A difficult case

Diogo Fitas,1,2 Marta Carvalho,2,3 Pedro Castro,2,3 Pedro Abreu,2,3
Goreti Moreira,4 Rosa Santos,2 Elsa Azevedo2,3
1

Department of Neurology,
Santa Luzia Hospital, Viana do
Castelo, Portugal
2
Department of Neurology, São
João Hospital Centre, Porto,
Portugal
3
Faculty of Medicine of
University of Porto, Porto,
Portugal
4
Stroke Unit of São João
Hospital Centre, Porto, Portugal
Correspondence to
Dr Diogo Fitas, Department of
Neurology, Centro Hospitalar
São João, Porto 4200 – 319,
Portugal; ​cd_​fitas@​hotmail.​com
Accepted 13 May 2018

To cite: Fitas D,
Carvalho M, Castro P, et al.
Pract Neurol Epub ahead of
print: [please include Day
Month Year]. doi:10.1136/
practneurol-2017-001871

Abstract
Carotid endarterectomy carries the risk of
several complications. We report a 55-year-old
woman with recurrent cerebral vasoconstriction
postoperatively. She had bilateral high-grade
internal carotid artery stenosis and underwent
right endarterectomy because of transient
left-sided sensory symptoms. She developed a
reperfusion syndrome with severe right-sided
headache, right frontotemporal oedema and
increased velocities in transcranial Doppler
ultrasound. Given her gradual increase of
velocities and Lindegaard index, together
with fixed left sensory and motor deficits,
we performed CT angiography, which
suggested cerebral vasoconstriction syndrome.
A subsequent left carotid endarterectomy
triggered a similar cerebrovascular response. We
highlight the need for continuous monitoring
of cerebral haemodynamics following carotid
endarterectomy.

A 55-year-old woman presented with
transient sensory symptoms in the left face
and upper limb. She was a heavy smoker
with a history of hypertension, dyslipidaemia, migraine and panic attacks. She
took paroxetine, rosuvastatin, aspirin
and atenolol. Doppler ultrasound scan
showed severe internal carotid artery
stenosis on the left (75%–80%, European
carotid surgery trial (ECST) method)
and moderate stenosis on the right
(65%–70%). MR brain imaging showed
right middle and anterior cerebral artery
watershed infarctions. She underwent
right carotid endarterectomy without
complications and was discharged home
after 48 hours. She was asymptomatic, her
neurological examination was normal and
blood pressure was 117/56 mm Hg.
Three days after surgery she developed episodes of severe, recurrent rightsided headache, with progressively
worsening apathy and somnolence. On
readmission to hospital on the eighth

postoperative day, her blood pressure was
183/63 mm Hg, her pulse was 67 beats
per minute and she was afebrile. Neurological examination was normal apart
from somnolence (National Institutes of
Health Stroke Scale (NIHSS) 1).
CT scan of head showed moderate
right cortico–subcortical frontotemporal
oedema, with effacement of the adjacent
sulci, and haemosiderin in the right frontal
and perisylvian sulci (figure 1A–C). Full
blood count and serum chemistry were
normal. Her erythrocyte sedimentation
rate was 57 mm/hour and serum C reactive protein 13.5 mg/L (moderately raised).
Coagulation tests were normal. Cervical
and transcranial Doppler ultrasound
excluded restenosis, but blood flow velocities were increased in the right middle
and anterior cerebral arteries, indicating
hyperaemia. She was transferred to the
stroke unit with the diagnosis of probable
reperfusion syndrome, based on the headache, somnolence and imaging findings.
Two days later, the CT scan appearances
had stabilised. Her headache subsided
and her mental status normalised, having
received antihypertensive drugs and acetaminophen. However, by the 13th day
post surgery, she began to experience
transient episodes of sensorimotor abnormalities on the left side of her face and
left hand. Initially, these were mild and
short lasting, but they became increasingly frequent, and were persistent by
the 16th day. Her blood pressure was
110/52 mm Hg. Electroencephalogram
and repeat CT scan of head were normal.
Serial transcranial Doppler traces
showed a gradual increase in middle
cerebral artery mean blood flow velocities (VMCA) and of Lindegaard index (LI)
(figure 3). Although LI can distinguish
hyperaemia from spasm in subarachnoid haemorrhage, we found it useful
to monitor haemodynamic changes in
this patient. Initially, this profile was

Fitas D, et al. Pract Neurol 2018;0:1–4. doi:10.1136/practneurol-2017-001871

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Cerebral vasoconstriction after
carotid endarterectomy

A difficult case

interpreted in the context of hyperaemia. On the 15th
day, reflecting her deteriorating clinical status, the VMCA
and LI reached the cut-off value, suggesting vasospasm
with a high risk for vascular events (VMCA >120 cm/s
and LI>3).1 We gave empirical oral nimodipine from
day 15 post surgery. However, on day 17, her measurements continued to worsen: VMCA217 cm/s and LI 4.1.
At this point, we felt that the likely diagnosis was
reversible cerebral vasoconstriction syndrome. Neurological examination showed left upper limb monoparesis more pronounced distally (2/5 using Medical
Research Council Scale) and left central facial paresis.
CT scan of head and CT angiography on day 19
showed recent right frontal infarction and segmental
narrowing involving the following segments of the
right side: A1 of anterior cerebral artery; M1 and M2
of middle cerebral artery and pre-bifurcation segment
of the internal carotid artery (figure 2A). We stopped
her paroxetine because of the known relationship
between selective serotonin reuptake inhibitors and
reversible cerebral vasoconstriction syndrome.2 Her

condition improved a little with neurorehabilitation,
and, having achieved clinical stability, we discharged
her to continue rehabilitation as an outpatient. At
1 month post surgery, her VMCA and LI were normal.
CT angiogram 1 year later showed complete resolution of the stenosis (figure 2B) and of her neurological
deficits.
One year later, a carotid Doppler ultrasound showed
left internal carotid artery stenosis of 70%–75%. Given
the slightly worsening in narrowing and the velocities criteria for >80% stenosis (pre-stenosis velocity
of 409/181 cm/s vs post-stenosis velocity of 47/21
cm/s), she underwent left carotid endarterectomy,
without acute complications. Arterial blood pressure
had been carefully monitored during and after surgery.
However, on day 5 she developed a left-sided headache. Neurological examination was normal (NIHSS
0). Transcranial Doppler ultrasound scan surveillance
of the left middle cerebral artery on days 11 and day
23 showed VMCA was 141 and 127 cm/s, and LI was
3.2 and 3.3; these values are above the cut-off value

Figure 2 Brain CT angiography (A, B first episode, C second episode): (A) at day 19 shows segmental narrowing of the right
middle cerebral artery (M1 and M2 segments), the A1 segment of the right anterior cerebral artery and terminal portion of internal
carotid artery (arrows). (B) Several months after shows reversal of arterial calibre abnormalities. (C) After the second operation, at day
9, CT angiography showed narrowing of the M2 segment of the left middle cerebral artery and the P1 segment of the left posterior
cerebral artery (arrows) and terminal portion of left internal carotid artery (not shown).

2

Fitas D, et al. Pract Neurol 2018;0:1–4. doi:10.1136/practneurol-2017-001871

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Figure 1 Brain CT (A–C) on admission: cortico–subcortical frontotemporal oedema on the right side, with effacement of the
adjacent sulci (A, B); haematic content fills the sulci over the right frontal convexity (C).

A difficult case

DISCUSSION
Carotid endarterectomy remains the gold standard
treatment for high-grade carotid stenosis. The most
common complications are early (stroke, hyperperfusion syndrome, cerebral haemorrhage, cranial nerve
injury and cardiac events) and late (recurrent stenosis
and false aneurysm).3
This patient’s presenting symptoms (headaches
and somnolence) initially resembled either migraine
aura (she had a history) or cerebral hyperperfusion
syndrome. When her transient sensorimotor deficits

began, the likely diagnoses appeared to be seizures and
vascular complications (such as transient ischaemic
attack or stroke). Other endarterectomy complications
listed above seemed less likely.
However, the initial findings on CT scan (cortico–
subcortical oedema) and on transcranial Doppler
(increased blood flow velocities) suggested that
hyperperfusion syndrome was more likely. When the
sensorimotor symptoms began, a normal EEG made
seizure attacks unlikely. The duration of her symptoms and the non-specific quality of her headaches
argued against migraine aura. When her symptoms
became permanent, and CT angiography showing
multiple vascular narrowings and frontal infarction,
it seemed much more likely that this was reversible
cerebral vasoconstriction syndrome complicated by
stroke. Hyperperfusion syndrome following carotid
endarterectomy tends to occur early, within the first
30 days.3 After the surgery there is usually an increase
in blood flow in the ipsilateral internal carotid artery.
This syndrome is defined by having a >100% increase
in cerebral blood flow compared with the preoperative
baseline.4 5 However, some patients develop symptoms
with only a slight increase in cerebral blood flow.4
This syndrome manifests with acute neurological

Figure 3 Distribution of mean flow velocities and Lindegaard Index (LI) in the middle cerebral artery (MCA). Red discontinuous line
indicates Lindegaard cut-off for vasospasm; blue discontinuous line indicates VMCA cut-off for vasospasm. When she was admitted to
our emergency department, VMCA was high and LI was normal, probably in the context of hyperaemia. By the 16th day post surgery,
when sensorimotor symptoms became irreversible, both VMCA and LI exceeded the cut-off value for vasospasm (VMCA >120 cm/s
and LI>3). So, there was a good correlation between clinical and TCD monitoring, which was very important in the suspicion of the
correct diagnosis. CEA, carotid endarterectomy; TCD, transcranial doppler.
Fitas D, et al. Pract Neurol 2018;0:1–4. doi:10.1136/practneurol-2017-001871

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to suspect a vasospasm/vasoconstriction. CT angiography on day 9 showed narrowing of the M2 segment
of the left middle cerebral artery, the P1 segment of
the left posterior cerebral artery and terminal portion
of left internal carotid artery (figure 2-C). MR scan of
brain at day 12 showed left-sided cortico–subcortical
parietal oedema, with effacement of the adjacent sulci,
without haemorrhage. We diagnosed recurrent reversible cerebral vasoconstriction syndrome. She made a
good clinical recovery and by day 25 the transcranial
Doppler scan was normal. MR scan of brain 1 month
later showed that most of the hyperintensity in left
middle cerebral artery territory had resolved.

A difficult case

4

syndrome. It is important to suspect this diagnosis in
patients with headache and neurological signs developing a few days after carotid surgery.
Key points
►► Reversible cerebral vasoconstriction syndrome is a rare

complication of carotid endarterectomy, but important
to consider when patients develop severe headache
and neurological signs several days after surgery.
►► Patients with reversible cerebral vasoconstriction
syndrome after carotid endarterectomy are at risk of
recurrence if they undergo contralateral surgery.
Contributors DF: conception and design, data collection,
literature search, drafting the article and critical revision of
the article. MC: conception and design, critical revision of
the article, supervision and final approval of the version to be
published. PC: data collection, critical revision of the article
and final approval of the version to be published. PA: drafting
the article and final approval of the version to be published.
GM: critical revision of the article and final approval of the
version to be published. RS: data collection, critical revision
of the article and final approval of the version to be published.
EA: conception and design, drafting the article, critical revision
of the article, supervision and final approval of the version to
be published.
Funding The authors have not declared a specific grant for this
research from any funding agency in the public, commercial or
not-for-profit sectors.
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned. Externally
peer reviewed by William Whiteley, Edinburgh, UK.
© Article author(s) (or their employer(s) unless otherwise stated
in the text of the article) 2018. All rights reserved. No commercial
use is permitted unless otherwise expressly granted.

References
1 Chen SP, Fuh JL, Chang FC, et al. Transcranial color doppler
study for reversible cerebral vasoconstriction syndromes. Ann
Neurol 2008;63:751–7.
2 Noskin O, Jafarimojarrad E, Libman RB, et al. Call-Fleming
syndrome) and stroke associated with antidepressants.
Neurology 2006;67:159–60.
3 Grenon M, Sidhu RS. Carotid revascularization: carotid
endarterectomy, 2009:21–36.
4 Karapanayiotides T, Meuli R, Devuyst G, et al. Postcarotid
endarterectomy hyperperfusion or reperfusion syndrome. Stroke
2005;36:21–6.
5 Adhiyaman V, Alexander S. Cerebral hyperperfusion syndrome
following carotid endarterectomy. QJM 2007;100:239–44.
6 Ducros A. Reversible cerebral vasoconstriction syndrome.
Lancet Neurol 2012;11:906–17.
7 Ducros A, Bousser MG. Reversible cerebral vasoconstriction
syndrome. Pract Neurol 2009;9:256–67.
8 Wu TY, Frith RW, Barber PA. Reversible cerebral
vasoconstriction following carotid endarterectomy. J Clin
Neurosci 2011;18:1725–8.
9 Chen SP, Fuh JL, Lirng JF, et al. Recurrent primary thunderclap
headache and benign CNS angiopathy: spectra of the same
disorder? Neurology 2006;67:2164–9.

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deficits associated with ipsilateral headache, seizures
and intracerebral haemorrhage occurring several days
after a carotid procedure. Risk factors include hypertension, tight stenosis, long duration of hypoperfusion
and impaired cerebral auto-regulation in the early
postoperative period.4 5
Reversible cerebral vasoconstriction syndrome is
very rare after endarterectomy. It is characterised by
(a) an acute and severe (often thunderclap) headache,
(b) uniphasic course without new symptoms after
1 month of clinical onset, (c) segmental vasoconstriction of cerebral arteries, (d) no evidence of aneurysmal
subarachnoid haemorrhage, (e) normal or near-normal
CSF and (f) normalisation within 12 weeks of clinical onset.6 7 Their most frequent precipitants are
pregnancy/puerperium, vasoactive medications, catecholamine-secreting tumours, immunosuppressants
or blood products and other miscellaneous factors
(head trauma, neurosurgery, endarterectomy).6 7 In
a review of six cases with reversible cerebral vasoconstriction syndrome following carotid endarterectomy, the symptoms appeared 2–8 days post surgery.
The presumed mechanism for vasospasm was hyperperfusion with further triggering of vasoconstrictive response in susceptible people.8 Other vascular
risk factors, namely arterial hypertension, migraine,
smoking and selective serotonin reuptake inhibitors,
were also possible triggers in this patient.
Transcranial Doppler scanning has a well-established role in monitoring cerebral haemodynamics and
vasospasm,1 although with no strong evidence that
therapy guided by this imaging after ischaemic stroke
or subarachnoid haemorrhage gives better outcomes.
By day 15 post endarterectomy, the velocities fulfilled
the criteria for mild vasospasm. Only about 13% of
reversible cerebral vasoconstriction syndrome cases
present with higher values (VMCA>120 cm/s and LI
>3), because those surrogate criteria were created for
subarachnoid haemorrhage.1 However, we used them
as risk markers for ischaemic complications in reversible cerebral vasoconstriction syndrome. After the
patient received nimodipine the flow velocities in the
middle cerebral artery and LI gradually fell (figure 3),
but we cannot establish a clear relationship with the
treatment, as this is also the natural history of reversible
cerebral vasoconstriction syndrome. However, even
after the headache had resolved, the changes in transcranial Doppler imaging remained, probably because
segmental vasoconstriction usually persists, even after
symptoms resolve. This clinico-radiological paradox
shows the importance of ultrasonographic follow-up.
Some literature suggests the value of routine surveillance at least beyond 1 month until the patient’s clinical state has normalised.9
In conclusion, reversible cerebral vasoconstriction syndrome is a rare but serious complication of
carotid endarterectomy, and may follow a reperfusion