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Diagnosis, Evaluation, and
Treatment of Stroke
Fariborz Khorvash, MD
Assistant Professor of Neurology
Topics






Definitions
Evaluation of Suspected Stroke
Evaluation of TIAs
Stroke Prevention
Evaluation & Treatment of Ischemic Stroke
Evaluation & Treatment of Hemorrhagic
Stroke
Case #1



62 year old woman presents after a abrupt onset
of blindness in her left eye while shopping today.
Sx resolved en route to ER via EMS about 20
minutes after they started.
VS Afeb; BP 148/78; P 68
Exam unremarkable in ER
What’s the diagnosis?
Case #2




76 yo male, rehabbing at local NH after recent hip
fx, has abrupt onset of slurred speech and left
arm/leg weakness.
Sx persistent in ER. Pt has no complaints.
VS Afeb; BP 188/96; P 72
Head CT is “negative”
What’s the diagnosis?
Case #3



33 yo woman presents with “worst headache of
her life”, abruptly starting 1 hour ago.
On exam, she is mildly confused, has mild nuchal
rigidity, but no other focal findings
VS Afeb; BP 155/82; HR 58
What’s the diagnosis?
Classification of Stroke

2 broad categories of stroke:
• Ischemia
• Inadequate blood supply (oxygen & nutrients) to an area
of the brain
• Hemorrhage-
• Leakage of blood into the closed cranial cavity
• Direct damage to tissue by compression/edema
Epidemiology of Stroke

Incidence in US

80-90% are ischemic
Male:Female ratio 1.25:1


• ~700K per year (~200K are recurrent)
• Ratio reverses after age 80
Higher rates in Blacks, Hispanics, & Native
Americans
Risk Factors








Heart disease
•
AFib, Valvular Dz, MI, endocarditis
Hypertension
Smoking
Diabetes/Metabolic Syndrome
Dyslipidemia
Pregnancy
Drug Abuse/Meds
Bleeding Disorders/Anticoagulant Use
Ischemic Stroke

Thrombosis
• In situ arterial obstruction
• Arteriosclerosis, dissection, FMD
• Superimposed thrombosis

Embolism
• Arterial obstruction from debris from another
source

Systemic Hypoperfusion
• Circulatory collapse
• Multiorgan involvement
Thrombosis

Large Vessel Disease
•
•


Common & Internal
Carotids
Circle of Willis &
proximal branches
Small Vessel Disease
•
•
Penetrating arteries
“Lacunar Stroke”
“Stuttering” course
Embolism

Cardiac
• Atrial fibrillation
• Heart valves, atrial thrombus, recent MI, dilated
CM, endocarditis, recent CABG

Aortic
Arterial (e.g. carotids)
Other/Unknown

Abrupt onset, rapid improvement


• DVT- “Paradoxical embolus”
Hypoperfusion

Shock

Sx are more diffuse/nonfocal
“Border-zone regions”

• Cardiogenic, septic, hypovolemic
• Cortical blindness
• Stupor
• Proximal Weakness
Hemorrhagic Stroke

Intracerebral
Hemorrhage (ICH)
•
•
•
•
•
Bleeding within the brain
tissue
Forms a hematoma
Growth stopped by
tamponade or leaking
into the ventricles or
CSF
Headache, vomiting,
delirium
Progressive sx
Causes of ICH




HTN
Trauma
Bleeding Disorder
•
•
Inherited
Acquired, i.e. meds
Amyloid




Drug use
•
•
Cocaine
Amphetamines
AVMs
Bleeding into tumor
Vasculitis
Hemorrhagic Stroke

Subarachnoid
Hemorrhage (SAH)
•
•
•
•
Bleeding into CSF on
outer aspect of brain
Quick rise in ICP
Sudden onset headache
in 97%
Aneurysm & AVMs are
most common cause
Differential Diagnosis





Seizure with Todd’s
Paralysis
Syncope
Migraine
Head Trauma
Brain tumor


Metabolic Causes
•
•
•
•
•
Hypoglycemia
Hyponatremia
Intoxication
Uremia/ARF
Hepatic Encephalopathy
Conversion Disorder
Initial Evaluation:Physical Exam

Vital signs

Pulses
Carotid Bruit
Cardiac Exam
Funduscopic exam
Skin exam
Signs of trauma





• Temperature, Pulse, Blood Pressure
Initial Evaluation:Physical Exam

Neurologic Exam
• Level of consciousness/GCS
• Language/Speech
• Cranial nerves
• Vertigo, diplopia, ataxia
• Visual deficits
• Weakness/Paralysis
• Reflexes/ Babinski
Initial Evaluation: Studies

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





CBC with platelets
Electrolytes, Bun, Cr
Glucose
LFTs
PT/PTT
O2 Sat
ECG
Chest XRay







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ESR
Blood Cultures
ANA
Tox screen
Alcohol level
Blood type & cross
Urine/Serum HCG
Hypercoaguability
Profile
Initial Evaluation: Imaging

CT Scan
•
“R/O Bleed”
•
stroke
Early signs (<6 hrs)
• Sensitivity much better after 24 hrs for ischemic
• May indicate worse prognosis
CT Scans of Stroke
Initial Evaluation: Imaging

MRI
•
•
•
T1/T2 images, DWI
Provides immediate
evaluation of ischemia
Not available for
emergency use in many
settings
Further Evaluation: Carotids

Carotid U/S for stenosis
If ASVD, but no stenosis…

If stenosis, consider…

Vertigo & Syncope are not considered
symptomatic

• Risk Factor Modification
• Carotid Endarterectomy
• ?Carotid Stenting
Treatment of Carotid Stenosis
with Symptoms




100% occlusion
•
No treatment
70-99% occlusion
•
If good 5-yr survival & risks <6%, early CEA (within 2
weeks)
50-69%
•
•
If above criteria & male, early CEA
If female, medical mgt
<50%
•
Medical management
Further Evaluation: Echo

Echocardiography indicated for
• Patients who may need anticoagulation
• Atrial fibrillation
• Risk of atrial thrombus
• Recent MI
• Risk for Endocarditis

TEE is more sensitive than TTE, but will it
change management?
Further Evaluation: Intracranial

Not necessary for all patients
Consider…

CTA vs. MRA vs. TCD

• Pts <50 without a clear source
• Pts with recurrent stereotyped TIAs
• Posterior circulation event without cardiac source
• Prior to CEA
Transient Ischemic Attack



Sudden onset of neurologic dysfunction that
lasts less than 24 hrs, brought on by
presumed transient ischemia to a portion of
the brain
May be better to describe as sx <1 hr with no
evidence of infarction
May have infarct even with sx lasting a few
hours (~50% of TIA patients have MRI
evidence of ischemia)
TSI?



Transient Sx Associated with Infarction
No established diagnostic criteria
In one case series, 15% of TSI pts had a
recurrent stroke in-hospital vs. 0% in TIA
group.
Hospitalize for TIAs?



Could consider home if able to expedite
urgent outpatient work-up
AHA does not make a recommendation re:
hospitalization
One study suggested cost-effective if 24-hr
stroke risk is >5%
Risk of Stroke post-TIA



NASCET trial suggested 90-day stroke risk of 20%
with non-retinal TIAs (higher than for true stroke)
2000 JAMA study
•
•
•
5% risk w/in 2 days
11% risk w/in 90 days
Higher risk with age >60, DM, sx >10 min, weakness,
speech impairment
2004 Neurology study: 21% risk of stroke/MI/death
within 1 year of TIA
ABCDs of TIAs
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
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
Age >60 = 1 pt
Blood Pressure >140/90 = 1
Clinical Features
•
•
•
Unilateral weakness = 2
Isolated speech deficit = 1
Other = 0
Duration
•
•
•
>60 minutes = 2
10-59 minutes = 1
<10 minutes = 0
Risk of “early stroke”
Score
≤ 3:
0%
4:
1-9%
5:
12%
6:
24-31%
Secondary Prevention of Stroke



Risk factor modification
Antithrombotic therapy
Anticoagulant therapy
Stroke Prevention: Risk Factors

Hypertension
• Goal <130/80
• SHEP Study, ISH in pts >60
• Dropped SBP from 155 to 143
• 36% reduction in stroke over 4 years
• Pts >80 may not benefit as much & aggressive
•
BP lowering may increase mortality
Diuretic +/- ACEI as 1st line
Stroke Prevention: Risk Factors

Smoking

Diabetes
• Stop it
• Goal A1c <7, i.e. normoglycemic
• Metabolic syndrome
Stroke Prevention: Risk Factors

Dyslipidemia
• Evidence not as strong as may think, but still a
•
good idea, especially given other vascular
disease
SPARCL Study
• Atorvastatin 80 mg/day in pts 1-6 months from CVA/TIA
• Mean LDL reduction 56
• Endpoint was stroke: 16% RRR, but only 2.2% ARR
(NNT ~50)
Stroke Prevention: Risk Factors

Dyslipidemia, continued
• For average-risk patient, goal LDL <100
• For high-risk, goal <70
• Diabetes
• Prior CAD
• Multiple RFs with continued smoking
Stroke Prevention: Risk Factors

Lifestyle Modification

Reduce alcohol intake, especially heavy
drinkers
?Homocysteine

• Weight loss
• Exercise
• Dietary changes
• Consider B12, B6, Folate (MVI doses OK)
Antiplatelet Therapy

Aspirin
• 20-25% reduction in stroke (& MI or other
•
•
•
vascular death)
Standard doses of 81-325 mg as good as higher
doses
81 mg dose just as good and less risk of bleeding
ASA-non-responders?
Antiplatelet Therapy

Clopidogrel (Plavix)
• 8% RRR vs. ASA for stroke/MI/Vasc death
• 5.3% vs. 5.8%: NNT ~200
• All for only $100+/month
• ?2nd-line therapy or ASA-allergic patients
• No increased bleeding vs. ASA, but combo
•
should be avoided
No neutropenia (like ticlopidine)
Antiplatelet Therapy

Dipyridamole
• Alone 50-100 mg TID
• Aggrenox (200mg ER-DP & 25mg ASA) BID
• 2 studies have shown ~3% ARR (NNT 33) over
•
•
ASA alone for stroke prevention
Some guidelines are suggesting this a 1st line
therapy over ASA alone for stroke prevention
Cost >$100/month
Anticoagulant Therapy

Warfarin has only been proven effective in
primary prevention of stroke in the setting of
atrial fibrillation
AF is responsible for 1/6th of all strokes in
patients older than 60
Risk reduction

“Low Risk” patients may consider ASA rx


• Warfarin about 3 times as effective as ASA
• Absolute annual risk reduction of ~3%
Risk of AF-Related Stroke
Annual Risk of Stroke
6%
5%
4%
3%
2%
1%
0%
50-59
60-69
70-79
Age
80-89
Risk Stratification for Stroke




Highest Risk: Prior Stroke or TIA
High Risk: Any of the following
• Prior thromboembolism
• Female >75 yo
• SBP >160
• Heart failure/LV dysfunction
Moderate Risk: None of above, but HTN
Low Risk: None of the above, no HTN
Choice of Medication
Risk
Category
Annual Stroke
Risk
NNT
Choice
Highest:
Prior CVA
10%
14
Warfarin
High
6%
33
Warfarin
Moderate
3%
66
Warfarin
Low
1%
>200
Aspirin
Based on SPAF-III Trial, Lancet 1996
Treatment of Ischemic Stroke




Thrombolysis
Blood Pressure Management
Antithrombotic Therapy
Management of Medical Complications
Thrombolysis of Acute Stroke

Time-sensitive
• Studies show that thrombolytics must be given
within 3 hours of symptom onset

Effective
• NINDS- Complete or near-complete recovery at 3
•

months post-event (38% vs. 21%, NNT=6)
No difference in mortality
Harmful
• At least 6% risk of ICH
Thrombolysis of Acute Stroke




Alteplase (tPA)
0.9 mg/kg dose up to 90 mg
• 10% as IV bolus, then 60 min infusion
Multiple exclusion criteria
Obtain informed consent (if possible)
"There is a treatment for your stroke called alteplase that must be given within three
hours after the stroke started. It is a 'clot-buster' drug that can lead to a complete or
near-complete reversal of a stroke in about one of every three patients treated.
However, it has a major risk, since it can cause severe bleeding in the brain in about
one of every 15 patients. If bleeding occurs in the brain, it can be fatal. When used to
treat large numbers of stroke patients, on average the potential benefits of this
treatment outweigh the risks; however, in any individual patient it is a very personal
decision."
Exclusion Criteria for tPA
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Stroke/head trauma <3 mos
Surgery <14 days
GI Bleed <21 days
Any prior ICH
Acute MI or MI < 3 months
LP < 7 days
Arterial puncture @
noncompressible site <7d
Rapidly improving or minor
sx
Seizure with postictal sx

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Sx of SAH, even if CT (-)
BP >185/110
Pregnancy
Active bleeding or trauma
Platelets <100K
Glucose <50, >400
INR >1.7 or elev PTT
Hemorrhage on CT
“Major” infarct on CT
Thrombolysis of Acute Stroke
100
90
100
80
70
60
50
40
30
20
22
10
0
All Stroke
Within 3 hrs
8
No Exclusions
Thrombolytic Treatment

Guidelines for In-Hospital Evaluation
• Physician Evaluation: 10 minutes
• Stroke Team Contact: 15 minutes
• Imaging: 25 minutes
• Interpretation: 45 minutes
• Thrombolysis Started: 60 minutes
• ?Coagulopathy- Don’t wait for labs unless on
Coumadin, Heparin, or Dialysis
Predictors of Success with tPA


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
Early Treatment
Less severe symptoms
Younger Age
Lack of systolic HTN
Normoglycemia
Blood Pressure Management




Blood flow in dilated, post-obstructive blood
vessels is BP-dependent
Aggressive BP lowering can increase
mortality
In one study, a fall in SBP >20 in first 24 hrs
was the most likely factor associated with
neurologic deterioration
This does NOT apply to hemorrhagic stroke
Blood Pressure Management

Do not treat BP unless >220/120, unless

Meds
• Given thrombolytics (goal <180/105)
• Acute coronary syndrome
• Acute heart failure/pulmonary edema
• Aortic Dissection
• Labetalol
• Nitroprusside
• Avoid SA nifedipine
Antithrombotic Therapy

ASA – YES
• IST- ASA 300 mg within 48 hrs
• Reduced 14 day recurrent stroke (NNT=100)
• Reduced nonfatal stroke & death (NNT=100)
• CAST- ASA 160 mg within 48 hrs
• Reduced mortality at 4 weeks (NNT=166)
• Slight increased risk of hemorrhagic stroke
• 2 per 1000 patients (11 ischemic strokes prevented)

Clopidogrel & Dipyridamole not tested
Antithrombotic Therapy

Heparin (UFH or LMWH)
• 2004 review of 23 trials, >23K patients
• No clear benefit over ASA alone
• Reduced recurrent ischemic strokes by 9/1000 patients,
but increased hemorrhagic strokes by same number
• ?Effective in some subsets
• “Stroke-in-evolution” or “Progressive Stroke”
• Many patients show neurologic deterioration in 1st 24 hrs
• No studies effectively define this population or prove a
benefit
Antithrombotic Therapy

Heparin for Atrial Fibrillation
• IST
• No difference between heparin & placebo in
•
•
stroke/death at 2 weeks
Reduction in new ischemic stroke (NNT=38)
Increase in new hemorrhagic stroke (NNH=42)
• Consider in patients with known intra-atrial clot or
•
•
repetitive “showering” sx
If used, no IV bolus
ASA is of benefit, though (as stated before)
Anticoagulant Therapy

Warfarin for Atrial Fibrillation
• Must r/o ICH
• For small infarcts, start when medically stable
• For large infarcts, consider after 2 weeks
• Goal INR 2-3
• Consider ASA as bridging therapy until INR >2
Management of Medical
Complications






Acute Coronary Syndromes/Heart Failure
Infections
•
•
Aspiration pneumonia
UTI
Venous thromboembolism
•
Consider DVT prophylaxis for all patients
•
•
SCDs for pts with bleeds
Heparin or Lovenox SQ for others
Malnutrition/Dehydration (consider Adv Directives)
Decubitus ulcers
Contractures
CONSIDER EARLY MOBILIZATION IN ALL PATIENTS!
Intracerebral Hemorrhage


Accounts for ~8% of all strokes
Presenting sx
• Headache (~50%)
• Seizures (7-9%)
• Delirium/Altered LOC
• Focal neuro sx (depends on area of brain)
Intracerebral Hemorrhage

Mortality 35-50%

Prognosis
• Half of deaths in 1st 24 hours
• Size & location of hemorrhage
• Age
• Glasgow Coma Score
• Comorbid conditions
• Prior antiplatelet/anticoagulant therapy
Treatment of ICH

Neurosurgical ICU
Constant monitoring
Bedrest
Pain control
Reverse coagulopathies

ICP control




• Vitamin K, FFP, Platelets
• Mannitol, Induced Coma, Hyperventilation
Treatment of ICH


Blood pressure management
Surgery
• Indicated for cerebellar bleeds >3 cm
• Supratentorial bleeds more controversial
• Depends on size, location, LOC, comorbidities

rFVIIa therapy
• Small studies show promise, but concern for prothrombotic effects
Subarachnoid Hemorrhage

High mortality rate, ~50%

Prognostic Factors
• 10% pre-hospital
• 25% within 24 hrs
• 45% within 30 days
• Level of consciousness
• Age
• Amount of blood on CT
Subarachnoid Hemorrhage

Diagnosis
• Head CT
• (+) in 92% of cases w/in 24 hrs
• Most sensitive in first 12 hrs
• Lumbar Puncture
• Not necessary for diagnosis but consider if clinical
•
•
suspicion & negative head CT
Elevated pressure & RBCs
Xanthochromia: pink/yellow tint due to RBC breakdown
Treatment of SAH








Neurosurgical ICU
Constant monitoring
Bedrest
Pain control
Reverse coagulopathies
DVT Prophylaxis (SCDs)
Blood Pressure Management
Management of Aneurysms/AVMs