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0148-396X/84/1501-0050$02.00/0
NEUROSURGERY
Copyright € 1984 by the Congress of Neurological Surgeons

Vol. 15, No. 1. 1984
Printed in U.S.A.

Cerebral Hyperperfusion after Carotid Endarterectomy: A

Cause of Cerebral Hemorrhage

Mark Bernstein, M.D., J. F. Ross Fleming, M.D., F.R.C.S.(C), and John H. N. Deck, M.D., F.R.C.P.(C)

Divisions of Neurosurgery and Neuropathology, Toronto Western Hospital and University of Toronto, Toronto, Ontario

Correction of a very high grade carotid stenosis by endarterectomy in a normotensive man was followed by the
development of severe unilateral head, eye, and face pain, seizures, and on the 6th day a fatal intracerebral hemorrhage.
Autopsy revealed changes in the cerebral hemisphere ipsilateral to the endarterectomy that resembled the changes seen
in malignant hypertension, whereas the opposite hemisphere was normal. These changes included hypercellularity and
edema of arterial and arteriolar walls, with necrosis, extravasation of erythrocytes, and exudation of fibrin. We propose
that the clinical and pathological features in this case were due to relative hyperperfusion of a cerebral hemisphere in
which autoregulation had been impaired because of preoperative chronic hypoperfusion with chronic maximal dilatation
of its blood vessels. This state of relative hyperperfusion is probably similar to the normal perfusion pressure breakthrough
that occasionally occurs after the resection of cerebral arteriovenous malformations. It is similar to the breakthrough
perfusion that occurs in severely hypertensive patients and results in hypertensive encephalopathy. (Neurosurgery 15:50-
56. 1984)

Key words: Carotid endarterectomy, Carotid stenosis, Cerebral hyperperfusion, Endarterectomy, Intracerebral hemor-

rhage, Malignant hypertension

Correction of high grade stenosis by endarterectomy may
result in an increase in cerebral blood flow to well above
normal values, with hyperperfusion of a cerebral hemisphere
that had been adapted to low perfusion and had been func-
tioning normally. Sundt et al. reported blood flow 2 to 3
times the preoperative values, with mean postoperative blood
flow rates in some cases as high as 85.5 ml/100 g/minute,
suggesting paralysis of autoregulatory mechanisms (12). The
clinical features of such hyperperfusion may include seizures,
unilateral migraine-like head, eye, and face pain, and intra-
cerebral hemorrhage. The relationship of postendarterectomy
migraine-like pain to hyperperfusion is not widely recognized,
and the triad of seizures, headache, and intracerebral hemor-
rhage occurring in one patient has not been previously re-
ported. When intracerebral hemorrhage occurs after endarter-
ectomy in the absence of obvious predisposing factors such
as recent cerebral infarction, hypertension, or anticoagulation,
hyperperfusion may be responsible.

Hyperperfusion after the correction of high grade carotid
stenosis is probably equivalent to normal perfusion pressure
breakthrough, a term coined by Spetzler et al. to describe the
malignant edema and hemorrhage that sometimes occur in a
cerebral hemisphere after the resection of an arteriovenous
malformation (9). The clinical and pathological features of
our patient make a strong case for the occurrence of an acute
hypertensive encephalopathy secondary to normal perfusion
pressure breakthrough (relative hyperperfusion) in a hemi-
sphere rendered susceptible by the loss of autoregulation
because of chronic hypoperfusion due to high grade carotid
stenosis.

CASE REPORT

A 56-year-old man was found to have bilateral carotid
bruits on routine physical examination. He had previously
been well except for bilateral femoral-popliteal bypass opera-
tions for leg claudication. He was not hypertensive. He had
had no symptoms suggesting cerebral or retinal ischemic
attacks. His neurological examination was negative. His blood

50

pressure was 150/80. Doppler flow studies showed bilateral
carotid artery disease, with severe stenosis of the left common
carotid bifurcation, failure of imaging of the left internal
carotid artery, and reversal of direction of the left orbital
blood flow; the lumen of the right internal carotid artery
appeared to be reduced by 50%. The patient was admitted for
further investigation.

Angiography revealed an extremely high grade stenosis at
the origin of the left internal carotid artery (Fig. 1). A left
common carotid arteriogram showed poor filling of the left
middle cerebral artery and no filling of the anterior cerebral
artery (Fig. 2). There was a moderate degree of stenosis at the
origin of the right internal carotid artery, but right carotid
injection showed good filling of the right anterior and middle
cerebral arteries, as well as some cross filling of the left anterior
and middle cerebral arteries (Fig. 3).

Because of the extreme degree of stenosis of the left internal
carotid artery, endarterectomy was decided upon. Left carotid
endarterectomy was performed 7 days after angiography. An
intraoperative shunt was not used. The patient was given a
single bolus of 7000 units of heparin before the artery was
clamped off. The heparin was not reversed after operation.
The clamp-off time was 41 minutes. There were no operative
complications.

The immediate postoperative period was uneventful. Treat-
ment with platelet antiaggregants (650 mg of enteric-coated
aspirin twice daily) was commenced on the 2nd postoperative
day. About 24 hours after operation, the patient began to
complain of severe, pounding left orbital frontal and temporal
headache. Thirty-six hours postoperatively, he had two grand
mal seizures. After the seizures, the patient was neurologically
normal, but he continued to experience severe left frontotem-
poral and periorbital pain. The pain continued during the
next few days and was sometimes severe enough to require
codeine. His blood pressure remained normal.

On the 6th postoperative day, the patient complained of
marked worsening of the left periorbital pain, and a few hours
later he began to vomit. He developed right hemiplegia that
rapidly progressed, and over the course of 30 minutes he

July 1984

Fic. 1. Angiogram shows an extremely high degree of stenosis at
the origin of the left internal carotid artery.

became profoundly comatose with bilateral dilated and fixed
pupils. A computed tomographic (CT) scan showed a large,
high density, irregularly shaped hematoma extending into the
frontal, temporal, and parietal lobes of the left hemisphere
(Fig. 4). His oculocephalic and corneal reflexes were lost.
Endotracheal intubation, hyperventilation, and intravenous
mannitol brought about no improvement. Because of the
devastated neurological condition and the extensive destruc-
tion of the left cerebral hemisphere, evacuation of the hema-
toma was not attempted. The patient deteriorated and died
12 hours after the onset of the hemorrhage.

At autopsy, the heart showed left ventricular hypertrophy
with a heart weight of 470 g. Coronary atherosclerosis was
severe, with 90% stenosis of the right coronary artery. A
subendocardial infarct of the posterior septum and the lateral
wall of the left ventricle was | week old.

CEREBRAL HYPERPERFUSION AFTER ENDARTERECTOMY St

The left carotid endarterectomy site was free of thrombus,
and the left common, internal, and external carotid arteries
were widely patent at all levels. Examination of the brain
revealed a fresh, massive hematoma in the left cerebral hem-
isphere (Fig. 5), resulting in herniation of the left hippocampal
gyrus, infarction in the left posterior cerebral artery distribu-
tion, and secondary hemorrhages in the upper brain stem.

Small arteries and arterioles throughout the left cerebral
hemisphere showed reactive changes consisting of swelling of
endothelial cells and hyperplasia of these and other blood
vessel cells indicated by hypercellularity and the presence of
occasional mitotic figures. Some of these vessels showed mar-
gination and extravasation of neutrophils. In the left parietal
lobe, small arteries showed, in addition, necrosis with extra-
vasation of erythrocytes and exudation of fibrin (fibrinoid
necrosis); there was marked edema of the adjacent brain.
These features are highly reminiscent of the changes seen in
cases of malignant hypertension. Small blood vessels of the
opposite hemisphere showed none of these changes (Figs. 6
to 9).

DISCUSSION

Intracerebral hemorrhage is an uncommon complication
after carotid endarterectomy. In published reports, the factors
most often associated with postendarterectomy cerebral hem-
orrhage include recent cerebral infarction (2-4, 11, 13, 15)
and severe postoperative hypertension (1, 2, 5, 8, 13). Other
factors that may be associated with postendarterectomy cere-
bral hemorrhage include frequent transient ischemic attacks
immediately before operation (1, 2), previous (old) cerebral
infarction (1), and the use of systemic anticoagulants postop-
eratively (10, 12). None of these factors was present in our
patient. He was a normotensive man with no history of
transient ischemic attacks or cerebral infarction; after the
surgical correction of a very high grade carotid stenosis, he
developed migraine-like head, eye, and face pain and seizures,
followed by intracerebral hemorrhage. He had not received
postoperative anticoagulants.

We suggest that the state of chronically reduced perfusion
pressure in the microcirculation of the left cerebral hemi-
sphere caused by the extremely tight left internal carotid
stenosis had rendered the microcirculation unusually suscep-
tible to injury. Injury analogous to that occurring in malignant
hypertension was precipitated by the sudden elevation of
perfusion pressure to more normal levels after endarterec-
tomy. The pathological findings in this case form the basis
for such an hypothesis. Evidence of beginning adaptation to
the altered hemodynamic state is manifest by active prolifer-
ation of the cells of small arterial walls, evidence of altered
vascular permeability, and fibrinoid necrosis of small arteries.
These changes were confined to the left cerebral hemisphere.

The reactive changes of small arteries in the left cerebral
hemisphere were not thought to be secondary to the mass
effect of the left parietal lobe hematoma because they were
present throughout the entire hemisphere in areas remote
from the hematoma and had features indicating an age greater
than the 12-hour interval between hemorrhage and death.
Nor were they a reaction to ischemia that might possibly have
occurred at the time of operation or postoperatively, for there
was no histological evidence of any ischemic change in the
brain parenchyma. The findings suggest that the microcircu-
lation had become ill-adapted to withstand normal perfusion
pressure and had reacted to it in a manner analogous to that
exhibited by normal vessels when exposed to suddenly ele-
vated perfusion pressure. as in malignant hypertension.

eee

52 BERNSTEIN et al. Neurosurgery, Vol. 15, No. 1

Fic. 2, Left common carotid injection of contrast medium (anteroposterior (/eft) and lateral (right) projections) shows poor filling of the left
internal carotid and middle cerebral arteries and no filling of the anterior cerebral artery.

Fic. 3. Right common carotid injection of contrast medium Fic. 4. CT scan 6 days after carotid endarterectomy shows a large,
shows good cross filling of the left anterior and middle cerebral irregularly shaped hemorrhage extending through the left frontotem-
arteries. poral and parietal lobes.

July 1984

Fic. 5. Section of the brain at autopsy 7 days after carotid end-
arterectomy shows massive fresh hematoma extending through the
left cerebral hemisphere.

OT

CEREBRAL HYPERPERFUSION AFTER ENDARTERECTOMY 53

A similar suggestion was made by Sundt et al. on the basis
of cerebral blood flow studies performed before and after
carotid endarterectomy (12). They reported a group of pa-
tients in whom blood flow in the affected cerebral hemisphere
was reduced preoperatively to values between 20 and 25 ml/
100 g/minute (40% of normal flow). After correction of very
high grade stenosis, flows increased by as much as 200% in
some patients, with values up to between 75 and 85 ml/100
g/minute. The occurrence of such marked hyperemia after
the restoration of normal perfusion pressure confirmed that
cerebral autoregulation was severely impaired. Sundt et al.
concluded that their data supported “the contention that
cerebral hyperperfusion can result in a form of unilateral
hypertensive encephalopathy.” Our findings show that there
is a structural basis for the hyperperfusion syndrome and that
it is indeed analogous to hypertensive encephalopathy.

The cerebral hemodynamics that we are proposing could
be considered analogous to the hyperperfusion syndrome seen
after the resection of some arteriovenous malformations. Spet-
zler et al. concluded that, in a hemisphere made chronically
ischemic by a steal caused by an arteriovenous fistula, normal

Fic. 6. A, penetrating cortical artery in the right posterior frontal lobe shows normal cellularity of endothelial cells with longitudinal nuclei
and smooth muscle cells. The adjacent neuropil is also normal. B, penetrating cortical artery in the corresponding portion of the left posterior
frontal lobe shows hypercellularity with plump and proliferating endothelial and smooth muscle cells. The adjacent neuropil is edematous.
(Hematoxylin and eosin stain (H&E), x 40.)

54 BERNSTEIN et al.

~ ’ i.

Neurosurgery, Vol. 15, No. 1

A

Fic. 7. Left parietal lobe shows fibrinoid necrosis of small blood vessels in association with extravasation of erythrocytes and marked edema

of the neuropil. (x 25.)

autoregulation is impaired and the arterial network in brain
tissue remote from the fistula is chronically dilated (9). When
normal perfusion is reestablished after removal of the fistula,
the regulating capacity of the vessels is surpassed and they
have no resistance to blood flow; because they cannot regulate
to the new pressure, edema and hemorrhage result. Spetzler
et al. termed this the normal perfusion pressure breakthrough
theory.

Extrapolating from the analysis put forward by Spetzler et
al., we propose that, because of chronic relative hypoperfusion
of the hemisphere distal to a high grade carotid stenosis, small
blood vessels remain maximally dilated to ensure maximal
blood flow. The chronic vasodilatation results in loss of
autoregulation. Upon correction of the high grade carotid
stenosis, blood flow at a normal or elevated perfusion pressure
is restored to the previously hypoperfused hemisphere. Be-
cause of paralyzed autoregulatory control, there cannot be
sufficient vasoconstriction to protect the capillary bed, and
“breakthrough” perfusion pressure results in edema and hem-
orrhage. Normal perfusion pressure breakthrough in a hypo-
perfused brain is also considered to be analogous to the
hypertensive breakthrough that occurs in the brains of patients
with malignant hypertension.

Unilateral headache not uncommonly occurs for a few days
after endarterectomy. Messert and Black, in reviewing 50
consecutive patients after endarterectomy, noted severe hem-
icranial pain ipsilateral to the side of operation in 5 patients:

they attributed the pain to injury or manipulation of the
carotid vessels or sheath (7). Leviton et al. reported 2 patients
with severe unilateral headache after endarterectomy and
attributed the headache to a transient disturbance in cerebral
autoregulation (6). The latter explanation is also endorsed by
Sundt et al., who found, in 6 patients with postoperative
unilateral headache, an increase in cerebral blood flow from
mean preoperative values of 43.2 + 16 to 83.2 + 39.8 ml/100
g/minute postoperatively (12).

Convulsions after carotid endarterectomy are uncommon.
Wilkinson et al. reported focal convulsions in three patients
4 to 6 days after endarterectomy (14). All three patients had
permanent neurological deficits after the onset of the seizures,
and the authors concluded that the seizures were secondary
to cerebral infarction caused by emboli from the endarterec-
tomy site. Seizures were also reported at the onset of a fatal
intracerebral hemorrhage following endarterectomy both by
Caplan et al. (3) and by Bruetman et al. (2). Seizures occurring
in the absence of postoperative cerebral infarction or occur-
ring several days before a postendarterectomy intracerebral
hemorrhage, as in our patient, were attributed to cerebral
hyperperfusion and the early stages of hypertensive encepha-
lopathy by Sundt et al. (10-12). Eleven of their patients
developed seizures between the 5th and 7th postoperative day;
their cerebral blood flows had increased from mean preoper-
ative values of 37.3 + 13.4 to 85.5 + 31.8 ml/100 g/minute
after operation (12).

July 1984

CEREBRAL HYPERPERFUSION AFTER ENDARTERECTOMY 35

Fic. 8. Left parietal lobe shows marked edema of the neuropil (A) and fibrinoid necrosis of arterioles (B). (A, H&E; B, phosphotungstic acid-

hematoxylin (PTAH) stain for fibrin; both, x 40.)

Intracerebral hemorrhage occurring after carotid endarter-
ectomy in the absence of predisposing factors, such as cerebral
infarction, hypertension, or anticoagulants, is most likely
related to cerebral hyperperfusion. Sundt et al. found that, in
five patients who had a postoperative intracerebral hemor-
rhage, the cerebral blood flow had increased from a mean
value of 29.6 + 20 to 76.8 + 18.5 ml/100 g/minute after
endarterectomy (12). The “breakthrough bleeding” that oc-
curs after the resection of some cerebral arteriovenous mal-
formations almost certainly represents an analogous situation
(9).

Our case is unique in that the clinical triad of unilateral
head, face, and eye pain, seizures, and delayed intracerebral
hemorrhage after endarterectomy has not hitherto been re-
corded in one patient. It is also unique because we were able
to demonstrate pathological changes in the blood vessels of
the affected cerebral hemisphere that are identical to those
seen in malignant hypertension, thus providing histological
evidence of the vascular reactivity to hyperperfusion that is
the basis for the clinical picture.

Several therapeutic implications emerge from our study of
this case. Correction of very high grade carotid stenosis may
be especially dangerous if performed within 3 or 4 weeks of
cerebral infarction, for there may be danger of hemorrhage
into the softened brain parenchyma when the perfusion is
increased. Uncontrolled hypertension after the correction of

very high grade carotid stenosis may be exceptionally hazard-
ous because of increased risk of hemorrhage into the already
hyperperfused brain in the absence of normal autoregulation.
The occurrence of unilateral head, face, and eye pain or
seizures after endarterectomy may reflect the development of
a unilateral hyperperfusion syndrome and should signal a
warning. Blood pressure should be diligently controlled in the
face of such symptoms; anticoagulants and even platelet
antiaggregants may increase the hazards, and their use should
be avoided when these symptoms occur after endarterectomy.

Received for publication, January 3, 1984; accepted, March 10,
1984.

Reprint requests: Dr. J. F. Ross Fleming, 25 Leonard Avenue,
Suite 207, Toronto, Ontario, Canada MST 2R2.

REFERENCES

1. Bland JE, Chapman RD, Wylie EJ: Neurological complications
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2. Bruetman ME, Fields WS, Crawford ES, DeBakey ME: Cerebral
hemorrhage in carotid artery surgery. Arch Neurol 9:458-467,
1963.

3. Caplan LR, Skillman J, Ojemann R, Fields WS: Intracerebral
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4. Hass WK, Clauss RH, Goldberg AF, Johnson AL, Imparato AM,

56 BERNSTEIN et al.

Neurosurgery, Vol. 15, No. 1

Fic. 9. Left parietal lobe shows marked hypercellularity of a small artery with a mitotic figure (arrow) in an adventitial cell, indicative of the

reactive proliferative process. (H&E, x 40.)

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8. Ojemann RG, Crowell RM, Roberson GH, Fisher CM: Surgical
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12. Sundt TM Jr, Sharbrough FW, Piepgras DG, Kearns TP, Messick
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COMMENT

This is a most interesting and instructive case. Surgeons
who perform carotid endarterectomy have long appreciated
that some patients complain of unilateral headache after the
procedure. Most often, the headache is self-limited and dis-
appears after some days or possibly several weeks. I personally
have never seen a patient with cerebral hemorrhage after
carotid endarterectomy unless the patient had sustained a
recent cerebral infarction. This report shows that headache
after carotid endarterectomy is not necessarily a benign con-
dition and may occasionally herald a parenchymal brain
hemorrhage.

The message seems to be that, if patients complain of severe
headache after carotid endarterectomy, it may be prudent to
treat the patient with antihypertensive drugs even if the blood
pressure is in the normal range.

Russel H. Patterson, Jr., M.D.
New York, New York