1. ACUTE ISCHEMIC STROKE
Olajide Williams, MD MS

2. Case # 1
91 y.o. woman with hypertension, atrial fibrillation, presents to the emergency room with sudden onset witnessed difficulty walking. She presents at 50 minutes from onset. She cannot remember her medications
BP 170/80, HR 68, RR 12.
Frail appearing, sitting in gurney

3. Case # 1
NIHSS 1 for leg drift with weakness that is worse in the foot. She walks with a limp
What would you do?

4. Case # 1
Social history: physically very active, goes to the doctor frequently, still active within the leadership in her church
INR is 1.1
Parallel history: how weak was she at ictus?

5. Case #1
Her daughter tells you that when symptoms began, she noticed that she had severe left facial weakness and left leg plegia, although her left arm appeared unaffected. The weakness improved between onset and ED arrival except for the leg drift you found on your exam.
Where does this lesion localize to?
What would you do now?

6. Treatment of minor stroke
Minor stroke is the second most common reason for tPA exclusion (up to 1/3) (Bambauer Arch Neurol 2006)
Definition of minor stroke is highly variable
NINDS trial excluded 13% who were considered too good to treat, and only 58 had an NIHSS < 5 (Khatri, Stroke 2009)
Case series show ~25% will go on to have a “bad outcome” (Smith, Stroke 2011)

7. Thrombolysis in Minor Stroke
Predictors of poor outcome without tPA:
Rapidly shrinking deficit (Nedeltchev, Stroke 2007; Smith Stroke 2005)
Major arterial occlusion (Rajajee, Neurology 2006)
NIHSS > 3 (Fischer, Stroke 2010)
Hemiparesis (Fischer, Stroke 2010)
No prior stroke (Willey, Int J Stroke 2011)
PRISMS Trial will study this further (Potential of rtPA for Ischemic Strokes with Mild Symptoms (PRISMS).

8. Quick comment on TIA’s
40% of clinical TIAs are actually strokes (i.e., MRI shows acute cerebral infarction).
Some patients who feel back-to-normal have significant deficits on examination, particularly those with neglect or anosoagnosia.
Stroke patients with resolving symptoms neurologically deteriorate ~25% of the time.
TIA and minor ischemic stroke patients may have short- and long-term disability (~15%).
The initial triage assessment may miss subtle neurological deficits that a more comprehensive examination would pick up. Therefore, patients with TIA should be assessed as quickly and in the same manner as those with stroke.

9. Case #2
A 70 year old man with new onset type 2 diabetes and HTN arrives at the ED 1 hour after waking up with disabling right sided hemichorea-hemiballismus. His wife said he looked fine when he woke up from sleep to go the bathroom 4 hours ago. His finger stick reveals a glucose of 420 and his BP is 170/90.
What do you do now?

10. Case #2
CT scan
Age 60-84
Characteristic MRI findings resolve after 3 – 6 months
Non ketotic hyperglycemia
Hyperkinetic state resolves with glucose control
Speculation: hyperviscosity secondary to hyperglycemia, leading to regional blood-brain barrier disruption and metabolic damage
T1 hyperintensity is most consistent finding (it is not a hemorrhagic infarct) – sometimes no T2 changes and sometimes +DWI

11. Case #2
MRI scan
What is the diagnosis?

12. Case # 3
58 y.o. woman with atrial fibrillation, stopped warfarin for a tooth extraction. Presented to the ER with witnessed aphasia and right hemiparesis at 30 minutes from onset.
Exam: transcortical sensory aphasia, gaze deviation, patchy right homonymous hemianopsia, R arm and leg plegia
INR 1.2
CT head: ASPECTS 10
What would you do next?
Incongrous horizontal homonymous sectoranopias from AchA

13. ASPECTS SCORE
10-point quantitative topographic CT scan score used in patients with MCA stroke. Segmental assessment of the MCA vascular territory is made and 1 point is deducted from the initial score of 10 for everyone of the 10 regions involved
Score of less < 7 predicts worse functional outcome at 3 mos and sICH

14. Endovascular Therapy
Class 1, Level of Evidence A — For certain stroke patients (proximal occlusions) to receive endovascular treatment within 6 HOURS based on five new clinical trials: MR CLEAN, ESCAPE, EXTEND-IA, SWIFT-PRIME, and REVASCAT.
(1) Newer devices (stent retrievers) with better recanalization rates; (2) Patients in these new studies had no treatment outside the randomized controlled trials (meaning only good candidates were included in the studies); (3) Earlier treatment time windows; (4) Better patient selection using CT angiography (CTA); and (5) Pretreatment with rt-PA.

15. Application
Results only apply in a minority of stroke patients— those with large proximal vessel occlusions (eg, terminal carotid and proximal middle cerebral arteries) successfully treated within 6 hours (most centers treat less than 20% with endovascular approaches).
Rate of functional independence in the intervention group in SWIFT PRIME (60%) was higher than that in MR CLEAN (33%) and similar to that observed in the ESCAPE trial (53%) and the EXTEND-IA trial (71%)
EXTEND IA[had to screen almost 8000 patients to find 75 or so who benefited from this therapy.
SWIFT PRIME ADVANTAGE - the earlier start of the intervention, the exclusion of patients with large core infarcts on the basis of imaging, and the greater reperfusion rate in our trial, as compared with the other trials
MR CLEAN did not do any advanced brain imaging to see who has an ischemic penumbra—who has salvageable tissue and who does not.

16. AHA Guidelines Prestroke modified Rankin Scale (mRS) score 0 to 1;
Acute ischemic stroke with receipt of intravenous recombinant tPA within 4.5 hours of onset;
Causative occlusion of the internal carotid artery or proximal (M1) middle cerebral artery (MCA);
Age 18 years or older;
National Institutes of Health Stroke Scale (NIHSS) score of 6 or greater;
ASPECT score of 6 or greater; and
Treatment that can be initiated (groin puncture) within 6 hours of symptom onset.
In carefully selected patients with anterior circulation occlusion who have contraindications to tPA, endovascular therapy is reasonable. Intra-arterial fibrinolysis initiated within 6 hours of stroke onset in carefully selected patients who have contraindications to the use of intravenous tPA might be considered, but the consequences are unknown
Endovascular therapy "may be reasonable (although benefits are uncertain)" for carefully selected patients who have causative occlusion of the M2 or M3 portion of the MCAs, anterior cerebral arteries, vertebral arteries, basilar artery, or posterior cerebral arteries; for some patients younger than 18 years of age; for those who have prestroke mRS score of greater than 1, ASPECT score less than 6, or NIHSS score less than 6

17. Patient selection
Intracranial vessel occlusion must be diagnosed with non-invasive imaging whenever possible before considering treatment with mechanical thrombectomy (Grade A, Level 1a)
If vessel imaging is not available at baseline, a NIHSS score of ≥ 9 within three, and ≥ 7 points within six hours may indicate the presence of large vessel occlusion (Grade B, Level 2a)
Patients with radiological signs of large infarcts (e.g. using the ASPECTS score) may be unsuitable for thrombectomy (Grade B, Level 2a) 
Imaging techniques for determining infarct and penumbra sizes can be used for patient selection and correlate with functional outcome after mechanical thrombectomy (Grade B, Level 1b)
High age alone is not a reason to withhold mechanical thrombectomy as an adjunctive treatment (Grade A, Level 1a).

18. Case # 3
Patient was treated with IV tPA in the CT scanner where he also obtained a CTA
CTA was normal
MRI showed an acute infarction, which surprisingly was not in the LMCA territory.
Where might this lesion be?

19. DAWN Trial
1ST to evaluate wake-up strokes and late window presentations (6hours to 24 hours)
 RCT design - functional outcomes at 90 days – 206 patients treated with mechanical thrombectomy vs medical therapy alone
Used multimodality imaging to identify mismatch — a small core infarct volume but a large area of brain at risk for ischemia yet still potentially salvageable
Reduced disability and improved functional independence at 90 days favoring intervention (48.6% vs 13.1%, probability of superiority >0.9999)