2. STROKE
• More than 36 million deaths worldwide are caused by non-communicable diseases (Pusdatin Kemenkes RI,
2015)
• 9 million deaths caused by PTM occur before the age of 60 and 90% occur in low and middle income
countries (Pusdatin Kemenkes RI, 2015)
• Stroke is included in the category of non-communicable diseases with a high incidence (Pusdatin
Kemenkes RI, 2015)
According to WHO, stroke is defined as a neurological deficit
of cerebrovascular cause that persists beyond 24 hours or is
Interrupted by death within 24 hours.
A stroke is caused by the interruption of the blood supply to
the brain, usually because a blood vessel bursts or is blocked
by a clot. This cuts off the supply of oxygen and nutrients,
causing damage to the brain tissue.
Therefore, stroke can be explained as death or dysfunction
of brain tissue due to occlusion or haemorrhage of brain’s
arteries. The pattern of resulting neurological damage
differs according to whether the supply to the posterior or
anterior artery has interrupted. (WHO, 2016)
• Transient ischaemic attack (TIA):
This means a focal deficit, such as a weak limb, aphasia or loss of vision lasting from a few seconds to 24 hrs.
there is complete recovery, the attack is usually sudden. TIAs have a tendency to recur, and may herald
thromboembolic stroke.
3. Stroke is a 4-D Problem
Disability, Disparity, Death, & Dollars
• Stroke is the 4th leading cause of death in the
US and the #1 cause of permanent disability
• Each year, 795,000 people experience a new
or recurrent stroke
• Every 4 minutes someone dies of stroke
• Americans pay about $74 billion/year in
stroke-related medical & disability costs
6. TYPES of STROKE
• Strokes can be classified into two
main categories, including the
following:
1. Ischaemic strokes (incidence- 85%)-
strokes caused by blockage of an
artery.
2. Haemorrhagic stroke (incidence-
15%)-strokes caused by bleeding.
8. PATHOPHYSIOLOGY of STROKE
• Haemorrhagic stroke
Haemorrhagic strokes are due to the rupture of a blood vessels leading to
compression of brain tissue from an expanding haematoma.
This can distort and injure tissue. In addition, the pressure may lead to a loss of
blood supply to affected tissue with resulting infarction, and the blood released
by brain haemorrhage appears to have direct toxic effects on brain tissue and
vasculature.
• Caused by rupture of a blood vessel and accumulation of blood within the brain.
This is commonly the result of blood vessel damage from chronic hypertension,
vascular malformations, or the use of medications associated with increased
bleeding rates, such as anticoagulants, thrombolytics, and antiplatelet agents.
Intracerebral haemorrhage
• The gradual collection of blood in the subarachnoid space of the brain dura,
typically caused by trauma to the head or rupture of a cerebral aneurysm.
Subarachnoid haemorrhage
9. ISCHAEMIC STROKE
1. Thrombotic stroke: It is caused by a
blood clot that develops in the blood
vessels inside the brain.
2. Embolic stroke: It is 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 blood stream.
10.
11. HAEMORRHAGIC STROKE
1. Subarachnoid haemorrhage: It occurs when blood enters the subarachnoid
space (where cerebrospinal fluid is housed) owing to either trauma, rupture of
an intracranial aneurysm, or rupture of an arteriovenous malformation (AVM).
2. Intracerebral haemorrhage: It occurs when a blood vessel ruptures within the
brain parenchyma itself, resulting in the formation of a hematoma. These types
of haemorrhages very often are associated with uncontrolled high blood
pressure and sometimes antithrombotic or thrombolytic therapy.
3. Subdural haematomas: It refers to collections of blood below the dura
(covering of the brain), and they are caused most often by trauma.
Haemorrhagic stroke, although less common, is significantly more lethal than
ischemic stroke, with 30-day case-fatality rates that are two to six times higher.
12. CLINICAL PRESENTATION
General:
• The patient may not be able to reliably report the history owing to cognitive or language
deficits. A reliable history may have to come from a family member or another witness.
Symptoms:
• The patient may complain of weakness on one side of the body, inability to speak, loss of
vision, vertigo, or falling. Ischemic stroke is not usually painful, but patients may complain of
headache, and with haemorrhagic stroke, it can be very severe.
Signs:
• Patients usually have multiple signs of neurologic dysfunction, and the specific deficits are
determined by the area of the brain involved.
• Hemi- or monoparesis occurs commonly, as does a hemisensory deficit.
• Patients with vertigo and double vision are likely to have posterior circulation involvement.
• Aphasia is seen commonly in patients with anterior circulation strokes.
• Patients also may suffer from dysarthria, visual field defects, and altered levels of
consciousness.
13. DIAGNOSIS
• Tests for hypercoagulable states (proteins S and C deficiency, antiphospholipid
antibody).
Laboratory tests:
• 1. CT scan: reveals an area of hyperintensity (white) in the area of haemorrhage
and will be normal or hypointense (dark) in the area of infarction. The CT scan
may take 24 hours (and rarely longer) to reveal the area of infarction.
• 2. MRI: reveals areas of ischemia with higher resolution and earlier than the CT
scan.
• 3. Diffusion-weighted imaging (DWI): reveals an evolving infarct within minutes.
• 4. Carotid Doppler (CD): determines whether the patient has a high degree of
stenosis in the carotid arteries supplying blood to the brain (extracranial disease)
• 5. Electrocardiogram (ECG): determines whether the patient has atrial fibrillation,
a potent etiologic factor for stroke.
• 6. A transthoracic echocardiogram (TTE): determines whether valve
abnormalities or wall motion abnormalities are sources of emboli to the brain.
• 7. A transoesophageal echocardiogram (TEE): more sensitive test for thrombus
in the left atrium. It is effective at examining the aortic arch for atheroma, a
potential source of emboli.
• 8. Transcranial Doppler (TCD): determines whether the patient is likely to have
intracranial arterial sclerosis (e.g., middle cerebral artery stenosis)
Other diagnostic tests:
14. MANAGEMENT of STROKE
Save max brain = lose min. function
• Movement
• Vision
• Sensation
• Taste, etc.
• Goals of treatment:
1. To reduce the ongoing neurologic injury and decrease mortality
and long-term disability.
2. Prevent complications secondary to immobility and neurologic
dysfunction.
3. Prevent stroke recurrence
Treating stroke
(intervention)
15. 1. Saver J. Stroke 2006;37:263-266.
2. Powers WJ, et al. Stroke 2019;50(12):e344-e418.
3. The European Stroke Organisation (ESO) Executive Committee and the ESO Writing Committee. Cerebrovasc Dis 2008;25(5):457-507.
Stroke awareness: Time is brain1
The goal is to decrease
stroke onset to
emergency department
(ED) arrival times, and
increase timely use of
thrombolysis and
thrombectomy2
Treatment delays are
often due to failure of
the general public to
recognise stroke
symptoms and call
emergency services
(EMS)3
Other potentially
avoidable delays are
the result of lack of
prioritisation of
potential stroke
patients by EMS and in-
hospital services3
EMERGENC
Y
112
1 2 3
4 5 6
7 8 8
17. 1. The European Stroke Organisation (ESO) Executive Committee and the ESO Writing Committee. Cerebrovasc Dis 2008;25(5):457-507.
2. Powers WJ, et al. Stroke 2019;50(12):e344-e418.
Emergency medical services (EMS)
Rapid assessment and
identification of a
suspect stroke by the
EMS and transport to
the nearest stroke care
facility is critical1
Prior notification to
the receiving hospital
of the impending
arrival of a potential
stroke patient can
prepare the stroke
team1,2
If transport to a stroke
care facility is difficult
or prolonged,
telemedicine can
facilitate access to
specialist stroke
services1,2
20. 1. Powers WJ, et al. Stroke 2019;50(12):e344-e418.
2. The European Stroke Organisation (ESO) Executive Committee and the ESO Writing Committee. Cerebrovasc Dis 2008;25(5):457-507.
Acute assessment of a suspected stroke
patient on arrival in-hospital
Stroke assessment scores
can be carried out rapidly
and accurately by trained
healthcare professionals to
assess the level of
neurological deficit: the
NIHSS is preferred1,2
Only the assessment of
blood glucose must
precede the initiation of
rt-PA in all patients; other
tests may be
necessary if there is
suspicion of coagulopathy,
but treatment should not
be delayed1
Baseline troponin
assessment is
recommended but should
not delay initiation of rt-
PA or mechanical
thrombectomy1
21. National Institute of Health Stroke Scale
(NIHSS)
No. Item Score No. Item Score
1 (a) Level of
consciousness
(b) Questions
(c) Commands
0-7 9 Limb ataxia 0-2
2 Pupillary response 0-2 10 Sensory 0-2
3 Best gaze 0-2 11 Neglect 0-2
4 Best visual 0-2 12 Dysarthria 0-2
5 Facial palsy 0-3 13 Best language 0-3
6 Best motor arm 0-3 14 Change from previous exam S/B/W
7 Best motor leg 0-3 15 Change from baseline S/B/W
8 Plantar reflex 0-3
Brott et al. Stroke 1989;20:864-870. 21
22. Assessing stroke severity in the field
Reliability of NIHSS for non-neurologists
Level of consciousness (0-3)
1: Response to oral stimuli
2: Accurate response to pain
3: Inaccurate response
Motor (0-4)
Test all 4 limbs at posture bearing
(10 sec superior limb; 5 sec inferior limb)
1: Falls but after time limit
2: Falls on the bed before time limit
3: Moves but unable to lift from bed
4: No movement
Aphasia (0-3)
1: Aphasia but able to have a conversation
2: Communication almost impossible
3: Muteness or coma
The National Institutes of Health Stroke
Scale (NIHSS) can be reliably used by non-
neurologists, providing they have been
trained and are familiar with the scale
A simplified version of the NIHSS can be
reliably used in the field by trained
paramedics to assess the severity of a
stroke prior to arrival at a stroke unit
Goldstein et al. Stroke 1997;28:307-310.
Meyer et al. Stroke 2002;33:1261-1266.
22
27. 1. Powers WJ, et al. Stroke 2019;50(12):e344-e418.
Cardiac evaluation
Baseline
electrocardiographic
assessment is
recommended in patients
presenting with AIS but
should not delay initiation
of rt-PA1
AF, atrial fibrillation
Cardiac monitoring is
recommended to screen
for AF and other
potentially serious
arrhythmias; cardiac
monitoring should be
performed for at least
the first 24 hours1
Echocardiography is
reasonable in some
patients to guide
selection of appropriate
secondary stroke
prevention1
28. 1. Powers WJ, et al. Stroke 2019;50(12):e344-e418.
2. The European Stroke Organisation (ESO) Executive Committee and the ESO Writing Committee. Cerebrovasc Dis
2008;25(5):457-507.
Brain imaging to determine eligibility for
thrombolysis
For acute brain
imaging, non-contrast
cranial CT remains the
imaging mode of
choice due to ability to
exclude ICH and cost
effectiveness1,2
24/7 direct access2 to
imaging on arrival at
the hospital saves
valuable time, and
door-to-imaging should
be achievable within
20 minutes1
Further imaging
studies should not
delay administration of
rt-PA, which can be
given in the imaging
suite1
ICH, intracerebral haemorrhage
29. Brain imaging for planning mechanical
thrombectomy
1. Powers WJ, et al. Stroke 2019;50(12):e344-e418.
Brain imaging should
also rule out
extracranial vessel
anomalies, such as
stenoses, occlusions or
dissections to identify
eligibility for MT1
Identification of a
clinical or perfusion-
diffusion mismatch on
MRI 6 h after onset of
stroke symptoms can
help identify patients
eligible for mechanical
thrombectomy1
When planning an
endovascular
approach, imaging of
the cerebral
vasculature will assist
in locating of the
occlusion1
MT, mechanical thrombectomy
30. Stroke networks and telemedicine
1. Powers WJ, et al. Stroke 2019;50(12):e344-e418.
2. The European Stroke Organisation (ESO) Executive Committee and the ESO Writing Committee. Cerebrovasc Dis
2008;25(5):457-507.
Telemedicine enables a
full remote consultation
and assessment of the
imaging (teleradiology) by
a stroke expert, who can
advise the physician in
the treating centre1
Telemedicine can
facilitate timely access to
IV rt-PA and earlier
reperfusion and can also
be used as a remote
triage to assess a patient
for transfer to more
advanced stroke services1
A stroke network can
offer 24/7 access to
specialist stroke services;
if direct transfer to a
stroke unit is not
possible, telemedicine is
an eligible alternative1,2
IV, intravenous
31. Administration of timely thrombolysis with
rt-PA
*rt-PA is not approved for administration after 4.5 hours of symptom onset.
1. Saver J. Stroke 2006;37:263-266.
2. Powers WJ, et al. Stroke 2019;50(12):e344-e418.
3. Berge E, et al. Eur Stroke J 2021;6(1):I-LXII.
The stroke team
should strive to keep
the door-to-needle
time to less than 60
minutes2
The time window for
IV thrombolysis is
<4.5 h, or up to 9 h
after onset of
symptoms in eligible
patients2,3*
Time is brain: the
earlier reperfusion is
established, the
greater the chance
of reducing
ischaemic injury1
32. *rt-PA is not approved for administration after 4.5 hours of symptom onset.
1. Berge E, et al. Eur Stroke J 2021;6(1):I-LXII.
Alteplase in AIS: Timing
(ESO Guidelines)
AIS of <4.5 h duration: IV thrombolysis with alteplase* is recommended1
AIS 4.5–9 h duration* (known onset time), and with no brain imaging other than
plain CT: recommend no intravenous thrombolysis1
AIS 4.5–9 h duration* (known onset time) and with CT or MRI core/perfusion
mismatch, and for whom mechanical thrombectomy is either not indicated or not
planned: IV thrombolysis with alteplase is recommended1
Key recommendations
34. Intravenous thrombolysis with rt-PA
The benefit of thrombolytic therapy with intravenous tissue plasminogen
activator (rt-PA*) is time dependent, therefore treatment should be
initiated as quickly as possible1
Intravenous rt-PA (0.9 mg/kg body weight, maximum 90 mg), with 10% of
the dose given as a bolus followed by a 60-minute infusion, is
recommended for eligible patients:
•In the US: Up to 3 h after ischaemic stroke onset and within 3-4.5 hours in
selected patients1
•In Europe: Within 4.5 hours2
Intravenous rt-PA may also be administered in selected patients aged 16–
17 years, and those over 802,3
For all patients with AIS, physicians have to balance the benefits of giving IV rt-PA with the risks when
making treatment decisions3
1. Powers WJ, et al. Stroke 2019;50(12):e344-e418.
2. Berge E, et al. Eur Stroke J 2021;6(1):I-LXII.
3. The European Stroke Organisation (ESO) Executive Committee and the ESO Writing Committee. Cerebrovasc Dis 2008;25(5):457-507.
Key recommendations
*rt-PA is not approved for administration after 4.5 hours of symptom onset.
35. 1. Powers WJ, et al. Stroke 2019;50(12):e344-e418.
2. The European Stroke Organisation (ESO) Executive Committee and the ESO Writing Committee. Cerebrovasc Dis
2008;25(5):457-507.
Intravenous thrombolysis with rt-PA
Blood pressure should be maintained <180/105 mmHg for the first 24 hours
after treatment1
Aspirin or other antithrombotic therapy should not be initiated within 24 h of
rt-PA administration2
Abciximab should not be administered concurrently with thrombolytic
treatment1
rt-PA should not be administered to patients who have received LMWH within
the previous 24 h1
In patients undergoing thrombolytic therapy, physicians should be prepared
to treat potential emergent adverse effects (e.g. bleeding complications and
angioedema)1
LMWH, low molecular-weight heparin
Key recommendations
37. Mechanical thrombectomy (MT)
1. Lavine SD, et al. Neuroradiology 2016;58(6):537-541.
2. Wahlgren N, et al. Int J Stroke 2016;11(1):134–147.
3. Powers WJ, et al. Stroke 2019;50(12):e344-e418.
IV rt-PA should be
administered to all
eligible patients who
are being considered
for MT and neither
procedure should delay
the other2
LVO can be identified
using non-invasive
vascular imaging
studies; if these are
not available, the
NIHSS score can be
predictive of LVO2,3
MT is the standard of
care for patients with
AIS due to large vessel
occlusion (LVO)1
AIS, acute ischaemic stroke
LVO, large vessel occlusion
38. Key recommendations
1. Wahlgren N, et al. Int J Stroke 2016;11(1):134–147.
2. Powers WJ, et al. Stroke 2019;50(12):e344-e418.
Mechanical thrombectomy
Mechanical thrombectomy, in addition to IV thrombolysis within 4.5
hours, when eligible, is recommended to treat acute stroke patients
with large artery occlusions in the anterior circulation up to 6 hours
after symptom onset1
Mechanical thrombectomy should be performed as soon as possible
after its indication1,2*
Mechanical thrombectomy should not prevent the initiation of IV
thrombolysis where it is indicated, and vice versa1,2
If intravenous thrombolysis is contraindicated, mechanical
thrombectomy is recommended as first-line treatment in large vessel
occlusions1
*In patients under consideration for mechanical thrombectomy, observation after rt-PA
administration to assess for clinical response should not be performed2
39. Key recommendations
1. Wahlgren N, et al. Int J Stroke 2016;11(1):134–147.
2. Powers WJ, et al. Stroke 2019;50(12):e344-e418.
Mechanical thrombectomy
Intracranial vessel occlusion must be diagnosed with non-invasive imaging
whenever possible before considering treatment with mechanical
thrombectomy1
The procedure should be performed by a trained and experienced
neurointerventionist1
Stent retrievers approved by local health authorities should primarily be
used1
The technical goal of the thrombectomy procedure should be reperfusion to
a modified Thrombolysis in Cerebral Infarction (mTICI) 2b/3 angiographic
result to maximise the probability of a good functional clinical outcome2
44. • Conclusions: In patients with acute non-cardioembolic ischemic stroke, especially that with large-artery
stenosis, LMWH treatment significantly reduced the incidence of END and RIS, and improved the
likelihood of independence (mRS 0–1) at 6 months compared with those with aspirin treatment. LMWH
was related to an increased likelihood of extracranial hemorrhage among all patients; however, the
difference in major extracranial hemorrhage and sICH was not significant.
LMWH vs ASPIRIN in AIS
45. ENOXAPARIN
Enoxaparin is an anti-clotting agent.
Enoxaparin is used for anti-clotting in
the treatment of DVT (deep vein
thrombosis), unstable angina, non-
STEMI and STEMI.
Enoxaparin works to increase the
speed of inhibition of enzymes and
blood clotting factors.
46. Heparin VS Enoxaparin
• Heparin is an anticoagulant/blood thinner, also known as standard heparin
or unfractionated heparin (UFH). Heparin is administered intravenously or
subcutaneously.
• Enoxaparin is a low molecular weight heparin (LMWH). It is usually given
once or twice daily as a subcutaneous injection.
48. Heparin VS Enoxaparin
ACTION MECHANISM
Enoxaparin and heparin have a similar mechanism of action.
They work by binding to a small protein molecule called antithrombin
and blocking the action of thrombin, factor Xa, and other enzymes involved in
blood clotting.
Although Enoxaparin is classified as a low molecular weight heparin
(LMWH), it is not the same as standard heparin.
50. • Conclusions: Enoxaparin was not the primary cause of thrombocytopenia
in prophylactic treatment. Enoxaparin is a 100% effective means to
prevent lower extremity DVT in average-risk patients, and it does not
increase the risk of bleeding.
ENOXAPARIN in AIS
51. • Results—After transient MCAO, enoxaparin at 231.5 mg/kg IV (2 and 24 hours
after insult) significantly reduced lesion size by 30% (P,0.05) and improved
neuroscore (P,0.01). This significant effect on lesion size and neuroscore was still
evident when treatment was started 5 hours after insult. Administered under the
same protocol with a 5 hours delay post permanent MCAO, enoxaparin reduced
lesion size by 49% (P,0.05) and improved neuroscore (P,0.01).
• Conclusions—This study indicates that standard nonhemorrhagic doses of
enoxaparin reduce ischemic damage with a wide therapeutic window. In addition
to its anticoagulant properties, other properties of enoxaparin could act in synergy
to explain its neuroprotective profile in ischemia.
52. • Patients suffering a primary intracerebral hemorrhage (ICH)
have a substantial risk of venous thromboembolism (VTE).
• Early studies showed that without prevention, deep venous
thrombosis (DVT) occurs in about half of all stroke patients
(47–53 %) and 3–16 % of them die of pulmonary embolism
(PE)
• In particular, those who have hemiparesis/hemiplegia run a
very high risk of VTE (75 %).
• The development of VTE in a patient with ICH adds further
detrimental complications to an already lethal disease, with
an increase in the one-month case fatality rate from 35% to
52%.
ENOXAPHARIN in ICH
Qian C, Huhtakangas J, Juvela S, Bode MK, Tatlisumak T, Savolainen M, et al. Early vs. late enoxaparin for the prevention of venous thromboembolism in patients with ICH: A double blind
placebo controlled multicenter study. Clin Neurol Neurosurg. 2021;202:106534. doi:10.1016/j.clineuro.2021.106534
53. • Kesimpulan:
• Pemberian enoxaparin 40 mg/hari sebagai profilaksis VTE pada pasien ICH
dapat dimulai baik secara awal (24 jam setelah onset) ataupun secara
lambat (72 jam setelah onset), dengan efikasi dan keamanan yang
sebanding. Tidak ada risiko pembesaran hematoma yang dikaitkan dengan
pemberian enoxaparin pada tahap awal, demikian juga pemberian
enoxaparin onset lambat tidak meningkatkan risiko VTE.
54. • Results: 139 patients were included for randomization in this study. Only 3
patients developed VTE, 2 in the early enoxaparin group and one in the late
enoxaparin group. No patients developed PE. Thromboembolic events (p = 0.901),
risk of hematoma enlargement (p = 0.927) and overall outcome (P = 0.904) did not
differ significantly between the groups.
• Conclusion: Administering 40 mg/d LMWH for prevention of VTE to a spontaneous
ICH patient is safe regardless of whether it is started 24 h (early) or 72 h (late) after
the hemorrhage. Risk of hemorrhage enlargement is not associated with early
LMWH treatment. Administering LMWH late did not increase VTEs.
55. • Results: The prophylaxis and treatment of VTE are of vital importance for patients with spontaneous ICH.
Prophylaxis measures can be mainly categorized into mechanical prophylaxis and chemoprophylaxis.
Treatment strategies include anticoagulation, vena cava filter, systemic thrombolytic therapy, catheter-
based thrombus removal, and surgical embolectomy. We briefly summarized the state of knowledge
regarding the prophylaxis measures and treatment strategies of VTE after spontaneous ICH in this review,
especially on chemoprophylaxis and anticoagulation therapy. Early mechanical prophylaxis, especially with
intermittent pneumatic compression, is recommended by recent guidelines for patients with spontaneous
ICH. While decision-making on chemoprophylaxis and anticoagulation therapy evokes debate among
clinicians, because of the concern that anticoagulants may increase the risk of recurrent ICH and
hematoma expansion. Uncertainty still exists regarding optimal anticoagulants, the timing of initiation,
and dosage.
• Conclusion: Based on current evidence, we deem that initiating chemoprophylaxis with UFH/LMWH within
24–48 h of ICH onset could be safe; anticoagulation therapy should depend on individual clinical
condition; the role of NOACs in this patient population could be promising.
