Stroke Management and rehabilitation David Blacker

Stroke Management and rehabilitation David Blacker

Neurologist & stroke physician,

Sir Charles Gairdner Hospital

Clinical Professor of Neurology

University of WA

Medical Director

Perron Institute (Formerly WA Neuroscience Research Institute)

Burden of Stroke

WORLD WIDE

• 1/6 people have a stroke

• Every 2 seconds someone has a stroke

• Every 6 seconds someone dies of stroke

• Every 6 seconds someone is disabled by stroke

• 1970-2010; incidence has fallen by 42% in high income countries, but doubled in low-middle

• Looming impact of smoking in China and India

Burden of Stroke• 53,000 strokes every year [1]

• 2nd leading killer in Australia after heart

disease [2]

• THE #1 Health Morbidity

• Costs $2.4 billion [3]

• 89% of acute stroke patients in Australia are

admitted to hospital [4][1] Cadilhac and Dewey et al. (2005). Unpublished report. NSF

[2] AIHW: Senes S 2006. How we manage stroke in Australia. Canberra

[3] Cadilhac 2005 Unpublished data.

[4] Thrift et al 2000; Stroke 31: 2087–92.

Stroke and TIA 2010/11

Southwest 275Great southern 120Midwest 106Goldfields 85Wheatbelt 72Pilbara 61Kimberley 51

80% Ischaemic

IV tPA meta-analysis – level 1 evidence

Lees et al Lancet 2010

NNT

4.5 9 14.1

Time is BRAIN!

Treatment effect

p<0.001

Interaction with

time p=0.03

4.5 hours

?Best Rx for large clots

Logistic regression curve representing an estimate of the probability for successful

recanalization of occluded vessels by intravenous thrombolysis (IVT) depending on thrombus

length.

Riedel C H et al. Stroke 2011;42:1775-1777

Copyright © American Heart Association

Solitaire FR Stentrieverpossibly the preferred option

Basilar thrombosis- SCGH case

Very early thrombectomy combined with intravenous tPA for acute ischaemic stroke; the Sir Charles Gairdner Hospital

(SCGH) experienceSSA 2011 Blacker DJ, Phatouros C, Singh TJ, McAuliffe W, Bynevelt M, Triplett

J, Bukhari W, Musuka T

Time to Treatment with Endovascular Thrombectomy and Outcomes fro Ischemic stroke: A Meta-Analysis

Saver et al JAMA Sept 27, 2016

Endovascular treatment

• Pooled individual data from 1287 patients in 5 trials

• Thrombectomy up to 7.3 hours after onset provided improved outcome

• < 3 hours 64% functional independence

• <8 hours 46 %

WA Distances

• Kununurra to Perth = 2220km

• (3255 by road)

Fastest RFDS AircraftHawker 800XP

813 km/h; range = 4670km

WA Distances

• So approx 3 hours flying time

• Logistics, circumstances, practicalities of moving patients

• Far flung WA to Perth < 7.3 hours; unlikely!!

Solutions

• Excellent organisation/networks/resources

• Telemedicine eg Victorian Model

• Wheat Belt WA; pathway under development

• Southwest; some chopper transfers already

• “Buying more time”

Slowing the clock Expanding the time window

Figure 1 The stroke emergency mobile unit with CT scanner on boardNote the CT scanner in

the back of the cabin and the separated shielded workstation on the right behind the door.

Weber J E et al. Neurology 2013;80:163-168

© 2013 American Academy of Neurology

Neuroprotective agents in the field

Pre-hospital therapies

• Jeff Saver California

• Unique pre-hospital stroke trial

• Ethics considerations

• Magnesium IV

• 1700 patients

• 72% enrolled < 60 mins post Sx onset

• >150 enrolled < 30 mins

• 62% ischaemic stroke

• 22% haemorrhage

• 13% TIAs

• 3% mimics

• Neutral results

• Model for the future

Neuroprotective agents in the field

• Peptides

• Hypothermia

• Minocycline

• Combinations

• Physical methods- TCD

Head positioning

Neuroprotection

Poly-arginine and arginine rich peptides are neuroprotective in stroke models

Bruno Meloni et al

J Cerebral Blood Flow and Metabolism Feb 11th

Arginine-rich Peptides

• We have discovered that arginine-rich and poly-arginine peptides have potent

neuroprotective properties

• Peptides between 8 – 32 amino acids in length

• Peptides are positively charged; arginine is a positively charged amino acid

• Peptide positive charge and arginine residues are critical for neuroprotection

Poly-arginine peptide neuroprotective

studies in rat stroke models

24h post-ischaemia

• Sprague Dawley rats

• Most severe stroke model

30, 60 or 120min

Infarct volume

assessment

Peptide: IV; 600µl over 6min

MCAO

Permanent and Transient MCAO stroke models

Results: Permanent MCAO Stroke Model

Study 1: Single dose study

• R9-D (D-isoform amino acid)

• Tx: 30min post-MCAO

• 1000nmol/kg

Tx: 30min post-MCAO

Infa

rct vo

lum

e m

m3

Vehicle R9D0

100

200

300

400

500

*

N = 12 N = 12

1000nmol/kg

Vince Clark, Laura Brooks, Jane Cross

Results: Permanent MCAO Stroke Model

Study 3: Dose response study

• R18: 100, 300, 1000nmol/kg

• TAT-NR2B9c: 100, 300, 1000nmol/kg

• Tx: 60min post-MCAO

0

100

200

300

400

500

Infa

rct vo

lum

e m

m3

Tx: 60min post-MCAO

Dose: nmol/kgTAT-NR2B9cR18

100 300 1000 100 300 1000Vehicle

N = 6 N = 6 N = 6 N = 6 N = 6 N = 6 N = 6

** P = 0.19

Positive control peptide: TAT-NR2B9c

• YGRKKRRQRRR-KLSSIESDV

• Best characterised TAT-fused neuroprotective peptide; >12 different animal studies

• Neuroprotective in rodent and non-human primate stroke models

• Reduces ischaemic brain lesions in humans following aneurysm surgery

• Phase 3 stroke trial is being planned using this peptide

• Designed to block NMDA receptor NOS activation and NO production

• Probably working by a TAT mediated effect

Diego Milani, Jane Cross

Is transfer required

For stroke?

• For neurological evaluation

Who is to benefit from the transfer?

• Patient?

• Family?

• Doctors?

Clarify advanced directives

Is it a stroke?

Mimics

• Seizure

• Syncope (note NOT VBI)

• Sepsis (“pseudo-stroke” exacerbation)

• Functional

• Migraine

• Metabolic

• TGA

Obvious v “tricky “ stroke

Anterior (MCA) circulation

• Limb paresis, sensory loss

• Cortical Sx

• Gaze deviation

Posterior (VB) circulation

• Vertigo, double vision, “crossed” Sx

• Coma, “seizure”

Hyperdense basilar artery sign

Lateral view

“Post –circ wipe out”

Stroke Units• In Utopia

• All patients should be managed in a stroke unit, since the evidence suggests better outcomes.

Stroke Units

Stroke Unit benefits

• Benefit 5.6/100

• reduced mortality (22% v 26%)

• reduced dependency (56% v 62%)

• reduced cost of care ($10-16 000 savings)

• LOS reduced 2-11 days

Stroke Units

Stroke unit features

• geographically distinct

• comprehensive assessment

• co-ordinated MDT

• early mobilisation (avoid bed rest)

• staff with interest; ongoing training and education

• team meetings (DC planning)

• encourage patient participation in rehab

Stroke Units

Reasons for benefit

• application of proven treatments

• ?more intense monitoring of physiology

• anticipation, early recognition, and treatment of complications

• volume of practice

• audit, review, QA, research

• enthusiastic, expert staff

Stroke Unit- Physician role

• Knowledge of stroke and TIA

• Accurate determination of mechanism

• Institution of appropriate Rx;

eg anti-coagulation for AF

CEA -symptomatic high grade stenosis

Correct Dx of mimics

Patients to transfer to teritary or “quaternary” centres

1. Acute therapy for ischaemic stroke; depends on system of care

2. Most cases of ICH (if active treatment planned)

3. Young massive MCA, candidates for decompression.

4. Cerebellar infarct > 3cm, candidate for decompression.

5. Carotid revascularization.

6. Dx unclear, advanced workup required (neuro

opinion, MRI, TOE, LP)

Cerebellar InfarctRequiring decompression

Consultant to consultant discussion

• Early advice on Dx

• Early advice on interventions

• In the future; IV tPA

• “Big picture” discussion on goals of transfer

• Chance for education

Figure 4DSA showing tight stenosis prox. basilar artery

Figure 7The patient in rehabilitation, less than 2 months later

Rehabilitation

• Communication between allied health staff; rural/metro

• Ongoing therapy input upon return

Robot

• Enables “mass” practice of arm movements

• Up to 1000 per hour

• “arm” moved whilst looking at screen

• “therapeutic games!”

• Virtual reality project; Murdoch Uni IT

accelerating neuro recovery

Continuous care from hospital to home

One clinician manages many patients

Clinical Hub

Connected by

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Patient portal – via TV or laptop screen

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Control devices – arm skate and handlebar

59

Devices and game software cleared for sale in Europe, US, Australia, NZ


Training material

60


Clinician console – prescription tools

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Clinician console – adherence data

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Hand Hub implementation study

n = 92; individuals and groups of 5

Typically outpatient phase, wide inclusion to reflect clinical practice, no control group

Administered by OT 0.2 FTE and healthcare assistant for more than 1650 rehab hrs

ableX and ableM devices, plus ReJoyce. No prescription.

18 hours of extra rehab per patient over 6 weeks

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J Rehabil Med 2016; 48: 522-528

(http://www.ncbi.nlm.nih.gov/pubmed/27068229)


http://www.ncbi.nlm.nih.gov/pubmed/27068229

Clinical Hub implementation

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Researchers’ commentary

“The Hand Hub not only improved patient outcomes, but also built capacity in the provision of subacuterehabilitation services and enhanced the quality of the rehabilitation by addressing problems of critical importance to patients.”

“Improvement …was independent of diagnosis, and importantly …irrespective of the variability, type or intensity of the Hand Hub programme.”

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“This information has implications for the future planning of clinical service delivery

models”© ableX healthcare Limited May 2017

Perron Institute

AbleX experience

• 4 stroke patients end of 2016

• LotteryWest application to study 10 stroke +10 MS patients with MS society

• Great potential for monitored, remote rehab with expert therapist oversight

Model for future therapies

Stroke Management and rehabilitation David Blacker

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