Cerebrovascular vasospasm is a consequence of subarachnoid hemorrhage following aneurysmal rupture. its types, causes, etiology, incidence, diagnois and treatment protocols should be understood for better identification and management of this condition.

1. Cerebrovascular Vasospasm
Presented By:
Dr. Rahul Jain
SR-2 Neurosurgery
Moderated by:
Dr V. C. Jha
Dr Nitish Kumar
Dr Gaurav Verma

2. INTRODUCTION
• Cerebral vasospasm is a prolonged, sometimes
severe, but ultimately reversible narrowing of the
cerebral arteries that begins days after
subarachnoid haemorrhage.
• Bleeding significant enough to cause vasospasm is
almost always due to rupture of a saccular
aneurysm.
• Vasospasm affects only the intradural arteries and
primarily, but not exclusively, arteries and large
arterioles located on the surface of the brain.

3. • The delayed onset and relative predictability of
vasospasm provide a unique therapeutic window
of opportunity not found with other types of
ischemic stroke.
• It remains one of the more important determinants
of outcome after aneurysm rupture.
• After aneurysm repair, minimizing harm from
vasospasm is the mainstay of SAH management.
• Vasospasm rarely complicates rupture of
arteriovenous malformations, brain tumor surgery,
and surgery for unruptured intracranial aneurysms
because significant bleeding into the subarachnoid
space is uncommon with these conditions.

4. Definitions
1. Radiographic vasospasm (AKA angiographic
vasospasm)
• Arterial narrowing demonstrated on cerebral angiography,
often with slowing of contrast filling.
• diagnosis is solidified by previous or subsequent angiograms
showing the same vessels with normal caliber.
• Peaks in severity at 1 week
• Incidence - around 50% (range: 20–100%).
2. Clinical vasospasm
• delayed ischemic neurologic deficit (DIND), or symptomatic
vasospasm.
• Clinically characterized by confusion or decreased level of
consciousness sometimes with focal neurologic deficit (speech
or motor).

5. 3. Delayed cerebral ischemia (DCI)
• Presence of focal neurological deficit or a decrease of at least 2
points on the Glasgow Coma Scale score lasting longer than 1
hour with no other identifiable cause.
• umbrella term that encompasses symptomatic vasospasm,
delayed ischemic neurological deficit (DIND), and
asymptomatic delayed cerebral infarction.
4. Early brain injury (EBI)
• refers to a number of factors including the transient increase in
ICP, reduction of CBF, apoptosis, and edema formation.
5. Delayed cerebral infarction
• Radiologic evidence of an infarct present after the time of DCI
within 6 weeks of SAH and 24 to 48 hours after aneurysm
repair.

6. EPIDEMIOLOGY
• Angiographic vasospasm typically occurs 4 to 14
days after SAH, peaking at days 7 to 10 and
resolving by day 21.
• Only about 40% of patients with vasospasm will
develop DCI.
• Rough estimates are that at least moderate
vasospasm in at least one cerebral artery will
develop in two-thirds of patients with ruptured
aneurysms, half of these patients will become
symptomatic as a result of ischemia, and delayed
cerebral infarction will develop in about half of
these patients.

7. PREDICTION
• Large volume of
persistent subarachnoid
clot is the most
important risk factor.
• Modified Fisher scale

8. • Intraoperative aneurysm rupture during surgical
clipping - not found to correlate with increased
risk.
• Other possible relationships -female sex, younger
age, Japanese ethnicity, cocaine use, and aneurysm
location with DACA aneurysms having unusually
high incidence.
• Endovascular coiling, as opposed to microsurgical
repair of ruptured aneurysms, is associated with a
lower risk.
• Spontaneous perimesencephalic or prepontine SAH
(or both) unassociated with aneurysm rupture is
typically a low-volume haemorrhage with low risk.

9. PATHOGENESIS
• Breakdown of subarachnoid blood clots forms
haemoglobin and other by-products, such as
methemoglobin, oxyhemoglobin, heme, and hemin.
• These products may trigger vasospasm through
vasoirritation resulting in
1. smooth muscle contraction,
2. alteration in endothelial cell function resulting in
production of potent vasoconstrictors, and
3. neuroinflammation.

10. Smooth Muscle Contraction
• Vasospasm is prolonged cerebral arterial
constriction caused by vascular smooth muscle
contraction.
• Hemoglobin in the subarachnoid  entry and
release of calcium  activation of
calcium/calmodulin-dependent MLCK 
phosphorylation of myosin light chains  actin-
myosin cross linkage  contraction
• Chronic vasospasm – occurs after several days and
lasts several weeks  Protein kinase C, Rho kinase,
and protein tyrosine kinase  shortening in the
absence of high intracellular calcium levels

11. • Contiguous and second-phase chronic vasospasm is
less reversible with pharmacologic vasodilators
• Sustained vasoconstriction is associated not only
with functional impairment of the vessel but also
with ultrastructural damage to the vascular wall
layers including vacuolization of endothelial cells,
loss of tight junctions, breakage of the internal
elastic lamina, and patchy myonecrosis in the
tunica media.

12. Endothelial Injury, Nitric Oxide,
and Endothelin-1
• Auto-oxidation of oxyhemoglobin 
methemoglobin and superoxide anion radicals 
lipid peroxidation  lipid peroxides and hydroxyl
radicals permeate vessel wall  endothelial injury.
• Endothelial damage  loss of endothelial NO
synthesis (powerful vasodilator) or overproduction
of endothelin-1 (ET-1 – powerful vasoconstrictor).
• Oxyhemoglobin has been shown to trigger the
release of ET-1 from endothelial cells, acts on
neighboring vascular smooth muscle ETA receptors,
and causes profound and sustained vasoconstriction.

13. • Decreased availability of the simple molecule NO
may contribute to the development of vasospasm
in the following ways:
(1) Endothelial nitric oxide synthase (NOS)
dysfunction in vasospastic vessels,
(2) NO scavenging by oxyhemoglobin;
(3) reversal of vasospasm by NO donors,
(4) disappearance of neuronal NOS activity from the
adventitia of vasospastic vessels,
(5) decreased cerebrospinal fluid (CSF) nitrite levels
along with increased levels of asymmetrical
dimethyl-l-arginine, the endogenous inhibitor of
NOS

14. Inflammation, Vessel Remodeling,
and Vasospasm
• Inflammatory cascades are activated after SAH, which
may contribute to vasocontraction or modify the vessel
wall extracellular matrix and smooth muscle cell
phenotype— a process known as vascular remodelling.
• Elevated serum tumor necrosis factor α, serum P-
selectin, serum L-selectin, peripheral blood
mononuclear cell Toll-like receptor 4 expression level,
blood neutrophil count, elevated CSF interleukin-6,
plasma complement C3a.
• CSF neutrophil percentage of greater than 62% to be
predictive of vasospasm

15. CLINICAL FEATURES
• Symptoms of ischemia appear 1 week after
aneurysm rupture, remain vigilant for this
complication for at least 2 weeks after SAH.
• Regular and careful bedside examination remains
the simplest and most effective means of detecting
early ischemia in awake patients.
• Subtle findings such as diminished attention, changes
in verbal output, or a slight but new pronator drift.
• Symptomatic vasospasm usually gradual onset,
sometimes heralded by increased headache and a
change in patient behavior—either agitation or
somnolence.

16. • Signs of symptomatic vasospasm are referable to
the territory that has become ischemic.
• MCA territory – monoparesis or hemiparesis and,
when the dominant hemisphere is affected,
aphasia.
• ACA territory – leg weakness, but often bilateral
confusion, drowsiness, poverty of speech, and
eventually abulia are characteristic signs.
• Symptomatic vasospasm is difficult to detect in
patients who remain in poor neurological condition
• These patients require clinical examination and
additional tests like CT angio or perfusion.

17. • Delayed neurological deterioration after
aneurysmal SAH has a number of causes apart from
vasospasm.
• One or more of these conditions can magnify even
a focal neurological deficit and therefore easily be
mistaken for vasospasm, which has a tendency to
be overdiagnosed in the setting of SAH.

18. Diagnosis

19. • Diagnosis of symptomatic vasospasm requires that
the other causes of delayed worsening listed earlier
be ruled out.
• Transcranial Doppler principle that as an artery
narrows, blood flow velocity within it increases.
Non invasive, bedside, easily done at bedside and
can be done on daily basis provided that the
patient has an adequate acoustic window in the
temporal region through which to insonate.
• TCD velocity of MCA and Lindegaard Ratio
(VMCA/VICA)

20. • CTA: specific for vasospasm, but may overestimate the
degree of stenosis. DSA is gold standard.
• MRA: may be useful for management of vasospasm (not
a practical alternative to conventional angiography as not
possible in critically ill)
• continuous quantitatively analyzed EEG monitoring in
the ICU
• decline of the percent of alpha activity (defined here
as 6–14 Hz) called “relative alpha” (RA) from a mean
of 0.45 to 0.17 can predict the onset of vasospasm
earlier than TCD or angiographic changes
• a decline of total EEG power (amplitude) was 91%
sensitive for predicting vasospasm.
• significant amount of manpower required for around-
the-clock real-time telemetry limits its clinical use.

21. • Cerebral microdialysis catheters bedside
measurement of extracellular concentrations of
glutamate, lactate, pyruvate, lactate/pyruvate ratio,
glucose, and glycerol in brain tissue.
• The markers with the most reliable prediction of
ischemia, are glutamate and lactate, as these peaked
24 hours before clinical ischemia.
• alterations in cerebral blood flow (CBF):
○ MRI: DWI and PWI may detect early ischemia
○ CT perfusion study
○ xenon CT: may detect large global changes in CBF, but
too insensitive to detect focal blood flow changes, and
does not correlate with increased TCD velocities,
positron emission tomography (PET), or SPECT scans
(nonquantitative, and takes longer than xenon studies).

22. • CT perfusion is one of the most widely used
investigation in patients with SAH. Perfusion
hemodynamics of a selected region are seen during
contrast bolus and Cerebral ischemia can be identified
with side to side differences in perfusion or absolute
threshold values for CBF, cerebral blood volume and
mean transit time.
• CTP can provide early detection of reduced CBF,
prolongation of MTP which is also indicative of
ischemia, and status of CBV which is normally
preserved in penumbra but markedly reduced in
infarcts.
• Sensitivity and specificity are 74 to 97% and 76 to 93%
respectively.
• Major limitations are that it is non continuous and has
high degree of variability owing to differences in
equipment used and post-processing method.

23. Patient presenting with weakness of the right arm and leg, 6 days after SAH related to
a ruptured saccular aneurysm of the left MCA bifurcation, which was clipped (bold
arrow). DSA showed moderate vasospasm on the distal carotid segment and severe
vasospasm on the A1 t of the left ACA and the M1 and proximal M2 of the left MCA
(A, black arrowheads). MIP image before (B) and after (C) intra-arterial infusion of
nimodipine showing resolution of the vasospasm (white arrowheads), and followed by
the resolution of the symptoms. At pretreatment PCT, MTT was increased in the left
MCA territory (D), CBF was normal (E), and a slight increase in CBV (F) was observed,
representing vasospasm related auto regulation mechanisms.

24. PREVENTION OF VASOSPASM AND
CEREBRAL PROTECTION
• Hypovolemia in the
acute stage of SAH
owing to volume
contraction from
natriuresis and
inappropriate
antidiuretic
hormone elevation.
• systematic review
on triple H therapy
found no difference
in clinical outcome.

25. • Medical morbidities associated with triple-H
therapy include pulmonary edema, myocardial
ischemia, hyponatremia, renal medullary washout,
indwelling catheter–related complications, cerebral
hemorrhage, and cerebral edema.
• After aneurysm repair, circulating blood volume
and systemic blood pressure should be maintained
in the normal range.
• Hyponatremia may increase the risk for vasospasm
and is associated with cerebral infarction in poor-
grade patients. Current AHA guidelines recommend
salt replacement in the form of NS or 3%
hypertonic saline combined with fludrocortisone
(Florinef) (0.3 mg/d) administration if the patient is
experiencing vasospasm.

26. • Blood transfusion has been associated with a
higher likelihood of both vasospasm and poor
outcome.
• Current guidelines suggest a transfusion threshold
of 8 g/dL in patients with SAH without symptomatic
spasm.
• Optimal ventilation and oxygenation, fever
prevention,glucose control, good nutrition, and
attention to concentration of all electrolytes in
addition to sodium are important in reducing the
impact of vasospasm and delayed ischemia.

27. REVERSAL OF VASOSPASM AND
CEREBRAL ISCHEMIA
• Augmentation of CBF through collaterals around
vasospastic vessels by elevating systemic blood
volume and pressure can reverse cerebral ischemia.
Triple-H Therapy: Hypervolemia, Hypertension, and
Hemodilution
• intended to improve cardiac output, increase CPP,
and optimize hemorheology for oxygen transport,
and for many years was the mainstay of treatment
for symptomatic vasospasm.
• Significant risks and morbidities of this therapy.

28. • Risks are greatest in elderly patients and patients
with intrinsic, preexisting cardiopulmonary disease.
• deliberate triple-H therapy combining all three
components has fallen out of favor in SAH
management.
• Current American Heart Association guidelines
recommend induction of hypertension (class 1,
level of evidence B) and maintenance of euvolemia
(class 1, level of evidence B) for treatment of DCI.
• When symptomatic vasospasm is diagnosed or
strongly suspected, hemodynamic treatment
should begin with volume expansion with an
isotonic crystalloid infusion only if required.

29. • In a healthy patient, modest volume expansion can
raise CBF in vasospastic territories without a
significant change in cardiac indices.
• A replete intravascular volume beyond which
additional expansion is probably of no further
benefit corresponds to a CVP between 8 mm Hg
and 10 mm Hg or a PCWP between 14 mm Hg and
16 mm Hg.
• Current guidelines do not recommend intentional
hemodilution.
• Hemodilution accompanies any deliberate volume
expansion, and reduced viscosity may contribute to
an improvement in oxygen delivery provided Hct
doesn’t fall below 30% and Hb below 9 g/dl.

30. • Induced hypertension is effective in improving
cerebral oxygenation in patients with vasospasm
and has fewer complications than hypervolemia.
• Provided that the ruptured aneurysm has been
repaired, it is recommended to treat symptomatic
vasospasm with the administration of a
vasopressor, the most commonly used being
phenylephrine or norepinephrine (α-agonist
vasopressors).
• Dobutamine or dopamine and another cardiac
inotrope, milrinone, has also been used after SAH.
• The key aspect of treatment if it is to be successful
in reversing ischemia is prompt elevation of blood
pressure, regardless of the agent chosen.

31. • 70% of patients with DCI clinically improve with
induced hypertension.
• If there is no clinical response to an initial target of
160 to 180 mm Hg systolic blood pressure, the
target is escalated every 30 minutes to a maximal
target of 220 mm Hg for SBP, 120 mm Hg for CPP,
and 140 mm Hg for MAP.
• If ischemic signs persist, hypertensive treatment
should be considered to have failed.
• The only randomized controlled trial of induced
hypertension in SAH was discontinued prematurely
owing to lack of benefit and slow enrollment.

32. Other Reversal Therapies
• Some evidence for targeting a cardiac index of >4.0
L/min/m2 for the treatment of DCI.
• Neurocritical Care Society guidelines suggest a
transfusion target of 9 to 10 g/dL in patients with
DCI, which is above the transfusion target of 8 g/dL
for prevention of DCI (evidence is lacking).
• Hypertonic Saline can be considered in patients
who are also experiencing high ICP.
• Therapeutic Hypothermia for a temperature target
between 33°C and 36°C but no objective evidence

33. • Intrathecal/Intraventricular Vasodilators
• In patients with severe and medically refractory
vasospasm
• Sodium nitroprusside, an NO donor, has been
administered into the lateral ventricles via a
ventriculostomy catheter or into the thecal sac via a
lumbar drain.
• Intrathecal nicardipine was found to reduce TCD
velocities within 8 hours of administration.
• Intra-aortic Balloon Counterpulsation and Aortic
Flow Diversion
• originally designed for the management of
cardiogenic shock.

34. • transfemoral aortic balloon that inflates on
aortic valve closure with each cardiac cycle and
augments diastolic flow proximally to the
coronary and cranial arteries and distally to the
peripheral circulation.
• reported to be feasible and effective in patients
with combined severe vasospasm and cardiac
failure.
• For patients at high risk of vasospasm but
normal cardiac function did not confer any
clinical benefit in a small, single-center
randomized controlled trial.

35. Endovascular Reversal of Vasospasm
• Indications- When maximal medical therapy fails in
patients with clinically symptomatic vasospasm.
• Options include percutaneous transluminal balloon
angioplasty (PTA) or transcatheter intra-arterial
vasodilator infusion or their combination.
• PTA is judiciously reserved for cases of severe,
refractory, proximal vessel vasospasm.

36. • Patient previously
underwent surgical
clipping of a blister
aneurysm of the
ophthalmic segment (D,
arrowhead).
• Anteroposterior (A and
C) and lateral (B and D)
angiograms obtained
before (A and B) and
after (C and D)
• angioplasty for severe
symptomatic
vasospasm. Arrows
show the dramatic
increase in diameter of
the middle cerebral
artery and distal ICA
(C).

37. • Verapamil at 5 to 20 mg per vascular distribution
(typically 5–10 mg) as first-line therapy for
angiographically significant vasospasm, especially
for distal spasm beyond the first-order branches of
the circle of Willis.
• Intra-arterial administration of verapamil has been
demonstrated to be safe in dosages between 2 and
20 mg per vessel. Neurological improvement is
seen in 30% to 66% of patients, and repeat
treatment is necessary in only 15% of patients.
• Nicardipine has a similar profile to verapamil in
relative tissue selectivity, with minimal cardiac
impact.

38. • Milrinone - better clinical results, excellent safety
profile, a synergistic effect of high-dose milrinone
and nimodipine infusion for endovascular rescue
therapy has been reported.
• To date, no evidence exists to confirm which intra-
arterial agent is more efficacious for the treatment
of refractory vasospasm.
• Continuous intraarterial infusion of calcium channel
blockers may provide additional advantages such as
needing fewer transports of unstable patients into
the radiology suite, allowing longer exposure to
intra-arterial drug therapy, and requiring fewer
arterial catheterizations, which then lessens the
risk of access complications.
• Drawbacks include systemic hypotension, infection,
and increased ICP.

39. • Prophylactic PTA in patients at high risk for
developing life-threatening cerebral vasospasm has
been reported but remains very controversial.
• In canine models of posthemorrhagic vasospasm,
prophylactic PTA on day 0 prevented the
development of vasospasm on day 7 in all animals.
• In one small clinical series, patients with
aneurysmal Fisher grade 3 SAH treated with
prophylactic PTA within 3 days of hemorrhage;
none of these patients developed delayed ischemic
neurological deficit (DIND) or clinically significant
abnormalities on transcranial Doppler imaging, but
the rate of mortality secondary to vessel rupture
was 8%.
• Currently no guideline for prophylactic PTA.

40. SUGGESTED APPROACH TO PREVENTION AND
TREATMENT
• Patients should be kept well hydrated and euvolemic with
isotonic crystalloid and intermittent albumin infusions (at
least 3 L/d, combined)
• ICP kept normal with external ventricular drainage, and CPP
optimized to levels higher than 70 mm Hg.
• No attempt should be made to lower mild or moderate
hypertension.
• TCD values greater than 200 cm/s in the MCA are indicative
of significant angiographic vasospasm in that artery.
• Regular clinical assessments searching for changes in
mentation, verbal output, and arm and hand control are
important; the best testing for developing vasospasm and
cerebral ischemia is regular bedside neurological
examinations through the vasospastic interval days 4 to 14
after SAH.

41. • All patients should receive nimodipine, 60 mg every
4 hours orally or via a nasogastric tube for 21 days
or as long as they remain in the hospital.
• Every effort should be made to avoid
hyponatremia, fever, and hypoxia, and patients
should be fed enterally as soon as possible.
• Symptomatic vasospasm detected in patients in
whom examination can be conducted and
moderate to severe angiographic vasospasm in
comatose, unexaminable patients should be
treated by infusion of a vasopressor to induce HTN.
• CVCs are preferred over peripheral IV caths.

42. • If signs do not respond quickly and completely or a
target blood pressure is difficult to reach,
endovascular treatment is indicated including
angioplasty for all narrowed arteries reachable with
a balloon-tipped catheter.
• CT scan must be performed first to rule out a large,
established infarction or a new haemorrhage.
• Failure of neurological deficits to improve with
hypertension and/or endovascular treatment often
indicates that deterioration was due to another
cause or ischemia has progressed to an established
infarction.

45. Conclusion
Treatment paradigms will continue to evolve as new
medications become available, diagnostic modalities
are discovered, and the pathophysiologic
characteristics of vasospasm are better understood.
Because of these promising future developments,
vascular neurosurgeons and interventionalists should
remain attuned to such changes and tailor treatment
regimens accordingly.

46. References
1. Greenberg 10th ed
2. Youman and winn 8th ed