1. Acute Stroke Treatment 2017

2. Disclosure
No financial or other relationship with any of the products, manufacturers or services discussed today.

3. Stroke Epidemiology Pathophysiology Incidence Prevalence Cost
80-90% of stroke is ischemic
Incidence
795,000 strokes per year per CDC
Prevalence
1 of every 15 people age 60 – 79
1 of every 6 people over age 80
Cost
$34 Billion annually

4. Dariush Mozaffarian et al. Circulation. 2016;133:e38-e360
Annual rate of all first-ever strokes by age, sex, and race (Greater Cincinnati/Northern Kentucky Stroke Study: 1999)
Dariush Mozaffarian et al. Circulation. 2016;133:e38-e360

5. Dariush Mozaffarian et al. Circulation. 2016;133:e38-e360
Prevalence of stroke by age and sex (National Health and Nutrition Examination Survey: 2009–2012).
Dariush Mozaffarian et al. Circulation. 2016;133:e38-e360

6. Dariush Mozaffarian et al. Circulation. 2016;133:e38-e360
Stroke Death Rates
Dariush Mozaffarian et al. Circulation. 2016;133:e38-e360

7. Pathophysiology of Cerebral Ischemia
Inadequate flow through cerebral vessels
Due to
Intrinsic disease of the affected vessel
Thromboembolism
Cardiac
Extracranial vessel
Decreased perfusion pressure
Especially in the context of a flow-limiting stenosis

8. Pathophysiology of Cerebral Ischemia
Duration
Transient (TIA)
Transient focal CNS ischemia without infarction
Seconds to minutes
Prolonged (Infarction)
Infarction
Less than 2 to 3 hours
Infarction of core
More than 2 to 3 hours
Infarction enlarges into penumbra

9. Ischemic Core and Penumbra

10. …

12. Intrinsic Cerebrovascular Disease
Fluid Attenuation Inversion Recovery
(FLAIR)
Diffusion Restriction
(DWI)

13. What Caused This Stroke?

14. Don’t Neglect the Right Hemisphere!

15. What Caused This Stroke?

16. The Brain is Complex

18. Recognizing Stroke You don’t need to be a neurologist!
You do need to look for acute deficits characteristic of stroke:
Language comprehension or fluency
Dysarthria
Vision
Gaze / Eye Movement Abnormalities
Visual Field Deficits
Facial or Limb Weakness
Limb or Gait Ataxia
Lateralized Sensory Loss or Extinction
Grading the deficits is of secondary importance

19. Stroke Mimics Syncope Hypoglycemia Seizure Migraine Aura
Transient Global Amnesia
Encephalopathy
Encephalitis
Myelopathy

20. Stroke as a Cause of Death
Prior to 2008
3rd after Heart Disease and Cancer
2016
Heart disease
Cancer
Chronic Lower Respiratory Diseases
Accidents
Stroke
-of-death.htm

21. Acute Stroke Treatment
December 1995: NINDS rtPA Stroke Trial
624 patients randomized
rtPA vs. placebo
3 hour time window
End point
Complete or nearly complete recovery at 3 months
Odds Ratio
1.9 with treatment
“At least 30% more likely to have minimal or no disability at 3 months compared to placebo.”
Tissue Plasminogen Activator for Acute Ischemic Stroke. N Engl J Med 1995;333:

22. The NIHSS Level of Consciousness Orientation Language Vision
Comprehension
Fluency
Vision
Gaze
Visual fields
Facial weakness
Dysarthria
Limb weakness
Limb ataxia
Sensation
Extinction (inattention)

23. NINDS Subgroup Analysis
Initial concerns that the apparent benefit from thrombolysis were an artifact of unequal severity of stroke between the two arms of treatment were not supported upon subsequent reanalysis of the NINDS data.
The impact of imbalances in baseline stroke severity on outcome in the NINDS rtPA Stroke Study. Ann Emerg Med. 2005;45:

24. Subsequent Trials found Similar Efficacy
ECASS I
ECASS II
Atlantis A
Atlantis B

25. Risk of Intracerebral Hemorrhage
NINDS
6.4%
45% were fatal
2.9% risk of fatal ICH
No difference in mortality between groups
17% with thrombolysis vs. 21% placebo
Tissue Plasminogen Activator for Acute Ischemic Stroke. N Engl J Med 1995;333:

26. Acute Stroke Treatment
2002: SITS-ISTR
Safe Implementation of Thrombolysis in Stroke – International Stroke Thrombolysis Register
11,865 patients treated within 3 hours of onset
56% likelihood of Modified Rankin score of 0-2
Risk of early sICH: 1.6% (1.4 – 1.8)
Guidelines for the Early Management of Patients with Acute Ischemic Stroke. Stroke March 2013 :

27. SITS-MOST 6483 patients in 285 European centers Rate of hemorrhage
Any hemorrhage (NINDS): 7.3%
Include minor petechial change
Symptomatic hemorrhage: 1.7%
Increase in NIHSS of 4 points or more
Thrombolysis with alteplase for acute ischaemic stroke: An observational study. Wahlgren N, et al. Lancet 2007 JAN 27;369(9558):

28. Acute Stroke Treatment
2014 Meta-Analysis
6756 subjects from numerous trials
Treatment within 3 hours led to a good outcome (mRS 0-1) for 33% of patients versus 23% for controls.
Benefit was similar regardless of
Patient age
Stroke severity
Le coup de gras pour cette vieux echelle NIHSS ?
Each 15-Minute reduction in time to treatment
increases likelihood of discharge to home, ambulatory by 3 – 4 %
Decreases risk of death and of ICH
Effect of treatment delay, age and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual pateint data from randomised trials. Emberson J. et al. Lancet ;384(9958):1929.

30. Earliest Possible Treatment is Important
Continuously improving likelihood (OR) for little or no neurological deficit (i. e. decreasing number to treat).
Faster process may allow additional patients to be treated due to time window.
Goal is DTN <60 minutes
May change to 45 minutes
Marler et al. Neurology. 2000;55:

31. J. K.
2100: 65 y/o male suddenly develops left-sided arm, leg and face weakness while getting ready for bed. Alerts wife who calls 911 immediately.
2112: Ambulance dispatched (L&S).
2130: Arrival on scene. Found to be awake, slurred speech, with left sided weakness and rightward gaze.
2148: Departure from scene. ACH notified of Code Stroke. IV access established, bloods drawn.
2212: Arrival at ACH

32. J. K.
2212: Arrival at ER 2222: CT Head is normal 2222: Seen by physician, moving arms and legs, but still with dysarthria, near-total left facial paresis, decreased sensation left side. (NIHSS =4) 2250: Telestroke initiated. 2353: tPA bolus administered -Onset to needle: 2:53 -Door to needle: 101 minutes 0024: Departure for MMC

33. Acute Stroke Treatment Components
Prehospital
Transport
Notification
ED Assessment
Imaging CT
CTA
Telestroke Assessment
Informed Consent
Mix and Administer tPA

34. Change in Paradigm
With the advent of effective treatment comes challenge for the healthcare system:
Management of a certain level of risk in order to achieve benefit
Logistical
Need for an accurate and detailed acute evaluation

35. T. K.
32 y/o mother of 3 who 27 weeks pregnant presents to ER approximately 90 minutes after onset of left sided weakness and confusion.
Examination shows
highly variable left sided weakness
occasional rightward gaze
variable left hemianopia
normal vital signs
CT scan is negative

36. T. K.
Social History: Patient reports husband is about to fly a sortie in a B2 bomber out of Qatar.
MRI is ordered.

37. T. K.
MRI shows a small area of diffusion restriction in the right parietal lobe.
CTA is ordered.

38. T. K.
CTA shows proximal (M1 segment) right MCA occlusion, otherwise normal.

39. CT and MR Angiography

40. T. K.
Patient is transported by helicopter to outside facility and brought directly to the cath lab, arriving 7 hours after onset of symptoms.
Initial assessment at that time showed a decreased level of consciousness, rightward gaze, left hemianopia and left hemiplegia
Initial angiographic images confirm a proximal right MCA thrombus with significant distal filling from collaterals

41. T. K.
A catheter is passed through the thrombus with successful retrieval.
Patient becomes more alert within 5 minutes, gaze normalizes and starts moving left side.
Patient walks out of the hospital 2 days later to drive home with her husband, with no neurological deficits.

42. Thrombus Retrieval
5 studies in 2015 showed benefit for mechanical clot retrieval
Meta-analysis
1287 patients
OR for mRS 0-2 is 2.35 (CI 1.85 – 2.98)
FDA approval for use within 8 hours of stroke onset
Used typically after intravenous tPA
Large vessel occlusion found on angiography
Large ischemic penumbra

43. Mechanical Thrombectomy
Acute ischemic stroke with
NIHSS of at least 2
ASPECTS score of at least 6
Proximal Arterial occlusion on CTA or MRA
ICA
MCA (M1 / M2)
ACA (A1 / A2)

44. Mechanical Thrombectomy
Superior to IV thrombolyis alone
Odds ratio 2.35 (95% CI )
Number to treat for little or no neurological deficit: 4
Is ordinarily used as an adjunct to IV thrombolysis
Can also be used in patients who are not candidates for IV thrombolysis
Time to treat of 6 hours – longer in selected cases
Location
Extent of tissue at risk
Effectiveness of collateral recruitment
Therapeutic anticoagulation

45. Acute Stroke Management
Blood Pressure Management
Goal
< 185/110: Prethrombolysis
< 180/105: Thrombolysis (x 24 hours)
< 220/120: Post Stroke Permissive Hypertension
Method
Acute
Labetolol
Nicardipine drip
Avoid hydralazine, nitroglycerin, nifedipine!
Subacute
OK to reintroduce baseline antihypertensives after hours if
Neurologically stable
Large vessel occlusion has been ruled out
Maintain Euvolemia
Isotonic saline without dextrose
Maintain glucose 60 to 180 mg/dl
Avoid Fever
Dysphagia screening
Nutrition within 48 hours is important

46. Identify and Treat the Pathophysiology
Imaging
MRI
Confirmation of infarction
Hints as to pathophysiology
Angiography
MRA
CTA
Carotid US
Poor assessment of the vertebral arteries
Can miss carotid and vertebral artery dissection

47. Cryptogenic Stroke 30 - 40% of all ischemic stroke Consider
Cardiac source of embolus
PAF
ASD
Hypercoagulable state
Less than age 50
Past or family history of thrombotic events

48. Identify and Treat the Pathophysiology
Echocardiography
Consider ASD
Saline contrast
Doppler
Consider TEE if high index of suspicion for cardiac source
Telemetry
Cardiac event loop monitor for ?PAF
30 days to 3 years

49. Initiate Secondary Prevention Strategies
Antithrombotic Therapy
Antiplatelet therapy
Aspirin
Aspirin with long-acting dipyridamole (Aggrenox)
Clopidogrel (Plavix)
Anticoagulation
Indicated for some cardiac sources of emboli
Atrial fibrillation, including PAF
Agents
Coumadin
NOAC

50. Initiate Secondary Prevention Strategies
Blood Pressure Control
Lipid Management
Check an admitting LDL
Start a statin if possible
Target LDL
Diabetes Management
Target A1C of 7.0 to 8.0
Smoking Cessation!

51. The Bottom Line
Ischemic stroke is a leading cause of death and disability
Acute and subsequent treatment of stroke must address underlying pathopysiology
Stroke is not difficult to recognize: a sudden development of a focal neurological deficit
Incidence and severity are impacted significantly by current management practices
Hyper acute management
Acute management
Primary and secondary prevention