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Stroke: Selected Diagnosis & Management Issues, & BGSMC's Stroke Center

Stroke: Selected Diagnosis & Management Issues, & BGSMC's Stroke Center. Douglas Franz MD Assistant Director, Banner Good Samaritan Stroke Center. July 2011. 1-1.5 Kg 100 Billion Neurons. 32,000 neurons die per second during a stroke. Stroke 2006;37;263. Ischemic Penumbra.

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Stroke: Selected Diagnosis & Management Issues, & BGSMC's Stroke Center

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  1. Stroke: Selected Diagnosis & Management Issues, & BGSMC's Stroke Center • Douglas Franz MD • Assistant Director, • Banner Good Samaritan Stroke Center July 2011

  2. 1-1.5 Kg • 100 Billion Neurons

  3. 32,000 neurons die per second during a stroke Stroke 2006;37;263

  4. Ischemic Penumbra Core Infarct Penumbra Benign Oligemia

  5. Cerebral Autoregulation • Autoregulation maintains constant perfusion for Mean Arterial Pressures between ~60-140 mm Hg • Physiologic dysfunction with MAP ≲ 60 mm Hg • Ischemia with CBF ≲ 20 ml/min/100 g CNS Spectr 2007;12(1):35

  6. Cerebral Perfusion Pressure • CPP=MAP-ICP (or MAP-JVP if JVP>ICP) • Normal: ICP ~7-15 mmHg, and MAP 50-150 mmHg • Normal CPP ~70-90 mmHg • Perhaps as low as 50 mmHg in adults • Children require at least 60 mmHg

  7. TINS 1999;22(9):391

  8. Epidemiology of Stroke • Stroke WAS the third leading cause of death, behind cardiovascular diseases and cancer • 150,000 deaths each year (US) • Approximately 780,000 strokes occur each year in the USA and 450,000 strokes each year in Europe • 600,000 first strokes (US) • 180,000 recurrent strokes (US) • Leading cause of disability in US • 350,000 survivors each year (US) • 7.6% of ischemic strokes and 37.5% of hemorrhagic strokes result in death within 30 days • Risk factors overlap significantly with cardiovascular disease • Our best treatment is prevention American Heart Association. 2003, 2008 Heart and Stroke Statistical Update. ESH-ESC Guidelines Committee. J Hypertens 2003; 21 (6): 1011–1053.

  9. Definitions • Stroke is the acute onset of a focal neurologic deficit resulting from decreased perfusion to the brain, causing permanent tissue damage • Strokes are usually the result of vascular disease • The symptoms of a stroke depend on the part of the brain involved • 85% are ischemic • 15% are hemorrhagic

  10. Stroke Subtypes • Hemorrhagic Stroke • Atherosclerotic Cerebrovascular Disease • Small Vessel Disease (“lacunes”) • Cardiogenic Embolism • Cryptogenic • Other Albers et al. Chest 2004; 126 (3 Suppl): 438S–512S.

  11. Ischemic Stroke lacune encephalomalacia

  12. Ischemic Stroke

  13. Hemorrhagic Stroke: Parenchymal Intracerebral Hemorrhage (ICH)

  14. Hemorrhagic Stroke

  15. Other ICH locations: • Cortex (amyloidosis) • Basal Ganglia • Thalamus • Pons • Cerebellum NEJM 2001;344(19):1450

  16. Stroke Risk Factors

  17. Previous TIA or stroke is the most important risk factor for stroke. Hypertension is the most prevalent. Stroke Risk Factors Non-modifiable risk factors Modifiable risk factors (PAR) • Hypertension (20-40%) • Diabetes mellitus (5-27%) • Atrial fibrillation (1.5-23.5%) • Carotid artery disease (2-7%) • Dyslipidemia(10-15%) • Cardiac disease (1.1-5.8%) • Cigarette smoking (12-18%) • Obesity (12-20%) • Others… • Older age • Male gender • Non-white genetic background • Family history • Prior stroke or TIA Hankey GJ. Cerebrovasc Dis 2003; 16 (Suppl 1): 14–19. Wolf PA. Adv Neurol 2003; 92: 165–172. Sacco et al. Stroke 1997; 28 (7): 1507–1517.

  18. Less Well Understood Risks • Insulin resistance • Sleep disordered breathing • Na intake > 2300 mg/d • Metabolic syndrome • Alcohol abuse • Hyperhomocysteinemia • Drug abuse • Hypercoagulable states • OCP use • Inflammatory processes • CMV, C. pneumoniae, periodontal disease, etc • Migraine • Lp(a) status

  19. TIA: Transient Ischemic Attack • Old Definition: stroke symptoms lasting less than 24 hours • New Definition: “a brief episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia without acute infarction” • TIA prevalence 7-40% in stroke patients, most in 30 days preceding first stroke, 41% lasting < 1 hour • In another study: 17% TIAs on day of stroke, 9% previous day, 43% in previous week Stroke 2009;40:2276

  20. Cumulative Stroke Risk after TIA or Minor Stroke Coull et al., BMJ 2004;328:326

  21. Acute Stroke Risk After TIA • meta-analysis of 18 cohorts, 10126 TIAs • 5.2% strokes in 7 days, 3.2% in 2 days • i.e., 1 in 20 patients will have a stroke soon after their TIA • TIA Management "Patchy" • ½ of strokes after TIA occur in 24 hours Neurology 2009;72:1941 Lancet Neurol. 2007 Dec;6(12):1063

  22. New TIA Guidelines • Neuroimaging, preferably MRI with DWI within 24 hours • Noninvasive cervicocephalic imaging • Consider noninvasive cranial vessel imaging if management would be affected • ECG ASAP after TIA • TTE reasonable if no other causes, TEE if indicated • CBC, CMP, PT/PTT, fasting lipids • Hospitalize if <72 hours from event, and ABCD2 ≥ 3, or if work-up can’t be completed in 2 days Stroke 2009;40:2276

  23. Hypertension Risk and Prevalence • JNC VII, 2003: • In patients > 50 years/age, SBP>140mmHg is a more important risk factor for cardiovascular disease than DBP • Beginning with 115/75mmHg, CV disease risk doubles with each increment of 20/10mmHg • Individuals who are normotensive at age 55 have a 90% lifetime risk of developing HTN • Odds ratio of developing HTN 4 at 50 years old • NHANES, 1999-2002:

  24. Hypertension Overall • Lowering BP by 10/5 mmHg lowers CHD by ¼ and stroke by ⅓ regardless of starting BP, vascular risks, and how it was done • Meta-analysis of 147 trials, 958,000 patients aged 60-69, over 42 years: ~40% reduction in stroke • In patients with DBP > 90 mmHg, over 60% RRR with combination therapy BMJ 2009;338:b1665

  25. Lipids: SPARCL • 4731 patients with stroke/TIA 1-6 mo before entry • LDL 100-190 mg/dl • atorvastatin 80mg vs placebo • LDL: 73 vs 129 mg/dl • 5-year stroke risk 0.84 (0.71-0.99) • 5-year decrease in major cardiovascular events: • ARR 2.2% (0.2-4.2), RRR 16% • RRR ischemic stroke 22% • Increase in hemorrhagic stroke (2.3% vs. 1.4%) • ARR 3.5%, RRR 20% NEJM 2006; 355: 549

  26. Lipids: SPARCL Net Benefit Prevent 22 events/1,000 treated/5 years 13.1% 1.4% 11.2% 2.3% 11.7% Events/5 Years (%) 8.9% n=2,366 n=2,365

  27. Carotid Stenosis Risk • Accounts for 15-20% of ischemic strokes • Carotid endarterectomy (CEA) surgery if symptomatic: • 70-99% stenosis: NNT 8 (2 years) • 50-69% stenosis: NNT 20 • Surgery if asymptomatic: • 60-99% stenosis: NNT 53 (3 years) • In US ½ - ⅔ of carotid surgeries are still on asymptomatic patients • <5% of asymptomatic patients will benefit from surgery, with 4-5% surgical risk NEJM 1991;325:445 Lancet 2003;361:107 JAMA 1995;273:1421

  28. Patent Foramen Ovale • Detected incidentally in ~20% of individuals • Over-represented (>50%) in young people (<55) with cryptogenic stroke • PFO alone confers no statistical risk (A) • PFO with septal aneurysm might (C) • Consensus: antiplatelet therapy if associated with cryptogenic stroke, antocoagulation for DVTs (U,A) • CLOSURE trial Neurology 2004;62:1042

  29. Acute Stroke

  30. Specific Treatment Targets • Blood Pressure: • SBP <185 after lytics • SBP < 160 in hemorrhage • SBP < 220 in general ischemia • Be aware of autoregulation, sudden changes • Euvolemia • Normoglycemia • Normothermia

  31. Stroke Mimics • Seizures, especially partial/focal ones • Hyper/hypoglycemia • Toxic/metabolic encephalopathy • Decompensation of old deficits • “Generalized” weakness • Hemorrhage • Tumors

  32. IV tPA

  33. SITS-MOST • 6,483 stroke patients in 285 European centers, 50% with little experience with tPA • Monitoring of safety profile of tPA in routine use Lancet 2007;369:275

  34. tPAMeta-Analysis • Pooled analysis of NINDS, ECASS, ATLANTIS trials • OR 1.4 (1.05-1.85) for favorable outcomes with OTT 181-270 mins Lancet 2004; 363:768

  35. ECASS-III • 821 pts; 403 placebo, 418 tPA (standard protocol) @ 3-4.5 hours • Primary outcome: dichotomized mRS: 0-1 vs. 2-6 • Secondary outcomes: combined global scores • Median administration time 3 hrs 59 mins NEJM 2008;359(13):1317

  36. ECASS-III: Outcomes • Favorable 52.4% (tPA) vs. 45.2% (placebo) • OR 1.34 (95% CI: 1.02-1.76, p=0.04) • Secondary outcomes: OR 1.28 (1.0-1.65, p<0.05) • ICH higher with tPA: 27.0% vs. 17.6%, p=0.001 • symptomatic 2.4% vs. 0.2%, p=0.001 • Mortality 7.7% vs. 8.4% (p=0.68) NEJM 2008;359(13):1317

  37. SITS-ISTR 3: Moderate disability; requiring some help, but able to walk without assistance Lancet Online; 9/15/08

  38. Intra-Arterial Therapies Indications: <6 hours, Significant disability, Gross thrombus in large vessels (M1/M2, PCA, basilar, ACA) Risks: 10-15% with complication/sICH Options: thrombolysis, thrombectomy Evidence: PROACT II, pending trials IMS III, MR RESCUE

  39. MERCI Retrieval System™ Stroke 2004;35:A294

  40. The Penumbra System™

  41. Benefit of Revascularization 90-day modified Rankin 53% 16% 31% 6% 32% 62% Saver / UCLA Stroke Center (MERCI)

  42. Harm in Revascularization

  43. Stroke Codes • Criteria: • any patient you think clinically is having a stroke • time of onset/last-well < 6 hours ago • “meaningful” deficits • Call 1-6666, ask for a “stroke alert” • On the floor, a SA is initiated by the MD or RRT, not the nurses • 6B/neuro-ICU nurse responds to guide process, gather data • Decision on disposition made in ~45 mins and discussed (we may call you sooner) • Calling office for doc-to-doc guarantees delays; if SA criteria are met, activate it

  44. Acute Stroke Labs • CBC • BMP • PT/INR/PTT • lipid panel/HgBA1c (no so acute) • Exotics: ESR/CRP, Hypercoagulable panels, vasculitis panels

  45. Imaging Acute Stroke • Non-contrast CT head • MR brain – obtained sub-acutely • Vascular Imaging • CT angiogram head/neck • MRA neck/brain • Carotid U/S • Acute Stroke <6 hours • CT angiogram/perfusion head and neck • Telemetry • TTE with bubbles, TEE in selected cases • Cerebral Angiogram selected cases

  46. Perfusion Imaging Artery Vein Tissue

  47. Cerebral Blood Volume (CBV) • mL/100gm • total volume of blood in a given unit volume of brain; including the blood in the tissues and the large capacitance vessels (arteries, capillaries and veins)

  48. Cerebral Blood Flow (CBF) • mL/100gm/min • volume of blood moving through a given unit volume of brain per unit time

  49. Mean Transit Time (MTT) • seconds • average time it takes for blood to travel from the arterial inlet, through the capillary bed, to the venous outlet

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