stroke management and rehabilitation david blacker
TRANSCRIPT
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 Unpublished report.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[3] Cadilhac 2005 Unpublished data.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
Plug & Play rehabilitation
Therapy games for stroke, brain injury and dementia56
© ableX healthcare Limited May 2017
Continuous care from hospital to home
One clinician manages many patients
Clinical Hub
Connected by
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© ableX healthcare Limited May 2017
Patient portal – via TV or laptop screen
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© ableX healthcare Limited May 2017
Control devices – arm skate and handlebar
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Devices and game software cleared for sale in Europe, US, Australia, NZ
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Training material
60
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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)
© ableX healthcare Limited May 2017
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