TIA: Updates and Management 2008 S. Andrew Josephson, MD Department of Neurology, Neurovascular Division University of California San Francisco Commonly Held TIA Misconceptions TIA is easy to diagnose using modern imaging modalities and laboratories TIA and stroke are distinct entities The natural history of TIA is benign Urgent treatment of TIA is of no proven benefit The speaker has no disclosures Case 1 A 67 year-old woman with a history of HTN presented to the ED after an unwitnessed 20 minute episode of left arm weakness that has since resolved. Her examination is normal. What is the most likely etiology of this spell? 1. TIA 2. Migraine 3. Partial Seizure 4. Porphyria 5. Conversion Disorder 1
Case 1 (con t) Within 30 minutes of the MRI, the patient experienced a witnessed spell of rhythmic shaking of the L arm followed by an extended period of paralysis. Chest X-Ray reveals large mass consistent with adenocarcinoma. Differential for Transient Focal Neurologic Deficit TIA Definition: A transient neurologic deficit attributable to a vascular cause that resolves completely within 24 hours (most are only minutes). The Big Three 1. Stroke/TIA 2. Seizure 3. Complicated Migraine Proven Markers of Migraine Motion Sickness Brain Freeze Headaches that occur at regular times related to the menstrual cycle Pain triggered by smells or repetitive noises Cyclic abdominal pain as a child Diagnosis of TIA Purely a clinical diagnosis No laboratory troponin for the brain No imaging study confirms or refutes Even experts don t agree (kappa=0.65) When in doubt, assume it is a TIA False positives are acceptable in this instance! Kraaijeveld CL Stroke 1984 2
Case 2 A 40 year-old man with no PMH comes to the ED after a 30 minute episode of aphasia and right arm weakness that has since resolved. The patient reports 5 days of neck pain after severe vomiting from a gastroenteritis Exam is normal What is the most likely etiology of this TIA? 1. Atrial Fibrillation-Related Embolus 2. Carotid Dissection 3. Small-Vessel Atherosclerosis 4. Endocarditis 5. Hypercoagulable State UCSF Stroke Protocol CT Obtained at UCSF in all suspected acute stroke and TIA patients 1. Non-contrast CT of the head 2. CT Angiography from aortic arch/heart through Circle of Willis 3. CT Perfusion study 4. Post-contrast CT of the head MRI in TIA Diffusion-weighted MR imaging very useful in stroke to distinguish from mimics In TIA, about 50% of patients will have infarction on MRI As duration of spell increases, so does percentage with infarction But not beyond 50-60% 3
MRI in TIA Therefore.. 1. The distinction between TIA and stroke is quite artificial 2. MRI looking for infarction is not a useful test to exclude the diagnosis of TIA Approach to Stroke/TIA Treatment Acute Stroke Therapy? No Anticoagulants? No Antiplatelets Shrinking Indications for Anticoagulation in Stroke 1. Atrial Fibrillation 2. Some other cardioembolic sources Thrombus seen in heart?ef<35?pfo with associated Atrial Septal Aneurysm 3. Vertebral and carotid artery dissection 4. Rare hypercoagulable states: APLA Cervical Artery Dissection Vertebral and Carotid Arteries Common etiology of stroke in young Pathophysiology Risk Factors Most idiopathic Vomiting, Coughing, Chiropractic Presentation: Neck Pain, HA Tx with anticoagulation Courtesy Wade Smith, MD, PhD 4
Case 3 A 65 year-old man with diabetes comes to the ED after 15 minutes of L arm weakness and slurred speech that has now resolved. Vitals: BP 160/80, HR 67, sat 100%, RR 12 Exam is normal What is the approximate 90-day stroke risk for this patient? 1. 1 percent 2. 5 percent 3. 15 percent 4. 50 percent 5. 80 percent Risk of Future Stroke with TIA: ABCD 2 Score Age >60 =1 point Blood Pressure SBP>140 or DBP>90 =1 point Clinical Features Unilateral weakness =2 points Speech disturbance without weakness =1 point Duration >60 minutes =2 points 10-59 minutes =1 point Diabetes=1 point Johnston SC, Lancet 2007 ABCD 2 Score 7-day risk overall 8.6-10.5 percent 2-day risk of stroke Score 6-7: 8.1 percent (high risk) Score 4-5: 4.1 percent (moderate risk) Score 0-3: 1.0 percent (low risk) Johnston SC, Lancet 2007 5
ABCD 2 Score: Common Sense? 1707 patients seen in the ED with TIA in Northern California before prediction rules were published Did ABCD 2 score correlate with decision to admit for further workup and treatment? No, only weak correlation (R 2 =0.036) Factors associated with admission had little relationship with factors in ABCD 2 score ABCD 2 Score: How Does It Work? The same 1707 patients seen in the ED with TIA in Northern California before prediction rules were published Expert neurologist reviewed all records retrospectively (ED and inpatient) to decide if event was a true TIA. ABCD 2 score was higher in those with true TIA Perhaps ABCD 2 partially works by identifying those with true TIA as opposed to alternative dx Josephson SA Stroke 2008 Josephson SA Stroke 2008 Appropriate TIA Workup and Treatment Imaging Workup of TIA All patients require head imaging, mainly to exclude mimics Non-contrast CT best, MR adds little value Enhanced CT/MR techniques provide further important information Vascular Imaging of Head and Neck 6
Vascular Imaging Utility: Case 4 A 70 year-old man with HTN, diabetes comes to the ED after 30 minutes of L arm weakness that has now resolved Large Vessel Occlusions Predict a poor outcome in Stroke and TIA patients Permissive (or induced) HTN is key in these patients to prevent further injury Likely mandates close observation Consideration should be given to intervention if the patient worsens Vascular Imaging Utility: Case 5 A 68 year-old woman with a history only of HTN presents with daily episodes of right eye blindness that completely resolve after 3 to 15 minutes. Exam is normal including fundoscopy Carotid Stenosis and TIA Along with afib, one of two etiologies of stroke/tia with the strongest evidence for intervention to prevent subsequent events Consensus guidelines urge urgent revascularization of symptomatic lesions Guidelines: After stroke, within 2 weeks TIA Experience: Within hours to days Chaturvedi S, Neurology 2005 7
Standard TIA/Stroke Workup Cardioembolic: afib, clot in heart, paradoxical embolus 1. Telemetry 2. Echo with bubble study Aortic Arch 2. Echo with bubble study Carotids 3. Carotid Imaging (CTA, US, MRA, angio) Intracranial Vessels 4. Intracranial Imaging (CTA, MRA, angio) Case 6 A 55 year-old woman with a hx of smoking presents after 1-hour of R leg weakness that has since resolved. Her only medication at home is ASA 81mg daily. Exam is normal. And evaluate stroke risk factors What is the appropriate secondary prevention medication for this pt? 1. Coumadin 2. ASA 325mg 3. Clopidogrel (Plavix) 4. 25mg ASA/200mg ER Dipyridamole (Aggrenox) 5. Nimodipine Approach to Stroke/TIA Treatment Acute Stroke Therapy? No Anticoagulants? No Antiplatelets 8
Antiplatelet Options 1. ASA 50mg to 1.5g equal efficacy long-term 2. Aggrenox 25mg ASA/200mg ER Dipyridamole ESPS-2, ESPRIT (Lancet 5/06) 3. Clopidogrel (Plavix) MATCH (Lancet 7/04) FASTER (Lancet Neurol 10/07) Aggrenox vs. Plavix Aggrenox Headache in first 2 weeks: 30% discontinue Perhaps not compatible with cardiac antiplatelet goals or with unstable angina Cannot be crushed in FT Plavix Less evidence directly from stroke trials Concerns regarding use with ASA PRoFESS trial results announced May 2008 PRoFESS Trial (NEJM 9/08) Randomized, double-blind trial of Aggrenox versus Plavix in over 20,000 patients with ischemic stroke (many very minor) Recurrent 4-year event rates basically identical between the two medications HR for Aggrenox 1.01 (95% CI, 0.92-1.11) Composite of stroke, MI, vascular death: 13.1% in each Major hemorrhagic events higher in Aggrenox group Antiplatelet Options If on no antiplatelet medication ASA or Plavix vs. Aggrenox If already on ASA Switch to Plavix vs. Aggrenox Note: There is no acute data for Aggrenox If already on Plavix or Aggrenox??? 9
Which of the following TIA patients are you most likely to admit? 1. 40F with DM following a 5-minute episode of aphasia 2. 85M with HTN (bp 160/90) and afib with 15 minutes of R arm weakness 3. 70M with HTN (bp 160/90), DM with 20 minutes of R leg weakness Which of the following TIA patients are you most likely to admit? 1. ABCD 2 =2 2. ABCD 2 =5 3. ABCD 2 =6 Is Urgent Evaluation of TIA Helpful or Necessary? To complete workup? To initiate secondary prevention strategies? Only for high-risk patients? To allow for t-pa to be given quickly if symptoms return? Until 2007, absolutely no evidence SOS-TIA Study: October 2007 1085 patients with TIA admitted to a 24- hour clinic (basically an inpatient center) All treated with standard therapy 74 percent discharged on same day 90-day stroke rate reduced by 80% compared with that predicted by ABCD 2 (5.96% to 1.24%) Lavallee PC Lancet Neurology 2007 10
EXPRESS Study: October 2007 Prospective before and after trial of patients with TIA or minor stroke Referral from ED to urgent assessment at a daily TIA clinic rather than waiting for PMD appointment Work-up completed, secondary prevention begun in clinic Reduced 90-day risk of recurrent stroke by 80% (10.3% to 2.1%, HR 0.20, 95% CI 0.08-0.49, p=0.0001) Take-Home Points TIA is a neurologic emergency Our version of unstable angina TIA is a purely clinical diagnosis If you think it s a TIA, it is The distinction between TIA and stroke is completely artificial TIA should be treated and worked up just like an ischemic stroke Rothwell PM, Lancet 2007 Take-Home Points Risk of subsequent stroke after TIA can be predicted with a high degree of accuracy Urgent evaluation and treatment of TIA patients substantially reduces this risk Whether this evaluation should occur in an inpatient setting or ultra-rapid outpatient clinic is dependent on the health care system involved 11