Don’t Let Me Be Misunderstood: New Definitions for Stroke and TIA Cathy Sila, MD The George M Humphrey II Chair in Neurology Professor and Director, Stroke & Cerebrovascular Center
Current Initiatives • AHA/ASA Scientific Statements – Definition and Evaluation of Transient Ischemic Attack, Easton JD, Chair, Stroke 2009; 40:2276-2293. – Redefining Stroke (in progress) Stroke 2010.
• NINDS Stroke Common Data Elements Project – Stroke Types and Subtypes Subgroup • FDA – Standardized Definitions for Cardiovascular Outcomes in Clinical Trials
Stroke Terminology 1950s-1970s • Transient Ischemic Attack (TIA)– focal episode of neurologic dysfunction – of presumed vascular origin – temporary, usually lasting 2-15 minutes, but up to 24 hrs – clearing without residua • Reversible Ischemic Neurologic Deficit (RIND)> 24 hours but < 1 week
• Completed Stroke- > 1 week, but often permanent • Partial Non-progressing Stroke- stable at 18-24 to 72 hr • Stroke-in-evolution / Progressing Stroke
Rationale for Updating the Definitions • Simple definitions, relied on – Clinical symptoms, Time, Recovery vs Residual • Presumption that a complete resolution of symptoms meant that there was no brain injury
– Predated any neuroimaging (1950-1970s) • No need to make a rapid diagnosis of stroke as there were no treatment options available for acute syndromes
Stroke 1974; 5:277, Stroke 1975; 6:563, WHO 1978 Stroke 2003; 34: 2995, Neurology 2000; 55:1649
New Definitions of TIA (and Stroke) • Transient Ischemic Attack (TIA)– transient episode of neurologic dysfunction – due to focal cerebral, spinal cord, or retinal ischemia – without evidence of acute infarction • Stroke- (in progress) – defined by evidence of tissue injury – regardless of symptom duration
Rationale for Updating the Definitions • No pathophysiologic basis for a 24 hour definition • Change the perception that TIAs are benign • Eliminate barriers to early interventions • Encourage early and sensitive diagnostic testing that will better determine the cause, identify high-risk patients and guide therapy
• Use of tissue injury is consistent with cardiovascular definitions
No pathophysiologic basis for a 24hr definition % with TIA symptoms resolved by time
% with + MR DWI
Symptom duration (hours)
Change the Perception that TIAs are benign • Hospitalization following PCP evaluation for recent TIA – 41% western US, 68% northwest US, 66% Germany • Evaluations for first –ever TIA (review of 27 primary care practices)
– 59% had any studies performed within 30 days – 23% Brain CT or MRI – 40% Carotid ultrasound – 18% EKG – 19% TTE Arch Int Med 2000;160:2941, Stroke 2007;38:1298, Acad Em Med 2006; 13:666
Eliminate a barrier to acute intervention TIAs in the ER or “too good to get tPA”
• 30-40% of stroke patients arriving within 3 hr are not given tPA due to mild or rapidly improving symptoms
– reluctance to treat lest the event is a TIA – 27% are not discharged home • 36% of those “to good to treat” had a major vascular occlusion – 18% early mortality – overrepresentation of impending right ICA occlusion Neurology. 2001; 56: 1015, Stroke 2005; 36: 2497
Encourage early and sensitive neuroimaging • AHA/ASA Scientific Statement 2009 – Patients with TIA should preferably undergo neuroimaging evaluation within 24 hours of symptom onset. MRI, including DWI, is the preferred brain diagnostic imaging. (Class I, Level of Evidence B)
• AAN Evidence-Based Guideline 2010 – MRI-DWI should be performed for the most accurate diagnosis of acute ischemic stroke (Level A). AHA/ASA Scientific Statement, Stroke 2009; 40:2276 AAN Evidence-Based Guideline, Neurology 2010; 75:177–185
TIA Triage by Time and Clinical Features 20%
ABCD2 Score
18% 16% 14% 12%
6-7 pts
10%
4-5 pts
8%
< 4 pts
6% 4% 2% 0%
• 2 pts- duration ≥ 60 min • 2 pts- unilateral weakness • 1 pt- speech impairment without weakness
• 1 pt- age ≥ 60 yrs • 1 pt- Diabetes • 1 pt- first BP >140 / >90
2 d 7 d 30 d JAMA 2000; 284: 2901, Lancet 2005; 366: 29 and 2007; 369: 283
Risk of Recurrent Stroke by Subtype Stroke at 1 week
Stroke at 1 month
Large Artery Atherosclerosis Cardioembolic
Cryptogenic
Lacunar 0
5
Petty et al, Stroke 2000; 31:1062
10
15
20
25
30
Neuroimaging improves Triage • Imaging Findings Impact on Early Stroke Risk – New infarct on brain imaging 2-15-fold increase – Vessel occlusion by MRA 4-fold increase
MCA occlusion
Borderzone ICA occlusion
Lacunar infarction
Multifocal cardioembolism
CMAJ 2004; 170: 1105, Stroke 2003; 34:2894, Ann Neurol 2005; 57: 848
Impact on Cost of Care • Shift in protocols to use MR DWI as the gold standard – Need for imaging capability 24/7 for ER, inpatients and outpatients
• Neuroimaging costs – Cost of CT brain – Cost of MRI brain – Cost of MRA
$1150 ($750- $4200) $2550 ($1650- $7300) $3200 ($1950- $9300)
Neurology 2010; 75:177–185, www.newchoicehealth.com
Impact on Costs of Care â&#x20AC;˘ Cost savings from accurate diagnosis, identification of high-risk or unstable patients and tailored therapy Stroke Treatment
2010 MS-DRG 64
Mean LOS 5.5 d
2010 Ave US Urban Medicare Payment $ 9,536
Medical Stroke
65
4.3 d
$ 6,048
66
3.1 d
$ 4,295
69
2.4 d
$ 3,807
Transient Ischemia
Epidemiologic Impact of CT on ICH • CT introduced in 1973, major impacts seen in 1975-1979 • Sharp increase in the incidence of ICH – Improved detection of smaller hemorrhages ~ 25% of ICH had been misdiagnosed as Infarcts
• Increased the 30d survival after ICH from 8% to 44% • Autopsy rate ~ 75% → 38%
Neurology 1984;34;653
Epidemiologic Impact of MRI on Stroke â&#x20AC;˘ Estimated that MR DWI use will decrease the incidence of TIAs by 33% and increase Ischemic Stroke by 7%
FDA Definitions for Cardiovascular Trials • Adopted the new TIA Definition • Stroke– rapid onset of neurological deficit – ≥ 24 hr OR < 24 hrs if resolved with intervention, death, or acute infarct or hemorrhage on neuroimaging – no other identifiable non-stroke cause – confirmation by: a specialist/ imaging/ LP/ other – and a proposal to include a measure of Stroke severity
Measuring Stroke Severity • 30 day mortality- poor indicator unless subtype specified –Subarachnoid Hemorrhage 57% –Intracerebral Hemorrhage 44% –Cardioembolic Infarct 30% –Cryptogenic Infarct 14% –Atherostenotic Infarct 8% –Lacunar Infarct 1.5% –Received IV-tPA for acute stroke 13% • Disability
mRS and Stroke Recovery
1m
3m
Neurology 2007; 68: 1583
6m
New Definitions: Rationale and Challenges • No pathophysiologic basis for a 24 hour definition
• Change the perception that TIAs are benign
• Eliminate barriers to early interventions
• Encourage early and sensitive diagnostic testing that will better determine the cause, identify highrisk patients and guide therapy
• Use of tissue injury is consistent with cardiovascular definitions
• Epidemiologic studies will require some time data capture to permit comparisons to historical data
• Perception of TIAs may not change if imaging is negative
• Diagnostic sensitivity of the tissue based definition will vary depending on imaging modality
• Infrastructure will need to change • Incidence of stroke will increase, event rates in trials will increase
• Impact on cost- increased charges may be offset by improved outcomes