2001 Stroke Odyssey (review) What do we know? When did we know it?
Stroke: Some Well-Established Rules of the Game
. In 1994 the annual economic costs of stroke due to health care expenses and lost productivity are estimated to be nearly $20 billion. 1
Decreasing Stroke Incidence
Identified arterial lesion
Atrial fibrillation (Framingham)
Past vascular event
Coronary Artery Disease
Modifiable stroke risks
Heart disease (Afib)
FRAMINGHAM ATRIAL FIBRILLATION
Quadruples stroke risk
Doubles Stroke Death Rate
Surgical M/M < 6%
TIAs in the past 6 months
Carotid stenosis > or = 70%
Stroke within 6 months and a carotid stenosis > or = 70%
TIAs + stenosis 50% to 69%
Progressive stroke and a stenosis > or = 70%
Mild or moderate stroke in the past 6 months and a stenosis 50% to 69%
1662 Patients, multiple centers
>60% carotid stenosis
<3% perioperative M/M
5 year risk of stroke/death
5.1% surgical patients
11% medical group
53% aggregate risk reduction
Known Carotid Lesion
Especially where heparin is ineffective
Surgical Management. For the patient who arrives with a continuing neurologic deficit due to cerebral ischemia, evidence for the efficacy of immediate surgical removal of an arterial obstruction is controversial and unproven. Several anecdotal reports support considering emergency surgery in selected cases.
Urgent carotid endarterectomy for recent ischemic stroke is generally limited to :
Stroke in evolution with a minimal fixed neurologic deficit
Moderately severe neurologic deficit of abrupt onset when the surgery can be completed within the first 3 hours after the onset of deficit
CCT without evidence of hemorrhagic transformation of an infarct or edema.
Preliminary results from the International Stroke trial suggest that aspirin use within 24 hours of stroke onset is associated with a reduction of recurrent ischemic stroke from 2.7% to 3.5%.
Other Antiplatelet agents
High dose Aspirin for aspirin failure?
ADP induced platelet-fibrinogen binding
Neutropenia and TTP
Hematologic monitoring required
TASS: Reduction in stroke risk compared to ASA was 34% for 5 yrs. In pts w/prev event
CATS: Reduction after stroke 33 over 3 years compared to placebo
Easy and safe
CAPRIE* No more effective than ASA in prevention of stroke.
ASA intolerant ? ASA failure?
*Clop v Asa in pts at risk for ischemic events-19000 pts
Early admission of most patients to a unit that has a specialized interest in the treatment of stroke is strongly recommended (Level of Evidence I, Grade A Recommendation). A team of physicians, nurses, and technicians that is devoted to the early care of patients with stroke should be assembled. Rapid transfer of a patient to a hospital that has a specialized stroke care unit is strongly recommended.
Stroke units: State of the Art
Admission to a unit that is dedicated to the care of stroke patients helps to reduce mortality and morbidity.
In addition to obtaining prompt neurological consultation for the high-risk TIA situations patients with particularly long or neurologically severe or frequent episodes should also have an urgent neurological consultation.
Binary decision: Heparinize or not
Major concern has seemed to be whether or not to heparinize.
There is no large clinical trial in the literature comparing i.v. heparin as traditionally administered to placebo
International Stroke Trial: compared s.q. heparin at comparable doses to asa and neither in 19435 patients: result: heparin was not beneficial
TOAST trial: indicated no benefit for a LMW heparinoid in stroke (ORG 10172)
May have some benefit for some subgroup(s?) of patients.
Heparin: candidates may include:
Patients with crescendo or multiple T.I.A.’s in specific vascular distribution
Doppler or other evidence of subtotal or near total occlusion
Stenosis of intracranial carotid or mca
Basilar distribution strokes
CT of the brain without contrast
Lateral cervical spine x-ray (if the patient is comatose or has cervical spine pain or tenderness)
Lumbar puncture (if subarachnoid hemorrhage is suspected and CT is negative)
Electroencephalogram (if seizures are suspected)
Recommeded Tests cont’d :Bloods
Complete blood count
Electrolytes Blood, glucose
Arterial blood gas levels (if hypoxia is suspected)
Renal and hepatic chemical analyses
Ultrasonography. extracranial Doppler ultrasonography and duplex scanning, with or without color-flow imaging, can be useful noninvasive techniques to screen for internal carotid artery stenosis.
Differentiation between stenosis of 95% and complete occlusion is usually not possible but demonstration of stenosis >60% is quite accurate
Trans-esophageal echo (TEE)
stroke related seizure
question of stroke vs encephalopathy
episodic events thought not to be TIA’s
Special blood work in non-atherogenic stroke
Angiogram in selected cases
Phospholipid (cardiolipin) antibody profile
Consider inflammatory/col vasc disease
Antithrombin III, protein C & S and C resistence
There is general agreement to recommend treatment of the sources of fever and use of antipyretics to control an elevated body temperature (Levels of Evidence III through V, Grade C). There are insufficient clinical data about the use of hypothermia to recommend this therapy.
Fever: rationale for treatment
Preliminary data shows that fever worsens prognosis for stroke patients
Fever increases cerebral substrate and oxygen consumption, a factor that may be critical in ischemic brain.
Treat any temperature elevations
Data is not in as to whether hypothermia may be protective
There is general agreement to recommend control of hypoglycemia or hyperglycemia after stroke (Levels of Evidence III through V, Grade C).
Hypo-osmolar fluids, such as 5% dextrose in water, may worsen edema.
D51/2NS or NS recommended
Mannitol (0.25 to 0.5 g/kg IV) given over 20 minutes rapidly lowers intracranial pressure and can be given every 6 hours. 57 The usual maximum daily dose is 2 g/kg. 57
Hyperventilation & ICP
Hyperventilation is an emergency measure that acts almost immediately; a reduction of the pCO2by 5 to 10 mm Hg lowers intracranial pressure by 25% to 30%.
STEROIDS IN STROKE
No improvement in clinical trials.
Infection more common
“not indicated in the emergent management of cerebral edema complicating ischemic stroke.”
An elevation of blood pressure may be a compensatory response to maintain cerebral perfusion pressure in a patient with a markedly elevated intracranial pressure. In such instances antihypertensive agents, particularly those that induce cerebral vasodilation, are avoided.
In general, antihypertensive drugs should be withheld unless the calculated mean blood pressure (the sum of the systolic pressure plus double the diastolic pressure, divided by three) is greater than 130 mm Hg or the systolic blood pressure is greater than 220 mm Hg
Elevated blood pressure usually declines spontaneously over the first 24 hours after stroke onset and overzealous use of a calcium antagonist and other antihypertensive drugs should be avoided because they can further reduce cerebral perfusion.
Minimal or no treatment of mildly to moderately elevated blood pressure during the first hours of ischemic stroke is supported by human and animal data. Because of the partial or complete loss of autoregulation in ischemic brain, cerebral blood flow in these regions depends almost entirely on the arterial blood pressure to maintain cerebral perfusion
Blood Pressure (preferred agents)
Preferred agents include low doses of intravenous labetalol or low doses of enalapril. Some investigators have also used small patches of nitropaste
Blood Pressure and hemorrhage
Control of elevated blood pressure has never been shown to decrease the risk of ongoing or recurrent bleeding in patients with intracerebral hemorrhage.
Recommend treatment of moderate and severe elevations of blood pressure (systolic blood pressure of greater than 180 mm Hg or mean arterial pressure of greater than 130 mm Hg).
Pharmacologic lowering of elevated blood pressure is recommended in patients with ischemic stroke who have a suspected aortic dissection or myocardial infarction to avoid worsening these conditions.
In stuporous or comatose patients it is important to maintain normal cerebral perfusion pressure, which could be compromised by aggressively lowering systemic arterial pressure.
CT Scan -1
CCT usually does not show changes of cerebral infarction for 24 to 48 hours after onset.
Subtle signs of ischemia may appear within 3 hours.
CT -2 signs of infarction
Signs include hypodensity in the region of the suspected ischemia, blurring of cortical gray and white matter differentiation, and loss of definition of gray and white matter in the basal ganglia.
Signs of cerebral edema include a local mass effect, ventricular distortion with midline shift and compression, and decreased size of adjacent cortical sulci and subarachnoid cisterns.
CT 3: Infarction
Large infarction produces edema more quickly, causing a localized mass effect.
The use of contrast media enhancement does not result in an earlier diagnosis
Spontaneous opacification of cerebral vessels may be a sign of poor prognosis (= thrombosis
Left hemisphere stroke
Stroke w/ spch arrest
Medical Management: Heparin
Stroke in progress
High grade stenosis in a vascular territory appropriate to the symptoms
Cardioembolic cause w/ hi risk recurrence
Attacks occurring with increasing frequency (“crescendo” TIA).
In these instances current practice suggests anticoagulant therapy, initially with heparin and continuing with warfarin if a mechanism requiring long term anticoagulation is found. There are no firm data to support this treatment's efficacy
No studies of evolving stroke have shown anticoagulants reduce tissue injury. The use of heparin initially and continued with warfarin is based on the historical observation that, if untreated, this syndrome often results in a poor neurologic outcome.
It is recommended that, after initial therapy, bolus injections of heparin be avoided because of reported symptomatic hemorrhagic transformation.
an initial dose of 5000 to 10,000 U?? and followed by continuous infusion of 10 to 20 U/kg/hr to keep the PTT at 50 to 60 seconds or about 1.5 to 2.0 times the patient's pretreatment PTT.
Low molecular heparin
One study of low molecular weight heparin administered within 48 hours of symptom onset showed a decrease in death or dependency 6 months after stroke.
Biller J, et al. A dose escalation study of Org 10172 (low molecular weight heparinoid) in the treatment of acute cerebral infarction. Neurology. 1989;39:262-265.
Low Mol Wgt Heparin
Studies indicate Variable Effectiveness
Jury is Still Out
Low-molecular-weight heparin for the treatment of acute ischemic stroke [see comments]CM: Kay-R; Wong-KS; et al. N-Engl-J-Med. 1995 Dec 14; 333(24): 1588-93
The brain infarctions most prone to bleeding are usually the result of emboli, are large, and are those showing hypodensity or hemorrhagic transformation on an early CCT.
SURGERY FOR ICH
The best candidates for surgery may be patients with moderate to large hematomas who are still awake. At the present time there is no definitive proof of the value of early evacuation of deep intracranial hematomas.
Prophylactic administration of heparin or low-molecular-weight heparins or heparinoids to prevent deep vein thrombosis is strongly recommended for immobilized patients
Stockings and mechanical motion devices
Excitotoxin, glutamate, glycine
SOD, free radicals
neuroptosis=mech’nism in each cell of cell death
Ion channel of NMDA- Aptiganel (Cerestat)
Antagonists of the glutamate site Selfotel
Glycine site- ACEA 1021, GV150526
Antagonists of polyamine site -Eliprodil
Sodium channel blockade-Lubeluzole, 619C89).
Siesjo BK. Calcium and ischemic brain damage. Eur Neurol. 1986;24:45-56.
Gelmers HJ, Gorter K, deWeerdt CJ, Wiezer HJA. A controlled trial of nimodipine in acute ischemic stroke. N Engl J Med. 1988;318:203-207.
Early mobilization and measures to prevent the subacute complications of stroke (aspiration, malnutrition, pneumonia, deep vein thrombosis, pulmonary embolism, decubitus ulcers, contractures, and joint abnormalities) are strongly recommended
CEREBELLAR HEM. AND INFARCTION
Hemorrhage or an infarction can rapidly produce critical brainstem compression and threaten the life of the patient. They are often surgical emergencies.
CEREBELLAR HEM & INFARCTION
Surgical removal of an edematous cerebellum or a cerebellar hematoma may be life-saving and the residual neurologic deficit negligible
Relatively young patients with severe hemispheric stroke, particularly in the nondominant hemisphere, who are progressively deteriorating because of severe brain edema refractory to maximal medical management may be considered for a decompressive hemicraniectomy.
Consider it early to prevent pneumonia
NPO for patients with significant deficit or those at risk for progression
Speech Therapy Evaluation
Water swallow test
DePippo KL, Holas MA, Reding MJ. Validation of the 3 oz. water swallow test for aspiration following stroke. Arch Neurol. 1992;49:1259-1261 .
If a 3-hour window of treatment can be met, thrombolytic therapy with intravenous t-PA can be beneficial for each of the major categories of ischemic stroke: atherothrombotic/atheroembolic, cardioembolic, and small vessel occlusive (lacunar) stroke
recommended a dose of 0.9 mg/kg (maximum 90 mg). The initial 10% is given as an intravenous bolus over one minute and the remaining t-PA infused over 60 minutes
T-PA for Acute Ischemic Stroke
624 patients randomized
3 hour window
at three mos. 30% less likely to have minimal or no disability
6.4% risk of hemorrhage
No change in mortality at 6 mos
In 624 patients studied within 3 hours after symptom onset, the chance of a total or near total recovery for a patient in the tissue plasminogen activator (t-PA [Activase]) group was 1.7 times greater than in the placebo group.
NIH Study - 2
All four outcome measures used (Barthel index, modified Rankin scale, Glasgow outcome scale, and the National Institutes of Health Stroke Scale showed a beneficial effect of t-PA at three months.
The National Institute of Neurological Disorders and Stroke re-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. NEJM. 1995; 333:1581-1587
.9 mg/Kg, 10% as bolus of t-PA, 90% over 60 minutes
no anticoags or antiplatelet agents for 24 hrs
maintain bp in normal range
repeat CT in 24 hours and 7-10 if ICH suspected
Ischemic stroke with clearly defined time of onset
Clear deficit measurable on NIHSS
Baseline CT negative for hemorrhage
CVA or head injury in past 3 mos
major surgery within past 14 days
History of ICH
rapidly improving or minor symptoms
symptoms suggesting SAH
HEMORRHAGE AND t-PA
Symptomatic intracranial hemorrhage (ICH) occurred in 6.4% of patients treated with t-PA in the NINDS-sponsored study
During cerebral angiography it has been found that it is possible to thread a fine guidewire and infusion catheter to and through an intravascular clot. It has been effective in the internal carotid artery or its branches and in the vertebrobasilar system for administration of intra-arterial thrombolytic agents to restore blood flow.
Sasaki O, Takeuchi S, Koike T, et al. Fibrinolytic therapy for acute embolic stroke: intravenous, intracarotid and intraarterial local approaches. Neurosurgery. 1995; 36:246-253
If thrombolytic therapy is not feasible, treatment should be carefully evaluated by repeated neurologic examination over the next few hours to be sure the stroke is not progressing. If there is progression, anticoagulants may be considered after a repeat CCT to be certain the cause is progression and not hemorrhage.
Carotid stenoses in the high cervical region and vertebral stenoses have been successfully dilated using intravascular inflatable balloons angioplasty and stenting