1. Improving Patient Outcomes in Acute Carotid Occlusion
Kendrick Johnson, MD
PGY-IV Resident, Department of Neurosurgery
Important Cause of stroke
Key Focus in INI Cerebrovascular Center

2. Full Disclosure of Presenter Financial Interests or Relationships
I declare that I or my immediate family do not have a financial interest or other relationship with any manufacturer/s of a commercial product/s which may be discussed at the conference.

3. Objectives
Describe the pathophysiology of stroke in the setting of acute carotid occlusion
Describe treatment options for acute carotid occlusion
Describe INI protocol and current clinical study regarding Carotid Thromboendarterectomy

4. Cerebral O2 Transport The human brain:
Comprises only 2% of total body weight
However, receives 15% of cardiac output
Furthermore, utilizes 20% of O2 and 25% of glucose produced by the body
90% of cerebral O2 is utilized by mitochondria to generate ATP
Metabolic demand highlights the importance of this organ system
Therefore, oxygen transport to the mitochondria is important in maintaining aerobic cellular respiration and energy production

5. Cerebral Energy Consumption
50% of the energy produced is needed for synaptic activity.
25% is used for restoring ionic gradients across cell membrane.
The remaining energy is spent on biosynthesis
If the synthesis of ATP is insufficient, homeostatic mechanisms deteriorate, intracellular [Ca2+] increases, and cell death is
inevitable.
Most of the energy is consumed by the neurons; although glial cells account for almost half of the brain volume, they have a much lower metabolic rate
Intracellular Ca flux is one of many signals of cellular death cascade

6. Cerebral Blood Flow CBF- blood supply to the brain at a given time
CBF= CPP = MAP-ICP
CVR CVR
CBF (ml/100g tissue/min)
Condition
>60
Hyperemia (CBF> demand)
45-60
Normal brain at rest
75-80
Gray matter
20-30
White matter
16-18
EEG alterations 15
Physiological paralysis 12
BAER changes 10
Alterations in cell membrane transport (cell death/stroke)
Move on to cerebral hemodynamic measures
CBF ~50 wnl

7. Approximate Time to infarct (min)
Cerebral Blood Flow
Tissue infarct in relation to CBF is time dependent
CBF (ml/100g tissue/min)
Approximate Time to infarct (min) 5
30 min 10
3 hrs 15
3.5 hrs 18
>4hrs

8. Cerebral Vascular Resistance
PaCo2 linear relationship with CVR, between PaCO mmHg
CVP also changed by CPP- by change in vessel tone
CVR for normal brain changes to maintain constant CBF= autoregulation- altered in pathological states

9. CT Perfusion AJR:198, January 2012 Nebulous
Basic physiology applied in clinical setting
CTP or physiological imaging is future of stroke care→ move away from time → imaging
AJR:198, January 2012

10. CT Perfusion
CT is a readily accessible and rapid technique that can aid in the detection of acute ischemic stroke
- CTP can help identify patients likely to benefit from early reperfusion
The advantages of perfusion CT include its widespread availability, speed of image acquisition, relative lower cost compared with MRI, and ease of patient monitoring.
Advantages
Disadvantages
Available
Speed of imaging
Physiological parameters (CBF, CBV, ect)
Clinical Implications*
Radiation
IV Contrast
Image processing*
Salient point in our treatment paradigm and study
Real time physiologic parameters in the evolving stroke patient

11. CT Perfusion Parameters
CBV- measure of the total volume of blood within an imaging voxel
CBF- total volume of blood moving through a voxel in a given unit of time
Mean Transit Time (MTT)- is the average transit time of all the molecules of contrast medium with the bolus through a given volume of brain measured in seconds- (MTT = CBV / CBF)
Time to Peak (TTP)- time from the start of the contrast injection to maximal enhancement measured in seconds
Normal perfusion parameters are:
gray matter
MTT: 4 s
CBF: 60 ml/100 g/min
CBV: 4 ml/100 g
white matter
MTT: 4.8 s
CBF: 25 ml/100 g/min
CBV: 2 ml/100 g
Data to be gleaned from CTP
Gray Matter is more metabolically active

12. CT Perfusion in Ischemia
Identify areas of decreased CBF and CBV
Increased MTT and TTP
Matched perfusion abnormalities in CBV, CBF and MTT= infarct core “unsalvageable”
Mismatched perfusion in prolonged MTT , diminished CBF, however CBV maintained = “penumbra”
In the evolving stroke CBF declines CBV remains stable in the compensated state, however matched decline in parameters – infarct

13. CT Perfusion- Core vs Penumbra
CT perfusion maps of cerebral blood volume (a) and cerebral blood flow (b) show, in the left hemisphere, a region of decreased blood volume (white oval) that corresponds to the ischemic core and a larger region of decreased blood flow (black oval in b) that includes the ischemic core and a peripheral region of salvageable tissue. The difference between the two maps (black oval = white oval) is the penumbra. DISABILITY VS HOME
(a)
(b)

14. Evaluation of Cerebrovascular Reserve
During stress, areas affected by cerebrovascular steno occlusive disease are at risk for ischemia because cerebrovascular reserve, in the form of collateral vessels and autoregulatory response, is limited.
Acetazolamide causes short-term vasodilatation of the cerebral arterioles and when used in conjunction with perfusion CT helps estimate cerebrovascular reserve
Cerebrovascular stenoocclusive disease is most commonly related to atherosclerotic disease and can result in diminished distal arterial perfusion pressure. There are, however, mechanisms for compensation including autoregulatory vasodilatation and collateral circulation.
Acetazolamide, a carbonic anhydrase inhibitor

15. Stages of Hemodynamic Failure
Stage 0- CPP normal- CBF matches resting metabolic rate→ resting balance between flow and metabolism (minimal variation in OEF)
Stage I- moderately reduced CPP- (minimal effect on CBF)
Vasodilation→ decreased CVR→ constant CBF
(autoregulation)
Stage II- severe reduction in CPP- vasodilatory compensation is exceeded; failure of autoregulation → decline in CBF → increased OEF “misery perfusion”

16. Response of CBF after 1g (ACZ)
Hemodynamic Failure- CTP
Response of CBF after 1g (ACZ)
Stage 0
Normal baseline CBF with 30-60% increase after ACZ
Stage I
Decreased baseline CBF with blunted response after ACZ (<10%)
Stage II
Decreased baseline CBF with paradoxical decrease in regional blood flow, “steal”
Patterns of computed tomographic (CT) and CT perfusion (CTP) imaging in 3 groups of patients with territorial perfusion deficits. In each panel, the upper left quadrant shows the initial CT scan and the lower left quadrant shows the initial CTP scan within 6 hours; the upper right quadrant shows the follow-up CT scan after 24 hours and the lower right quadrant shows the follow-up CTP scan. A, Six patients treated with recombinant tissue-type plasminogen activator showed reperfusion on the follow-up CTP scan and infarctions smaller than the initial area of the perfusion deficit (ie, nutritional reperfusion). B, In 2 patients treated with intravenous heparin, the area of infarction on the follow-up CT scan corresponded to the area of the initial perfusion deficit despite reperfusion on the follow-up CTP scan (ie, nonnutritional reperfusion). C, In 2 patients with recombinant tissue-type plasminogen activator therapy, reperfusion was not achieved and the area of the initial perfusion deficit corresponded to the infarction on the follow-up CT scan.

17. Clinical Implications of Hemodynamic Failure
Grubb et al, JAMA, 1998.
Is Stage II Failure (increased OEF on PET) an independent risk factor for subsequent stroke in medically treated patients?
Design: Prospective, blinded, cohort
Patients: 419 referred, 81 enrolled, avg f/u 31.5 mo
Outcomes Measure: All stroke, ipsilateral stroke, death
Results: Stroke in 11/39 with Stage II failure, 2/42 with Stage I failure (P=0.004)
Basic Science and Imaging Characteristics, but why is this important
Stage II Failure is associated with a significantly higher risk of stroke

18. Carotid Artery Occlusion
Comprises 10-15% of pts with carotid stroke/TIA, high rate of subsequent stroke
Associated with poor outcomes:
Permanent Disability 40-69%
Death in 16-55%
Good Recovery in only 2-12% (FB Myer et al 1981 Annals Surg)
Variable presentation: asymptomatic to death- “Rule of thirds”
Pathophysiology of ischemia:
emboli to COW from distal thrombus
stump emboli to ECA
emboli from CCA, ECA, Aorta through
collaterals
hypoperfusion*
Basics of CAO

19. Historical Perspective
Acute ICA occlusion presents a therapeutic challenge.
ICA occlusion has historically been managed conservatively with at times IV tPA and antiplatelet/ anticoagulants
Small series have attempted Endovascular/ IA Rx/ combo
However, no large RCT and ICA occlusion is largely managed expectantly
Variable efficacy

20. STA-MCA Bypass
Newell SNI
Paper preceded COSS

21. STA-MCA Bypass
The STA–MCA bypass is an elegant procedure developed by M. G. Yasargil and was first applied in the treatment of occlusive cerebrovascular disease in 1967
First patient treated had Dx of Marfan with MCA occlusion
Past indications include: Acute stroke, Vasospasm, ICA occl, Tumor, Aneurysm
Past indications widely used!

22. COSS Study
Powers et al, JAMA, 2010 Inclusion criteria: TIA or ischemic stroke within 120 days PET showing ipsi to contra mean regional OEF >1.13 Outcome: all stroke or death within 30 days of surgery. Ipsi stroke within 2 yrs Projected outcomes: 40% medical, 24% surgical Sample size 372 Randomly assigned to surgery or medical management
Remised if COSS not mentioned
Changed the face of CAO treatment and STA-MCA bypass indications
Bypass vs medical management in CAO and Stage II failure

23. COSS Study
Stopped secondary to futility at 195 pts No sig diff in 2yr outcome: 21% surgical, 22.7% medical 30 day event rate 15% is surgical group
Greatly narrowed the indications for bypass

24. Management of Carotid Artery Occlusion
Hafner et al, Surgery, 1981.
10 year, retrospective review
47 thromboendarterectomies for recent ICA occlusion
Patency rate related to duration of occlusion 7 days, mo), overall patency 68%
Petro/cavernous reflux is a positive predictive factor in better surgical outcomes*
Early series of Surgical Treatment with CTEA for CAO
Important observation angiographic appearance of occlusion

25. CTEA Procedure Kasper et al, J Vasc Surg, 2001.
Neurophysiological monitoring
Standard CEA positioning and exposure, Heparin bolus 80U/kg
Initial CCA and ECA control
Small arteriotomy→ manual/ backbleeding to expel thrombus, then ICA control may be obtained
If clot not able to be retrieved, mechanical thrombectomy with 2-3Fr Fogarty balloon
Selective shunting
Arteriotomy repair with patch vs. primary closure
Decadron and Mannitol perioperatively

27. Endovascular Therapy for Carotid Occlusion
Small Dutch series of Endovascularly Rx patients

28. Endovascular Therapy for Carotid Occlusion
Dutch Single center, retrospective review
3000 stroke admissions from
16 patients with extra-cranial Carotid occlusion by CTA criteria
10 patients with “true” occlusion on subsequent DSA
6 patients with “pseudo” occlusion
Treatment success defined as TICI grade 2-3 or NIHSS improved by 10 pts or NIHSS 0-1 at discharge
Recanalization in 83% of patients with pseudo-occlusion
60% in patients with true occlusion
Good outcomes in 50% of patients with pseudo, 40% of patients with true occlusion
4 patients died
All had >15% of hemisphere infarcted ***
Place for physiologic imaging to determine appropriate patient selection

29. INI Retrospective Review Of CTEA in Acute Carotid Occlusion

30. BNI Review of CTEA
Impetus for the study

31. BNI Review of CTEA
Study Design: Single Center, Retrospective Review of surgically managed acute carotid occlusion
42 total patients:
- Diagnostic Protocol: unenhanced CT, DSA
- Documented complete occlusion
- Presenting symptoms: 68%TIA, 28% new fixed deficit, AF 28%, Stroke in evolution 9%
At time of publication, mounting levels of evidence for CTEA in acute occlusion, however retrospective small series

32. BNI Review of CTEA Results: Mean time to intervention 42 hrs
24 (52%) carotids successfully reopened
9 (20%) stumpectomies w/ ECA CEA
4 (9%) stumpectomies w/ subsequent EC-IC bypass
73% long term patency rate
Complications
3 transient perioperative deficits
1 (2%) pts with permanent profound deficits
DSA Reflux correlates to success of revascularization ***
- supraclinoid ICA- 25% success
- Cavernous ICA- 50%
- Petrous ICA- 71%
3 pts lost to f/u
Degree of reflux

33. BNI Review of CTEA

34. INI Retrospective Review
Study Design: Single Center, Retrospective Review
Objective: Does urgent CTEA improve hemodynamic status and outcomes in patients with acute Carotid Occlusion and Stage II Hemodynamic Failure?
Patients: Screen all CEA from , Goal of 10 patients with CTA/DSA proven Acute Carotid Occlusion, with pre and post intervention CT perfusion
Outcomes Measure: Primary- Return to Stage 0, Stage I Hemodynamic Status, Secondary outcomes: mRS, NIHSS, Stroke free survival
Opening Carotid WORKS, but on whom?

35. INI Review Baseline Patient Data
10 Patients Included for Review with requisite imaging
Mean Age at Intervention 61 yrs
60 % Males
90% Caucasian
Pertinent Comorbid Conditions (HTN 70%, HLD 70%, Tobacco 90%)
All (10/10) had Stage II Hemodynamic Failure by CTP Criteria Preoperatively
All (10/10) had at least petrocavernous reflux by Angiographic Evaluation

36. INI Review Patient Data
Mean Preoperative NIHSS: 6.6
Mean Time to Intervention 49 hrs (2-240 hrs)
27 hrs if outlier removed
One outlier early on in the protocol
Gotten more efficient with patient evaluating when presenting with CAO

37. INI Review Results 100% of patients were able to be recanalized
None required stumpectomy
No patients worsened postoperatively
Immediate postop NIHSS: 6
NIHSS at d/c: 4.1
NIHSS at last f/u: 1
No patients experienced Stroke/Death within 30 days postoperatively
Mean mRS at d/c: 2.3 and at last f/u 1.7
9/10 patients had postoperative vascular imaging, of those 100% showed
patency of the operated artery
Promising results thusfar

38. INI Retrospective Review
Average LOS 7.8 days
Disposition
60% home
1 patient to inpatient Rehab
3 patients to SNF

39. INI Retrospective Review
Pre-Op
Post-Op
Steal phenomena after Diamox in Rt MCA territory
Postoperative normalization of hemodynamic state

40. INI Retrospective Review
Occlusion at ICA Origin with cervico-petrous reflux
Underwent successful CTEA and postop CTA shows wide patency of the operated artery

41. CTEA Intraoperative Algorithm
Eliminates the stumpectomy arm of operative algorithm

42. INI Review Conclusions
Thromboendarterectomy for acute carotid occlusion can be performed safely and appears to provide partial or complete restoration of normal cerebral hemodynamics in patients presenting with documented stage 2 hemodynamic failure. Consideration should be given to routine hemodynamic assessment of patients presenting with symptomatic carotid occlusion with subsequent CTEA for select patients with stage 2 failure.

43. Conclusions
A thorough understanding of basics of Cerebral Oxygen Metabolism is essential in understanding current and developing novel therapies for ischemic stroke patients
Our study represents a potentially novel multimodality approach to treatment of patients with acute carotid occlusion. Our hope is to prevent devastating neurological outcome, and improve functional independence.
Patient selection is key in evaluating who will benefit from Carotid revascularization (Clinical, CT Perfusion, Angiography)