terson syndrome)
• NIHSS score
  • Reliable interrater testing
  • Weighted towards anterior stroke syndromes as posterior stroke symptoms/signs receive fewer points and ataxia often scored as absent if weakness is present
  • Good outcome associated with score <=5 for anterior strokes and <=8 for posterior strokes
  • Bias towards detection of dominant hemisphere strokes also
  • While the score may not be as high for posterior circulation strokes, the use of NIHSS combined with truncal ataxia, nystagmus and test of skew testing is extremely sensitive for posterior stroke (99.3% sensitive vs. MRI at 24 hours)

Nystagmus

• Direction-changing nystagmus
  • Direction of fast phase changes depending on direction of vision
  • Need to look left and right for at least 15-30 seconds as non-sustained nystagmus at extremes of lateral vision is normal
  • Do NOT ask the patient to fixate on finger as this may suppress nystagmus
  • Just ask them to look left and then look right

Stroke syndromes

Anterior cerebral artery syndrome

• Rare. 0.5-3% of all strokes.
• Contralateral sensory and motor symptoms in lower extremity (homunculus in medial aspect of frontotemporal lobe) and sparing of hand and face
• Left-sided lesions shows akinetic mutism but repetition maintained
• Right-sided lesions cause confusion and motor hemineglect

Middle cerebral artery syndrome

• Most commonly involved vessel
• Contralateral hemiparesis, facial plegia and sensory loss
• Face and upper extremity > lower extremities
• If dominant hemisphere – aphasia
• If non-dominant hemisphere – inattention, neglect, extinction with simultaneous stimulation, dysarthria without aphasia and constructional apraxia
• Homonymous hemianopsia and gaze preference towards side of infarct may be seen

MCA – Superior division

• Always supplies frontal convexity
• Brachiofacial hemiparesis
• Dominant – Broca’s aphasia
• Non-dominant – Neglect

MCA – Inferior division

• Always supplies temporal lobe
• Causes homonymous hemianopia or upper quadrantanopia
• Dominant – Wernicke’s aphasia
• Non-dominant – Neglect

Posterior cerebral artery syndrome

• Classical – Ataxia, nystagmus, ALOC, vertigo
  • Often more subtle than this
• Crossed neurological deficits e.g. ipsilateral cranial nerve with contralateral limb motor nerve palsy indicates brainstem lesion until proven otherwise
• Symptoms
  • Unilateral limb weakness, dizziness, blurry vision, headache and dysarthria
• Signs
  • Visual field loss, unilateral limb weakness, gait ataxia, unilateral limb ataxia, CN VII palsy, lethargy and sensory deficits
• Contralateral homonymous hemianopia and unilateral cortical blindness are specific for posterior circulation syndromes
• Motor dysfunction is often minimal

Posterior circulation ischaemia

• Common symptoms
  • Motor deficits (anywhere)
  • Crossed signs (highly predictive)
  • Sensory deficits (anywhere)
  • Homonymous hemianopia
  • Ataxia, disequilibrium
  • Vertigo
  • Diplopia secondary to ophthalmoplegia
  • Dysphagia or dysarthria
  • Isolated coma (basilar)

Lateral medullary syndrome

• Intracranial vertebral artery infarct aka Wallenberg syndrome
• Can also be caused by PICA occlusion
• Nystagmus and Vertigo
• Ipsilateral Horner’s and hiccups
• Ipsilateral facial sensory loss (with initial pain sometimes) with contralateral hemisensory loss to pain and temperature
• Bulbar weakness – Dysarthria, Hoarseness, Dysphagia

Medial medullary syndrome

• Ipsilateral tongue weakness
• Contralateral hemiparesis of arm and leg
• Hemisensory loss to touch and proprioception

Pons ischaemia

• Hemiparesis or hemisensory loss, ataxic hemiparesis, dysarthria, horizontal gaze palsy
• Locked in syndrome with complete infarction

Top of the basilar stroke

• Somnolence
• Confusion (thalamic infarct)
• Bilateral loss of vision with denial of blindness (bilateral occipital lobe infarct)

PICA syndrome

• Truncal ataxia
• Vertigo
• Lateral medullary syndrome

Posterior cerebral artery

• Contralateral homonymous hemianopia (occipital infarction)
• Hemisensory loss (all modalities – thalamic infarct)
• Hemi-body pain (usually burning – thalamic infarct)

Basilar artery syndrome

• Symptoms – Unilateral limb weakness, dizziness, dysarthria, diplopia and headache
• Signs – Unilateral limb weakness, CN VII palsy, dysarthria, positive Babinski and oculomotor signs
• Dysphagia, nausea, vomiting, dizziness and Horner’s all associated
• Locked-in syndrome
• ‘Herald hemiparesis’ has been described to occur initially followed by more pronounced deficits, often with the unaffected side showing some degree of motor or reflex abnormality
• Paraesthesias can occur unilaterally or bilaterally depending on degree of bilateral pontine involvement

Vertebrobasilar syndrome

• Proximal posterior circulation stroke
• Symptoms – Dizziness, nausea, vomiting, headache, dysphagia, unilateral limb weakness and unilateral CN V symptoms
• Signs – Unilateral limb ataxia, nystagmus, gait ataxia, CN V signs, limb sensory deficit and Horner’s

Cerebellar syndrome

• Often non-specific dizziness (+- vertigo), nausea and vomiting, gait instability, headache, limb ataxia, dysarthria, nystagmus and CN abnormalities
• Mental status from alert to comatose
• CT is inadequately sensitive so DWI-MRI is gold standard
• CT angio or MR angio is useful to identify vascular lesions once diagnosis made
• Rapid deterioration due to brainstem pressure from oedema can occur
• Close monitoring of gaze palsy and level of consciousness is crucial
• Obtain early neurosurgical consult for cerebellar infarcts (whether ischaemic or haemorrhagic) as emergency posterior fossa decompression may be warranted
• Acute obstructing hydrocephalus requires treatment of raised ICP and emergent surgical decompression

Lacunar infarcts

• Small non-cortical infarcts caused by occlusion of a single small calibre penetrating artery arising off of a large artery i.e. off the Circle of Willis, ACA, PCA, MCA or basilar artery
• This explains particular association with hypertension
• Thought to be primarily due to hypertension-induced microangiopathy AND/OR branch atheroma formation
• Lacunar syndromes
  • Pure motor hemiparesis
    • ~50% of lacunar strokes
    • Weakness without cortical signs (aphasia, agnosia, neglect, apraxia or hemianopsia) or sensory deficit
    • A series of hemiplegic TIAs preceding the established motor deficit is termed ‘capsular warning syndrome’
  • Pure sensory stroke
  • Ataxic hemiparesis
    • Ipsilateral weakness and limb ataxia out of proportion to the motor deficit
    • Some patients have dysarthria, nystagmus and gait deviation
    • No cortical signs apparent
  • Sensorimotor stroke
    • Weakness and numbness of face, arm and leg on one side of the body in the absence of cortical signs
  • Dysarthria-clumsy hand syndrome
    • Facial weakness, dysarthria, dysphagia and slight weakness and clumsiness of one hand
    • No sensory or cortical signs
• Diagnosis
  • Vessels are too small to identify on CT-A so diagnosis relies on clinical syndrome + small non-cortical infarct identification on CT or MRI
• Treatment
  • Subgroup analysis of large stroke thrombolysis trials seem to show benefit is maintained in lacunar stroke
• Prognosis
  • Better prognosis in short-term up to 1 year than other stroke subtypes
  • Long-term prognosis for good neurological outcome and death appears similar (likely underpinned by common risk factors for both)

Carotid and vertebral artery dissection

• 10-25% of cases
• More prevalent among young and middle-aged patients
• Risk factors
  • History of neck trauma in days to weeks prior is a prominent risk factor (trauma usually minor)
  • Connective tissue disease
  • History of migraine
  • Large vessel arteriopathies
• (Hypertension and atherosclerosis are NOT risk factors according to de Alwis)
• Unilateral headache (68%), neck pain (39%) or face pain (10%)
  • Pain may precede other symptoms (median 14 days)
  • If headache is first symptom though, other symptoms arise in median time of 15 hours
• Symptoms may be transient or persistent
• CTA 92-100% sensitive for dissection. MRA 87-100% sensitive. CTA best for vertebrals and MRA best for carotids.

Carotid artery dissection

• Headache mostly frontotemporal
• May mimic SAH, temporal arteritis or pre-existing migraine
• Partial Horner’s (miosis, ptosis not anhydrosis) has traditionally been linked to carotid artery dissection but occurs in only 25% of patients
• Associated cranial nerve palsies seen in 12% of patients
• Can progress to cerebral ischaemia or retinal infarction

Vertebral artery dissection

• Neck pain (66%), headache (65%) – may be unilateral or bilateral
• Headache typically occipital (vs. frontotemporal for carotid) but can be frontal or bilateral
• Other symptoms and signs
  • Unilateral facial paraesthesia
  • Dizziness, vertigo
  • Nausea/emesis
  • Diplopia
  • Ataxia
  • Limb weakness/numbness
  • Dysarthria
  • Hearing loss
  • Cervical radiculopathy (C5 level in 1%)

Treatment of carotid and vertebral artery dissection

• IV heparin or antiplatelet therapy in concert with specialist consultation
• No randomised control trial level evidence of which treatment most effective
• Endovascular techniques may also be employed but unproven at this stage

Time recommendations (AHA/ASA)

Imaging

Non-contrast CT brain

• To detect haemorrhage, mimics, >1/3 MCA territory infarcts, established infarcts or tumors
• Not sensitive for ischaemic stroke within first few hours**
• 50% show changes at 24 hours in ischaemic stroke
• Early signs of ischaemic stroke
  • Loss of grey-white differentiation
  • Hyperdense clot in major vessel
    • Earliest sign of MCA infarct and is the longitudinal equivalent of the MCA dot sign and hyperdense basilar tip sign
    • Usually due to thrombus in vessel with differential of calcified atherosclerosis, polycythaemia and HSV encephalitis
  • ASPECTS score can be used to quantify changes

CT angiogram

• Current AHA/ASA guidelines strongly recommends angiography in those eligible for endovascular clot retrieval
• Should not delay tPA
• Australian Stroke Management Guideline
  • In ischaemic stroke and TIA patients, routinely imaging vasculature is encouraged to improve diagnosis, recognition of stroke aetiology and assessment of prognosis
  • Contrast should not be delayed while renal function pending
  • Post-hydration is advisable
  • Vascular imaging should NOT be performed for syncope or other non-focal neurological presentations
  • All TIA patients with anterior circulation symptoms should undergo early CTA

Ct perfusion studies

• Identifies size of penumbra vs. core infarct and can guide further therapy for patients who fall outside established time ranges for thrombolysis or where time of symptom onset is unclear

MRI

• Standard MRI 90% sensitive for ischaemic stroke at 24 hours on T2 images
• FLAIR can determine acute vs chronic haemorrhage
• DWI shows early ischaemia/infarction
• MRI strongly indicated for posterior fossa and brainstem strokes where CT has poor accuracy

Treatment of acute ischaemic stroke

• Correct dehydration
• Target normoxia (supplemental O2 without hypoxia of no benefit and may cause harm)
• Identify fever and treat with paracetamol/active cooling if >39.5
• Hypertension
  • If not candidate for thrombolysis or reperfusion measures – Permissive hypertension unless >220/>120 or other reason to lower blood pressure. If decision made to treat, aim for 15% reduction in SBP over first 24 hours
  • If for thrombolysis or reperfusion – Actively treat to <185/<110 as cannot receive tPA otherwise
• Maintain glucose 7-10
• Aspirin 325mg loading within 24-48 hours of stroke onset (but not within 24 hours of tPA therapy
  • Reduces recurrent stroke at 4 weeks and 6 months

Hypertension management with tPA

• BP monitoring frequency during and after tPA
  • 0-2 hours: Every 15 minutes
  • 3-8 hours: Every 30 minutes
  • 9-24 hours: Every hour
• If BP >180/>105
  • Labetalol 10-20mg IV then infusion 2-8mg/min
  • Nicardipine infusion
  • Hydralazine boluses
• If BP refractory to this or DBP >140
  • Sodium nitroprusside 0.5-10mcg/kg/min

Thrombolysis

• NINDS trial (1995)
  • First randomised control trial rtPA within 3 hours of onset (50% received within 90 minutes) showing benefit (previous trials used different agents, doses or treatment windows)
  • No difference at 24 hours
  • At 3 months OR for favourable outcome was 1.7 with rtPA with 11-13% absolute risk reduction benefit (NNT 8-9)
  • 31-50% of patients in rtPA group had favourable outcome at 3 months vs. 20-38% of non-rtPA group
  • Benefit found regardless of ischaemic stroke subtype and maintained at 1 year
  • Symptomatic ICH in 6.4% of rtPA group (45% mortality) and 0.6% of placebo group (50% mortality)
  • Mortality rate unchanged at 3 months despite rise in symptomatic ICH and percentage of patients left severely disabled was lower in tPA group

• Concerns around NINDS trial
  • Only 624 patients (half of whom received tPA)
  • ACEM position paper
    • tPA within 3 hours may increase odds of better functional outcome, while at the same time increasing the odds of intracranial haemorrhage and conferring no mortality benefit
    • Informed decision making and consent is crucial 
    • NNT to achieve functional independence (mRS 0-1) is 10
    • NNT to achieve functional independence (mRS 0-2) is 13
    • NNTH for symptomatic ICH is 42 
    • NNTH for fatal ICH is 122
• Only 2/13 thrombolysis trials showed benefit; both of which were marginal and had significantly more severe stroke severities in the placebo group

Subsequent thrombolytic trials

• ECASS III
  • Demonstrated functional improvement up to 4.5 hours
  • No change in mortality
  • NNT = 14
  • Now standard of care
• IST-3
  • Largest study to date (3035 patients)
  • Up to 6 hours
  • No upper age limit and increased allowable BP
  • No difference at 6 months
  • Mortality at 6 months was the same
  • Those who received tPA between 3 and 4.5 hours had worse outcomes but rest had improvement
• Meta-analysis 2012
  • Concluded trend towards functional improvement and that early treatment better than late treatment, with possible benefit up to 6 hours
• EXTEND
  • Terminated early after results of WAKE-UP published after only 75% recruitment
  • 113 and 112 in each group
  • Lysis vs. placebo at 4.5 to 9 hours post-onset OR within 9 hours of mid-point of sleep
  • Patient criteria
    • mRS <2
    • NIHSS 4-26
  • Radiological criteria
    • Cerebral blood flow reduced 30%
    • Tmax >6 seconds
    • Mismatch ratio >1.2
    • Core <70mL
    • Penumbra >10mL
  • mRS 0-1 in 35.4% of lysis group and 29.5% of placebo group (p = 0.04)
  • No benefit in terms of ordinal analysis
  • Now a strong recommendation in Australian Stroke Guidelines
• WAKE-UP
  • Unknown time of onset MRI-guided lysis
  • Independent prior (mRS <2)
  • Mismatch between DWI and FLAIR
  • Results
    • mRS 0 or 1 in 53.3% of lysis group and 41.8% in placebo group at 90 days
  • Now a weak recommendation for patients out of the 9 hour window to undergo MRI perfusion to identify a subgroup that may benefit from lysis

Thrombolysis

• Traditionally NIHSS score of 4-22, however, some strokes with lower NIHSS scores may have significant disability for that patient i.e. aphasia
• BSL is the only blood test required prior to thrombolysis unless suspicious of coagulopathy
• Alteplase 0.9mg/kg IV with 10% given over 1 minute, then rest over 60 minutes
• BP and neuro checks every 15 minutes for 2 hours
• DO NOT give antiplatelets or anticoagulants within 24 hours of therapy

Absolute exclusion criteria (AHA/ASA)

• Significant head trauma or prior stroke in last 3 months
• Symptoms suggestive of SAH
• Arterial puncture at non-compressive site <=7 days ago
• Hx of previous ICH (ever)
• Intracranial neoplasma, AVM or aneurysm
• Seizure with post-ictal residual neurological impairments
• Recent intracranial or intraspinal surgery
• Pretreatment SBP >185 or >110 despite therapy
• Active internal bleeding

Absolute exclusion criteria (AHA/ASA)

• Platelets <100 (if therapy started already should be stopped)
• Use of heparin within last 48 hours and APTT > ULN
• INR >1.7
• Current use of NOAC’s with elevated coags
• BSL <2.7
• Non-con CT shows multilobar infarction (hypodensity >1/3 cerebral hemisphere or ICH/neoplasm

Relative exclusion criteria (AHA/ASA)

• Minor or rapidly improving stroke symptoms
• Pregnancy
• Seizures at onset (unless residual neurological impairments are thought to be stroke-related vs. post-ictal)
• Major surgery or serious trauma within preceding 14 days
• Previous GI or urinary tract haemorrhage in last 21 days
• Previous MI within 3 months

Antiplatelet therapy

• Oral aspirin 325mg (300mg in Australia) within 24-48 hours of stroke onset but NOT within 24 hours of thrombolysis
  • Significant reduction in mortality and morbidity (at 4 weeks and 6 months) if delivered within 48 hours
  • Reduces recurrent stroke
  • NNT is 100
• DAPT
  • UpToDate advises this for minor stroke (NIHSS <=5) for total 21 days
  • Also advised for stroke in presence of large intracranial vessel atherosclerosis for total 90 days

Post-thrombolysis bleeding

• Cease infusion
• FBC, Coags (q2h until resolved) 
• X-match PRBC/FFP/cryoprecipitate and platelets
• Urgent imaging
• Emergent neurology, neurosurgery and haematology consultation
• Reverse fibrinolysis
  • FFP 2U q6h for 24 hours
  • Cryoprecipitate 10IU
  • Tranexamic acid 1g IV
• Reverse antiplatelets – Platelets adult 1 bag, DDAVP 0.3mcg/kg
• Reverse anticoagulants – Protamine
• Consider palliation

Severity scores

Modified rankin scale

• mRS
  • 0 – No symptoms
  • +1 – No significant disability despite symptoms; able to carry out all usual duties and activities
  • +2 – Slight disability; Unable to carry out all previous activities but able to look after own affairs without assistance
  • +3 – Moderate disability; Requiring some help but able to walk unassisted
  • +4 – Moderately severe disability; Unable to walk and attend bodily needs without assistance
  • +5 – Severe disability; bedridden, incontinent and requiring constant nursing care and assistance
  • +6 – Dead
• The Modified Rankin Scale is a measure of disability after stroke
• 0-1 = Excellent outcome
• 0-2 = Functional independence

NIHSS

• National Institute of Health Stroke Scale
• A measure of stroke severity used in prognostication and determining who may benefit from IV-tPA and endovascular clot retrieval techniques
• Score of 0 (no symptoms/signs) to 42

ASPECTS

• Alberta Stroke Program Early CT score
• Originally devised to quantify early ischaemic changes on non-contrast CT brain with acute ischaemic infarct of anterior circulation
• 1 point deducted from 10 for any evidence of ischaemic changes for each defined region
• Lower score = more widespread ischaemic involvement
• A 2017 systematic review and meta-analysis showed favorable outcomes for patients undergoing endovascular clot retrieval for high baseline ASPECTS
• The lowest ASPECTS at which benefit is lost is unclear. More study required.

Endovascular clot retrieval

• MR CLEAN (2015)
  • Game changer
  • Endovascular therapy within 6 hours using modern retrievable stents (82%) showed significantly improved mRS scores at 90 days without an increase in mortality
    • mRS 0-1 (excellent): 11.6% vs. 6%
    • mRS 0-2 (functional independence): 32.6% vs. 19.1%
• EXTEND IA, ESCAPE, SWIFT PRIME and REVASCAT
  • All stopped early once MR CLEAN published with positive significant improvement in mRS at 90 days
• HERMES meta-analysis
  • Common OR favoured endovascular clot retrieval with modern stents (and 80% received tPA prior) except in those under 50, ASPECTS 0-5 and M2 lesions (underpowered for these groups anyway)
• DAWN (2017)
  • Trevo thrombectomy plus IV tPA vs. IV tPA alone 6-24 hours after last seen well
  • <1/3 MCA territory involved; occlusion of intracranial ICA and/or MCA-M1 on MRA or CTA
  • Clinical:imaging mismatch on MR-DWI or CT-perfusion
  • Results
    • 2-point difference in mRS at 90 days
    • 35% absolute increase in number of patients achieving functional independence
    • 73% relative risk reduction of dependency in ADL’s (mRS 3 or more)
    • NNT for lower disability 2.0
    • NNT for functional independence = 2.8
• DEVT
  • 33 stroke centres in China
  • Patients with ICA or M1 lesions within 4.5 hours
  • Excluded if mRS 2 or more
  • 1:1 endovascular treatment vs. IV thrombolysis + endovascular treatment
  • 0.9mg/kg alteplase with 10% as bolus
  • Ceased early after 194 patients when met pre-defined non-inferiority significance
  • mRS 0-2 at 90 days 54.6% with ECR alone vs. 47.4% in combination therapy
  • Same mortality and symptomatic ICH equal (6.1% vs. 6.8%)
• SKIP
  • 23 stroke centres in Japan with ICA or M1 lesions within 4.5 hours
  • mRS 3 or more excluded and patients had to be NIHSS 6 or more
  • Received 0.6mg/kg alteplase (vs. 0.9mg/kg in other studies)
  • mRS 0-2 at 90 days in 59% of ECR vs. 57.3% with combination therapy
  • Non-inferiority margin not met
  • ICH at 36 hours in 33.7% of ECR alone group vs. 50.5% of combined group but symptomatic ICH in 7.9% and 11.7% respectively (not significant)
• DIRECT-MT
  • 41 stroke centres in China
  • ICA, M1 or M2 lesions with NIHSS 2 or more within 4.5 hours
  • mRS 2 or more excluded
  • 1:1 ECR vs. combined with alteplase 0.9mg/kg
  • mRS 0-2 at 90 days non-inferior in ECR vs. combination group
  • Mortality 17.7% vs. 18.8%
  • Symptomatic ICH 4.3% vs. 6.1% in combination group
• AURORA
  • Individual patient data meta-analysis and systematic review
  • Patients randomly assigned to endovascular thrombectomy vs. standard medical care from 6 to 24 hours from time last seen well with proximal anterior circulation occlusions
  • Primary outcome was mRS at 90 days analysed by ordinal logistic regression
  • Key safety outcomes were symptomatic ICH and mortality within 90 days
  • 505 patients’ data included across 6 major randomised studies
  • Adjusted common odds ratio of 2.54 favouring intervention arm -> NNT for reduced mRS score by 1 = 3
  • mRS 0-2 at 90 days was 45.9% in thrombectomy group vs. 19.3% in standard care group
  • No difference in mortality at 90 days (16.5 vs. 19.3%)
  • No difference in sICH (5.3 vs. 3.3%)
  • All patients had baseline ASPECT scores measured and majority had to meet angiographic or perfusion-based criteria to quality
  • Included witnessed stroke onset 6-24 hours prior, reducing the risk that the benefit seen in ‘late’ thrombectomy in previous trials was simply due to their stroke having started just prior to wake up
• For basilar artery occlusion?
  • Single RCT of 16 patients found favourable
  • Recanalisation is a surrogate marker for good outcome on meta-analysis and is more likely with endovascular therapy vs. tPA (77% vs 59%)
  • Needs more study
• Australian Stroke Management Guidelines
  • Strong recommendation to commence within 6 hours if ICA, M1 or tandem occlusion on CT-A
  • Strong recommendation to provide IV tPA while concurrent ECR ongoing
  • Strong recommendation to consider for basilar artery occlusion
  • Consensus recommendation to consider for major occlusions presenting between 6-24 hours and those with more distal occlusion (M2)

Carotid endarterectomy/stenting

• In TIA patients with medically treated high-grade internal carotid artery stenosis, endarterectomy should be performed promptly (with greatest benefit seen within 2 weeks)
• CREST and ICSS trials showed carotid stenting as a viable alternative (especially if <70yo)

Decompressive craniectomy

• Pooled analysis of three European trials (DECIMAL, DESTINY, HAMLET) for massive MCA ischaemic stroke showed better outcomes with decompressive craniectomy than medical treatment only
• HeADDFIRST trial showed less mortality at 180 days in medically treated patients than previously reported (40% vs. 50-70%) and no difference between medical treatment only or decompressed patients

Transient ischaemic attack

• Definition: Transient episode of neurological dysfunction caused by focal brain, spinal cord or retinal ischaemia without acute infarction
• TIA usually lasts <1-2 hours, however, duration of symptoms is an unreliable indicator between TIA and infarction
• Analogous to unstable angina – ominous harbinger of future vascular event
• OR for stroke <1 month after TIA is 30 and 90-day stroke risk is around 9.5%
  • 2, 30 and 90 day risk = 3.5, 8 and 9.2% respectively
• 50% of these subsequent events occur within 2 days
• Risk factors for subsequent stroke:
  • HTN
  • DM
  • Symptoms >10 minutes
  • Weakness
  • Speech impairment
  • Male
  • Age >= 65
  • Dyslipidaemia
  • Dysarthria
  • CT or MRI changes of infarction

Classic TIA

• Motor weakness in one or more body segments
• Dysphasia
• Sensory loss in two or more body segments
• Hemianopia or quadrantanopia
• Monocular visual loss
• Vertigo plus
• Diplopia plus
• Dysarthria plus
• Ataxia plus

Non-consensus TIA

• Vertigo only
• Diplopia only
• Ataxia only
• Dysarthria only
• Bilateral decreased vision only
• Single segment sensory loss

OXVASC trial looked at prospective outcomes of patients with non-consensus TIA and found similar rates of 90-day recurrent TIA/stroke as classical TIA. These syndromes need to be taken seriously and treated as TIA for prevention to be initiated in the form of antiplatelet therapy and risk factor modification.

Rosier score

• Used to identify stroke in ED
• Acute onset of:
  • Asymmetric face weakness
  • Asymmetric arm weakness
  • Asymmetric leg weakness
  • Speech disturbance
  • Visual field defect
  • Seizure activity (-1) 
  • Loss of consciousness or syncope (-1)

ABCD2 score

• Score
  • Age >=60 (1 point)
  • BP >- 140/90 (1 point)
  • Clinical
    • 0 = Absent
    • 1 = Speech impairment without unilateral weakness
    • 2 = Unilateral weakness
  • Duration
    • 0 = Absent
    • 1 = 10-59 min
    • 2 = >= 60 min
  • Diabetes (1 point)

• Prognosis
  • 2-day risk of stroke
    • Score 0-3 = 1%
    • 4-5 = 4.1%
    • 6-7 = 8.1%
  • 7-day risk of stroke
    • Score 0-3 = 1.2%
    • 4-5 = 5.9%
    • 6-7 = 11.7%
• Subsequent studies have refuted these rates
• Meta-analysis showed ABCD2 inadequate in predicting future stroke for treatment decisions if used in isolation

Alternative to ABCD2

• Canadian Stroke Guideline High Risk Factors
  • Unilateral weakness
  • Speech or language disturbance
  • Posterior circulation symptoms

Management

• Some experts recommend all TIA patients be admitted for monitoring, education, antiplatelet initiation, rapidly treat subsequent stroke (if occurs), assess stroke risk factors, implement preventative measures and perform carotid endarterectomy/stenting in appropriate patients
• Others recommend beginning workup in ED, starting antiplatelets, educating patient/family about recurrent symptoms and risk modification with early follow-up
• May depend on healthcare resources and social situation more than medical factors
• Early Ix and intervention can prevent 80% of further strokes
• Admission criteria
  • 4 TIA’s in 2 weeks or 2 within 24 hours
  • 3 within 72 hours (Crescendo)
  • High-grade carotid stenosis (hence benefit of early CTA)
  • Presumed cardiac source i.e. AF
  • Embolic TIA despite anticoagulation
  • ABCD2 >= 3
• PAH Admission criteria
  • New AF
  • Culprit large vessel stenosis >50%
  • Patients with TIA on therapeutic anticoagulation

Australian Stroke Management Guidelines

• ABCD2 >=3, and/or any one of AF, carotid territory symptoms or crescendo TIA should undergo urgent brain imaging (MRI with DWI) as soon as possible
  • All TIA patients with carotid territory symptoms should undergo early CTA
• TIA patients with AF should commence anticoagulation therapy early after brain imaging has excluded haemorrhage (but Tintinalli suggests as an inpatient NOT outpatient basis as significant risk of haemorrhagic transformation – liaise with Neurology team)
  • Australian Stroke Guidelines recommend initiating anticoagulation after ischaemic stroke without haemorrhagic transformation at 48 hours for mild-moderate stroke and day 6-7 for major stroke
• Those with ABCD2 <4 without crescendo symptoms, AF or carotid territory symptoms or who present more than one week after last symptoms should undergo CTA as soon as possible (i.e. within 48 hours)
• National Stroke Foundation recommends for this group, discharge from ED on antiplatelets, outpatient appointment within 1 week, advice not to drive or enter other risk situations, cease smoking and see GP within 24-48 hours
• Routine testing for suspected TIA should include FBC, Chem20, ESR, lipid profile, glucose level, ECG, CT and CTA

Benefit of cardiac monitoring

• If cryptogenic TIA/stroke then Holter monitoring will pick up paroxysmal AF in up to 20% of patients vs. inpatient tele only 10%
• Benefit in echo for PFO also lies in the cryptogenic group

Management

• Dual antiplatelets for high-risk TIA (ABCD >=4) and minor ischaemic stroke not receiving thrombolysis should be started immediately
  • Aspirin 300mg + Clopidogrel 300mg load then
  • Aspirin 100mg per day and Clopidogrel 75mg per day for 3 weeks only
  • Then reduce to single antiplatelet agent
    • If aspirin naive: continue aspirin only
    • If TIA occurred despite aspirin: Continue clopidogrel only
• Single antiplatelet therapy is suitable for lower risk TIA patients
  • aspirin or switch to clopidogrel if already on aspirin
• Atorvastatin 80mg daily
• Driving restriction 2 weeks for private license, 4 weeks for commercial
• Aspirin
  • CAST and IST trials
  • 1/3000 patients started on aspirin will have disabling or fatal stroke within 2 weeks
  • 1% risk of stroke in 2 weeks vs. 2.5% risk if not on aspirin
• Aspirin + Dipyramidole
  • Large meta-analysis (ESPRIT trial) showed combination superior to aspirin alone for prevention of vascular events after stroke or TIA
  • More haemorrhagic events than dipyramidole alone
  • No more haemorrhagic events than aspirin alone
  • Less haemorrhagic events than aspirin + clopidogrel
  • Increased rate of withdrawal vs. aspirin alone due to headache primarily
  • If intolerant, can give aspirin or clopidogrel alone
• Aspirin + clopidogrel
  • Initially was not recommended (MATCH trial) as does not appear to reduce risk compared to either agent alone and has increased bleeding risk (used DAPT for up to 2 years though)
  • More recent studies have shown short duration of DAPT reduces stroke risk with only a possible small increase in bleeding risk and no increase in mortality
• Decision based upon bleeding risk, comorbid conditions and other antiplatelet/anticoagulant use
• EXPRESS trial (Rothwell et al. 2007)
  • Showed early management of TIA reduces stroke risk by up to 80%
  • Phase 2 involved rapid access walk-in clinic without appointments and treatment initiation as soon as diagnosis confirmed
  • Showed 10.3% reduced to 2.1% 90 day risk of stroke
• FASTER trial (Kennedy et al. 2007)
  • Aspirin + Clopidogrel vs. Aspirin + Placebo and Atorvastatin vs. placebo within 24 hours
  • Showed trend towards benefit of DAPT without increase in mortality and non-significant increase in ICH
  • Stopped early
• CHANCE trial (Wang et al. NEJM 2013)
  • Minor stroke or TIA (NIHSS 3 or less) with moderate to high recurrent stroke risk (ABCD2 score 4 or higher)
  • All done in China
  • Clopidogrel + Aspirin decreases 90 day stroke risk without increase in haemorrhagic complications compared to aspirin alone
  • Started within 24 hours and continued DAPT for 21 days
  • Reduced from 11.7 to 8.2% stroke rate at 90 days
  • Follow-up study (Circulation 2015) showed persistent benefit up to 1 year
  • 0.3% moderate-severe haemorrhagic complication rates in both groups
• POINT trial (Johnston et al. NEJM 2018)
  • Validated CHANCE trial in international cohort
  • DAPT reduced ischaemic events at 90 days from 6.5% to 5% with majority in first week
  • Major haemorrhage in 0.9% of DAPT group and 0.4% of aspirin only group (p = 0.02)
• If DAPT started within 72 hours and limited to 21 days resulted in 1.5-3.5% decreased risk of stroke with possible minor significant increase in bleeding

Anticoagulation

• TIA in the setting of acute AF
  • Anticoagulation should NOT be initiated in the ED but rather in the inpatient setting
  • Risk of stroke <5% over next 48 hours; risk of haemorrhagic conversion of stroke highest in first 48 hours
  • Australian Stroke Guideline suggests initiating anticoagulation at 48 hours for mild-moderate ischaemic stroke without haemorrhagic transformation and day 6-7 for major stroke
  • No benefit of anticoagulants in acute stroke and increased risk of ICH even in the presence of AF
  • If already on anticoagulation for good indication
    • Can be restarted at 48 hours if well after TIA (liaise with stroke team)
    • Day 6-7 if major stroke (1-2 weeks as per Stroke team)
• Smoking cessation
  • 66% relative risk reduction of stroke

Carotid endarterectomy or stent

• Beneficial outcome of urgent surgery for symptomatic carotid stenosis with anterior TIA’s and minor strokes with carotid stenosis of 70-99%
• Endarterectomy for >80% stenosis = Stroke risk reduced by 50%
• Endarterectomy for 70-80% stenosis = Stroke risk reduced by 25%
• This may extend to stenosis of 50% in select patients
• CREST trial showed endarterectomy slightly more effective than stenting but stenting more suitable for those with major comorbidities
• Indications
  • TIA in carotid territory within 6 months
  • >70% stenosis of ipsilateral carotid OR >50% on catheter angiography
  • Otherwise fit for surgery with expected perioperative stroke or mortality risk <6%

Stroke in young people

• Cervical arterial dissection in 20% of cases and cardioembolic in 20% of cases
• Cardioembolic events due to mitral valve prolapse, rheumatic heart disease or paradoxical embolism (PFO in 20% of population and 40% of those who have a stroke)
• Migrainous stroke (infarction associated with typical migraine attack)
• Risk factors
  • Smoking, substance abuse (heroin, cocaine, amphetamines), migraine with aura, pregnancy (late 3^rd trimester and 6 weeks post-partum), HIV
• Causes of ischaemic stroke in young people
  • Large vessel occlusion (carotid stenosis), extracranial (carotid/vertebral dissection), intracranial (basilar dissection)
  • Cardioembolic
  • Small vessel lacunar infarcts
  • Infections – TB, meningitis, syphilis, VZV, HIV
  • SLE
  • Antiphospholipid
  • Haematological – Sickle cell, leukaemia, intravascular lymphoma, TTP

Stroke in pregnancy

• Women at increased risk of ischaemic and haemorrhagic strokes during pregnancy (mostly late third trimester and first 6 weeks post-delivery)
• 34/100 000 deliveries
• Overall RR 2.4 compared to non-pregnant females
• Risk far higher in post-partum period
  • RR 8.7 for ischaemic stroke and 28.3 for haemorrhagic stroke
• Particularly susceptible to cerebral venous sinus thrombosis presenting as headache
• Treatment requires early consultation with obstetrics, neurology and neonatologists respectively

Complications of stroke

• Cerebral oedema and raised ICP
• Haemorrhagic transformation
• Seizures – Treat as per normal. Prophylaxis not required
• Aspiration pneumonia
• Hypoventilation
• DVT
• PE
• UTI
• Pressure areas

Intracerebral haemorrhage

• Hypertension most common cause followed by amyloid angiopathy
• 25-50% mortality at 6 months
• Poor prognostic factors
  • Blood in ventricles
  • Low GCS (3-4)
  • Haematoma volume >30mL
  • Age >80
  • High NIHSS score
  • Infratentorial
• Operative decompression
  • Controversial intervention
  • If <1cm from cortical surface, may benefit from early decompression
  • If GCS <8 = universally poor outcome
  • Ideally within 6 hours
• EVD if intraventricular extension to prevent hydrocephalus
• Treatment
  • Reversal of coagulopathy
  • Platelet transfusion only if undergoing neurosurgical procedure
  • BP management
    • If 150-220mmHg - Drop to 140mmHg
    • If SBP >220mmHg  Target 140-160mmHg
    • Labetalol/hydralazine preferred
  • ICP monitoring
    • If GCS <8, clinical evidence of herniation or signficant IVH or hydrocephalus
  • Cooling not advised for ischaemic or haemorrhagic stroke
  • Target Na 145-155mmol/L
  • Seizure prophylaxis not encouraged and avoid phenytoin

Interact 2

• Death and severe disability the same in intensive BP lowering to <140mmHg within one hour versus traditional target <180mmHg
• Improved modified Rankin scores though

AtAch 2

• No difference in death or disability among patients with acute ICH between
  • Target 110-139mmHg vs. 140-179mmHg
  • Renal adverse events higher in intensive treatment group

Rule of 4’s

• Blood supply of brainstem
  • Paramedian branches  Medial brainstem syndromes
  • Long circumferential branches  Superior cerebellar artery (SCA), Anterior inferior (AICA) and posterior inferior (PICA)
• 4 rules
  • 4 structures in midline starting with M
  • 4 structures to the side starting with S
  • 4 cranial nerve in medulla, 4 in pons and 4 above the pons (2 in midbrain)
  • 4 motor nuclei in midline that divide equally into 12 (except 1 and 2) = 3, 4, 6 and 12 (5, 7, 9 and 11 are in the lateral brainstem
• 4 median structures
  • Motor pathway (corticospinal tract) = Contralateral weakness of arm/leg
  • Medial lemniscus = Contralateral vibration and proprioceptive loss
  • Medial longitudinal fasciculus = Ipsilateral INO (ipsilateral failure to adduct and contralateral nystagmus when attempting to abduct)
  • Motor nucleus and nerve = Ipsilateral 3, 4, 6 or 12
• 4 side structures
  • Spinocerebellar = Ipsilateral ataxia
  • Spinothalamic pathway = Contralateral pain/temp loss
  • Sensory nucleus of 5^th cranial nerve = Ipsilateral pain/temp loss on face
  • Sympathetic pathway = Ipsilateral Horner’s
• 4 cranial nerve above pons
  • 1, 2 above
  • 3, 4 in midbrain
• 4 cranial nerves in pons = 5, 6, 7, 8
• 4 cranial nerve in medulla = 9, 10, 11, 12
• If signs of both lateral and median involvement, suspect basilar artery pathology

Transient global amnesia

• Definition
  • Predominantly anterograde amnesia (impaired laying down of new memory) with recovery in less than 24 hours
  • Variable retrograde amnesia
  • Disorientation to self or impaired consciousness excludes this differential
  • Headache in up to 40%
  • DDx
    • TIA – Usually other neurological features e.g. visual field
    • Seizure – Usually lasting <1 hour, occurs on waking, retrograde > anterograde
    • Hypertensive encephalopathy – More predominant confusion vs. pure memory issue
• Imaging
  • CT/CTA is reasonable to exclude small chance of stroke
  • MRI useful within 12-72 hours to make positive diagnosis (hippocampal abnormalities) to exclude seizure for driving limitations
• Treatment
  • Not usually started on antiplatelets unless white matter infarcts seen on MRI

Last Updated on June 12, 2024 by Andrew Crofton