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Stroke treatment is a long process of recovery from this life threatening condition.
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Prepared By: Rohit Upadhyay
Affects > 780,000 persons per year
3rd major cause of death & long-term
disability
Estimated U.S. cost for 2008 = $65.5 billion
In Trivandrum, annual incidence rates was
135/100 000
Stroke. 2009;40:1212-1218
Pre-hospital management
Initial assessment and emergency
management
Thrombolysis
Acute stroke intervention
Medical support
Antiplatelet agents
Anticoagulation
Surgery
0 10 20 30 40 50 60 70 80 90
minutes
Penumbra
Core
CEREBRAL
BLOOD
FLOW
(ml/100g/min)
CBF < 8
CBF 8-18
TIME (hours)
1 2 3
20
15
10
5
PENUMBRA
CORE
Neuronal dysfunction
Neuronal death
Normal function
Time is Brain
Diminishing Returns over Time Favorable Outcome (mRS 0-1, BI 95-100, NIHH 0-1) at Day 90 Adjusted odds ratio with 95% confidence interval by stroke onset to treatment time (OTT) ITT population (N=2776)
Pooled Analysis NINDS tPA, ATLANTIS, ECASS-I, ECASS-II
~4h 40min
Courtesy Brott T et al
NNT 5
NNT 20
Penumbra damaged by:
Hypoperfusion
Hypoxia
Acidosis
Hyperglycemia
Fever
Seizure
Guidelines Ischaemic Stroke 2008
Emergency care in acute stroke depends on a
four-step chain:
Rapid recognition of, and reaction to, stroke signs and symptoms
Immediate EMS contact and priority EMS dispatch
Priority transport with notification of the receiving hospital
Stroke vs Stroke mimikers
Time of onset of the stroke
Brief clinical evaluation, NIHSS score
Vitals, Blood sugar by glucometer
Check list for thrombolysis
Imaging
Is it stroke?
Type of stroke
Ischemic
Stroke
Clot occluding
artery
Intracerebral
Hemorrhage
Bleeding
into brain
Subarachnoid Hemorrhage
Bleeding
around brain
85% 10% 5%
Cranial Computed Tomography (CT)
Immediate plain CT scanning distinguishes reliably between haemorrhagic and ischaemic stroke
Detects signs of ischaemia as early as 2 h after stroke onset
Helps to identify other neurological diseases (e.g. neoplasms)
Most cost-effective strategy for imaging acute stroke patients
Wardlaw J et al. Stroke (2004) 35:2477-2483
von Kummer R et al. Radiology (2001) 219:95-100
HYPERACUTE STROKE ON CT
EARLY ISCHEMIC CHANGES (EIC)
1. HYPERDENSE MIDDLE CEREBRAL ARTERY (HDMCA)
2. ATTENUATION OF LENTIFORM NUCLEUS (ALN)
3. LOSS OF INSULAR RIBBON (LIR)
4. EFFACEMENT OF SULCI
5. LOSS OF CM DIFFERENTIATION
WINDOW PERIOD UPTO 6 HOURS
INSULAR RIBBON?
Hyperdense MCA sign (HMCAS)
NCCT CTA
MCA dot sign
NCCT CTA
Specificty-100% : Sensitivity -38% Leary MC Stroke 2003;34:2636-40
86 year old with acute onset of rt side weakness,leg more weak than arm
and difficulty in speech ,came in 1.5 hrs of onset. CT scan shows hyperdense
left ACA. CTA shows clot in left ACA
Hyperdense ACA
Hyderdense ICA (HICAS)
Specificity 100% Ozdemir O et al.Stroke 2008;39:2011-16.
52 yr old with acute diplopia and ataxia and left INO .
CTA shows thrombus in the top of basilar and left P1 occluded.
Basilar artery
thrombus
M1
C
IC
L
A
I
P
M2
M3
M4
M5
M6
A
P
Fig 1a
52.6
6.44.5
10.6 13.5
20
9.5
40
0
5
10
15
20
25
30
35
40
8-10 8-10 8-10 3-7 4-7 4-7 0-2 0-3 0-3 NINDS ATLANTIS ECASS-2 NINDS ATLANTIS ECASS-2 NINDS ATLANTIS ECASS-2
ASPECTS
n 201 424 280 89 104 119 10 21 5
DISADVANTAGE OF CT
Less sensitive than MRI
Posterior fossa stroke
Stroke mimics diagnosis is inferior to MRI
Window period 3 to 6 hours- identification of penumbra
not possible
Diffusion-weighted MRI (DWI) is more sensitive for detection of early ischaemic changes than CT
Posterior circulation stroke
Detects even small intracerebral haemorrhages reliably on T2* sequences
MRI is particularly important in acute stroke patients with unusual presentations
In most instances, CT will provide the
information to make decisions about
emergency management (Class I, Level of
Evidence A).
The brain imaging study should be
interpreted by a physician with expertise in
reading CT or MRI studies of the brain (Class I,
Level of Evidence C).
Multimodal CT and MRI may provide additional information that will improve diagnosis of ischemic stroke (Class I, Level of Evidence A).
Class II Recommendations Vascular imaging is necessary as a preliminary
step for intra-arterial administration of pharmacological agents, surgical procedures, or endovascular interventions (Class IIa, Level of Evidence B).
Class III Recommendations
Emergency treatment of stroke should not be delayed in order to obtain multimodal imaging studies (Class III, Level of Evidence C).
Vascular imaging should not delay treatment of patients whose symptoms started
I. Triage10 min Review t-PA criteria
Page acute stroke team
Draw pre t-PA labs
II. Medical Care25 min Place O2 , 2 NS IVs
Obtain BP, weight, NIHSS
Obtain 12-lead ECG
Send patient to CT
III. CT & Labs45 min Obtain lab results
Read CT
Return pt to ED
IV. Treatment60 min Start IV t-PA
Monitor for ICH sxs
HTN, headache neuro status
IV thrombolysis
NINDS, ECASS I + II, ATLANTIS OTT Odds Ratio for normal at 3 mo. Hemorrhage
0-1.5 h 2.81 3.1%
1.5-3 h 1.55 5.6%
3-4.5 h 1.40 5.9%
4.5-6 h 1.15 6.9%
The ATLANTIS, ECASS and NINDS rt-PA Study Group Investigators, Lancet 2004
Infuse 0.9 mg/kg (maximum dose 90 mg) over 60 minutes
10% of the dose given as a bolus Neurological assessments every 15 minutes during the infusion every 30 minutes thereafter for the next 6 hours hourly until 24 hours after treatment
Discontinue the infusion if worsening, raised ICP features Obtain emergency CT scan.
Measure blood pressure
every 15 minutes for the first 2 hours
every 30 minutes for the next 6 hours
hourly until 24 hours after treatment.
Delay placement of nasogastric tubes,
indwelling bladder catheters, or intra-arterial
pressure catheters.
Follow-up CT scan at 24 h before starting
anticoagulants or antiplatelet agents.
ECASS III
% Normal at 3
mo.*
Symptomatic
ICH**
tPA 52% 2.4%
Placebo** 45% 0.2%
Hacke, N Engl J Med 2008
*OR 1.34 (1.02-1.74) P = 0.04
**p = 0.006
< 3.0 Hours
No upper age limit
No limit on stroke size
Can give if taking warfarin &
INR < 1.7
3.0-4.5 Hours
Do NOT give if:
Pt > 80 yr
NIHSS > 25
DM / previous stroke
Taking warfarin at all
Mismatch Concept
Treatment need to be individualised
Heterogeneous Disease: Infarction at different rates
1 Hr 3 Hr 6 Hr
average
slow
fast
CT perfusion
Parameters
Definition of Penumbra
Advantages Limitations
CT Perfusion
CBF, CBV,
MTT, TTP
MTT
threshold at
145%
Combined with plain
CT
Available
Fast
Limited brain coverage
Poorly sensitive to posterior circulation
Iodonated contrast
DWI-PWI MRI
CBF, CBV,
MTT, TTP,
ADC
Relative
TTP (or
MTT) delay
>45s and
normal DWI
Sensitive
No radiation
Limited availability
Patient cooperation required
Frequent contraindications
Muir KW et al. Lancet Neurology 2006; 5:755-768
Diffusion and Perfusion Imaging Evaluation
for Understanding Stroke Evolution
(DEFUSE)
Echoplanar Imaging Thrombolytic Evaluation
Trial (EPITHET)
Lancet Neurol 2008;7:299309.
Lancet Neurol 2008;7:299309.
Ann Neurol. 2006 Nov;60(5):508-17
N = 101
RCT Placebo controlled
non-significantly lower rates of infarct
growth were seen in PWI/DWI mismatch
patients who received rt-PA
Contraindication for IV thrombolysis
Stroke onset ; anterior circulation ; 6-8 hrs
Posterior circulation stroke (12-24 hrs)
Concomitant vascular stenosis or dissection/
Large vessel occlusion
Poor NIHSS score > 20
Large salvageable territory (>20% on perfusion imaging)
Hyperdense MCA sign
Suspected hard embolus (calcified debris)
Intra-arterial thrombolysis
Bridging therapy
(0.6 mg/kg IV) + (10-22 mg IA);
Mechanical thrombolysis
EKOS - MicroLys infusion catheter (EKOS) Neurosurg Clin N Am. 2009 Oct;20(4):419-29
FDA-approved for recanalizing acutely occluded cerebral arteries.
Multi-MERCI study - Patients who did not improve immediately after IV rt-PA underwent mechanical embolectomy within 8 hours of symptom onset.
Partial or complete recanalization occurred in 74% of patients,
Symptomatic intracerebral hemorrhage (sICH) rate of 6.7%.
Baseline angiogram
demonstrates complete occlusion
of the right ICA terminus (black
arrow).
Post treatment angiogram demonstrates
complete reperfusion of the right ICA
territory after 1 pass of the Merci L6
device.
Available in 3 different sizes aimed to treat different vessel diameters.
Thromboaspiration is achieved by connecting the microcatheter (black arrows) to an
aspiration pump.
The separator (white arrows) is then advanced in and out of the microcatheter tounclog any obstructive thrombus.
Autoregulation is impaired/abolished in stroke.
CBF follows perfusion pressure
Chronic Hypertensive
Blood pressure >220 systolic or > 120 dystolic BP only needs
emergency treatment if no end organ damage
Hypertensive encephalopathy Symptomatic ischemic heart disease Congestive cardiac failure Rapidly progressive renal dysfunction Before and after thrombolytic therapy Deterioration of patient due to hmgic conversion of infarct. Aortic dissection
Guidelines for the Early Management of Adults With Ischemic Stroke,
AHA/ASA Guideline, Stroke. 2007
Ideal Drug
Short acting
easily titrated
predictable response
Drug used
Labetolol
Nicardipine infusion
sodium nitroprusside (if refractory)
Avoid Drugs that dilate intracranial
vessels and increase
ICT .e.g. -
nitroglycerine
Use of nifidepine
strongly discouraged
Hypoglycemia
Mimicker
Can compromise penumbra
Hyperglycemia
Related to poor outcome in both thrombolysis and non-thrombolysis patients
Majority of trials addresses secondary
prevention
2 major trials (International Stroke Trial (IST)
and Chinese Acute Stroke Trial (CAST)]
evaluated the benefit of aspirin in AIS
associated with a significant reduction in
death or dependence (OR 0.95, 95% CI 0.91
to 0.99; p=0.008) and recurrent ischemic strokes (OR 0.77, 95% CI 0.68 to 0.86;
p
Asprin 150-325 mg to be given within 24-48
hrs (Class I, Level of Evidence A)
Fast Assessment of Stroke and Transient
Ischemic Attack to Prevent Early Recurrence
(FASTER) pilot trial Trend towards better benefit with clopidogrel +
Asprin but no statastical significance
Stroke. 2007;38:1655-1711
Heparin
Controversial
Meta-analysis of 24 trials involving 23748 participants
showed no benefit with regards to death and dependency or death alone in patients with AIS
Cochrane Database Syst Rev 2008 Not recommended in acute ischemic stroke
Cochrane Database Syst Rev 2008 Cochrane Database Syst Rev 2008 Cochrane Database Syst Rev 2008
Low molecular weight heparin
No benefit on stroke outcome for low molecular heparin (nadroparin, certoparin, tinzaparin,
dalteparin)
Heparinoid (orgaran)
TOAST trial neutral
TOAST Investigators: JAMA (1998) 279:1265-72.
High dose statins
SPARCL study
recent stroke or TIA
without known coronary heart disease,
80 mg of atorvastatin per day reduced the
overall incidence of strokes and of
cardiovascular events,
despite a small increase in the incidence of
hemorrhagic stroke.
Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. N Engl J Med 2006
Admission shortly after ictus Elevated systolic BP of >160mm Hg (Broderick J, Stroke 2007)
Irregular shape of clot Liver dysfunction
Coagulation abnormalities Markers of vascular injury & inflammation (high TLC, fibrinogen levels, low platelet count, high levels of IL-6, TNF-, MMP-9, c-Fn)
ICH on Heparin Protamine sulphate 1 mg/100 units of heparin
ICH - on Warfarin 5-25 mg Vitamin K1
FFP (10-20 ml/ kg)
Recombinant factor VIIa ICH on Thrombolytic therapy 4 -6 units of cryoprecipitate or FFP
The INTERACT study, 2008: showed a trend toward lower relative and absolute growth in hematoma volumes from baseline to 24 hours in the intensive treatment group compared with the control group.
In addition, there was no excess of neurological deterioration or other adverse events related to intensive BP lowering.
The study provides an important proof of concept for early BP
lowering in patients with ICH, but the data are insufficient to recommend a definitive policy.
Another study, the Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH) trial,also confirms the feasibility and safety of early rapid BP lowering in ICH.
Ref: Anderson CS, Huang Y, Wang JG et al. INTERACT Investigators. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol. 2008
Class II b , Level of evidence C
Management of raised ICP
Cerebellar hematoma > 3 cms or > 40 ml
Vermian hematoma
lobar clots >30 mL and within 1 cm of the
surface
For rest of the ICH, surgery is uncertain
SIHCPA
RCT -2003 71 pts, 36 randomised
to surgery Statistically
significant reduction in the volume of clot
No reduction in mortality at 6 months
High risk of rebleeding 22%
MISTIE
RCT , 2007
ongoing
Clot reduction in
46% in surgery arm
vs 4% in control arm
Adverse events
within safety limits
rtPA, urokinase
May improve survival significantly
(Cochrane Database Syst Rev 2002;(3))
Clear IVH trial (Clot Lysis Evaluating Accelerated
Resolution of IVH)
Appears to have a fairly low complication rate, efficacy and safety of this treatment is uncertain and is considered
investigational (Class IIb; Level of Evidence: B)
Acute stroke treatment should be initiated as
early as possible
IV thrombolysis to be administered at the
earliest in eligible candidates
Medical management to be optimized to
ensure adequate perfusion of penumbra
Adams HP et. al., Guidelines for the Early Management of Adults With Ischemic Stroke. AHA/ASA Guideline. Stroke. 2007;38:1655
Novakovic R et. al. Review of current and emerging therapies in acute ischemic stroke. J NeuroIntervent Surg 2009
Guidelines for Management of Ischaemic Stroke and Transient Ischaemic Attack 2008. Available at http://www.esostroke.org
Indications for the Performance of Intracranial
Endovascular Neurointerventional Procedures. AHA
scientific statement. Circulation. 2009;119:2235-
2249
Morgenstern LB et. al. Guidelines for the
Management of Spontaneous Intracerebral
Hemorrhage. AHA/ASA guideline.
Stroke. 2010;41:2108
A. ASPECTS 25
C. Age > 65
D. Coronary A. Disease
A. Hypertension should not be aggressively
treated unless SBP > 220
B. Short acting antihypertensive to be used
C. Nitroglycerine infusion is recommended for
BP control during IV thrombolysis
D. Aggressive reduction in BP associated with
poor outcome
Thalamic bleed
Intraventricular bleed
Lobar ICH
Brainstem bleed