How to approach a case of Stroke in Hospital setting

1. Basics of Stroke andBasics of Stroke and
Alteplase (Actilyse)Alteplase (Actilyse)
Dr(Lt Col) Ashutosh OjhaDr(Lt Col) Ashutosh Ojha
151 Base Hospital151 Base Hospital

2. What Is Stroke ?
A stroke occurs when blood flow
to the brain is interrupted by
a blocked or burst blood vessel
When brain tissue is deprived of blood flow,
neurons die within minutes. Surrounding a core
of infarction is an “ischemic penumbra,” poorly
perfused but viable tissue at risk for imminent
infarction.
The goal of acute stroke care is the revival and rescue of the ischemic
penumbra by rapid restoration of blood flow.
The goal of acute stroke care is the revival and rescue of the ischemic
penumbra by rapid restoration of blood flow.

3. What is specific to stroke in India?What is specific to stroke in India?
• Analysis of community surveys from different regions of India shows a
crude stroke prevalence rate of about 203 per 100,000 population
above 20 years of age, amounting to a total of about 1 million cases.
• Most studies carried out in India show that about 10% to 15% of strokes
occur in the population below 40 years, which is a higher proportion
compared with other countries
ACNR •2007

4. Time is brainTime is brain
• The phrase “time is brain” emphasizes that
human nervous tissue is rapidly and irretrievably lost
as stroke progresses and that
- therapeutic interventions should be
emergently pursued.
• This general call to action in acute stroke care was
adapted from its predecessor in acute coronary care
(“time is muscle”), both tracing their lineage to
Benjamin Franklin’s original aphorism, “time is
money.”
Stroke ,2006

5. Estimated Pace of Neural Circuitry Loss in TypicalEstimated Pace of Neural Circuitry Loss in Typical
Large Vessel, Supratentorial Acute IschemicLarge Vessel, Supratentorial Acute Ischemic
StrokeStroke
Stroke ,2006
Every minute if stroke is untreated, the average patient loses 1.9 million
neurons, 13.8 billion synapses, and 12 km (7 miles) of axonal fibers.
Each hour in which treatment fails to occur, the brain loses as many neuron as
it does in almost 3.6 years of normal aging.

6. Blood Supply to BrainBlood Supply to Brain
 The brain represents about 2% of totalThe brain represents about 2% of total
body weightbody weight
 The brain accounts for 15-20% of theThe brain accounts for 15-20% of the
body’s blood supplybody’s blood supply
 Brain cells have the highest priority forBrain cells have the highest priority for
bloodblood

7. Blood Supply to the Brain
The carotid and vertebrobasilar arteries form the Circle of Willis
Other arteries arise from here and travel to all parts of the brain:
• Anterior cerebral artery (ACA)
• Middle cerebral artery (MCA)
• Posterior cerebral artery (PCA)

8. Transient IschemicTransient Ischemic
AttackAttack
 TIA was traditionally defined as a neurologicalTIA was traditionally defined as a neurological
deficit, the symptoms of which are defined CUREDdeficit, the symptoms of which are defined CURED
completely within 24 hourscompletely within 24 hours
 The current definition of TIA isThe current definition of TIA is
 Acute onset neurological dysfunction, due to focalAcute onset neurological dysfunction, due to focal
brain ischemia, which completely resolves within 60brain ischemia, which completely resolves within 60
minutesminutes
 No evidence of cerebral ischemiaNo evidence of cerebral ischemia

9. Stroke - DefinitionStroke - Definition
 A stroke is defined by the sudden onset of aA stroke is defined by the sudden onset of a
neurologic deficit that is attributable to a focalneurologic deficit that is attributable to a focal
vascular causevascular cause
 Therefore stroke can be explained as death orTherefore stroke can be explained as death or
dysfunction of brain tissue due to occlusion ordysfunction of brain tissue due to occlusion or
hemorrhage of brain’s arterieshemorrhage of brain’s arteries
 The pattern of resulting neurological damage differsThe pattern of resulting neurological damage differs
according to whether the supply to the posterior oraccording to whether the supply to the posterior or
anterior artery has interruptedanterior artery has interrupted

10. There are two types of stroke:
Strokes can be classified into two main categories, including the following:
•Ischemic strokes (Incidence - 85%) - strokes caused by blockage of an artery.
•Hemorrhagic strokes (Incidence - 15%) - strokes caused by bleeding.
Ischemic stroke
•An ischemic stroke occurs when a blood vessel that supplies the brain becomes
blocked or "clogged" and impairs blood flow to part of the brain.
•The brain cells and tissues begin to die within minutes from lack of oxygen and
nutrients.
•The area of tissue death is called an infarct.

11. •About 85 percent of strokes fall into
this category. Ischemic strokes are
further divided into two groups,
including the following:
•Thrombotic strokes - caused
by a blood clot that develops in
the blood vessels inside the brain.
•Embolic strokes - caused by
blood clot or plaque debris that
develops elsewhere in the body
and then travels to one of the
blood vessels in the brain via the
bloodstream.
Ischemic stroke

12. Hemorrhagic stroke
•Hemorrhagic strokes occur when a blood
vessel that supplies the brain ruptures and
bleeds.
•Hemorrhagic strokes are divided into two
main categories, including the following:
•Intra-cerebral hemorrhage -
bleeding from the blood vessels within
the brain.
•Subarachnoid hemorrhage -
bleeding in the subarachnoid space (the
space between the brain and the
membranes that cover the brain).

13. PathophysiologicalPathophysiological ClassificationClassification

14. What Are the Effects of Stroke?What Are the Effects of Stroke?

15. Symptoms of StrokeSymptoms of Stroke
 Ischemic StrokeIschemic Stroke
 Sudden numbness or weakness ofSudden numbness or weakness of
face, arm or legface, arm or leg
 Sudden confusion, difficulty inSudden confusion, difficulty in
speech and understandingspeech and understanding
 Sudden difficulty in vision in one orSudden difficulty in vision in one or
both eyes, include loss of vision &both eyes, include loss of vision &
double visiondouble vision
 Sudden difficulty in walking,Sudden difficulty in walking,
dizziness, loss of balance anddizziness, loss of balance and
coordination including limb ataxiacoordination including limb ataxia
 Hemorrhagic StrokeHemorrhagic Stroke
 Sudden severe headacheSudden severe headache
 Sudden decline in level ofSudden decline in level of
conciousness (may includeconciousness (may include
fainting, confusion, convulsions orfainting, confusion, convulsions or
coma)coma)
 Rapid onset of nausea andRapid onset of nausea and
vomittingvomitting

16. Signs of StrokeSigns of Stroke
 Abrupt onset of cognitive, motor and/or sensoryAbrupt onset of cognitive, motor and/or sensory
deficitsdeficits
 Dysphasia and dysarthriaDysphasia and dysarthria
 Disturbance in coordinationDisturbance in coordination
 Facial droopFacial droop
 Loss of conciousnessLoss of conciousness

17. What are the risks factors for IschemicWhat are the risks factors for Ischemic
Stroke?Stroke?
 Modifiable RisksModifiable Risks
– HTNHTN
– CAD/Carotid Disease/PVDCAD/Carotid Disease/PVD
– Atrial FibrillationAtrial Fibrillation
– DiabetesDiabetes
– WeightWeight
– High Cholesterol/DietHigh Cholesterol/Diet
– Lack of exerciseLack of exercise
– ETOH/Drug abuseETOH/Drug abuse
– Coagulopathy- Cancer, SickleCoagulopathy- Cancer, Sickle
Cell AnemiaCell Anemia
– PFO- Patent Foramen OvalePFO- Patent Foramen Ovale
 Non-Modifiable RisksNon-Modifiable Risks
– Age->55Age->55
– Race- African Americans haveRace- African Americans have
2x the risk of death and2x the risk of death and
disability. Asians have 1.4x thedisability. Asians have 1.4x the
risk of death and disability.risk of death and disability.
– Sex- 9% greater chance inSex- 9% greater chance in
men. (61% of stroke deathsmen. (61% of stroke deaths
occur in women)occur in women)
– Previous Stroke or TIAPrevious Stroke or TIA
– Family History of StrokeFamily History of Stroke

18. STROKE TREATMENT

19. ACT F.A.S.T.ACT F.A.S.T.
FFACE ACE
ASK THE PERSON TO SMILE.ASK THE PERSON TO SMILE.
DOES ONE SIDE OF THE FACE DROOP?DOES ONE SIDE OF THE FACE DROOP?
AARMS RMS
ASK THE PERSON TO RAISE BOTH ARMS.ASK THE PERSON TO RAISE BOTH ARMS.
DOES ONE ARM DRIFT DOWNWARD?DOES ONE ARM DRIFT DOWNWARD?
SSPEECHPEECH
ASK THE PERSON TO REPEAT A SIMPLEASK THE PERSON TO REPEAT A SIMPLE
SENTENCE.SENTENCE.
ARE THE WORDS SLURRED? CAN HE/SHEARE THE WORDS SLURRED? CAN HE/SHE
REPEAT THE SENTENCE CORRECTLY?REPEAT THE SENTENCE CORRECTLY?
TTIME IME
IF THE PERSON SHOWS ANY OF THESEIF THE PERSON SHOWS ANY OF THESE
SYMPTOMS, TIME IS IMPORTANT. SYMPTOMS, TIME IS IMPORTANT.
CALL FOR EMERGENCY OR GET TO THECALL FOR EMERGENCY OR GET TO THE

20. Immediate Diagnostic Studies: Evaluation of aImmediate Diagnostic Studies: Evaluation of a
Patient With Suspected Acute Ischemic StrokePatient With Suspected Acute Ischemic Stroke
Stroke 2007;38;1655-1711;

21. Management of strokeManagement of stroke
• Management of stroke, ischemic stroke in particular, has undergone a sea
change since the landmark
- National Institute of Neurological Disorders and Stroke (NINDS)
Recombinant Tissue Plasminogen Activator (rt-PA) stroke Study earned US-
FDA approval in 1996.
• The window of opportunity for salvaging the ischemic tissue at risk is first 3 h
since onset of stroke.
• Trials/Guidelines now support the window till 4.5 hrs in treatment of stroke
MJAFI, Vol. 65, No. 1, 2009

22. Critical Time windowCritical Time window
• From the moment the patient arrives at the door, every minute counts, and
the only justifiable delays would be for performing brain imaging studies to
exclude hemorrhage and for obtaining the results of a few simple laboratory
tests.
Every minute matters during a strokeEvery minute matters during a stroke

23. Alteplase only thrombolyticAlteplase only thrombolytic
approved for treatment of Acuteapproved for treatment of Acute
ischemic strokeischemic stroke

24. Mode of ActionMode of Action
•The active ingredient of ACTILYSE®
is alteplase, a recombinant human tissue-type
plasminogen activator, a glycoprotein, which activates plasminogen directly to
plasmin
•When administered intravenously, alteplase remains relatively inactive in the
circulatory system
•Once bound to fibrin, it is activated, inducing the conversion of plasminogen to
plasmin leading to the dissolution of the fibrin clot

25. Pharmacokinetics
•ACTILYSE® is cleared rapidly from the circulating blood and metabolised mainly by
the liver (plasma clearance 550 - 680 ml/min.)
• The relevant plasma half-life T1/2 alpha is 4 - 5 minutes
•This means that after 20 minutes less than 10% of the initial value is present in the
plasma. For the residual amount remaining in a deep compartment, a beta-half-life
of about 40 minutes was measured.

26. StorageStorage
 Protect the lyophilised substance from lightProtect the lyophilised substance from light
 The reconstituted solution can be kept for 8The reconstituted solution can be kept for 8
& 24 hours in room temperature and& 24 hours in room temperature and
refrigerator respectivelyrefrigerator respectively
 During reconstitution the solution needs toDuring reconstitution the solution needs to
be mixed with gentle swirl, not to be shakenbe mixed with gentle swirl, not to be shaken

27. IndicationIndication
1. Thrombolytic treatment in acute myocardial infarction.
90 minutes (accelerated) dose regimen for patients in whom treatment can be
started within 6 h of symptom onset;
3 hour dose regimen for patients in whom treatment can be started between 6
12 h after symptom onset.
2.Thrombolytic treatment in acute massive pulmonary embolism with hemodynamic
instability
The diagnosis should be confirmed whenever possible by objective
means such as pulmonary angiography or non-invasive procedures such as lung scanning
3.Thrombolytic treatment of acute ischaemic stroke
Treatment should only be initiated within 3 hours after the onset of
stroke symptoms and after exclusion of intracranial haemorrhage by appropriate imaging
techniques such as cranial computerised tomography (CT).

28. Ischemic StrokeIschemic Stroke
The recommended dose is 0.9 mg/kg (maximum of 90 mg) infused over 60 minutes
with 10% of the total dose administered as an initial intravenous bolus. Therapy
should be initiated as early as possible within 3 hours after onset of symptoms.
Adjunctive therapy:
The safety and efficacy of this regimen with concomitant administration of heparin
and acetylsalicylic acid during the first 24 hours after the symptom-onset has not
been investigated sufficiently.
Therefore, administration of acetylsalicylic acid or
intravenous heparin should be avoided in the first 24
hours after treatment with ACTILYSE®

29. Pulmonary embolismPulmonary embolism
A total dose of 100 mg should be administered in 2 hours. The most experience available
is with the following dose regimen:
10 mg as an intravenous bolus over 1 - 2 minutes, 90 mg as an intravenous infusion over
two hours.
The total dose should not exceed 1.5 mg/kg in patients with a body weight below 65 kg.
Adjunctive therapy:
After treatment with ACTILYSE®
heparin therapy should be initiated (or resumed) when
aPTT values are less than twice the upper limit of normal. The infusion should be adjusted
to maintain aPTT between 50 - 70 seconds (1.5 to 2.5 fold of the reference value).

30. In the indication acute ischemic stroke the following contraindications apply in addition:
•symptoms of ischemic attack began more than 4.5 hours prior to infusion start or when time of
symptom onset is unknown
•symptoms of acute ischemic stroke that were either rapidly improving or only minor before start of
infusion
•severe stroke as assessed clinically (e.g. NIHSS>25) and/or by appropriate imaging techniques
•seizure at the onset of stroke
•history of previous stroke or serious head-trauma within three months
•a combination of previous stroke and diabetes mellitus
•administration of heparin within 48 hours preceding the onset of stroke with an elevated activated
partial thromboplastin time (aPTT) at presentation
•platelet count of less than 100,000 / mm3
•systolic blood pressure > 185 or diastolic blood pressure > 110 mmHg, or aggressive management
(IV medication) necessary to reduce blood pressure to these limits
•blood glucose < 50 or > 400 mg/dl
ACTILYSE®
is not indicated for the therapy of acute stroke in children and adolescents under 18 years
or adults over 80 years of age.
Contraindications

31. Interactions
No formal interaction studies with ACTILYSE® and medicinal products commonly administered in
patients with acute myocardial infarction have been performed.
Medicinal products that affect coagulation or those that alter platelet function may increase the
risk of bleeding prior to, during or after ACTILYSE® therapy.
Concomitant treatment with ACE inhibitors may enhance the risk of suffering an anaphylactoid
reaction, as in the cases describing such reactions a relatively larger proportion of patients were
receiving ACE inhibitors concomitantly.
Pregnancy and lactation
There is very limited experience with the use of ACTILYSE® during pregnancy and lactation. In
cases of an acute life-threatening disease the benefit has to be evaluated against the potential
risk.
It is not known if alteplase is excreted into breast milk.

32. Thumb Rules of ThrombolysisThumb Rules of Thrombolysis
 AISAIS
 Onset of symptoms within 4.5 hoursOnset of symptoms within 4.5 hours
 Age – 18 to 80 yearsAge – 18 to 80 years
 NIHSS – 4-25NIHSS – 4-25
 BP - <185/110 mm of HgBP - <185/110 mm of Hg
 Blood glucose - <50-400 ml/dlBlood glucose - <50-400 ml/dl

33. Treatment of AIS – follow-upTreatment of AIS – follow-up
during & post thrombolysisduring & post thrombolysis
 Neurological assessments – every 15 minutes during theNeurological assessments – every 15 minutes during the
infusion, every 30 minutes thereafter for 6 hours, then hourlyinfusion, every 30 minutes thereafter for 6 hours, then hourly
until 24 hoursuntil 24 hours
 Measure BP – every 15 minutes for the first 2 hours, every 30Measure BP – every 15 minutes for the first 2 hours, every 30
minutes for the next 6 hours, then hourly until 24 hours. BPminutes for the next 6 hours, then hourly until 24 hours. BP
has to be kept within 180/105 mm of Hghas to be kept within 180/105 mm of Hg
 Delay placement of nasogastric tubes, catheters etcDelay placement of nasogastric tubes, catheters etc
 A follow-up CT at 24 hours before starting anticoagulantsA follow-up CT at 24 hours before starting anticoagulants
 An emergency if patient develops severe headache, acuteAn emergency if patient develops severe headache, acute
HT, nausea or/and vomitingHT, nausea or/and vomiting

34. Complications of IVComplications of IV
Thrombolysis with AlteplaseThrombolysis with Alteplase
 Include intracranial and extracranial hemorrhagesInclude intracranial and extracranial hemorrhages
 Most common and dreaded complication ICHMost common and dreaded complication ICH
 ICHs are divided into symptomatic and asymptomatic ICHsICHs are divided into symptomatic and asymptomatic ICHs
 Symptomatic ICHs are mostly large hemorrhages, found asSymptomatic ICHs are mostly large hemorrhages, found as
parenchymal hematomas in CTparenchymal hematomas in CT
 Asymptomatic ICHs occur commonly during the naturalAsymptomatic ICHs occur commonly during the natural
course of cerebral infarct and don’t have significant negativecourse of cerebral infarct and don’t have significant negative
impact on the final outcomeimpact on the final outcome

35. Bleeding and its ManagementBleeding and its Management
 It is not necessary to replace the coagulation factors due to the shortIt is not necessary to replace the coagulation factors due to the short
half life and moderate effect of Alteplase on systemic coagulationhalf life and moderate effect of Alteplase on systemic coagulation
factorsfactors
 Most bleeds can be managed by interruption of thrombolytic &Most bleeds can be managed by interruption of thrombolytic &
anticoagulant therapy, volume replacement or manual pressureanticoagulant therapy, volume replacement or manual pressure
applied to an incompetent vesselapplied to an incompetent vessel
 Patients who don’t respond transfusion products may be usedPatients who don’t respond transfusion products may be used
judiciouslyjudiciously
 Transfusion of fresh frozen plasma, cryoprecipitates, platelets shouldTransfusion of fresh frozen plasma, cryoprecipitates, platelets should
be considered with clinical and laboratory reassessment after eachbe considered with clinical and laboratory reassessment after each
administrationadministration
 Antifibrinolytic agents are available as last alternativeAntifibrinolytic agents are available as last alternative

36. Characteristics of Patients With IschemicCharacteristics of Patients With Ischemic
Stroke Who Could Be Treated With rt-PAStroke Who Could Be Treated With rt-PA
 Diagnosis of ischemic stroke causing measurable neurological deficitDiagnosis of ischemic stroke causing measurable neurological deficit
 The neurological signs should not be clearing spontaneously.The neurological signs should not be clearing spontaneously.
 The neurological signs should not be minor and isolated.The neurological signs should not be minor and isolated.
 Caution should be exercised in treating a patient with major deficits.Caution should be exercised in treating a patient with major deficits.
 The symptoms of stroke should not be suggestive of subarachnoidThe symptoms of stroke should not be suggestive of subarachnoid
hemorrhage.hemorrhage.
 Onset of symptoms <3 hours before beginning treatment ( has beenOnset of symptoms <3 hours before beginning treatment ( has been
increase to 4.5hr as per 2008 ESO guidelines , 2010 ISA guidelines andincrease to 4.5hr as per 2008 ESO guidelines , 2010 ISA guidelines and
also by ASA in specific condition)also by ASA in specific condition)
 No head trauma or prior stroke in previous 3 monthsNo head trauma or prior stroke in previous 3 months
Stroke 2009, Stroke 2007

37. Characteristics of Patients WithCharacteristics of Patients With
Ischemic Stroke Who Could Be TreatedIschemic Stroke Who Could Be Treated
With rt-PAWith rt-PA
 No myocardial infarction in the previous 3 monthsNo myocardial infarction in the previous 3 months
 No gastrointestinal or urinary tract hemorrhage in previous 21 daysNo gastrointestinal or urinary tract hemorrhage in previous 21 days
 No major surgery in the previous 14 daysNo major surgery in the previous 14 days
 No arterial puncture at a noncompressible site in the previous 7 daysNo arterial puncture at a noncompressible site in the previous 7 days
 No history of previous intracranial hemorrhageNo history of previous intracranial hemorrhage
 Blood pressure not elevated (systolic <185 mm Hg and diastolic <110 mmBlood pressure not elevated (systolic <185 mm Hg and diastolic <110 mm
Hg)Hg)
 No evidence of active bleeding or acute trauma (fracture) on examinationNo evidence of active bleeding or acute trauma (fracture) on examination
 Not taking an oral anticoagulant or, if anticoagulant being taken, INR≤ 1.7Not taking an oral anticoagulant or, if anticoagulant being taken, INR≤ 1.7
Stroke 2007;38;1655-1711;

38. Characteristics of Patients With IschemicCharacteristics of Patients With Ischemic
Stroke Who Could Be Treated With rt-PAStroke Who Could Be Treated With rt-PA
 If receiving heparin in previous 48 hours, aPTT must be in normalIf receiving heparin in previous 48 hours, aPTT must be in normal
range.range.
 Platelet count ≥100 000 mm3Platelet count ≥100 000 mm3
 Blood glucose concentration ≥ 50 mg/dL (2.7 mmol/L)Blood glucose concentration ≥ 50 mg/dL (2.7 mmol/L)
 No seizure with postictal residual neurological impairmentsNo seizure with postictal residual neurological impairments
 CT does not show a multilobar infarction (hypodensity >1/3CT does not show a multilobar infarction (hypodensity >1/3
cerebral hemisphere).cerebral hemisphere).
Stroke 2007;38;1655-1711;

39. Key pointsKey points
 Young stroke patientsYoung stroke patients
 Time is at premiumTime is at premium
 Early identificationEarly identification
 Early institution of RxEarly institution of Rx
 Good and very satisfying resultGood and very satisfying result
 Drug available ,Neuro-imagingDrug available ,Neuro-imaging
availableavailable
 Previous cases encouraging resultPrevious cases encouraging result

40. Thank You….!!!!Thank You….!!!!