Update in Neurology Update in Neurology 29 August, 2008 29 August, 2008 ..http://epilepsy.kku.ac.th E-mail : [email protected]Topics Topics Status epilepticus : Status epilepticus : European clinical practice European clinical practice Stroke prevention : Stroke prevention : PROFESS trial PROFESS trial SPARCL trial SPARCL trial Status Epilepticus in Europe Status Epilepticus in Europe Status epilepticus classification Status epilepticus classification Drug available in Europe Drug available in Europe Efficacy of new AED iv in status epilepticus Efficacy of new AED iv in status epilepticus New standard practice in Europe New standard practice in Europe General concern in SE 1. VPA are sufficient for inclusion in protocol 2. Continuous EEG monitoring (20%) 3. Protocol at AE 4. PB is still justified Survey of Adult GCSE 45 physicians from 26 countries 41/45 were neurologist 79% from university hospital 16% from private, public hospital 5% from research institute 64% have protocol for SE at AE Pre Pre- hospital management hospital management Prognosis of SE related with time to control Prognosis of SE related with time to control Success rate to control seizure related early treatment Success rate to control seizure related early treatment Mortality rate related success rate of seizure control Mortality rate related success rate of seizure control Pre Pre- hospital treatment is very important hospital treatment is very important IV or rectal benzodiazepine IV or rectal benzodiazepine Buccal Buccal or intranasal or intranasal midazolam midazolam
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Reg.f.SEReg.f.SE, registered for use in SE., registered for use in SE.aaValproateValproate intravenous (IV) is licensed but not marketed.intravenous (IV) is licensed but not marketed.
Annex 1. Availability and licensing of drugs for SE in European Annex 1. Availability and licensing of drugs for SE in European countries.countries.
United Kingdom United Kingdom yesyes nono yes yes yes yes yesyes yesyes yesyes yesyes yesyes nono yesyes yesyes
United States of United States of
America America yesyes nono yes yes yes yes yesyes nono yesyes yesyes yesyes nono yesyes nono
Reg.f.SEReg.f.SE, registered for use in SE., registered for use in SE.aaValproateValproate intravenous (IV) is licensed but not marketed.intravenous (IV) is licensed but not marketed.
Survey of licensed drug for SE : 25 countries in Europe
�Sodium valproate 2:22 (registered: available)
�Phenytoin 24:24(registered: available)
�Sodium valproate : Hungary, Norway
�No Phenytoin : Russia
Intravenous benzodiazepine �First line
�DZP 66%
�LOR 29.5%
�MID 4.5%
�Second line
�DZP 26%
�LOR 18%
�MID 56%
Intravenous AED after BZP
43.516VPA
2818PB
2.523FOS
2643PHT
Second line(%)First line (%)
Anesthetic agent in RSE
1428Midazolam
3023.5Propofol
148.5Phenobarb
4240Thiopental
Second line (%)First line (%)
New generation of anticonvulsant �Non-GABAergic mechanisms
�Topiramate
�Levetiracetam
�Blockade of NMDA receptor
�MK-801
Newer therapy � IV VPA is another choice for treatment in elderly
�Loading dose 15 mg/kg @ 70 mg/kg
�Safety and tolerability of rapid infusion rate
�Low risk of hypotension,
respiratory depression sedative
VPA for SE in Srinagarind hospitalVPA for SE in Srinagarind hospital
�� First line drug 41%First line drug 41%
�� Second line drug 54.5%Second line drug 54.5%
��Third line drug 4.5%Third line drug 4.5%
��Dosage 15Dosage 15--25 mg/kg/dose, mean 16.8225 mg/kg/dose, mean 16.82
��Total dose/day 750Total dose/day 750--2700 mg, mean 10252700 mg, mean 1025Somsak Tiamkao,et al 2007
Outcome of seizure controlOutcome of seizure control
��Recovery to sameRecovery to same previous previous
neurological deficit 14%neurological deficit 14%Somsak Tiamkao,et al 2007
Newer therapy �IV levetiracetam, July 2006 available
�1000 @ 6000 mg
�23% respond (3/13)
�38% undetermine
�31% no respond
Newer therapy in RSE �Topiramate nasogastric
�Ettectvie dose 300 @ 1600 mg/day
�Most of cases : CPSE
Table 1. Classification of SETable 1. Classification of SE
1. NCSE occurring in the neonatal and infantile epilepsy syndrom1. NCSE occurring in the neonatal and infantile epilepsy syndromeses
1a. 1a. OhtaharaOhtahara syndromesyndrome
1b. West syndrome1b. West syndrome
1c. Severe 1c. Severe myoclonicmyoclonic encephalopathy of infancy (SMEI; encephalopathy of infancy (SMEI; DravetDravet syndrome)syndrome)
1d. NCSE in other forms of neonatal or infantile epilepsy1d. NCSE in other forms of neonatal or infantile epilepsy
2. NCSE occurring only in childhood2. NCSE occurring only in childhood
2a. NCSE in early2a. NCSE in early--onset benign childhood occipital epilepsy (Panayiotopoulos syndronset benign childhood occipital epilepsy (Panayiotopoulos syndrome)ome)
2b. NCSE in other forms of childhood epileptic 2b. NCSE in other forms of childhood epileptic encephalopathiesencephalopathies, syndromes, and etiologies , syndromes, and etiologies
(e.g., Ring chromosome 20, (e.g., Ring chromosome 20, AngelmanAngelman syndrome, syndrome, RettRett syndrome, syndrome, myoclonicmyoclonic--astaticastatic epilepsy, epilepsy,
other childhood other childhood myoclonicmyoclonic encephalopathiesencephalopathies))
2c. Electrical status epilepticus in slow wave sleep (ESES)2c. Electrical status epilepticus in slow wave sleep (ESES)
3. Convulsive SE occurring only in childhood3. Convulsive SE occurring only in childhood
3a. Febrile SE3a. Febrile SE
4. NCSE occurring in both childhood and adult life with epilepti4. NCSE occurring in both childhood and adult life with epileptic encephalopathyc encephalopathy
4a. NCSE in the Lennox4a. NCSE in the Lennox--GastautGastaut syndromesyndrome
i. Atypical absence SEi. Atypical absence SE
ii. Tonic SEii. Tonic SE
4b. Other forms of NCSE in patients with learning disability or 4b. Other forms of NCSE in patients with learning disability or disturbed cerebral development disturbed cerebral development
(cryptogenic or symptomatic) without epileptic encephalopathy(cryptogenic or symptomatic) without epileptic encephalopathy
4c. Typical absence SE in idiopathic generalized epilepsy4c. Typical absence SE in idiopathic generalized epilepsy
Table 1. Classification of SETable 1. Classification of SE
4d. Complex partial SE:4d. Complex partial SE:
i. Limbici. Limbic
ii. ii. NonlimbicNonlimbic
4e. NCSE in the 4e. NCSE in the postictalpostictal phase of tonicphase of tonic––clonic seizuresclonic seizures
4f. Subtle SE (4f. Subtle SE (myoclonicmyoclonic SE occurring in the late stage of convulsive SE)SE occurring in the late stage of convulsive SE)
4g. Aura continua [with: (i) sensory, (ii) special sensory, (iii4g. Aura continua [with: (i) sensory, (ii) special sensory, (iii) autonomic, (iv) cognitive ) autonomic, (iv) cognitive
symptoms]symptoms]
5. Convulsive forms of SE occurring in childhood and adult life5. Convulsive forms of SE occurring in childhood and adult life
5a. Tonic5a. Tonic––clonic status epilepticusclonic status epilepticus
5b. Epilepsia partialis continua (EPC; simple partial motor SE)5b. Epilepsia partialis continua (EPC; simple partial motor SE)
5c. 5c. MyoclonicMyoclonic SESE
6. NCSE occurring in late adult life6. NCSE occurring in late adult life
6a. De novo absence SE of late onset6a. De novo absence SE of late onset
7. Boundary 7. Boundary syndromessyndromesaa
7a. Some cases of epileptic encephalopathy7a. Some cases of epileptic encephalopathy
7b. Some cases of coma due to acute brain injury with 7b. Some cases of coma due to acute brain injury with epileptiformepileptiform EEG changesEEG changes
7c. Some cases of epileptic behavioral disturbance or psychosis7c. Some cases of epileptic behavioral disturbance or psychosis
7d. Some cases of drug induced or metabolic confusional state wi7d. Some cases of drug induced or metabolic confusional state with th epileptiformepileptiform EEG changesEEG changes
aaBoundaryBoundary syndromes are defined as cases in which it is not clear to whatsyndromes are defined as cases in which it is not clear to what extent the extent the
continuous continuous epileptiformepileptiform electrographic abnormalities are contributing to the clinical ielectrographic abnormalities are contributing to the clinical impairment.mpairment.
Status epilepticus : SEStatus epilepticus : SE
• Non-convulsive SE : NCSE
- NCSE in neonatal, childhood, adult
- NCSE : absence, CPS, subtle
••Convulsive SE : CSEConvulsive SE : CSE
- CSE in childhood, adult
- CSE : tonic-clonic, myoclonic, EPC
PrePre--hospital managementhospital management
�� Prognosis of SE related with time to controlPrognosis of SE related with time to control
�� Success rate to control seizure related early treatmentSuccess rate to control seizure related early treatment
�� Mortality rate related success rate of seizure controlMortality rate related success rate of seizure control
�� PrePre--hospital treatment is very importanthospital treatment is very important
�� IV or rectal benzodiazepineIV or rectal benzodiazepine
�� BuccalBuccal or intranasal or intranasal midazolammidazolam
Protocol for in-hospital treatment of tonic-clonic SE
Stage 1 : stage of early status (0 - 10/30 min)
Stage 2 : stage of established status (10/30 – 60/90 min)
Stage 3 : stage of refractory status (> 60/90 min)
Stage 1 : early status (0 - 10/30 min)
- Lorazepam : 4 mg IV bolus
(can be replaced once 5-10 min)
- If seizures continue after 30 min
Drug used in the stage early tonicDrug used in the stage early tonic--clonic SEclonic SE
Route of administrationRoute of administration Adult doseAdult dose
- Phenobarbital : IV infusion 10 mg/kg at a maximum
rate of 100 mg/min
- Phenytoin : IV infusion 15 mg/kg at a maximum rate
50 mg/min
- Fosphenytoin : IV infusion 15 mg/kg at a maximum
rate 50 mg/min
- Valproate : IV infusion 25 mg/kg at 3-6 mg/kg/min
- Levetiracetam : IV bolus 2000 – 4000 mg
New PracticeNew Practice
34
Stroke in ThailandStroke in Thailand
� Bangkok metropolis (1983) = 690 : 100,000 age over 20
(Viriyavejakul A, et al. 6th Excerpta Medical No.22; 1983: 10)
� Stroke in the elderly (1998); overall 1.12%
Central 1.99 North 0.6
South 1.5 Northeast 0.6
(Viriyavejakul A, et al. J Med Assoc Thai 1998; 81: 497-505)
�Thai Epidemiology Stroke Study (TES Study 2004): Stroke in age 45-80 years = 2.46%
Prevalence
CINP Asia pacific Regional Meetng March 14-17, 2006, Pattaya, Thailand Abstracts P54-55
35
Secondary
Prevention:
Antiplatelets
therapy
ASA for Secondary Prevention
Dipyridamole plus ASA and ASA alone: ESPS 2
38
CClopidogrellopidogrel versus versus AASA in SA in PPatients at atients at RRisk of isk of IIschemic schemic EEventsventsObjectiveObjectiveObjectiveObjective
- To assess the relative efficacy of Clopidogrel and ASA in
reducing the incidence of ischemic stroke, MI, Vascular death
among patients who had survived a recent ischemic stroke,
recent MI, or had symptomatic atherosclerotic peripheral arterial
disease
- To assess the relative safety and tolerability of Clopidogrel
Efficacy of Clopidogrel vs Aspirin in MI, Efficacy of Clopidogrel vs Aspirin in MI, Ischemic Stroke, or Vascular Death Ischemic Stroke, or Vascular Death (N=19,185)(N=19,185)11
Diener H-C et al for the MATCH Investigators. Lancet. 2004;364:331-337.
Patient Population
▪ Patients with recent TIA
or IS, and at high risk for
recurrent events
� Previous IS, MI,
angina, DM, or
symptomatic PAD
Patient Population
▪ Patients with recent TIA
or IS, and at high risk for
recurrent events
� Previous IS, MI,
angina, DM, or
symptomatic PAD
Primary End Point
▪ First occurrence of MI, IS, vascular
death, or rehospitalization for acute
ischemic event
Primary End Point
▪ First occurrence of MI, IS, vascular
death, or rehospitalization for acute
ischemic event
MATCH
Study DesignStudy Design
44† ITT analysis.
MI=myocardial infarction; IS=ischemic stroke.
Diener H-C et al for the MATCH Investigators. Lancet. 2004;364:331-337.
6.4%†
Overall
Relative Risk
Reduction
P=0.244
Months of Follow-Up
Cu
mu
lati
ve
Ev
en
t R
ate
(%
)
Clopidogrel+ ASA
Clopidogrel+ Placebo
0
4
8
12
16
20
0 3 6 9 12 15 18
N=7,599
Primary End Point: MI, IS, Vascular Death, Primary End Point: MI, IS, Vascular Death, or Rehospitalization for an Acute Ischemic or Rehospitalization for an Acute Ischemic Event Event
Type of Bleeding Events (%)Type of Bleeding Events (%)
73 (2%)
81 (2%)
16 (<1%)
ASA + ASA +
ClopidogrelClopidogrel
(n=3,759)(n=3,759)
1.36 (0.86,1.86)
1.15 (0.59, 1.71)
0.13 (-0.14, 0.40)
% Absolute % Absolute
DifferenceDifference
(95% CI)(95% CI)
<0.0001
PP--valuevalue
Main Safety OutcomesMain Safety Outcomes
* Defined as “Life threatening”: any fatal bleeding event, or a drop in hemoglobin of ≥5g/dL, or significant hypotension with the need for inotropes (hemorrhagic shock), or symptomatic intracranial hemorrhage, or requiring transfusion of ≥4 units of RBC or equivalent amount of whole blood.
† Defined as “Major bleeding”: significantly disabling (with persistent sequelae), or intraocular bleeding leading to significant loss of vision, or requiring transfusion of ≤3 units of RBC or equivalent amount of whole blood.ASA=aspirin; CI=confidence interval.
1. Diener H-C et al for the MATCH Investigators. Cerebrovasc Dis. 2004;17:253-261.2. Diener H-C et al for the MATCH Investigators. Lancet. 2004;364:331-337.
MATCH
Stroke Mortality Rate by Age1
Blood Pressure and Stroke Mortality
Stroke mort al ity rate in each decade o f age vs. usual b lood pressure at the star t of the decade.
A meta-analysis involving 1 mill ion parti cipants in 61 cohort studies to determine the relevance of
blood pressure to risk of disease in patients of di fferent ages.1. Prospective Studies Collaboration. Lancet 2002; 360:1903-1913.
6
Treatment HT and Stroke
PERINDOPRIL PROTECTION AGAINST RECURRENT STROKE STUDY
The firs t randomized trial of ACE
inhibitor-bas e d tre atment in patients
with a his tory of c ere brovas cular
dis e as e
Nea l B, Ma cMa hon S. J Hype rtens . 19 95 ;13:18 69 -1 87 3.
The Losartan I ntervention For Endpoint Reductionin Hypertension Study
An invest igator init iated community-based study in 945
sites in 7 countries enrolling 9,193 patients
Steering Committee Chair/ Vice-Chair B. Dahl?f, D. Devereux
European/ US Coordinators S.E. Kje ldsen, S. Julius
Data and Safety Monitoring Committee Chair J. Kjekshus
Clinical Endpoint Classif ication Committee D. Levy, K. Thygesen
LIFE
Reduction in the Risk of Stroke1
No significant difference in CV death and MI vs. ateno lol. Risk reduction = relative risk vs. atenolol.
• Estimate adjusted for age, sex, race, hypertension, index year, time to cholesterol measurement, SBP and DBP, coronary heart disease, atrialfibrillation, diabetes, tobacco use, and use of statins
Adapted from Tirschwell DL et al. Neurology. 2004;63:1868-1875.
Total Ischemic Stroke (95% CI)
Total Cholesterol (mmol/L)
Total Cholesterol (mg/dL)
4 5 6 7 8
4
3
2
1
0.5
Od
ds R
ati
o (
95
% C
l)
Mea
n v
alu
e o
f lo
west q
uin
tile
150 175 200 225 250 275 300 325
(n=1242)
Statin Therapy Is Statin Therapy Is NotNot Associated With Associated With Increased Risk for Hemorrhagic StrokeIncreased Risk for Hemorrhagic Stroke
Adapted from Amarenco P. et al. Stroke. 2004;35:2902-2909; Yano K et al. Stroke. 1989;20:1460-1465;
Iso H et al. N Engl J Med. 1989;320:904-910.
Favors Statin Favors Control
Trials Odds Ratios (95% Cl)
HPS*
GREACE†
MIRACL‡
KLIS§
LIPIDıı
CAREıı
SSSS*
AFCAPS¶
OVERALL (95% Cl)Heterogeneity
0.90 (0.65–1.22)P=.15
1.00.50.20.05 3.0 10.0
* Simvastatin vs placebo.† Atorvastatin vs usual care.‡ Atorvastatin vs placebo.§ Pravastatin vs conventional treatment.ııPravastatin vs placebo.¶ Lovastatin vs placebo.
Primary PreventionPrimary Prevention
–11*–9*
–27†
–48‡–50
–45
–40
–35
–30
–25
–20
–15
–10
–5
0WOSCOPS ALLHAT-LLT ASCOT-LLA CARDS
Rela
tiv
e R
isk R
ed
ucti
on
fo
r S
tro
ke (
%)
Adapted from Sever PS et al. Lancet. 2003;361:1149-1158; Shepherd J et al. N Engl J Med. 1995;333:1301-1307; ALLHAT
Officers. JAMA. 2002;288:2998-3007; Colhoun HM et al. Lancet. 2004; 364:685-696.
WOSCOPS=West of Scotland Coronary Prevention Study; ALLHAT-LLT=Antihypertensive and Lipd-Lowering Treatment to
*P=NS (pravastatin vs placebo or usual care).†P=.024 (atorvastatin vs placebo).‡P=not reported (atorvastatin vs placebo).
(n=6595)(n=10,355)
(n=10,305)
(n=2841)
Prevention of Stroke in Patients Without Prevention of Stroke in Patients Without Documented Cardiovascular DiseaseDocumented Cardiovascular Disease
.016
.024
.31
.57
P Value
–48*46 (40)28413.9Atorvastatin 10 CARDS
–2437 (35)10,3053.3Atorvastatin 10 ASCOT-LLA
–924 (17)10,3554.8Pravastatin 40 ALLHAT-LLT
–1150 (26)65954.9Pravastatin 40 WOSCOPS
Relative Risk
Reduction
Between-Group Difference in LDL-C
Reduction, mg/dL (%)
Number of Patients
Follow-up, y
Statin Dose, mgTrial
Adapted from Sever PS et al. Lancet. 2003;361:1149-1158; Shepherd J et al. N Engl J Med. 1995;333:1301-1307;ALLHAT Officers. JAMA. 2002;288:2998-3007; Colhoun HM et al. Lancet. 2004;364:685-696; Newman C et al.
Accepted for presentation at the American Heart Asssociation Scientific Sessions 2005; Dallas, TX. November 13-16, 2005.
* 95% CI for the HR = 0.31–0.89.
ASCOTASCOT--LLA: Atorvastatin Lowers Stroke Risk LLA: Atorvastatin Lowers Stroke Risk in Patients With Good Blood Pressure Controlin Patients With Good Blood Pressure Control
ASCOT-LLA = Anglo-Scandinavian Cardiac Outcomes Trial–Lipid-Lowering Arm; HR = hazard ratio.Adapted from Sever PS et al. Lancet. 2003;361:1149-1158.
0
1
2
3
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5
Years
Pro
po
rtio
n o
f P
ati
en
ts (
%)
HR=0.73 (0.56–0.96)
P=.0236
27%
reduction
Atorvastatin 10 mg Number of events 89
Placebo Number of events 121
(n=10,305)
CARDS: Stroke Prevention CARDS: Stroke Prevention in Diabetic Patients Without CHDin Diabetic Patients Without CHD
Adapted from Colhoun HM et al. Lancet. 2004;364:685-696; Newman C et al. Accepted for presentation at
the American Heart Association Scientific Sessions 2005; Dallas, TX. November 13–16, 2005.
(n=2841)
Prevention of Stroke in Patients With Prevention of Stroke in Patients With Documented Cardiovascular DiseaseDocumented Cardiovascular Disease
–30*– 31†
– 19‡
– 25§
+3ıı
– 22ıı
– 47¶
– 13#
– 25**
–50
–45
–40
–35
–30
–25
–20
–15
–10
–5
04S CARE LIPID HPS
PROSPER
KLIS GREACE ALLIANCE TNT
Rela
tiv
e R
isk R
ed
ucti
on
fo
r S
tro
ke (
%)
Adapted from LaRosa JC et al. N Engl J Med. 2005;352:1425-1435; Scandinavian Simvastatin Survival Study Group. Lancet. 1994;344:1383-1389; Sacks FM et al. N Engl J Med. 1996;336:1001-1009; LIPID Study Group. N Engl J Med. 1998;339:1349-1357; HPS Collaborative Group. Lancet. 2002;360:7-22; Shepherd J et al. Lancet. 2002;360:1623-1630; KLIS Study Group. J AtherosclerThromb. 2000;7:110-121; Athyros VG et al. Curr Med Res Opin. 2002;18:220-228; Koren MJ et al. J Am Coll Cardiol. 2004;44:1772-1779.
* P=.024 (simvastatin vs placebo).† P=.03 (pravastatin vs placebo).‡ P=.048 (pravastatin vs placebo).§ P<.0001 (simvastatin vs placebo).ıı P=NS (pravastatin vs placebo or conventional treatment).¶ P=.034 (atorvastatin vs usual care).# P=NS (atorvastatin vs usual care).
**P=.02 (80 mg vs 10 mg atorvastatin).
(n=4444) (n=4159) (n=9014) (n=20,536)
(n=5804)
(n=3853) (n=1600) (n=2442) (n=10,001)
Atorvastatin is not indicated for secondary prevention of CVD.
Stroke Reduction in TNTStroke Reduction in TNT
0 1 2 3 4 5 6
Time (years)
0
0.01
0.02
0.04
0.03
HR = 0.75 (95% CI 0.59, 0.96)P=.02
RRR 25%
Atorvastatin 10 mg (n=5006)
Atorvastatin 80 mg (n=4995)
Pro
po
rtio
n o
f P
ati
en
ts W
ith
Even
t
TNT = Treating to New Targets; RRR = relative risk reduction.
Atorvastatin is not indicated for secondary prevention of CVD.
Adapted from LaRosa JC et al. N Engl J Med. 2005;352:1425-1435.
Statin Therapy for Stroke Prevention Statin Therapy for Stroke Prevention in ACS: MIRACLin ACS: MIRACL
Adapted from Waters DD et al. Circulation. 2002;106:1690-1695.
0
0.5
1
1.5
2
0 4 8 12 16
Time Since Randomization (weeks)
Cu
mu
lati
ve I
ncid
en
ce (
%)
Relative risk = 0.49P=.04
95% CI 0.24–0.98
Atorvastatin (n=1538)
Placebo (n=1548)
Placebo
540 Planned Primary End Points
4732
Patients
• ~200 sites worldwide
• Previously documented stroke or TIA
• No history of CHD
• LDL-C levels ≥100 mg/dL and ≤190 mg/dL
Atorvastatin 80 mg/d
Double-Blind PeriodPopulation
Primary End Point
Time to First Occurrence of a Fatal or Nonfatal Stroke
SPARCL: Study DesignSPARCL: Study Design
TIA= transient ischemic attack.
The SPARCL Investigators. Cerebrovasc Dis. 2003;16:389-395.
SPARCL: SPARCL: Secondary End PointsSecondary End Points
• Time to occurrence of
– Cerebrovascular event (includes TIA)
– Major coronary event, consisting of cardiac death, nonfatal MI, or resuscitated cardiac arrest
– Major cardiovascular event, defined as a major coronary event or fatal or nonfatal stroke
– Any CHD event, defined as an acute coronary event, coronary revascularization procedure, or angina/ischemia requiring emergent hospitalization
– Any revascularization procedure (coronary, carotid, or peripheral)
– Any cardiovascular event (any event except noncardiovascular death)
– All-cause mortality (death from any cause)
The SPARCL Investigators. Cerebrovasc Dis. 2003;16:389-395.
• MI, resuscitated cardiac arrest, or unstable angina
• Absolute and percent changes in serum lipids/lipoproteins
• Stroke impact as measured by
– Modified Rankin Scale (MRS) (handicap)
– Barthel Index (BI) (disability)
– NIH Stroke Scale (NIHSS) (impairment)
NIH=National Institutes of Health.
The SPARCL Investigators. Cerebrovasc Dis. 2003;16:389-395.
SPARCL: SPARCL: Secondary End Points (contSecondary End Points (cont’’d)d)