There have been significant developments in the diagnosis and management of ischaemic stroke.   This started with trials showing a benefit for decompressive craniectomy after a malignant hemispheric stroke in patients under 60 undergoing surgery within 48 hours.   The evolution of CT and MRI have enabled us to better image not only the ischaemic core of the stroke, but also the surrounding hypo-perfused brain at risk of ischaemic death; the penumbra. CT and MR angiography now allow rapid, non-invasive detection of occlusions in the major neck and intracranial arterial vessels.  These techniques are key to the appropriate selection of patients for therapeutic interventions aiming at rapid and effective arterial recanalisation to restore blood flow. Intravenous thrombolysis with rt-PA is effective if given early and no later than 4.5 hours. The benefit of intravenous thrombolysis for patients with severe stroke due to large artery occlusion is limited but these patients may be candidates for mechanical thrombectomy. Since 2014, several trials have confirmed the effectiveness of thrombectomy for patients with anterior circulation artery occlusion with a number needed to treat of less than 3 for improved functional outcome. Two recent trials have also shown that in selected patients, the benefit of thrombectomy extends to at least 24 hours, increasing the number of patients eligible to receive this treatment.   The rate of intravenous thrombolysis remains low in many Australian centres, especially in regional areas and only a few metropolitan centres provide a thrombectomy service.  With the recent expansion of the time window, the logistics of patients being transferred to these centers has improved but good selection of patients with advanced imaging is a prerequisite to ensure that health resources are used efficiently.   There is a need to improve health services to better manage stroke patients in Australia and worldwide. This has the potential to improve outcome for stroke victims.  

1. Massive stroke: no longer a death
sentence?
Candice Delcourt, MD PhD FRACP

2. Burden of stroke
Age standardized incidence of ischaemic stroke in 2010 per 100,000 person-years
(GBD)
Australia in 2017
• 56,000 new and recurrent stroke
(~80% ischaemic vs~20%
haemorrhagic)
• 475,000 stroke survivors
• 65% of survivors with a disability

3. Definition of a massive stroke
• Is a catastrophic disease which
o Is life threatening
o In case of survival is always associated with long-term disability
• Clinically:
o Sensory and motor changes
o Cortical signs: Speech disturbance, Visual field deficit or
Navigational difficulty (loss of spatial awareness)
o Drowsiness
• NIHSS: National Institute of Health Stroke Scale > 15

4. Assessment Response (0-42)
Level of consciousness 0=alert to 3=unresponsive
2 questions (month, age) 0 to 2, aphasia or stuporous=2, intubated=1
2 commands (open and close eyes; grip and release
paretic hand)
0 to 2
Best gaze 0=normal to 2=forced deviation
Visual fields 0=no visual loss to 3=bilateral hemianopia
Facial palsy 0=symmetrical movement to 3=complete paralysis
Motor function of arms and legs 0=no drift to 4=no movement and 9=amputation,
joint fusion
Limb ataxia 0=absent to 2 present in 2 limbs and 9
Sensory function 0=no sensory loss to 2=severe to total sensory loss
Best language 0=no aphasia to 3=global aphasia
Dysarthria 0=normal to 2=severe and 9 for intubated
Extinction and inattention 0=no abnormality to 2=profound hemi-inattention
Right sided hemiplegia, sensory loss,
expressive aphasia and hemianopia
TOTAL NIHSS= 18/42

5. Brain imaging: What is a massive stroke?
Brain CT scans Left: small stroke (lacunar stroke)
Right: Massive ischaemic stroke in the right hemisphere

6. Massive stroke: treatment options
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7. Decompressive hemicraniectomy

8. Patient selection for hemi-craniectomy (1)
• Age 18-60 years
• No previous disability
• Massive stroke based on NIHSS and imaging
• Within 48 hours
• Decreased LOC ≥ 2 points on GCS and signs of
herniation
Brain MRI DWI: right middle
cerebral artery infarction

9. • Importantly:
o willingness to live with at least mild to moderate
disability
o knowing that the chance of surviving with severe
disability is 30%
o respecting the fact that the alternative is death with a
probability of ~70%
Patient selection for hemi-craniectomy (2)

10. Hemicraniectomy: expected outcome at 12 months
NNT to prevent mRS 5-6 =2
The Lancet Neurology, 6(3), 215 - 222, March 2007
The modified Rankin scale (mRS)

11. Case Study: 53 y old man
• Woke up with left sided hemiparesis and dysarthria
• Ambulance to hospital
• CT scan: Large right middle cerebral artery stroke
with an occluded right internal carotid artery and
middle cerebral artery

12. Day 1

13. Day 2

14. Day 3

15. Two months later

16. Massive stroke: treatment options
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18. mRS at 90 days
NNT 14

19. The benefit of IV rt-PA falls as time passes
Odds ratio (OR) of a good outcome
NNT 4.5
NNT 9.0
NNT 14
NNT 21
Number Needed to Treat (NNT) for one patient to have no or minor disability after
thrombolysis (0-90, 0-180, 180-270 and 270-360 minutes)
Adapted from Lancet, 6 August 2014

20. Efficacy of IV rtPA: Dragon score
• Onset to treatment time (OTT)
• Pre-treatment disability
• Age
• Baseline glucose
• Early infarct signs on admission CT
• Hyper-dense cerebral artery sign
• Stroke severity (NIHSS) Strbian et al. Neurology, 2012; Stroke, 2013

21. Paper from Mazya
Functional outcome (modified Rankin score) after intravenous thrombolysis by stroke
severity (NIHSS) (Mazya, Neurology 2015)
StrokeseveritybyNIHSS
Disability by mRS

22. Pathophysiology of efficacy
Imaging factors:
• Core
• Penumbra
• Pre-existing cerebral perfusion
impairment
• Large vessel disease
• Small vessel disease
• Collateral “damage”
• Clot characteristics
• Size
• Composition

23. RAPID automated image analysis

24. Site of
occlusion
Early
Recanalization
after IV tPA*
ICA
terminus
(n=17+23)
5% (2/40)
MCA M1
(n=166+65)
30% (70/231)
MCA M2
(n=116+13)
42% (54/129)
Basilar
(n=10+25)
11% (4/35)
Overall
(n=331+127)
30% (136/458)
Pooled results of Saqqur et al Stroke 2007 & Bhatia et al Stroke 2010

25. Pathophysiology of risk of haemorrhage (~7% vs 1%)
Safety impediments
• Clinical
• Age
• Stroke severity
• Co-morbidity
• Antithrombotic drugs
• Imaging safety impediments
• Small vessel disease – “fragility”
• White matter “disease”
• Hypertension
• Amyloid angiopathy

26. Tenecteplase instead of alteplase: not in massive stroke
IIb recommendation: “Tenecteplase administered as a 0.4-mg/kg single IV
bolus has not been proven to be superior or noninferior to alteplase but
might be considered as an alternative to alteplase in patients with minor
neurological impairment and no major intracranial vessel occlusion”

27. Massive stroke: treatment options
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28. HERMES collaboration
• In 2015: 5 trials showed the benefit of
thrombectomy in ischaemic stroke with large vessel
occlusion within 6 hours of onset
• MR CLEAN
• ESCAPE
• REVASCAT SWIFT PRIME
• EXTEND IA
• Data were pooled analysis by the authors under the
HERMES collaboration
Goyal et al. Lancet. 2016

29. Results of the pooled analysis : mRS at 90 days
• 1287 patients (endovascular thrombectomy vs control)
• Endovascular is superior to control: NNT to reduce disability by at
least one level on mRS was 2.6
• No difference between sub-groups
• 80 or older IV rt-PA eligible
• Size of ischaemic core
• No difference in mortality

30. Endovascular thrombectomy: extending the time window
• Hermes: Groin puncture within 6-hours of stroke symptom
onset
• DAWN: Groin puncture between 6 – 24-hours
• Defuse-3: Groin puncture between 6 – 16-hours

31. DAWN eligibility criteria
• Age ≥18
• Within 6-24 hours of time last known to be well
• No significant pre-stroke disability and NIHSS ≥ 10
• Intracranial ICA and M1 only
• A clinical-core mismatch according to age using RAPID:
o Age ≥ 80 y old: NIHSS ≥ 10 and infarct volume < 21 mL
o Age < 80 y old: NIHSS 10 to 19 and infarct volume < 31 mL
o Age < 80 y old: NIHSS ≥ 20 and infarct volume < 51 mL

32. DEFUSE 3
• Within 6-16 hours of time last known to be well
• NIHSS ≥ 6 and baseline mRS ≤ 2
• Occlusion of cervical or intracranial ICA or M1 segment of the MCA
• 18-90 y old
• Target mismatch on CTP or MRI:
o Ischaemic core < 70 mL and
o Mismatch ratio > 1.8 (perfusion lesion/core) and
o Mismatch volume > 15 mL (perfusion lesion – volume of core)

33. • Modified Rankin scale (0-2) at 90 days
Intervention Medical
Odds or risk
ratio (95% CI)
DAWN 48.6% 13.1%
2.1 (1.20 –
3.12)
Bayesian probability
of superiority
>0.9999
DEFUSE 3 45% 17%
2.67 (1.60 –
4.48)
P value < 0.001
Outcome of DAWN and DEFUSE 3
NNT 2.5
• Death 14% vs 26% (P = 0.05) in DEFUSE 3
• No difference in symptomatic intracerebral haemorrhage

34. Australian guidelines
“ For patients with ischaemic stroke caused by a large vessel occlusion in
the internal carotid artery, proximal cerebral artery (M1 segment), or
with tandem occlusion of both the cervical carotid and intracranial
arteries, endovascular thrombectomy should be undertaken when the
procedure can be commenced within 24 hours after they were last
known to be well if clinical and CT perfusion or MRI features indicate the
presence of salvageable brain tissue ”

35. Case Study: 77 y old woman
• 16:00 sudden onset of right sided weakness
• Non smoker, normotensive, No hypercholesterolemia, not diabetic
• No previous stroke, no AF
• No family history of stroke

36. 16:00 Symptoms
17:30 Hospital arrival
17:46 IV rtPA
Timing of the events

38. Pass Technique Result
1 solumbra 0 – 3
L M1
G
A
angio 17:45 1h 45
groin 18:04 2h 04
Final TICI 18:35 2h 35
procedure time 0h 31

39. Follow-up brain CT scan
53

40. Give IV rtPA first: ”Drip and Ship”
• “ Eligible stroke patients should receive intravenous thrombolysis
while concurrently arranging endovascular thrombectomy, with
neither treatment delaying the other”
• Recent EXTEND TNK: Tenecteplase might be better than alteplase as
a bridging therapy (Campbell, NEJM 2018)
• Tenecteplase 0.25 mg/kg versus Alteplase within 4.5 hours
• 202 patients eligible for thrombectomy
• Higher incidence of reperfusion
• Better functional outcome

41. Procedure
• General anesthesia or conscious sedation might be used for
endovascular therapy (Brinjikji, Stroke 2017)
• Blood Pressure (BP):
• BP < 180/105 prior to IV rtPA
• Systolic BP 150-180 mm Hg prior to reperfusion and < 140 after
• No clear guidelines on peri-procedural BP

42. Summary
• Thrombectomy is an effective treatment for large vessel ischaemic stroke
• Time window is important for both IV rt-PA and thrombectomy
• Presence of salvageable tissue is even more important
• Local thrombectomy protocols are used with simplified inclusion criteria
from the DAWN and DEFUSE trials
• Access to CT Perfusion in small centers will allow transfer to centers
where endovascular therapy is available
• Health services need to be organised to provide access to reperfusion
therapy