SHAZIA KHAN Assistant Prof. of Clinical Medicine. USC

Transcription

1 SHAZIA KHAN Assistant Prof. of Clinical Medicine. USC

2 Learning objectives Review the pathophysiology, signs and symptoms of ischemic stroke. Familiarize our selves with the signs and symptoms. Use of ABCD, NIHSS. Primary and Secondary Prevention.

3 Epidemiology Incidence of stroke in USA is 795,000/ year in the United States of America Stroke kills about 140,000 Americans each year that s 1 out of every 20 deaths Stroke: 4 th killer in USA (used to be third) 2 nd killer in world

4 Definition Acute brain injury caused by occlusion or rupture of a blood vessel in the brain. Ischemic stroke: Reduced blood supply to a region of the brain resulting in brain ischemic and neuronal death (87%) Hemorrhagic stroke: Primary brain hemorrhage resulting in compression of normal brain tissue (13%)

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7 Anterior and Posterior Cerebral Arterial Circulation Internal carotid arteries and their branches: supply the anterior circulation Vertebral arteries and the basilar artery (and their branches): supply the posterior cerebral circulation

8 Hemorrhagic Stroke INTRACEREBRAL HEMORRHAGE. More common in Asian countries. Two distinct pathologies exist 1. Basal Ganglia Cerebellum 2. Lobar likely secondary to Cerebral myloid angiopathy. Higher Mortality then Ischemic Stroke.

9 Sub Arachnoid Hemorrhage. Likely from rupture of a saccular aneurysm Rare causes are AVM, Mycotic Aneurysm. Diagnosis : Ct head, Lumbar puncture. LP: Erythrocytes and Xanthochromia.

10 Mechanism of Ischemic Stroke and Transient Ischemic Attacks Atherosclerotic cerebrovascular disease (20%): 1. Extracranial carotid or vertebral artery disease 2. Intracranial cerbrovascular disease Penetrating small arterial disease (25%) Cardiogenic source (20%): 1. Atrial fibrillation & other arrythmias 2. Myocardial infarction 3. Valvular disease 4. Ventricular thrombi 5. Aortic plaque Unusual causes (<5%): dissection, migraine, illicit drugs, vasculitis, venous strokes, hypercoagulability, Cryptogenic source 30 %(no mechanism identified)

11 Transient Ischemic attack (TIA) Definition: duration of transient neurologic symptoms lasting less than 1 hour Transient reduction of blood flow to a region in brain in the absence of evidence of infarction on brain imaging Mechanisms for TIA similar as for ischemic stroke Reconstitution of flow to the hypoperfused region hence the resolution of symptoms Significance of TIAs is increased risk of stroke after a TIA specifically early on after a TIA Prompt evaluation of mechanism and appropriate treatment

12 Transient Ischemic Stroke ABCD2 score Age 60 years: score 1 HTN ( 140/90): score 1 Diabetes mellitus: score 1 TIA duration: min (score 1); 60min (score2) Clinical: Hemiparesis with or without speech deficit (score 2); speech impairment without hemiparesis (score 1).

13 Higher ABCD2 scores are associated with greater risk of stroke during the 2, 7, 30, and 90 days Definite admission for ABCD2 score of 4 Caution to work the TIA patients urgently to address underlying source and treat appropriately

14 STROKE Signs and Symptoms

15 Acute Onset of Any of the Below Symptoms Hemiparesis or quadriparesis ( latter in basilar occlusion) Facial weakness Aphasia Dysarthria Limb/truncal/gait ataxia +/- nausea & vomiting Vertigo, tinnitus, hearing deficit (posterior circ.) Impairment of vision in homonymous visual field defect Monocular impairment of vision (amaurosis fugax) Diplopia Impairment or loss of consciousness or confusion Hemineglect (visual or sensory) Headache (non-specific symptom) Adopted from AHA New onset seizure (3-4%) or acute new movement abnormality

16 Differential Diagnosis Space occupying lesion (tumor, infection/ abscess, Epidural, Subdural Hematomas) Subarachnoid hemorrhage Hypoglycemia Migraine Syncope Labyrinthine disorders Seizures

17 NIH Stroke Scale Designed for acute stroke trials. Quick (5-10 min) & reproducible. Requires speech/language cards & safety pin. Quantifies clinical stroke deficit: o < 4 = mild stroke o > 15 = poor prognosis if no treatment o > 22 = risk for ICH

18 Code Stroke

19 Evaluation &Treatment

20 Initial Evaluation and Management Urgent transport to the nearest stroke receiving hospital via 911 system Notification of the destination ED Alert ED of the need for urgent CT

21 Initial Evaluation STAT CT brain ABC.Pulse ox. IV c-xray CBC, Platelet, PT, PTT Accucheck & blood glucose, serum electrolytes Cardiac markers, ABG s Blood alcohol level, Toxicology screen, Pregnancy test

22 Initial Evaluation and Rx IV line: IVF bolus/hydration 2 nd IV line in anticipation of IV t-pa Non contrast CT: rule out hemorrhage Usually later but may need stat: Ct angiogram,mri perfusion MRI and MR-a, CT-a brain and cerebral vessels

23 Acute Therapy NINDS Stroke Study group: randomized placebo controlled clinical trial (N Engl J Med 1995) Intravenous recombinant tissue Plasminogen Activator (IV t-pa) given within 3 hour of symptoms onset in acute ischemic strokes N=624 patients (IV t-pa or placebo):dose 0.9mg/kg, 10% IV bolus, then the remainder is IV drip over 1 hour

24 NINDS Stroke Study Patients in the t-pa arm were at least 30% more likely to have minimal or no disability at 3 months Symptomatic Intracranial Hemorrhage was 6.4% in the t-pa group versus 0.6% in the placebo arm Mortality at 3 months was not statistically different between t-pa and placebo The benefit of IV t-pa was sustained at one year follow up The earlier the treatment the better the outcome

25 ECASS III Trial ECASS 3: N Eng J Med sept 2008 This study showed persistent benefit of IV t-pa up to 4.5 hours from onset in acute ischemic stroke Excluded patients>80 years of age Excluded patients with severe deficit NIHSS>25 Excluded patients who have combination of previous stroke and diabetes Excluded patients who were on anticoagulation regardless of the INR

26 Intravenous t-pa Standard FDA approved therapy for acute stroke Rx Window of treatment has been prolonged after ECASSIII to 4.5 hours Not all patients are eligible for the 3 to 4.5 hour window

27 Inclusion Criteria for IV t-pa Ischemic Stroke clinically Persistent neurologic deficit beyond an isolated sensory deficit / ataxia CT brain: No Blood Initiation of Rx within 3 hours

28 Exclusion Criteria Onset to treatment >3 hr (NINDS) Rapid improvement Blood on CT Oral anticoagulant & PT>15 sec, INR>1.7 Heparin (last 48 hr) & increased PTT Platelet<100,000 SBP >220 or DBP>110 Aggressive treatment of b.p. Stroke or head trauma (3 months) Major surgery (2 wks)

29 Cont d Exclusion Criteria Prior ICH GI tract/ Urinary bleed (14 d) Seizure at onset Signs & Sx s of SAH Non-compressible site of arterial puncture (7d)

30 Additional Exclusions for the 3 to 4.5 Age 80 years Hour Any use of anticoagulant regardless of the PT/PTT NIHSS 25 Coexistent history of stroke and diabetes mellitus

31 Management Post Thrombolysis Admit to ICU BP monitoring (Q 15 m x2 h, Q 30 m x6 h, Q 1 h x16 h) Treat SBP for a goal <185 and DBP<110 No anticoagulants, no anti-platelet for 1 st 24 hr post t-pa

32 Cont d Management of Patients Post-thrombolysis Worsening of neurologic state---ct brain ICH---Neurosurgery consult Possible surgical intervention Preferably: no foley or NG for 2 hr > t-pa (t1/2-t-pa = 8-12 min)

33 Endovascular Rx Mechanical thrombectomy: Add on-rx to the standard FDA approved stroke Rx IV t-pa in cerebral infarction with proximal large arterial occlusion within 6 hours from onset. DAWN and DEFUSE3 Trials Select patients LVO treated up to 24 hours based on CT perfusion selection.

34 What do we do given this data? 1.All patients eligible for IV t-pa should receive it..quickly! 2.Patients with in 6 hours should recieve a CTA to look for a large vessel occlusion (LVO) 3.If LVO is present, endovascular therapy should occur,even following IV-tPA regardless of perfusion data.

35 4. If the patient has a LVO and presents between 6-24 hours,ct perfusion required and selects patients who should receive endovascular therapy

36 Poor Outcome Predictors in Ischemic Stroke Age Elevated blood sugar Initial NIHSS score which is a measure of the patient s initial deficit Cerebral infarction changes on CT brain

37 Anti platelet therapy Aspirin after 24 hours of Iv t-pa. 160mg 300mg. In patients with minor stroke,treatment for 21 days with dual therapy (aspirin and plavix ) can be beneficial for secondary stroke prevention for a period of 90 days.(chance)

38 Oxygen : >94 % Blood pressure :< 180 /105 Temp <38 Glucose mg/dl DYSPHAGIA SCREEN Nutrition :Enteral diet should be initiated within 7 days DVT Prophylaxis Depression Screen REHAB!!

39 Is Stroke Preventable??

40 Prevention Primary prevention Secondary prevention

41 Primary Prevention Primary prevention starts at the level of the physician playing the role of the primary care and occasionally at the level of the cardiologist and the stroke neurologist Key is identification of underlying risk factors and modification and treatment of modifiable risk factors

42 Primary Prevention Elements Establishing good medical history and family history Identifying the patient s vascular risks including medical illnesses, habits such as smoking and substance use and genetic predisposition through review of significant family history for cardiovascular risk factors and stroke Exam elements which are key: pulse (rate and establishing how regular), blood pressure, carotid auscultation (bruits), cardiac auscultation (murmurs and abnormal rhythm), symmetry and detection of pulses, diabetic peripheral changes

43 Identification of Risk Factors for Stroke Non-modifiable risk factors Modifiable risk factors

44 Modifiable Risk Factors

45 Non-modifiable Risk Factors Age: the risk of stroke doubles with every decade after the age of 55 years Sex: lifetime risk in Male>Female but risk in F>M after age of 80 years Race and ethnicity: Stroke incidence and subtypes: higher in African Americans and Hispanics >Caucasians Stroke related mortality is higher in African American population Asian population has an increased risk of hemorrhagic stroke subtype compared to Caucasians

46 Non-modifiable Risk Factors Genetic Factors Family history: inherited susceptibility, inherited predisposition to risk factors, similar culture and lifestyle Hyperhomocysteinemia:) Inherited coagulopathies: FV Leiden mutations, prothrombin gene mutation PC, PS deficiencies Anticardiolipin antibodies/la are genetic in 10% cases Others CADASIL: Cerebral autosomal dominant arterof iopathy with subcortical infarcts and leukoencephalopathy: NOTCH 3 gene mutation on chromosome 19 Others: Marfan and NF I and II, Fibromuscular dysplasia (FMD), Ehlers-Danlos syndrome IV, polycystic kidney disease Novel genes identified which may have specific associations with large artery stroke

47 Well Documented Modifiable Risk Factors Hypertension Smoking Diabetes Mellitus Carotid disease Cardiac disease: Atrial Fibrillation, Myocardial infarction secondary to coronary artery disease Dyslipidemia or hyperlipidemia (high cholesterol, high LDL, low HDL) Migraine with aura in women Obstructive sleep apnea

48 Less-Documented Potentially Modifiable Risk Factors Obesity Lack of exercise Poor diet Alcohol abuse Hyperhomocysteinemia Illicit drug abuse Hypercoagulopathy Sickle cell disease Estrogen/HR hormonal therapy Inflammation Infection

49 Hypertension

50 Hypertension (HTN) Prevalence in USA is 29%- Improved control of HTN over the years 50% More than 2/3 of patients 65 yrs of age have hypertension Major risk factor for ischemic and hemorrhagic strokes the higher the blood pressure the greater the risk of stroke HTN is undertreated It s prevalence is increasing partly due to increased prevalence of patients who are overweight and obese One of the most important modifiable risk factors for stroke

51 Hypertension Evaluation and Treatment Current Guidelines Regular blood pressure screening Behavioral life style modifications : management of obesity/ weight loss, diet: low salt, encourage vegetables. Reduce red meat (AHA, DASH, Mediterranean diets) Encouragement of exercise Treatment with antihypertensive agents to achieve BP< 140/90 mm Hg

52 Cigarette Smoking Cigarette smoking doubles the risk of ischemic stroke It also increases subarachnoid hemorrhage by 2-4 folds Inconsistent data for parenchymal intracerebral hemorrhage Inconsistent data with second hand smoking Contributes to increased risk of stroke by: Increased thrombus generation in atherosclerotic arteries Increased atherosclerosis

53 Diabetes Mellitus Close to 11% of US population are estimated to have diabetes mellitus Studies have shown that diabetes mellitus increases the risk of stroke fold This increase in stroke risk is related to increased risk of atherosclerosis & increased pro-atherogenic risk factors in diabetic patients

54 Interventions to Reduce Stroke in Diabetes Mellitus?

55 Diabetes Mellitus: Glycemic control? North Manhattan Study: subjects who had diabetes and fasting blood glucose (FBG)> 126 mg/dl had 2.7 fold increase in stroke risk versus no increase in risk if FBG<126 mg/dl 3 clinical trials: ACCORD, ADVANCE, and a trial which enrolled US veterans Failure to demonstrate reduction in stroke in the group of intensive glycemic control ACCORD: halted earlier due to increased all-cause mortality in the intensive-glycemic control group

56 Diabetes mellitus: Glycemic Control Use standard guidelines for glycemic control Avoid lowering of HbA1c<6.5 in patients with cardiovascular disease or the presence of vascular risk factors

57 Diabetes Mellitus and Lipid Altering Rx Clinical evidence of the benefit of statins in stroke risk reduction in diabetic patients No supportive evidence for fibrates in stroke prevention in diabetic patients

58 Use of Aspirin in Primary Prevention of Stroke in Diabetes Mellitus No statistically significant benefit from aspirin in prevention of stroke in diabetes mellitus has been found Use in patients with established carotid disease or coronary artery disease

59 Lipids Modest association of elevated total cholesterol or LDL with increased risk of ischemic stroke Association between low HDL and increased risk of ischemic stroke Relationship between low total cholesterol as well as LDL-C and a higher risk of hemorrhagic stroke

60 ACC/AHA Guidelines for the Treatment of Blood Cholesterol in Primary Prevention Recommendations based on the 10 year risk for cardiovascular disease Shifts away from specific cholesterol goals Estimated risk dictates intensity of statin Rx: high risk mandates high intensity statin Rx Atorvastatin 10 mg is moderate intensity statin Rx and 40 t0 80 mg is high intensity 10 year Risk calculator

61 Statins in Secondary Prevention of Stroke Statin therapy with intense lipid lowering effect is recommended to reduce stroke risk in the population of ischemic stroke and TIA patients (SPARCL) Target LDL-C<70 mg/dl or 50% lowering of baseline LDL May use other agents if patient can not take statins (Niacin, Gemfibrozil) No established benefit in stroke reduction

62 Carotid Endarterectomy Indicated with proven benefit in severe symptomatic extracranial carotid artery disease Symptomatic = clinical or radiologic evidence of stroke in the distribution of that carotid artery Stenting is an alternative in patients who are not eligible for CEA

63 Asymptomatic Carotid Disease

64 Asymptomatic Carotid Artery Disease Increased risk of stroke with carotid artery stenosis Asymptomatic Carotid Artery Study (ACAS) Asymptomatic Carotid Surgery Trial (ACST) Number needed to treat to prevent 1 stroke patient was 40 The low benefit may not justify the risks of carotid revascularization: individualize patients and assess risk factors The annual rate of stroke associated with asymptomatic carotid stenosis has significantly declined with intensive medical management 1% (Statins and antiplatelet Rx)

65 May consider carotid revascularization in severe asymptomatic carotid artery stenosis but with perioperative and surgical risk <3 %

66 Cardioembolic sources of Stroke Cardiac arrhythmias with increased risk of cardiac clots and cardioembolism: atrial fibrillation Coronary artery disease, myocardial infarction/ ischemic cardiomyopathy Valvular heart disease (septic embolism or thromboembolism) Aortic arch atheroma Paradoxical embolism: presence of right to left shunt such as a PFO in the presence of a venous thrombus

67 Atrial Fibrillation Both persistent and paroxysmal atrial fibrillation are potent predictors of first as well as recurrent stroke Atrial fib >2 million Americans Increases with age Atrial fibrillation patients with prior strokes and TIAs have the highest risk of recurrent stroke Other risk factors: age, HTN, CHF, diabetes mellitus

68 CHADS2 Age 75 years (1) HTN (1) DM (1) CHF (1) Ischemic stroke or TIA (2) Total score: (maximum is 6)

69 Antithrombotic Rx in Atrial Fibrillation Anticoagulation: CHADS2 >1 Antiplatelet Rx for CHADS=0 CHADS2=1 either anticoagulation or antiplatelet ASA plus clopidogrel maybe used in patients who have contraindication to anticoagulation If there is Stroke/TIA with atrial fibrillation then anticoagulation is the recommendation Patient has to be cleared for the absence of fall risk

70 Oral Anticoagulants Warfarin (valvular and non-valvular A.Fib.) Apixaban((approved for non-valvular A.Fib.) Rivaroxaban(approved for non-valvular A.Fib.) Dabigatran (approved for non-valvular A.Fib.)

71 Migraine with Aura An independent risk factor for stroke in women It is still unknown if migraine preventive therapy will reduce the risk of stroke A woman who has migraines with aura, who smokes tobacco and who is on oral contraceptive pills has a 7-9 fold increase in the risk of stroke Cessation of smoking and consideration of avoiding OCPs in patients with migraines with aura

72 Obstructive Sleep Apnea (OSA) Increases risk of stroke and cardiovascular disease Screening for symptoms of OSA and appropriate referrral to sleep center for evaluation and treatment when appropriate

73 Hormonal Replacement Therapy and Oral Contraceptive Pills Some increased risk of ischemic stroke May avoid or stop using if additional risk factors for stroke Stop/avoid use if patient is a smoker and esp. if it is a woman who has migraines with aura

74 Substance Use Alcohol beyond 2 drinks/day for men and beyond 1 drink /day for women increases the risk of stroke Illicit drug use increases the risk of intracerebral hemorrhage (ICH) and ischemic strokes esp. with Cocaine and Amphetamines/ derivatives Substance use increases the risk of development of poorly controlled BP and its complications Cessation should be recommended however with the help of detox and rehab programs

75 Antiplatelet Therapy in Primary Stroke Prevention: No Benefit No benefit in primary prevention Consider in diabetic patient with high risk factors and carotid artery disease Recent FDA warning about use of aspirin in primary prevention due to increased hemorrhagic risks which are not offset by any significant benefit.

76 Summary Goal should be primary prevention in stroke Role of the primary care and sometimes the neurologist and cardiologist in assessing risk factors for stroke Intervention with education about life style modification and treatment of risk factors for stroke

77 Summary Family history: identify people who have higher risk and counseling those patients Genetic counseling for rare genetic disorders Non-invasive imaging/ screening for patients with specific disorders: screen for cerebral artery aneurysms in patients with 2 first degree members with SAH/cerebral aneurysms, EDS IV, polycystic kidney disease

78 Summary: Physical activity is recommended: Moderate to vigorous intensity aerobic Suggested 40 min/ time, 3-4 days /wk 2013 AHA/ACC guidelines Weight reduction for BMI 25 Dietary restriction of salt and increased potassium in diet (HTN conrtol) DASH, AHA, Mediterranean diets

79 Summary: Primary Prevention Cessation of smoking esp. in women who have migraines with aura and who are on OCPs Cessation of illicit drugs Cessation of alcohol or limitation to 1 drink/day for women and 2 drinks/day for men

80 Summary: Primary Prevention Control of BP<140/90 mm Hg Control of blood sugar but avoid intensive glycemic control Use of statins in diabetic patients maybe protective and particularly if high risk factors Maximize medical management with statins and antiplatelets in carotid artery disease Anticoagulation is reserved for atrial fibrillation and cardiac thrombi or potent hypercoagulable states (latter in secondary prevention)

81 Summary: Primary Prevention Use of ACE Inhibitors and or an angiotensin II receptor blocker (ARB) in diabetes mellitus No documented benefit for aspirin in primary prevention of stroke (may consider patients with high risk factors) with the exception of some possible benefit for women>65 years old

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