The document discusses the concept of vasospasm in relation to delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH), emphasizing the complexities surrounding its management and treatment outcomes. It outlines definitions, associated risks, and clinical guidelines for SAH management, including the use of intravenous nimodipine and the effects of induced hypertension. Additionally, it examines the challenges in establishing a direct relationship between angiographic vasospasm and poor clinical outcomes.

1. DILATING THE
DOGMA OF
VASOSPASM
R. LOCH MACDONALD, M.D., Ph.D.
COMMUNITY NEUROSCIENCES INSTITUTE
FRESNO, CALIFORNIA, USA

2. Fresno, CA

3. Origins of Concept of Vasospasm
Macdonald, Stroke 47:e11-e15, 2016

4. Angiographic VSP - DCI
40 year old female, WFNS grade 2

5. DCI – Induced Hypertension, Balloon Angioplasty
Day 1 Day 3 preangioplasty Day 3 postangioplasty

6. Death
Day 11 Day 12

7. Angiographic VSP
Blood clot leads to angiographic VSP leads to infarction and
poor outcome
Vasoconstriction of large cerebral arteries due to hemoglobin
component of subarachnoid blood
“Pharmacologic” dose response related to the location,
duration of presence and concentration of the
hemoglobin/blood clot
Subarachnoid blood leads to angiographic vasospasm (?leads
to cerebral infarction [DCI] leading to poor outcome)

8. Definitions
Angiographic vasospasm – radiologic appearance
of arteries on CT, MR or catheter angiogram
DCI – clinical deterioration with no obvious cause
(doesn’t require angiographic vasospasm) and/or
cerebral infarction, delayed fashion, not due to
aneurysm-securing procedure, etc.
Vergouwen, et al., Stroke, 2010;41;2391

9. 9
0
10
20
30
40
50
60
70
80
Patients
with
moderate/severe
vasospasm
(%)
% are based on n
Exact 95% C.I.
*Fisher‘s exact test VAS_S01_P
n = 85 n = 95 n = 95 n = 79
All patients (per-protocol)
*p = 0.0027
*p = 0.0003
*p < 0.0001
Clazosentan
1 mg/h 5 mg/h 15 mg/h
Placebo
CONSCIOUS-1 Results

10. 10
All patients (per-protocol)
*p = 0.0027
*p = 0.0003
*p < 0.0001
CONSCIOUS-1 Results

11. Initial event (rupture of aneurysm)
Blood clot
Angiographic
Vasospasm
Ischemia,
Infarction
Poor outcome
• aVSP doesn’t cause poor outcome
• Effect size of treating aVSP on
outcome
• Sample size too small
• Outcome scale not sensitive
• Benefit of reducing vasospasm
balanced by adverse effects of
treatment
• Rescue therapy (induced hypertension,
angioplasty) works
• Other causes for delayed deterioration
Why Treating aVSP Has
Minimal Effect on Outcome

12. Relationship between angiographic vasospasm
and infarction
Cerebral
infarction
None/mild
(209)
Moderate
(118)
Severe (54) Total (381)
No 203 (97%) 106 (90%) 29 (54%) 338 (89%)
Yes 6 (3%) 12 (10%) 25 (46%) 43 (11%)
Crowley, et al., Stroke 42:919, 2011

13. Pathophysiology of SAH
• Early brain injury
– Within 72 hours of SAH
– Transient global cerebral ischemia, detrimental effects of
subarachnoid / intracerebral / intraventricular blood
• Delayed neurological deterioration
– 4-14 days post SAH
– Angiographic vasospasm / DCI / other causes

14. Subarachnoid Blood

15. Stroke 25:1342, 1994

16. aVSP, DCI in SAH

17. Delayed Cerebral Ischemia

18. What Causes DCI?
THERE IS INSUFFICIENT EVIDENCE TO
PROVIDE A RECOMMENDATION...
Angiographic vasospasm
– We sure focus a lot on diagnosing and treating it
Cortical spreading ischemia
– Nimodipine is a good antagonist and it improves
outcome without affecting aVSP (but just because
acetaminophen cures headaches doesn’t mean
headaches are due to acetaminophen deficiency)
Microthromboembolism
– Randomized clinical trial(s) – no effect of aspirin on
outcome

19. SAH Management
• Oral nimodipine should be administered to all patients with aneurysmal SAH
(AHA guidelines, Class 1 level of evidence A, Connolly, et al., Stroke 43:1711,
2012)
• Early aneurysm clipping or coiling (Class 1, level of evidence B)
• Class 2-3, Level of evidence B:
– Euvolemia - > 1.5 ml/kg/day
– Hemoglobin > 8 g/dl
– BP control prior to aneurysm clipping
– TCD, neurological and hemodynamic monitoring
– Avoid hypoglycemia, fever, hypervolemia
– Connolly, et al., Stroke 43:1711, 2012

20. Management SAH and DCI
Statins, magnesium, antifibrinolytic drugs -
NO
Hemoglobin concentration > ? 8 g/dL
Control the BP before the aneurysm repair
(what BP?)
Management of ventricular drainage?
Who gets anticonvulsants? What drug?

21. l 41 patients randomized, adjusted risk ratio for poor outcome with induced hypertension: 1.0
(95% CI 0.6-1.8), serious adverse events: 2.1 (95% CI 0.6-1.8)
l 25 analyzed for CTP, induced hypertension did not significantly improve CBF
l Stroke 49:76, 2018
HIMALAIA

22. Results: Rescue Therapy for DCI
R
R
RESEARCH
Parachute use to prevent death and major trauma when jumping
from aircraft: randomized controlled trial
Robert W Yeh,
1
Linda R Valsdottir,
1
Michael W Yeh,
2
Changyu Shen,
1
Daniel B Kramer,
1
Jordan B Strom,
1
Eric A Secemsky,
1
Joanne L Healy,
1
Robert M Domeier,
3
Dhruv S Kazi,
1
Brahmajee K Nallamothu
4
On behalf of the PARACHUTE Investigators
BMJ 2018:363:k5094 | doi:
10.1136/bmj.k5094
Parachutes are routinely used to prevent death or major
traumatic injury among individuals jumping
aircraft. However, evidence supporting the efficacy of
parachutes is weak and guideline recommendations
for their use are principally based on biological
plausibility and expert opinion. 1 2 Despite this widely
held yet unsubstantiated belief of efficacy, many
studies of parachutes have suggested injuries related
to their use in both military and recreational settings, 3 4
and parachutist injuries are formally recognized in
the World Health Organization’s ICD-10 (international
classification of diseases, 10th revision). 5

23. Results: Rescue Therapy for DCI
R
R
RESEARCH
Parachute use to prevent death and major trauma when jumping
from aircraft: randomized controlled trial
Robert W Yeh,
1
Linda R Valsdottir,
1
Michael W Yeh,
2
Changyu Shen,
1
Daniel B Kramer,
1
Jordan B Strom,
1
Eric A Secemsky,
1
Joanne L Healy,
1
Robert M Domeier,
3
Dhruv S Kazi,
1
Brahmajee K Nallamothu
4
On behalf of the PARACHUTE Investigators

24. l No other prospective, randomized clinical trials
l Indicated for deterioration due to DCI (?angiographic
vasospasm)
l ?May benefit a subgroup of patients with impaired
cerebral perfusion
l Complications
Induced Hypertension

25. l “Reasonable…”, “may be considered…” for vasospasm-
related DCI.
l DCI symptoms / signs refractory to hemodynamic therapy
l Intervention based on aggressiveness of hemodynamic
intervention, patient tolerance, presence/degree of aVSP,
expertise available
Mechanical /Pharmacologic Angioplasty

26. Mechanical /Pharmacologic Angioplasty

27. The Future of “Vasospasm”
• Challenger explosion January, 1986
• Neisser + Harsch 7 question survey to 106 students
(where were they when they heard the news, etc.).
• 2.5 years later, asked the same students the same
questions.
• On average only 3/7 questions answered the same (25%
scored zero).
• Neisser, U., & Harsch, N. (1992). Phantom flashbulbs: False recollections of hearing the news about
Challenger. In E. Winograd & U. Neisser (Eds.), Emory symposia in cognition, 4. Affect and accuracy in
recall: Studies of "flashbulb" memories(pp. 9-31).

28. 31, female, WFNS 2, cocaine, methamphetamine

29. 6 days post-SAH, GCS 15
Day 1
Day 6
Day 6
Day 1

30. 6 days post-SAH, GCS 15
MCA Basila
r
Day R L Prox
2 87 65 44
3 36 92 58
4 23 48 46
5 26 30
6 111 146
7 17 13 45
8 174 19 42
9 77 77 27

31. 9 days post-SAH, decreased LOC, right paresis

33. Conclusions
• Emergency aneurysm repair (rebleeding, clot removal)
• Clot clearance (lumbar drainage?, intrathecal
fibrinolytics)
• Diagnosis and treatment thresholds for DCI
• Randomized clinical trials – induced hypertension,
endovascular rescue therapies

35. 0