Tony Goddard MRCP FRCR

Consultant Interventional Neuroradiologist

Trust Members Meeting

Wed 28th Jan 2015

Overview:

Differences between the ‘stroke’ types

Why urgent treatment matters

Standard treatment available

Development of non-invasive treatments

Major trials and major shift in approach

Future directions and challenges

Uncommon type of ‘stroke’

Bleeding onto the surface of the brain

Cause usually an aneurysm:

Brain aneurysms rarely cause symptoms until they bleed/rupture

Very characteristic headache:

1. Back of the head

2. Thunderclap

Sickness

Light makes headache worse (photophobia)

Stiff neck

Affects 11,000 patients per year

Incidence 9 per 100,000 population

45-70 yrs of age most common

Average age is 55 yrs

65-70% women

50% mortality from a ruptured aneurysm

Subarachnoid Haemorrhage: diagnosis

• Brain scan (CT scan) ASAP

• If negative and clinical suspicion is high- a lumbar

puncture (spinal tap) is carried out to sample fluid

around the brain and test for blood

• If CT scan is positive the patient should be transferred

to a hospital that specialises in dealing with brain

haemorrhages.

• In Yorkshire this is Leeds General Infirmary

Subarachnoid Haemorrhage: diagnosis

• If aneurysm is not secured quickly it could burst again

• Risk is 50% in first 3-4 weeks

• If aneurysm is not treated most survivors will die of re-bleeding

within a year

• Risk is highest in first 1-3 days after initial bleed

• Minimum 50% immediate mortality with re-bleeding

• NCEPOD guidelines are to treat within 48 hours

• Most centres aim to treat within 24 hours 5/7 and

7/7 if enough operators

• Some patients cannot be saved due to very rapid re-bleeding

within hours

Natural History of Ruptured Brain Aneurysms

• Open surgery has been available for over 50 years

• Very effective treatment

• Evidence-based

PROS:

• Actual treatment risk similar to endovascular treatment

• Aneurysm is ‘cured’

• No imaging follow up for the aneurysm or re-treatment required

BUT:

• Requires craniotomy

• Long recovery

• Risk of seizures and infection

• Cannot drive for minimum 6 months

• Cosmetic deformity

Neurosurgical Treatment

So, if surgery is so good, why were coils developed?

Some aneurysms inaccessible, very high risk

Development of Electrolytically detachable coils

Guglielmi G, Viñuela F, Sepetka I, Macellari V. Electrothrombosis of saccular aneurysms via endovascular approach. Part 1: Electrochemical basis, technique and experimental results. J Neurosurg 1991;75:1-7 Guglielmi G, Viñuela F, Dion J, Duckwiler G. Electrothrombosis of saccular aneurysms via endovascular approach. Part 2: Preliminary clinical experience. J Neurosurg 1991;75:8-14

15 patients, all awake Aneurysms 70-100% occluded 1 transient aphasia

FDA Multicentre study

Development of Electrolytically detachable coils

- Stainless steel delivery wire

- Electrolytic detachment

- Platinum Coils

Aim

To compare the safety and efficacy of an endovascular treatment policy of ruptured intracranial aneurysms with a conventional neurosurgical treatment policy in an eligible population.

To determine whether an endovascular treatment policy compared with a neurosurgical treatment policy, reduces the proportion of patients with a moderate or poor outcome (Rankin 3 or worse) by 25% at one year.

To determine whether endovascular coil treatment is:

• As effective as surgery at preventing re-bleeding

• Results in a better quality of life

• Is more cost effective

• Improves neuropsychological outcome

•ISAT Terminated by steering committee by fax to neuroscience

centres 03/05/02

• Relative reduction in adverse outcome at 1 yr (mGOS 3-5 )

of 22.6%

• Absolute reduction = 6.9%

• Endpoint of trial reached, “unethical” to continue randomisation

• Full 1yr f/u data presented AANS/CNS Feb 2003:

relative risk reduction 26.8%

absolute risk reduction: 8.7%

Immediate shift of significant workload to radiology in a Disorganised, ad hoc fashion without shift in finances or

personnel (ODAs, anaesthetists)

rebleed coil clip

<30 days 20 8

<1 yr 45 39

>1yr 7 2

0.2% p.a. >1yr for coiling

0.15% p.a. >1yr for clipping

Return to work Coil (%) Clip (%)

Same job 25.6 19.3

Variation 8 8.3

Other 5.4 5

Basic Coiling Procedure

Expensive radiology equipment…

6/12 f/u

Small

SAH

Complications: Aneurysm Perforation

New and Emerging Technologies

* Please read full “Instructions for Use” prior to use of the product.

** Fluoroscopy may be used up this point at the physician’s discretion .

1. Access Aneurysm Site

with Microcatheter

Gain vascular access

according to standard

practice and access

aneurysm site with a

microcatheter

2. Advance Stent Delivery

System

Flush device. Seat the

introducer in the catheter

hub. Advance stent system

through microcatheter until

distal edge of delivery wire

reference marker enters the

Introducer.**

3. Position & Deploy [Recapture & Reposition]

Position stent by aligning

stent positioning marker of

delivery wire with target site.

Unsheath to deploy.

Recapture and reposition

once, if necessary, before

deployment.

4. Coil Aneurysm

Proceed with coiling

procedure through stent

cells according to the

detachable coil

“Instructions for Use.”

Stenting for Aneurysms

Stent is a permanent implant.

Patient requires Aspirin and

Clopidogrel beforehand, otherwise

high risk of acute thrombosis with

c 50% mortality.

Always causes groin problems!!!!

• Game-changing technology

PROS:

• Simplifies procedure as aneurysm does not have to be entered at all

• Large aneurysms treated with coils tend to come back and need

re-treatment or at the very least long-term surveillance

• Allow more difficult aneurysms to be treated without surgery

CONS:

• Expensive: £10,000 per device

• Need antiplatelet therapy therefore risk of ulcers and bleeding

(like cardiac stents)

• Can be difficult to deploy

• Strong evidence for their efficacy is lacking, despite more than 25,000

Worldwide being treated this way to date

• As procedure is simpler, wider variety of physicians (esp in U.S.) are

treating aneurysms this way: neurosurgeons, neurologist, cardiologists etc

LEO 5.5mm x 7.5cm

5.5mm x 40cm

5.5mmx 30mm

• Career longevity: stressful

• Not enough trainees

• Lack of opportunities to train in more than one centre

• Providing a seven day service

• De-skilling of neurosurgeons:

- aneurysm clipping is no longer a core requirement for trainees

- 95% of all ruptured aneurysm were treated by endovascular

means in 2014

Link:

Leeds

Hull

Sheffield

Networking!

Ischaemic Stroke

Pathogenesis of Acute Ischemic Stroke

What is Stroke ?

Definition:

It is a term used for acute focal or diffuse

neurological deficit lasting for more than

24 hours and caused by a focal or

diffuse insult to the brain that is of a

vascular origin (WHO).

Pathogenesis of Acute Ischemic Stroke

What is Stroke ?

Stroke involves a blockage of blood vessels

(temporary or permanent) and damage to brain

substance as a result.

CLINICAL BURDEN:

• About 150,000 strokes occur in the UK each ear

• Stroke accounts for 53,000 deaths in the UK /yr

• Third biggest killer after coronary artery disease and cancer

• Leading cause of disability in the UK

• 300,000 living with disability in the UK

• 25% occur in those younger than 65 yrs of age

• 20,000 younger than 45

ECONOMIC BURDEN:

• Average patient cost: £15,000-£30,000

• £2.8 billion per annum in 2003-2004

• £1.8 billion in indirect costs (loss of earnings etc)

Acute management:

• Direct transfer to LGI within Leeds

• Straight to A&E resus after pre-alert call

• Accurate and detailed assessment (NIHSS) by

stroke nurse specialist

• CT scan within 1 hour

• If suitable, consider for intravenous thrombolysis

Normal scan

Extensive right-sided

stroke

Why time matters:

- Central area of infarcted brain

- Surrounding area where there is not enough blood to maintain normal

brain function

- This area will recover if blood flow is restored (PENUMBRA)

- If blood flow is not restored, the area of irreversibly dead brain will increase

in size until there is no penumbra left and no treatment will help,

and may actually cause further harm

- This process occurs within 3-6 hours

Pathophysiology of stroke

For each minute of occlusion/infarction the following are lost: 1.9 million neurons 14 billion synapses 12km of nerve fibres

The aim of

pharmacological or

neuro-intervention is to

restore anterograde

perfusion, thus salvaging

ischaemic brain

First Thrombolysis in 1958

• Sussman BJ, Fitch TSP

Thrombolysis with Fibronolysin in cerebral

arterial occlusion.

JAMA 1958; 167:1705-1709

• 3 patients: 1 ICA, 1 MCS and 1 ACA

occlusion

• 2 no change, 1 improved

“Early recanalisation is strongly associated with improved

functional outcome and reduced mortality”

Stroke, 2007; 38:967-973

“Recanalisation within 6 hours of onset increase the odds of a

non-disabled outcome 6 fold”

It has taken 49 years to prove that rapidly opening a

blocked blood vessel in the brain

benefits patients in clinical trials!

Neurovascular Revascularization

NINDS (National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group)

Objective: Examine outcomes of intravenous recombinant tissue

plasminogen activator (IV-rt-PA) in comparison to placebo.

Design: Prospective, Randomized, double-blind.

Primary Endpoint: Clinical outcome assessed by Barthel Index, mRS, Glasgow

Outcome, NIHSS.

Selected Secondary

Endpoints: Mortality at 90 days, Symptomatic ICH.

Number of Patients: n = 624

Key Take-Away: First clinical trial to approve a treatment (IV t-PA) for acute

ischemic Stroke that treats the underlying vascular

occlusion.

*AJNR 30:859-75: May 2009

Neurovascular Revascularization

Confidential. For internal ev3 use only. Do not distribute.

N/A

Inci

denc

e R

ate

(%)

IV-rtPA Placebo

NINDS (National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group)

*AJNR 30:859-75: May 2009

Key Take-Away:

NINDS demonstrated that IV-

tPA is safe and more

effective than Placebo in the

0-3 hour window.

“21.25% of patients had acute vessel re-opening of a proximal

occlusion following IV rTPA (thrombolysis)”

Stroke, 2010; 41:2254-2258

Ischemic Stroke: Large Vessel

Occlusion • Large Vessel Occlusion Stroke is defined as an occlusion of

the proximal carotid, middle or anterior cerebral (M1, A1),

vertebral, or basilar arteries.

• LVOs restrict blood supply to a large portion of the brain,

causing significant debilitation.

www.Stroke.org

ev3

“68% final recanalisation rate”

BUT

Only 36% patient were

independent 90 days

Stroke, 2008; 39:1205-1212

81.6% of the treated vessels were successfully

revascularised”

BUT

Only 29% of patients

were independent at

90 days”

Stroke, 2009, 40: 2761-2768

Successful re-opening in 90.9%

50% independent

Stroke, 2010; 41:2559-2567

First IA stroke treatment 1982

• Zeumer H, Hacke W, Kolman HL,

Poeck K.

Fibrinolysetherapie bei

Basilaristhrombose.

Dtsch Med Wschr 1982; 107: 728-31

• Successful treatment of a 27 y o woman

with basilar artery occlusion treated with

intra-arterial streptokinase

Experience in Leeds, UK

• Gradual increase in numbers of IA treatments

• Several ‘high-profile’ treatments

• National press coverage

• Increased public awareness of what is available

Boy, 5, is saved

by stroke op

A STROKE victim aged five has

become the youngest person to

undergo a new stent operation.

At hospital in Leeds he then threaded a stent

through the paient’s thigh to remove a clot

blocking an artery to his brain, allowing blood

to flow again.

The 20-minute op saved Saad’s life and —

after further surgery to reduce brain swelling —

he is now recovering at home in Bradford,

West Yorks.

Dad Safdar, 44, said: “It’s a miracle. All the

doctors and nurses have done such a great

job.”

22nd February 2012

BBC2: “Keeping Britain Alive”

Dr Tufail ‘Jazz Hands’ Patankar

With Dr Hannah Stockley

Dr Sapna Puppala offering moral support

18th October 2012

Stroke ‘live on TV’

• 19 yr old leaving lecture

• Stroke in front of camera

• Arrival 15 minute

• IV lysis

• Long MCA clot

• Not improving

• Successful thrombectomy and complete

recovery

It felt like a firework in my brain': Mother receives

life-saving treatment that cured stroke in two hours

Jacqueline had a stroke that left her paralysed and

unable to talk

She was cured after surgeons removed the blood

clot using a tube containing a tiny mesh basket

'It almost felt like fireworks in my head,' the mother

said

She is now fully recovered

By DAILY MAIL REPORTER

PUBLISHED: 13:26 GMT, 4 December

2012 | UPDATED: 13:27 GMT, 4 December 2012

Read more: http://www.dailymail.co.uk/health/article-

2242746/It-felt-like-firework-brain-Mother-receives-life-

saving-hour-stroke-cure.html#ixzz2wKl1hUaQ

Follow us: @MailOnline on Twitter | DailyMail on

Facebook

Anecdote not evidence…

But it DOES work!

UK Status

• 33 Neuroscience centers

• Population 65 million

• 91 Interventional neuroradiologists

• Non-funded gradual increase in numbers

The region....

Heart attack

Hypertension

Stroke

Obesity

• A&E

• Radiology

• HASU

• Neurology

• Neurosurgery

• Neuro ITU

• Neuro HDU

• Paediatric neurology

• Paed neurosurgery

The place......

The people....

• 2 interventional neuroradiologists

• 8 stroke physicians working 24 hours on call

• 9 surrounding hospitals

• 8 Brain Attack team (BAT) nurses; on call 24/7

• On call radiographers

• On call nurse x 2

• Anaesthesia available 24/7

A&E

CT

Angiography

Clinical criteria:

• Clinically significant stroke

• <4.5 hours from stroke onset

• Patient less than 80 yrs of age (probably…)

• Patients who cannot have thrombolysis (e.g. on Warfarin)

• CT shows absence of large infarct

• No haemorrhage

Stroke Infrastructure in Leeds: Decision for IA lysis

Make a decision quickly and stick to it.

Don’t wait for IV lysis to work

Stroke Infrastructure in Leeds:

Decision for IA lysis

• Place stent across occlusion: leave in position for 10-20 min

• Reperfuse brain

• ‘Relax’ and plan your strategy

• Most clot will lyse naturally or improves efficacy of IV tPA

• Withdraw stent slowly

Procedural Details I • Requires simultaneous and immediate availability of :

- Neuroanaesthesia team

- Neuroradiology team

- Neurology team

• Local anaesthesia versus general still debated

• Team member to talk to family

• Arrange for a HASU or HDU bed to go afterwards

You have to be the conductor!

Clinical Cases

First Leeds Thrombectomy 16 yr old

Previously fit and well

Facial droop whilst having tea

Mum had seen F.A.S.T. posters

Straight to A&E Huddersfield

NIHSS 12

Time from onset: 1.5 hrs

Friday 5pm!!!!

At LGI and intubated 6:20pm

Single pass Solitaire thrombectomy

CT at 48 hrs

Lateral lenticulostriate infarct

Clinically intact

CTA: Acute MCA bifurcation

occlusion

Anaesthesia mobilised

GA 4pm

Case 2

Case 3

• M 10 yr old

• Prev F&W

• Onset dysphagia, dysarthria

• CT: 10pm 26/1/12 hyperdense BA (missed)

• MRI: 11am 27/1/12 BA thrombosis

• 2pm GCS 15/15 to 7/15

• Transfer to Leeds

Case 3

Revive 5 passes

Procedure terminated

Patient heparinised

I hoped clot would dissolve....

Clinical deterioration 3/7 later:

Locked in. Moving eyes only.

CT day 3: worsening central ischaemia

2nd attempt

Revive 4 passes

Patient Ages

0

1

2

3

4

5

6

7

8

<10 11 to 20 21-30 31-40 41-50 51-60 61-70 >70

MRS at 90 days

MRS 0-2 = 48%

5 deaths were in basilars that failed to recanalise

Poorer outcomes in patients over 70 years

0

1

2

3

4

5

6

7

8

0 1 2 3 4 5 6

Tips on improving case load:

• Don’t just be a technician

• Take credit for your success

• Audit results – especially those cases where

NO other treatment can be offered

• Present your cases

• Analyse cases with poor outcome

• Realise that some are ‘no lose’ situations and

occasional poor outcomes are inevitable

• PISTE

ORIGINAL ARTICLE A Trial of Imaging Selection and Endovascular Treatment for Ischemic Stroke

Chelsea S. Kidwell, M.D., Reza Jahan, M.D., Jeffrey Gornbein, Dr.P.H., Jeffry R. Alger, Ph.D., Val Nenov, Ph.D.,

Zahra Ajani, M.D., Lei Feng, M.D., Ph.D., Brett C. Meyer, M.D., Scott Olson, M.D., Lee H. Schwamm, M.D.,

Albert J. Yoo, M.D., Randolph S. Marshall, M.D., Philip M. Meyers, M.D., Dileep R. Yavagal, M.D., Max

Wintermark, M.D., Judy Guzy, R.N., Sidney Starkman, M.D., and Jeffrey L. Saver, M.D. for the MR RESCUE

Investigators

N Engl J Med 2013; 368:914-923March 7, 2013DOI: 10.1056/NEJMoa1212793

CONCLUSIONS

A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit

from endovascular therapy for acute ischemic stroke, nor was embolectomy shown to be superior to

standard care.

(Funded by the National Institute of Neurological Disorders and Stroke; MR RESCUE

ClinicalTrials.gov number,

METHODS

In this study, we randomly assigned patients within 8 hours after the onset of large-vessel, anterior-circulation

strokes to undergo mechanical embolectomy (Merci Retriever or Penumbra System) or receive standard care.

All patients underwent pretreatment computed tomography or magnetic resonance imaging of the brain.

Randomization was stratified according to whether the patient had a favorable penumbral pattern

(substantial salvageable tissue and small infarct core) or a nonpenumbral pattern (large core or small or

absent penumbra). We assessed outcomes using the 90-day modified Rankin scale, ranging from 0

(no symptoms) to 6 (dead).

But: in the last 2 months…

RESULTS

We enrolled 500 patients at 16 medical centers in the Netherlands

(233 assigned to intra-arterial treatment and 267 to usual care alone).

The mean age was 65 years (range, 23 to 96),

and 445 patients (89.0%) were treated with intravenous alteplase before randomization.

Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to

intraarterial treatment.

The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.30).

There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2)

in the rate of functional independence (modified Rankin score, 0 to 2)

in favor of the intervention (32.6% vs. 19.1%).

There were no significant differences in mortality or the occurrence of symptomatic

intracerebral hemorrhage.

MR CLEAN: A Randomized Trial of Intraarterial Treatment for

Acute Ischemic Stroke

Since MR CLEAN reported, three other trials evaluating endovascular

interventions:

- ESCAPE (Endovascular Treatment for Small Core and Proximal

Occlusion Ischemic Stroke)

- EXTEND IA (Extending the Time for Thrombolysis in Emergency

Neurological Deficits - Intra-Arterial)

- SWIFT PRIME (Solitaire FR as Primary Treatment for Acute

Ischemic Stroke)

Have been stopped after early interim analyses showed benefit in the

intervention group.

i.e. unethical to continue randomisation.

So what next….?

• IA therapy probably ought to be offered to patients 24/7 across the UK

• 2 people cannot do this in Yorkshire

• 4 maybe?

• Need to improve speed of diagnosis and hospital transfer

• Look to Germany……

Thank you for your attention