ER Procedure: Differential Diagnosis In stroke patients, clinical features are usually sufficient to enable at least preliminary diagnosis. CT scanning is instrumental in documenting cerebral haemorrhage, neuroinfection or brain injury, but does not help to exclude possibilities such as syncope, partial epileptic seizure with Todd’s paresis, migraine attack with aura, hypoglycaemia, hysteria, intoxication, meningitis or multiple sclerosis. In this context, it is important to remain aware that confirmatory tests should supplement – rather than replace – conventional clinical skills. In practice, the most important distinction is between ischaemic stroke and intracranial haemorrhage. The clinical features of these conditions may overlap, but their treatment is markedly different. 1 Early distinction between the various subtypes of ischaemic stroke is also becoming important (i.e. lacunar vs large artery or cardioembolic stroke), as there is evidence that these may respond differently to different treatments. This is a situation in which neuroimaging techniques such as CT scanning can be invaluable, although clinical scoring systems based on the presence or absence of specific clinical features can also be strongly predictive. One such system – the Allen score – has been found to be 90% accurate in the identification of haemorrhage. 2–4 References 1. European Ad Hoc Consensus Group. European strategies for early intervention in stroke: a report of an Ad Hoc Consensus Group meeting. Cerebrovasc Dis 1996; 6: 315–24. 2. Allen CMC. Clinical diagnosis of the acute stroke syndrome. Q J Med 1984; 208: 515–23. 3. Sandercock PAG, Allen CMC, Corston RN et al. Clinical diagnosis of intracranial haemorrhage using Guy’s hospital score. Br Med J 1985; 291: 1675–7. 4. Celani MG, Righetti E, Migliacci R et al. Comparability and validity of two clinical scores in the early differential diagnosis of acute stroke. Br Med J 1994 ; 308: 1674–6 27
Stroke thrombolysis Dr Sanjay Jaiswal,consultant nerologist,Jaiswal Hospital and neuro institute,kota,Rajasthan,India
THROMBOLYSIS IN ACUTE
Experience at our stroke unit in
DR Sanjay Jaiswal, D.MDR Sanjay Jaiswal, D.M
Member World Stroke OrganizationMember World Stroke Organization
Senior Consultant Neurologist &Senior Consultant Neurologist &
Stroke NeurophysicianStroke Neurophysician
Jaiswal Hospital and Neuro Institute, KOTAJaiswal Hospital and Neuro Institute, KOTA
The burden of disease & Stroke FactsThe burden of disease & Stroke Facts
Stroke mimicsStroke mimics
Pre thrombolysis work up.Pre thrombolysis work up.
Safety and efficacy of IVSafety and efficacy of IV t PA .t PA .
Inclusion and Exclusion criteria's.Inclusion and Exclusion criteria's.
How Tpa is administered.How Tpa is administered.
Time frame (Door to needle time)Time frame (Door to needle time)
Our stroke teamOur stroke team
THE BURDEN OF STROKE
Anually more than 15 million people world wideAnually more than 15 million people world wide
suffer a stroke, 5.5 million die and 5 million are leftsuffer a stroke, 5.5 million die and 5 million are left
with permanent disability.with permanent disability.
Stroke is 2nd most common cause of death.Stroke is 2nd most common cause of death.
In India 1.5million people suffer from Acute StrokeIn India 1.5million people suffer from Acute Stroke
every year.every year.
1880 people die every day in India due to1880 people die every day in India due to
World wide some one dies of stroke every 6World wide some one dies of stroke every 6
Every two second some one some where inEvery two second some one some where in
world suffers from stroke.world suffers from stroke.
Stroke kills more people each year than AIDS,Stroke kills more people each year than AIDS,
TB, and Malaria put together.TB, and Malaria put together.
Incidence of stroke is increasing in India andIncidence of stroke is increasing in India and
other developing countriesother developing countries
80 % of strokes are Ischemic .80 % of strokes are Ischemic .
Only 15 % of stroke patients reach inOnly 15 % of stroke patients reach in
hospital within 3 hrs.hospital within 3 hrs.
1-5% are thrombolysed1-5% are thrombolysed
Reasons for lack of thrombolysis
1. Patient’s inability to recognize stroke symptoms.
40% of stroke patients can’t name a single symptom40% of stroke patients can’t name a single symptom
of stroke.of stroke.
85% of patients believe that their symptoms are not85% of patients believe that their symptoms are not
serious enough to seek urgent treatment.serious enough to seek urgent treatment.
2. Physician’s lack of experience with stroke
thrombolysis and therefore reluctance to “risk”
3. Lack of organized delivery of care in most of the
medical centers throughout the country.
Nandigram et al 2003
Observed lack of knowledge regarding strokeObserved lack of knowledge regarding stroke
thrombolysis among medical professionals inthrombolysis among medical professionals in
Significant majority of the GPs were not awareSignificant majority of the GPs were not aware
of the beneficial effects of thrombolysis.of the beneficial effects of thrombolysis.
CASE 1CASE 1
76 Yr old Retired Head Master, relative of a doctor.76 Yr old Retired Head Master, relative of a doctor.
No H/O HTN, DM,CADNo H/O HTN, DM,CAD
Presented with H/O Acute onset Rt hemiparesis withPresented with H/O Acute onset Rt hemiparesis with
difficulty in walking independently at 6.30 PM ,wasdifficulty in walking independently at 6.30 PM ,was
brought on wheel chair.brought on wheel chair.
Reached to our hospital at 7.50 PM.Reached to our hospital at 7.50 PM.
CT head –No e/o hemorrhage ,haematological investCT head –No e/o hemorrhage ,haematological invest
done. Clinical work up completed. by 9.00 PM.done. Clinical work up completed. by 9.00 PM.
Consent received at 10 .00 PM ( 1 hour wasted byConsent received at 10 .00 PM ( 1 hour wasted by
relatives in giving consent )relatives in giving consent )
Thrombolysis started at 10.00 PMThrombolysis started at 10.00 PM
Motor power started improving during thrombolysis.Motor power started improving during thrombolysis.
In 24 hrs pt was able to walk with little support.In 24 hrs pt was able to walk with little support.
Discharged on 6 day with mild Neurodeficit.Discharged on 6 day with mild Neurodeficit.
A doctor who is relative of the patient playedA doctor who is relative of the patient played
important role in explaining beneficial effects ofimportant role in explaining beneficial effects of
76 Yr old male F/O a Doctor had stroke.76 Yr old male F/O a Doctor had stroke.
At 8.30 AM had left sided weakness with slurred speech and confusedAt 8.30 AM had left sided weakness with slurred speech and confused
state ,not able to walk.state ,not able to walk.
Brought into hospital at 9.30 AM.Brought into hospital at 9.30 AM.
Pt wheeled straight into CT scan.Pt wheeled straight into CT scan.
Pt shifted to stroke unit, IV Line started and blood withdrawn.Pt shifted to stroke unit, IV Line started and blood withdrawn.
k/c HT, CAD, H/O Angioplasty 15 yrs ago, on anti HT +k/c HT, CAD, H/O Angioplasty 15 yrs ago, on anti HT +
ASAASA.(missed ASA for 2 days).(missed ASA for 2 days)
Lt UL– Lifting against gravity but weak grip.Lt UL– Lifting against gravity but weak grip.
Lt LL –2- /5, not able to walk independentlyLt LL –2- /5, not able to walk independently
Poor comprehension with dysarthriaPoor comprehension with dysarthria
CT--. No hemorrhage seenCT--. No hemorrhage seen
RBS– 118 MG%, CBC, PT , APTT- Normal.RBS– 118 MG%, CBC, PT , APTT- Normal.
Option of thrombolysis given to his son.Option of thrombolysis given to his son.
Consent for tPA taken.Consent for tPA taken.
IV tPA started at 11.30 am. (stroke to needle time 3 hrs)IV tPA started at 11.30 am. (stroke to needle time 3 hrs)
By the time infusion was finished , pt became alert and hisBy the time infusion was finished , pt became alert and his
motor power improved significantly.motor power improved significantly.
By evening (6 hrs post thrombolysis) pt. was walkingBy evening (6 hrs post thrombolysis) pt. was walking
independently and and had normal speech.independently and and had normal speech.
Discharged on 3Discharged on 3rdrd
day with no neurodeficit, WITHday with no neurodeficit, WITH
COMPLETE RECOVERY.COMPLETE RECOVERY.
CASE 3CASE 3
68 Yr old male,68 Yr old male,
k/c HT, CAD, h/o CABG 10 yrs ago, on anti HT + ASA.k/c HT, CAD, h/o CABG 10 yrs ago, on anti HT + ASA.
At 9.30 PM had right sided weakness with slurred speech .At 9.30 PM had right sided weakness with slurred speech .
Rt L/L Power 1-2 /5, Rt UL 3/5, dysarthria+Rt L/L Power 1-2 /5, Rt UL 3/5, dysarthria+
Brought into hospital at 11.00 PM.Brought into hospital at 11.00 PM.
Pt shifted to stroke unit, IV Line started and blood withdrawn.Pt shifted to stroke unit, IV Line started and blood withdrawn.
CT scan head showed no e/o haemorrhage.CT scan head showed no e/o haemorrhage.
Consent for tPA takenConsent for tPA taken
IV- tPA started at 12.30 AM. (stroke to needle
time 3 hrs.
During the infusion pt started moving Rt leg.
and his grip had improved significantly.
By next morning (6 hrs post thrombolysis) pt
was walking independantly and with no
Patient discharged without any neurodeficit.
2 Million Neurones are lost every minute
in the period in which stroke is untreated
ischemic penumbraischemic penumbra is the area of the brainis the area of the brain
surrounding the infarcted core,and is preservedsurrounding the infarcted core,and is preserved
by a tenacious supply of blood from collateralby a tenacious supply of blood from collateral
This area can be rescued if the occludedThis area can be rescued if the occluded
vessel can be reopened up to 3-8 hours fromvessel can be reopened up to 3-8 hours from
symptom onsetsymptom onset
Penumbrae of Ischemic
Stroke Penumbrae is the target of
any reperfusion therapy
The fate of brain tissue
Cerebral blood flow
Occluded arterial flow
Collateral blood flow
Time is brain-We have to
act fast to rescue the
Hyperacute Stroke: Modern
Approach of Tt
Aim: Revascularization of penumbraAim: Revascularization of penumbra
Break down Clot!Break down Clot!
Methods: IV, IA, MechanicalMethods: IV, IA, Mechanical
Most practical, with proven efficacy atMost practical, with proven efficacy at
place like KOTA : IV thrombolysis withplace like KOTA : IV thrombolysis with
Pre thrombolysis work upPre thrombolysis work up
Should be individualizedShould be individualized
All Pts must have emergently :All Pts must have emergently :
1.1. NCCT BRAINNCCT BRAIN
3.3. CBC,Plat count, B groupCBC,Plat count, B group
4.4. B GlucoseB Glucose
5.5. Coagulation-PT with INR,APTTCoagulation-PT with INR,APTT
6.6. Other metabolic tests-RFT, LFT, etcOther metabolic tests-RFT, LFT, etc
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
EARLY SIGNS ARE ASSOCIATED WITH POORER OUTCOMES
Left and middle: Hyperdense left MCA sign (yellow arrow), hypoattenuated left basal
ganglia (red arrow), and cortical swelling (blue arrows) in the same patient. Right:
Dot sign (yellow arrow) in the left sylvian fissure.
Early CT signs in acute MCAEarly CT signs in acute MCA
NIHSS SCORENIHSS SCORE
NIHSS SCORING CAN BE PERFORMEDNIHSS SCORING CAN BE PERFORMED
IN 7 MINUTES .IN 7 MINUTES .
ESSENTIAL TO BE CALCULATEDESSENTIAL TO BE CALCULATED
PREDICTOR OF STROKE OUTCOME ANDPREDICTOR OF STROKE OUTCOME AND
USED AS A EXCLUSION CRITERIAUSED AS A EXCLUSION CRITERIA ..
Inclusion CriteriaInclusion Criteria
Clinical signs and symptoms consistent withClinical signs and symptoms consistent with
Patient last seen normal within 4.5 hrs.Patient last seen normal within 4.5 hrs.
Measurable neurological deficit.Measurable neurological deficit.
Any hemorrhage on neuroimaging.Any hemorrhage on neuroimaging.
Symptoms s/o SAH.Symptoms s/o SAH.
Seizure at stroke onset with post ictal neurol deficit.Seizure at stroke onset with post ictal neurol deficit.
Hypodensity greater than 1/3 cerebral hemisphere onHypodensity greater than 1/3 cerebral hemisphere on
SBP>185 & DBP>110SBP>185 & DBP>110
RBS <50 or > 400 mg%RBS <50 or > 400 mg%
Stroke with major neurol deficits-NIHS >22.Stroke with major neurol deficits-NIHS >22.
Minor/isolated/spontaneously clearing neurol signs.Minor/isolated/spontaneously clearing neurol signs.
Platelet count <1 lac/mm3Platelet count <1 lac/mm3
Elevated APTT.Elevated APTT.
Past h/o ICHPast h/o ICH
Arterial puncture at non compressible site in 7 days.Arterial puncture at non compressible site in 7 days.
Major surgery in past 14 days.Major surgery in past 14 days.
GI bleed or hematuria in past 21 days.GI bleed or hematuria in past 21 days.
Ischemic stroke, Myocardial infarction or serious headIschemic stroke, Myocardial infarction or serious head
trauma in last 3 months.trauma in last 3 months.
Evidence of active bleeding or ac trauma (fracture onEvidence of active bleeding or ac trauma (fracture on
Stroke Thrombolysis at 3-4.5 Hrs
additional Exclusion Criterias
Age >80 yearsAge >80 years
On oral anticoagulants regardless of INROn oral anticoagulants regardless of INR
NIHSS of >25 (Severe stroke)NIHSS of >25 (Severe stroke)
History of both stroke and diabetes.History of both stroke and diabetes.
I.VI.V t PAt PA :: Safety and efficacySafety and efficacy
Evidence for tPA < 3Evidence for tPA < 3
NINDS t PA stroke trial(1995)
NEJM 95:333,1581-87NEJM 95:333,1581-87
624 patients randomized624 patients randomized
3 hour window3 hour window
At three months 30% more likelyAt three months 30% more likely
to have minimal or no disabilityto have minimal or no disability
6.4% risk of hemorrhage6.4% risk of hemorrhage
NINDS tPA Stroke Trial
tPA tPAPlacebo Placebo
p < .05
New England Journal, 1995
NINDS TPA Stroke Trial
Global outcome statistic: OR=1.7, 50% v. 38%= 12% benefit
Excellent outcome at 3 months on all scales
N Engl J Med 1995;333:1581-7
Time is brain( EARLIER THE BETTER) benefit from rt-
PA declines with increasing delay from onset to
3 hours 6 hours
Upper and lower 95% confidence limits
Line of no effect
For every 100 patients treated withFor every 100 patients treated with t PAt PA ,,
32 benefit, 3 harmed32 benefit, 3 harmed
Saver JL et al , Stroke 2007; 38:2279-2283
better outcome by 1 or more grades on the mRS
Thrombolytic therapy must be given byThrombolytic therapy must be given by
an experienced physicianan experienced physician after theafter the
imaging of the brain is assessed byimaging of the brain is assessed by
physicians experienced in reading thephysicians experienced in reading the
imaging studyimaging study22
1: Hacke W et al.: Lancet (2004) 363:768-74
2: Wahlgren N et al.: Lancet (2007) 369:275-82
Stroke Thrombolysis:Stroke Thrombolysis:
Evidence forEvidence for t PAt PA at 3 – 4.5at 3 – 4.5
Time is Brain :Time is Brain : NINDS Recommended Stroke EvaluationNINDS Recommended Stroke Evaluation
Targets for Potential Thrombolytic CandidatesTargets for Potential Thrombolytic Candidates
Target time framesTarget time frames
Door to doctorDoor to doctor 10 minutes10 minutes
Door to CT completionDoor to CT completion 25 minutes25 minutes
Door to CT readingDoor to CT reading 45 minutes45 minutes
Door to drug treatmentDoor to drug treatment 60 minutes60 minutes
How to administer IV t PA
Infuse 0.9mg/kg(max 90 mg ) over 60 mnts with 10 % ofInfuse 0.9mg/kg(max 90 mg ) over 60 mnts with 10 % of
the dose given as bolus over 1 mnt.the dose given as bolus over 1 mnt.
Admit pt in neuro ICU or stroke unit.Admit pt in neuro ICU or stroke unit.
Perform neurological assessment every 15 mnts duringPerform neurological assessment every 15 mnts during
the infusion and every 30 mnts thereafter for next 6 hoursthe infusion and every 30 mnts thereafter for next 6 hours
then hourly until 24 hours after treatment.then hourly until 24 hours after treatment.
If pt develop severe headache,ac HTN, nausea,orIf pt develop severe headache,ac HTN, nausea,or
vomitting discontinue infusion and obtain emergency CTvomitting discontinue infusion and obtain emergency CT
Risk of hemorrhagic
hyperglycemia orhyperglycemia or
CT >1/3CT >1/3 cerebralcerebral
Increasing strokeIncreasing stroke
Low platelet countsLow platelet counts
Higher NIHSS scoreHigher NIHSS score
Longer time toLonger time to
~ Stroke. 2002~ Stroke. 2002
If intracranial hemorrhage present:
Obtain fibrinogen results.Obtain fibrinogen results.
Prepare for administration of 6 to 8 units of cryoprecipitatePrepare for administration of 6 to 8 units of cryoprecipitate
containing factor VIII.containing factor VIII.
Prepare for administration of 6 to 8 units of platelets.Prepare for administration of 6 to 8 units of platelets.
Consider alerting and consulting a hematologist orConsider alerting and consulting a hematologist or
Consider decision regarding further medical and/or surgicalConsider decision regarding further medical and/or surgical
Consider second CT to assess progression of intracranialConsider second CT to assess progression of intracranial
A plan for access to emergent neurosurgical consultation isA plan for access to emergent neurosurgical consultation is
highly recommended.highly recommended.
Acute Ischemic Stroke Protocol
Triage nurse confirm stroke onset time < 4.5 hours
ER Resident performs
Rapid evaluation (5 minutes)
1.exact time of onset
3.quick neurological evaluation
STAT CT and blood work
Neurology Resident receives
ER stroke page and
proceeds to ER
brief history & physical exam
Page Stroke consultant
Head CT findings, laboratory data, NIH stroke scale
Confirm the criteria fulfilling thrombolytic therapy for ischemic stroke
Family’s agreement for thrombolytic therapy
Stroke onset < 4.5 hours
Patient is admitted to Stroke ICU for intensive monitoring/care
Stroke onset 4.5-8 hours
IA t therapy /device
Case tPA given in 3.30 hrs.Case tPA given in 3.30 hrs.
Case tPA given in 3 hrs.Case tPA given in 3 hrs.
Case tPA given in 3 hrsCase tPA given in 3 hrs
All made excellent recovery.All made excellent recovery.
Earlier protocol ---Earlier protocol ---
window period -- 3hrs.window period -- 3hrs.
Latest ECASS 3 trial---Latest ECASS 3 trial---
window period extended upto 4.5 hrs.window period extended upto 4.5 hrs.
TAKE HOME MESSAGE
IV r TPA IS RECOMMENDEDIV r TPA IS RECOMMENDED
THEREPY FOR SELECTED PATIENTSTHEREPY FOR SELECTED PATIENTS
WHO REACH HOSPITAL WITHIN 4.5WHO REACH HOSPITAL WITHIN 4.5
HOURS OF STROKE ONSET.HOURS OF STROKE ONSET.
Thrombolysis is possible in kota.Thrombolysis is possible in kota.
Need to rush from bed to bedside.Need to rush from bed to bedside.
TAKE HOME MESSAGETAKE HOME MESSAGE
At 3 months 30% more likely to have minimalAt 3 months 30% more likely to have minimal
or no disability following thrombolysis.or no disability following thrombolysis.
There should be no protocol violation otherThere should be no protocol violation other
wise more complications.wise more complications.
We have to increase awareness among patients,We have to increase awareness among patients,
general public and doctors regarding beneficialgeneral public and doctors regarding beneficial
effects of stroke thrombolysis.effects of stroke thrombolysis.
World Stroke day- 29 octoberWorld Stroke day- 29 october
WSO Slogan- entitled ‘Because I care..WSO Slogan- entitled ‘Because I care..
Because I care…
I want you to know the facts about stroke
I want you to learn how to prevent the assault of stroke
I will break the myths surrounding stroke, e.g., “stroke only happens later in
I want you to have access to the best possible
I will ensure that you receive quality treatment, care
I will be with you every step of the way towards your full