Acute management of ischaemic stroke 2012

1. Early Management of
Ischemic Stroke
DR SANJAY JAISWAL, MD,DM
Member world stroke organization
Consultant Neurologist
Jaiswal Hospital and Neuro Institute
Kota ,Rajasthan.

2. Reference
 Guidelines for the Early Management of
Adults With Ischemic Stroke Stroke
2007;38;1655-1711
 Acute ischemic stroke N Engl J Med 2007;
357:572-579, Aug 9, 2007

3. Brain Attack!
 Acute stroke = ‘brain attack’
 Every minute matters: ‘time is
brain’
 Combat therapeutic nihilism

4. Time is Brain…why?
The typical patient loses 1.9 million neurons each
minute in which stroke is untreated
The ischaemic penumbra

5. WHO DEFINITION OF STROKE
A NEUROLOGICAL DEFICIT OF
 Sudden onset
 With focal rather than global dysfunction
 In which, after adequate investigations,
symptoms are presumed to be of non-traumatic
vascular origin
 and last for >24 hours

6. New definition of TIA
 A brief episode of neurological dysfunction
caused by focal brain or retinal ischaemia with
clinical symptoms lasting less than one hour
without evidence of infarction

7. Types of Stroke
85% 15 %
Ischemic hemorrhagic

8. Left MCA Syndrome
•Language loss (aphasia)
•Right hemiparesis
•Right hemisensory loss
•Right visual field cut
•Left gaze preference

9. Right MCA Syndrome
•Left hemi-neglect
visual,spatial,
•Left hemiparesis
•Left hemisensory loss
•Left visual field cut
•Neglect of deficits
“anasgnosia”

10. Stroke is due to sudden vascular occlusion
ACA
MCA

11. Vascular occlusion causes stroke symptoms
•50-70% of all stroke is due to embolism
(cardiogenic and artery-to-artery)
•80 % of acute strokes are due to MCA
territory ischemia
• Arterial occlusion is seen in 80-90%
within 6-24° of symptom onset
• Spontaneous recanalization seen in ~
20% within 6 ° of symptoms

12. Stroke Risk Factors Non-modifiable
 AGE
 Gender -male
 Race – Blacks > Asians or Hispanics>
Whites
 Family Hx.
 Coagulation Disorders
 Cardiac Disease

13. Stroke Risk Factors Modifiable
 Hypertension  Alcohol Abuse
 Oral Contraceptives
 Diabetes mellitus
 Pregnancy
 Hypercholesterolemia
 Migraine Headaches
 Elevated LDL or Low  Obesity
HDL  Sleep apnea
 Elevated homocystein  Carotid stenosis
 Smoking A combination of these risk
 Drug abuse factors will increase risk of
stroke!

14. Many Causes of Stroke

15. THE BURDEN OF STROKE
 Anually more than 15 million people world wide suffer a
stroke, 5.5 million die and 5 million are left with permanent
disability.
 Stroke is 2nd most common cause of death(9.7%).
 Incidence of stroke is on the increase in India and other
developing countries.
 More than 80% of stroke occurs in underdeveloped and
developing countries.
 Cruide annual incidence rate for first ever stroke (FES) is
145 per 100,000 Persons.

16.  Case fatality rate at 28 days after FES was 29.8%.Of the
surviving patients 38.5% had moderate to severe disability.
Hypertension (BP>140/90 alone or in various combination) was
present in 82.8% cases. (dalal et al, Mumbai stroke registry,2005-
2006).
 WHO estimated that in 1990 ,out of a total 9.4 million deaths in
India , 619,000 deaths were due to stroke. This gives stroke
mortality rate of 73 per 100,000 population. 1880 people die
every day in India due to stroke.
 In 1990 the estimated no of death due to stroke were 22 times that
due to malaria,1.4 times that due to tuberculosis,4 times that due
to RHD, and almost equal to IHD.
 Stroke mortality rate is declining in USA and other developed
countries it is likely to increase in India.

17. Stroke is a treatable condition.
 IV tPA is approved for use within 3 hours ( 4.5 hours) .
(NINDS)
 Intra-arterial therapy has proven to be safe and effective
within 6 hours (PROACT II)
 Combined IV/IA may be more effective than IV t-PA
(Interventional Management of Stroke -IMS)
 Mechanical and laser catheter technologies are showing great
promise (Angio-Jet)

18. Stroke: The Challenge
 Only 1-3% of all stroke victims receive
treatment with tPA in the US .
 25% of Acute MI patients receive treatment
(lytics or PTCA) in the US .
 Mean time to presentation
 AMI: 3hrs
 Acute Stroke: 4-10hrs.

19. Reasons for lack of treatment:
1. Patient’s inability to recognize stroke symptoms
 40% of stroke patients can’t name a single sign or
symptom of stroke or stroke risk factor.
 75% of stroke patients misinterpret their symptoms
 86% of patients believe that their symptoms aren’t
serious enough to seek urgent care
2. Physician’s lack of experience with stroke treatment and
therefore reluctance to “risk” treatment
3. Lack of organized delivery of care in many medical
centers throughout the country.

20. Current Status of Specific Treatment for Acute
Ischemic Stroke
Yes
 1. Tissue plasminogen activator within 3-4.5
hrs.
 2. Aspirin within 48 hrs.
 3. Management in SCU
May Be
 1. Neuroprotection
No ?
 1. Heparin, Heparinoids
 2. Hemodilution
 3. Steroids

22. Acute Stroke Treatments
% patients Prevention Prevention
that can death/dependency per death/dependency per
benefit 100 treated 100 admitted
Stroke Unit 90% 5 4.5
10%
Thrombolysis
ischaemic 12 1
0-3hr
strokes
65%
Aspirin
ischaemic 1 0.5
0-48hr
strokes
0.5%
Hemicraniectomy
Ischaemic 22 0.1
0-48hr
strokes
Slide by Prof G Ford, presented at UKCRN 21.11.2007 ,adapted from Gilligan et al 2005

23. Pre of hospital recognition of stoke. FAST
 Facial Weakness  Stroke Association campaign to
 Can person smile raise awareness
 Has mouth dropped  Practice staff should be trained
 Arm Weakness to inform doctor immediately if
 Can person raise both arms patient calls with symptoms
 Speech problems identifiable
 Can person speak clearly and
understand what you say
 Ambulance crews now trained
to use FAST score to prioritise
 Test all three symptoms
Calls and dispatch.
 Act FAST call 108 ambulance.

24. Section 1 Slide30
Onset to Entry (By referral method)
70
60
50
999
Pt Numbers
40
GP
Other
30 GP+999
20
10
0
0-<1 1-<2 2-<3 3-<4 4-<5 5-<6 6-<9 9-<12 12-<24 >=24
Hours
ASIST data 1999

26. Pre Hospital care
 Ambulance services ,health care professionals and
general public should receive education concerning
the importance of early recognition of stroke,
emphasing stroke is a medical emergency.
 Stroke patients should be given a high priority by
ambulance service.
 Ambulance services should be trained to identify
stroke by various tools and protocols.
 Ambulance services should transfer suspected
patients to hospital with stoke unit care.

27. EMS response to 108 call:
WILL QUESTION:
 Time of onset of stroke symptoms.
 Determine nature of neurological symptoms (F.A.S.T.).
 NIH Stroke Scale or Glasgow Coma Scale
(language/motor response/eye movement).
 Hx: recent illness, surgery or trauma.
 Recent use of medication/illicit drugs.
 Notify receiving hospital that patient appears to be an
acute stroke and gives time window.

28. Guidelines for EMS management of patients
with suspected stroke
Recommended Not recommended
 Manage ABCs  Dextrose containg fluid in
 Cardiac monitoring non hypoglycemic patients
 Intravenous access  Hypotension/excessive BP
 O2(if spo2,92%) reduction
 Excess IV fluids
 Assess for hypoglycemia
 NBM
 Alert receiving ED
 Rapid transfer to closest stroke
centre

31. Stroke units: State of the Art
Admission to a unit that is dedicated to
the care of stroke patients helps to
reduce mortality and morbidity.

38. Stroke: Differential Diagnosis
 Syncope  Subarachnoid
 Partial epileptic seizure haemorrhage
with Todd’s paresis  Neuroinfection
 Migraine attack (aura)  Neoplasm
 Hypoglycaemia  Brain injury
 Hysteria  Multiple sclerosis
 Intoxication  Peripheral vertigo

39. PHYSICAL EXAM
 GPE,ABCs, Pulse Oximetry,temp.
 Carotid Bruits, JVP, Irregular Rhythm
 Head and Neck, Chest, Abdomen
 Skin –Jaundice, Purpura, Petechia

42. Early diagnostic tests
ALL PATIENTS SELECTED PATIENTS
 Non contrast brain CT or  LFT
brain MRI  Toxicology screen
 Blood glucose  Blood alcohol level
 RFT,S. electrolytes  Pregnancy test
 ECG  ABG
 Chest radiography
 Markers of cardiac ischemia
 LP-if SAH is suspected and CT
 CBC, Plat count*
is negative
 PT,INR,*APTT*
 EEG –if seizures are suspected.
 O2 Saturation

43. EARLY DIAGNOSIS:
NON CONTRAST CT SCAN OF BRAIN
 Initial imaging modality in hyper ac stroke
 Widely available, quick, easy to perform
 Accurately identifies ICH,SAH
 EARLY SIGNS OF CEREBRAL ISCHAEMIA
 Hyper dense MCA artery sign
 Hyper dense dot sign
 Hypo density of insular ribbon
 Hypoensity of basal ganglia
 loss of grey white matter differentiation in cortical ribbon
 sulcal effacement
 EARLY SIGNS ARE ASSOCIATED WITH POORER OUTCOMES

44. Early Hypodensity
Hypodensity

45. Hyperdense middle cerebral artery
Hyperdense middle cerebral
artery

46. BRAIN IMAGING (CONTD)
MULTI MODEL CT
 (A) Perfusion CT- more sensitive and specific to detect ischaemia.
 (b) CT Angio-for intra and extra cranial vasculatureMULTIMODEL MRI
 T1,T2,PD
 DWI-Early visualization of ischaemic regions within minutes of stroke.
 PWI,MRA,FLAIR,
MRI MORE SENSITIVE THAN CT(26%CT VS 83 %MRI) FOR AC
ISCHAEMIC STROKE
 VASCULAR IMAGING
 TCD USG,CAROTID DUPLEX SONO,CATHETER ANGIO.

47. Multimodal CT Imaging
CT PCT CTA
Tissue Status Perfusion Status Vessel Status
Bioenergetic Hemodynamic Occlusions or
Compromise Compromise Stenoses

48. Acute Stroke: CT vs. MRI

55. Multimodal Diffusion-Perfusion MRI
DWI PWI MRA
Tissue Status Perfusion Status Vessel Status
Bioenergetic Hemodynamic Occlusions or
Compromise Compromise Stenoses

58. Arterial Hypertension
 Management of hypertension is controversial.
 Data are inconclusive,or conflicing.
 Elevations of BP >160 mm of hg are detected in
>60 % patients.
 Many patients have spontaneous decline in BP
during first 24 hours onset of stroke.
 Both elevated and low bp are associated with poor
prognosis.

59.  A reasonable goal is to lower BP by 15% during first
24 hours after onset of stroke.
 It is generally agreed that antihypertensive medicines
can be restricted
24 hours after the stroke, in patients who have pre
existing hypertension and are neurologically stable.
DO NOT USE SUB LINGUAL NIFEDIPINE.IT

60. Treatment of Arterial Hypertension
(for patients who are not candidates for r TPA)
 The consensus is that antihypertensive agents should be
withheld unless the diastolic blood pressure is >120
mm Hg or unless the systolic blood pressure is >220
mm Hg (level V)

64. ARTERIAL HYPOTENSION
 SBP<100 and DBP <70 is associated with higher
mobidity and mortality.
 Causes of hypotension should be sought. Potential causes
are aortic dissection, volume depletion, blood loss,
decreased cardiac output sec to MI or cardiac arrhythmia.
 hypovolemia should be corrected with normal saline.

66. T-PA for Acute Ischemic Stroke
 NEJM 95:333,1581-87
 624 patients randomized
 3 hour window
 at three month. 30% less likely to have minimal or
no disability
 6.4% risk of hemorrhage
 No change in mortality at 6 mos

67. Cerebral infarct <3hrs
Onset
Infarct
Ischaemic
penumbra

68. Cerebral infarct 6hrs
Infarct
Ischaemic
penumbra

69. Cerebral infarct 24hrs
Infarct
Ischaemic
penumbra

70. Intravenous thrombolysis
 The US FDA approved the use of r tpa in 1996 on the basis of
the results of the NINDS r TPA stroke Study.
 Patients treated with tpa were 30 % more likely to have minimal
or no disability at 3 months compared with placebo treated
patients.
 Treatment with tpa resulted in 11 to 13 % absolute increase in
the number of patients with excellent outcomes.
 Mortality rate at 3 months was 17 % in tpa group and 21 % in
placebo treated group.
 Symptomatic intracerebral haemorrhage occurred in 6.4% of pts
receiving tpa vs 0.6% of the palcebo group.

72. CRITERIA FOR THROMBOLYSIS WITH
rTPA
INCLUSION CRITERIA
 Clinical signs and symptoms consistent with ischaenic stroke.
 MEASURABLE NEUROLOGIC DEFICIT
 NEUROLOGICAL SIGNS SHOULD NOT BE CLEARING
SPONTANEOUSLY.
 Neurological signs should not be minor or isolated.
 Onset of symptoms <3 hour before beginning treatment
 Caution should be exercised in treating a patient with a major deficit.
 Symptoms of stroke should not be s/o SAH.
 No head trauma or prior stroke in previous 3 months.
 No MI in previous 3 months.
 No GI OR urinary tract haemorrhage in previous 21 days.

73. Cont..
 No major surgery in previous 14 days.
 No arterial puncture at a noncompressible site in previous 7 days.
 NO H/O previous intra cranial haemorrhage.
 Systolic BP<185 and diastolic <110
 No evidence of active bleeding or ac trauma on examn
 Not taking oral anticoagulant or if being taken INR <1.7
 If receiving HEPARIN in previous 48 hours A PTT must be normal range.
 Platelet count <1 lac mm3
 Blood glucose >50 mg %
 No seizure with postictal residual neurol impairements.
 CT does not show a multilobar infarction (hypodensity >1/3 cerebral
hemisphere)
 The patient or family understands the potential risks and benefits of
treatment.

74. New England Journal, 1995
NINDS tPA Stroke Trial
30 Hemorrhage
30
p < .05
20
20
31
9 20
20 10
10
8
0 0 1
tPA Placebo tPA Placebo
NIHSS Excellent Total Death
Recovery (%) Rate (%)

76. IV administration of tpa.
 Infuse 0.9mg/kg(max 90 mg ) over 60 mnts with 10 %
of the dose given as bolus over 1 mnt.
 Admit pt in neuro ICU or stroke unit.
 Perform neurological assessment every 15 mnts during
the infusion and every 30 mnts thereafter for next 6
hours then hourly until 24 hours after treatment.
 If pt develop severe head ache,ac HTN, nausea,or
vomitting discontinue infusion and obtain emergency
CT scan.

78.  Besides bleeding complications r tpa have potential side effect
of angioedema that may cause partial air way obstruction.
 A patient with seizure at the time of onset of stroke may be
eligible for tpa if physician is convinced that residual
impairements are secondary to stroke not a postictal
phenomenon.
 IV streptokinase is not recommended .
 IV ancrod, tenecteplase,reteplase,desmoteplase,urokinase
outside the setting of clinical trial is not recommended

79. Time is Brain
“The typical patient loses 1.9 million neurons each minute in which
stroke is untreated”
4.0 Upper 95% CI
favourable Outcome
3.5 Mean
3.0 Lower 95% CI
2.5
Odds Ratio
2.0
1.5
(corrected; 95% CI)
1.0
NNT: NNT: NNT: NNT:
0.5 3.5* 7* 9* 11*
(11)** (13)** (>30)**
0.0
60 90 120 150 180 210 240 270 300 330 360
Symptom-to-needle time in minutes
* NNT at absolute point of time ** NNT for each 90 min interval
Slide by Prof G Ford, presented at UKCRN 21.11.2007 based on Saver, Stroke 2006

80. Time is brain: benefit from rt-PA declines with
increasing delay from onset to treatment time
Benefit
Upper and lower 95% confidence limits
Line of no effect
Harm
IST-3 protocol 3 hours 6 hours

81. rt-PA for stroke per million pop'n Thrombolysis in Europe
60
Finland
Austria
50 Sweden
Norway
40 Belgium
Spain
Germany
30
Netherlands
Denmark
20 Italy
UK
10 Greece
France
Portugal
0
Slide donated by P. Sandercock, IST-3 trialists meeting, Brussels 2006

82. Intra arterial Thrombolysis
 PROACT II
 Intra arterial Prourokinase
 6 Hour time window
 Relative risk reduction of 15% in functional outcome
 No difference in mortality
 Procedural complication 9%
 Early Intra cerebral haemorrhage 10%
 INTRA ARTERIAL THROMBOLYS IS REASONABLE IN
PATIENTS WHO HAVE C/I TO USE OF IV TPA LIKE
RECENT SURGERY.

83. Guidelines for
Anticoagulant Therapy
Urgent administration of anticoagulants has not yet been
associated with lessening the risk of early recurrent stroke or
improving outcomes. Because it can increase the risk of brain
hemorrhage, routine use cannot be recommended.
American Heart Association, 2003

84. Guidelines for
Anticoagulant Therapy
Anticoagulants are not recommended for any subgroup
of patients with acute stroke based on any presumed
mechanism or location (e.g., cardioembolic, large
vessel atherosclerotic, vertebrobasilar, or “progressing”
stroke) because data are insufficient.
American Academy of Neurology / AHA, 2003

85. Acute Treatment with Antiplatelet Agents
 Aspirin (initial dose is 325 mg) should be given within 24 to 48
hours of stroke onset in most patients (Class 1, level A).
 The administration of aspirin as an adjunctive therapy, within 24
hours of the use of thrombolytic agents, is not recommended (Class
3,level A).
 Aspirin should not be used as a substitute for other acute
interventions, especially intravenous administration of rtPA, for the
treatment of acute ischemic stroke (Class 3,level B).
 No recommendation can be made about the urgent administration of
other antiplatelet aggregating agents alone or in combination with
aspirin (Class 3,level C).
 Outside the setting of clinical trials IV administration of antiplatelet
agents that inhibit the glycoprotein 2b/3a ptor is not recommended.
(Class 3,level B).

86. Benefit of Early Aspirin Treatment in Acute
Ischemic Stroke
9 patients benefit per 1000 treated (p<0.001)
2000 Aspirin, n=20,207 Control, n=20,190
1843
1662
1500 1327
1231
1000
636
496
500
205 168
0
Recurrent Hemorrhagic Death Death or Nonfatal
Ischemic Stroke Stroke Stroke
Combined Data from IST, CAST, MAST-I

87. Hemodilution,Vasodialators,and
induced hypertension
 Hemodilution with or without venesection and volume
expansion is not recommended for treatment of ac
ischaemic stroke.(Class 3,level A)
 Vasodialators like pentoxifyline is not recommended
for treatment of ac stroke.(Class 3 ,level A)
 Drug induced hypertension outside the setting of
clinical trials is not recommended .)

88. MERCI TRIAL
 Anterior circ strokes only
 Treatment <8 hours
 151 patients entered

89. MERCI RESULTS
 Recanalization in 46%
 Historical 18%
 Complication rate 7% (SAH, device fx,
embolization)
 With recanalization, good outcome (46% vs.
10%) and mortality improved (32% vs. 54%)
 ICH rate 7.8%

91. Thrombolysis Augmentation
 Ultrasound
 With or without micro-bubbles
 Micro-bubbles containing TPA
 Combination with G2B3A inhibitors

92. Neuroprotective agents
 At present no neuroprotective agent is found to
be effective in improving outcomes after
stroke,and therefore none currently can be
recommended(class 3,level A)

93. General Ac treatment after Hospitalization
 25 %of patients may have neurological worsening during first
24-48 hours.
 The use of stroke unit is recommended to improve general
management.
 Early mobilization of less severely affected patients is
recommended.
 Assessment of swallowing before staring eating or drinking is
recommended.
 Patients with suspected pneumonia,UTI should be treated
with antibiotics.

94.  Sub cut anticoagulants are recommended for treatment of
immobilized patients to prevent DVT.Ideal timing for
starting these medications is not known.
 The use of intermittent external compression devices is
recommended for treatment of patients who can not
receive antcoagulants.(Class 2a ,level B)
 Pulmonary embolism accounts for 10% of deaths after
stroke,and complicaton may be detected in 1%of patients
who have had a stroke.

95.  Patients who cannot take food and fluids orally should
receive nasogastric,nasodudenal or PEG feedings to
maintain hydration and nutrition.The timing of PEG is
uncertain.
 Nutritional supplements are not needed.
 Prophylactic administration antibiotic is not
recommended.
 If possible the placement of indwelling bladder
catheters should be avoided because of associated risk
of UTI.(class3 ,level C)

96. Treatment of ac neurological Complications
Brain Edema
Development of brain edema is gradual and occurs most frequently
3- 5 days after stroke.
Brain edema is most frequent neurological cause of death in
patients with stroke.
Early CTscan hypodensity,defined as <12 hours after onset ,of >50
%of the MCA territory and presence of hyperdense MCA signs
are independent predictors of neurological deterioration.
Large hypodensity>2/3 of MCA terrority on CT and large
hypoperfusion on CT perfusion maps predicted development of
malignant MCA infarct.

97. Management of brain edema and increased ICP
 Modest fluid restriction
 Avoidence of hypo osmolar fluids like GDW.
 Control of fever,hypoxia,hypercapnia.
 Elevation of head end of bed by 30 degree.
 Hyperventilation to a partial co2 pressure of 28-
30 mm of hg.

98.  Administration of mannitol 0.25-0.50gm /kg IV
over 30 mnts every 6 hours.
 Diuresis(furosemide 40 mg IV).
 Drainage of CSF.
 Resection of infarcted tissue./decompressive
surgery.
 Antihypertensive agents particularly those
causing cerebral vasodilation should be avoided.

99. Contd……
 Patients with ac hydrocephalus in ischaemic stroke most commonly
affecting cerebellum can be treated with placement of a ventricular
drain.(class 1 level B)
 Decompressive craniectomy is indicated for treatment of large
cerebellar infarcts in patients with clinical deterioration and
evidence of early brain stem compression or hydrocephalus.This is
potentially life saving measure and clinical recovery may be very
good.(class 1 ,level B)
 Decompressive surgery for malignant brain edema may be life
saving in selected patients with complete MCA infarction who are
significant risk for developing trans tentorial herniation.Timing of
surgery is poorly defined,with some opting for early surgery (in 24
hours)
 Suboccipital craniotomy is the treatment to relieve both
hydrocephalus and brain stem compression caused by large
cerebellar infarctions.

100.  No specific recommendation is made for treatment of
patients with asymptomatic haemorrhagic
transformation after ischaemic stroke.
 Corticosteroids are not recommended for treatment of
cerebral edema and increased ICP(class 3,level A)
 Prophylactic administration of anticonvulsants in
patients of stroke who have not had seizures is not
recommended(class 3 ,level C)

105. Thank you ! ! !