HISTORY OF ACUTE ISCHEMIC

STROKE TREATMENT
Applicability of Acute Ischemic Stroke Treatment

7%
 ASPIRIN
• 400 BC Hipocrates from willow tree
• 1832 French Chemist, creates salicylic acid
• 1897 Hoffmann, introduced salicylic acid for
pain and fever
• 1899 Bayer distributes ASA commercially
• 1948 Lawrence Craven prescibed to prevent
heart attack
ASPIRIN
1997

1997
 ASPIRIN
• IST & CAST 8838 ON ASA ALONE

• ASA GIVEN WITHIN 48 HRS

• AHA/ASA Guidelines on Prevention of

Recurrent Stroke

• Stroke Society of the Phil Guidelines

 OTHER ANTIPLATELETS
• DIPYRIDAMOLE

• CLOPIDOGREL

• CILOSTAZOL

• TRIFLUSAL

• TICAGRELOR
 Tetrasperma salyx
(Indian willow)

Lake Kalin-an, Sibulan, Negros Or

ACUTE STROKE UNIT
ST RO K E IN A SIA
ASIANSTROKE ADVISORYPANEL
S E CON D E DI TI ON

NIJASRI C. SUWANWELA
JOSE C. NAVARRO
 Table 1. “Landmarks” in the History of Stroke unit care, adapted with
permission from Stroke Units: an evidence based approach (6)

1950 First published reports of organized stroke care (18)

1962 First published RCT of a system of stroke rehabilitation (19)

1970 Reports (no RCT) of stroke intensive care units (9)

1980 First large (>300 patients) RCT of a stroke unit shows only short term
benefits (33)

1985 RCT of a mobile stroke team (20)

1988 King’s Fund Consensus Conference statement critices stroke services (21)

1990 Small systematic review suggests possible benefit of stroke unit care (22)
1991 RCT of stroke unit provides convincing evidence of benefit (16)

1993 First RCT on an acute unit (intervening only in the first few days (23)

1993 Systematic review (ten RCT’s) suggest stroke unit care may prevent
premature deaths (24)

1995 Pan American Consensus Meeting supports organized stroke unit care (25)

1997 Updated systematic review (18 RCT’s) shows a reduction in dependency

(26,27)
Development of SU in the Phil
Stroke Society of
the Philippines
Guidelines
 SSP Guidelines Recommendations
on Stroke Unit
• Stroke patients should be treated in the stroke
unit (Class I, level A). Admission to the ASU
decreases death, dependency and
institutionalization.

• Stroke unit should provide coordinated

multidisciplinary care given by the medical,
nursing and healthcare staff who specialize in
stroke care (Class I)
 • SSP should support the
establishment of Stroke Units in the
different hospitals in the Philippines
 Process

Hospital write letter of intent

SSP check requirements

Lectures / workshop

Certification
 Minimum Requirements for
Certification of SU
• 1. Floor plan of the existing or proposed SU
and number of beds

• 2. Availability of 24hr CT scan or MRI

• 3. Availability of 24hr laboratory facilities

 Minimum Requirements for
Certification
• 4. Availability of medical personnel who will
head the SU (in the following order:
Neurologist, other specialist preferably
neurosurgeon, cardiologist, internist or
physiatrist with special interest in stroke,
other physicians

• 5. Availability of nursing staff

 SU in the Philippines

• 1999 – 2 SU
• SEPT 2017 – 46 SU
• Metro manila – 26
• Luzon – 11
• Visayas – 3
• Mindanao – 6
 REPERFUSION THERAPHY
• 1. IV rTPA

• 2. IA rTPA

• 3. SONOTHROMBOLYSIS

• 4. MECHANICAL THROMBECTOMY
IV rTPA
 Early Development of Thrombolytics

1933 1947 1948 1958

Tillett and Garner Macfarlane and Isolated by Lack Sussman and
Certain strains of Pilling from Fitch
Streptococcus From human Staphylococcus Use of a

Staphylokinas
Streptokinase

could dissolve urine, extracted a strains thrombolytic

Urokinase

fibrin clots potent activator agent

Plasmin
Clinical of plasminogen (FIBRINOLYSI
effectiveness to form plasmin N) in acute

e
described in 1955 ischemic stroke

Rother, J et al., Cerebrovasc Dis 2013; 35: 313-319

Published in 1958 in
JAMA

Treated 3 patients with IV

plasmin for 4-6 days,
where 1 patient showed
clinical improvement

First publication with a thrombolytic agent

in stroke.
Rother, J et al., Cerebrovasc Dis 2013; 35: 313-319
 Early Development of Thrombolytics

In the earlier studies, using streptokinase or urokinase

 ICH was a leading cause of death
 No clear benefit

Limitations in study design and technology

 CT was not available until the mid 1970s

Used angiography as a diagnostic method

Used different combination of agents: anticoagulants,

thrombolytics
Rother, J et al., Cerebrovasc Dis 2013; 35: 313-319
 Streptokinase is Dangerous in Acute Stroke
 3 randomized, double-blind placebo controlled trials were
terminated early because of excess early mortality and
intracranial bleeding associated with streptokinase

Trial Streptokinase Dose Time No. of Patients

Window
Multicenter Acute 0.5 MU <6 h 622
Stroke Trial – Italy
(MAST-I, 1994)
Multicenter Acute 1.5 MU <6 h 200
Stroke Trial – Europe
(MAST-E, 1995)
Australian Streptokinase 1.5 MU <4 h 340
Trial (ASK, 1995)
Sonothrombolysis
 Background
• Large Vessel Occlusion (LVO) is associated with
greater neurological deficits and poor outcome

• Proximal vessel occlusion is associated with poor

recanalization rate

• Early treatment of tPA during the golden period

of stroke is related to good outcome and fewer
neurological deficits.
 CLOTBUST
A Phase II, Randomized, Controlled Trial
New Engl J Med 2004;351;2170-2178.
 CLOTBUST Trial
Time Flow Chart:

Both Groups Target Group

If worsening > 4 NIHSS points
Dx TCD Dx TCD detected within 72 hours,
perform repeat CT Rankin
CT
TCD NIHSS
NIHSS NIHSS
monitoring
NIHSS NIHSS
TCD Fixation Device
bolus 2 hours 24 hours 72 hours 3 month
after bolus after onset

Informed consent and randomization time repeat NIHSS

Arrival If worsening > 4 NIHSS
points detected with 72 hours,
Brief Dx TCD perform repeat
vessel CT Rankin
assessment
NIHSS NIHSS
Headframe
placed
(all pts)
NIHSS NIHSS
TPA bolus 2 hours 24 hours 72 hours 3 month
Control Group
Sonothrombolysis Experience in the Philippines

Name Age Baseline NIHSS 24 hours NIHSS Outcome at 3 months

BC 38 11 3 mRS 0
HN 70 20 14 expired
PC 62 11 4 mRS 1
CH 57 13 7 mRS 0
SA 62 9 3 mRS 0
EA 76 19 4 mRS 1
GE 64 13 9 mRS 2
GG 58 23 33 expired
MO 64 20 13 no follow-up yet
AD 44 12 4 no follow-up yet
GG 80 12 8 mRS 1
RV 63 12 8 mRS 0
Endovascular Treatment
IA rTPA
IV rTPA
Hemicraniectomy