Transient Focal Cerebral
Ischemia as a Presenting Mdestation of
Umptured Cerebral Aneurysms
Marc Fisher, MD, Robin I. Davidson, MD, and Elliott M. Marcus, MD

Few reports have described an association between cerebral transient ischemic attacks (TIAs) and unruptured
cerebral aneurysms. This study presents seven patients with TIA who had aneurysms in a vascular distribution
appropriate to their clinical symptoms. In three patients, angiographic evidence of embolization was present distal
to the aneurysm without another apparent cardiac or extracranial arterial source for the emboli. The most reasonable pathogenesis for TIA in a patient with an associated saccular aneurysm would be thrombosis of the aneurysmal
sac with subsequent embolization. However, subarachnoid blood can cause permanent focal intracranial narrowing, and this appeared to be a factor in at least one patient. The results imply that patients with symptoms of TIA
should have their intracranial arterial circulation visualized as part of the diagnostic evaluation.
Fisher M, Davidson RI, Marcus EM: Transient focal cerebral ischemia as a presenting manifestation of
unruptured cerebral aneurysms. Ann Neurol 8:367-372, 1980
Many mechanisms have been proposed to explain
transient cerebral ischemic attacks (TIAs). Possible
causes have included: vasospasm, generalized hypotension with regional variation of effect, cardiac
embolization, hypercoagulability, nonatherosclerotic
vasculopathies, and artery-to-artery embolization of
platelet cholesterol material [51. Unruptured cerebral
aneurysms are found relatively uncommonly either at
autopsy o r as an incidental finding during cerebral
angiography. The possibility needs to be explored
that such unruptured “asymptomatic” aneurysms
found “incidentally” during the evaluation of patients
with TIA may indeed contribute to t e s e ischemic
events. Intracerebral saccular aneurysms have not
been mentioned as a possible cause qf TIA in several
large reviews [ 5 , 2 13, although several authors have
alluded to the rare association of TIA and unruptured
aneurysms, especially aneurysms gf the middle cerebral artery tree [ 14, 27, 301. In recent years we have
studied seven patients with TIA associated with unruptured saccular aneurysms.

Patient Histories
Clinical data and angiographic findings are summarized in the Table.

with associated dysphasia and persistent nausea and vomiting. The patient denied headache, stiff neck, dizziness, or
visual symptoms. General physical and neurological examinations were unremarkable, as were lumbar puncture,
electroencephalogram (EEG), and CT scan. An electrocardiogram (EKG) demonstrated evidence of an old anterior
wall myocardial infarction but no arrhythmias. Angiography revealed an aneurysm at the left middle cerebral artery trifurcation with narrowing in the proximal portion of
the artery (Fig 1A). Follow-up angiography three weeks
later revealed persistent narrowing. The patient was discharged on aspirin therapy after an uneventful nine-week
course of bed rest. During the following three months she
experienced brief episodes of weakness of the right arm
and difficulty with speech.
At readmission six months following her initial episode,
angiography revealed multiple small embolic occlusions of
peripheral middle cerebral artery branches with collateralization from the posterior and anterior cerebral arteries, as well as the previously noted aneurysm and persistent narrowing of t h e proximal portion of the left middle
cerebral artery (Fig 1B). The extracranial vessels were unremarkable, as they had been previously. She was given
sulfinpyrazone, 200 mg four times a day, and over the ensuing twelve months had only four episodes of weakness
and dysphasia.

Patient 2
Patient I
A 64-year-old woman was admitted with a six-day history
of four brief episodes of weakness of the right arm and face
From the Departments of Neurology and Neurosurgery, Universky of Massachusetts Medical Center, Worcester, MA.

Received Nov 2 7 , 1979, and in revised form Jan 20, 1980. Accepted for publication Feb 2, 1980.

A 51-year-old woman was admitted with a one-week history of episodic speech disorder. The patient reported 2- to
10-minute episodes of thick speech and difficulty expressAddress reprint requests to Marc Fisher, MD, Department of
Neurology, University of Massachusetts Medical Center, 55 Iake
Ave N, Worcester, MA 01605.

0364-5 134/80/100367-06$01.25 @ 1979 by Marc Fisher

367

Summary of Clinical Data and Angiographic Findings in Seven Patients with Unruptured Cerebral AneuryJms
Patient No.,
Age (yr),
and Sex

Site

2. 51, F
3. 51, F
4 . 53, F
5. 47, M

L MCA
trifurcation
L ICA
Bilateral ICA
L ICA
Bilateral ICA

6. 55, F

L ICA

7. 43, F

R MCA trifurcation

1. 64, F

Transient
Symptoms

Emboli
Demonstrated

Therapy

R arm, face weakness; dysphasia

+

ASA, sulfinpyrazone

Dysphasia; R arm, leg weakness
Dysphasia; R arm weakness
Dysphasia
R arm, face weakness, numbness, and dysphasia
R arm weakness and numbness
L arm, face weakness and
numbness

+

0

ASA, clip ligation
None
ASA
Dipyridamole, ASA; normal
exploratory surgery
None

0

Clip ligation

+
0
0

MCA = middle cerebral artery; ASA = acetylsalicylic acid; JCA = internal carotid artery.

ing words. She once had difficulty in writing names. She
had no associated symptoms such as headache, diplopia,
weakness, or visual loss. General physical examination,
neurological examination, EKG, EEG, and nuclide brain
scan were normal. Angiographic study revealed a saccular
aneurysm originating from the left internal carotid artery
distal to the origin of the ophthalmic artery. A branch of
the left middle cerebral artery supplying the inferior
parietal region was occluded (Fig 2), but extracranial vessels were normal. The patient was discharged on aspirin
therapy.
Six months later she experienced sudden onset of weakness of the right arm and leg that fluctuated over several
hours. Neurological examination showed only mild right
central facial weakness, which cleared within 24 hours. Angiographic studies again disclosed the aneurysm of the left
internal carotid artery, but the previously occluded middle
cerebral artery branches had recanalized. The patient did
well for two months but then had a recurrent episode of
headache with right-sided weakness. Neurological examination disclosed minimal weakness of the right arm and leg
as compared to the left. A lumbar puncture at that time
showed clear cerebrospinal fluid. The patient underwent
operative clipping of the aneurysm without sequelae and
remained symptom free over the ensuing four years.

Patient 3
A 51-year-old woman gave a history of sudden onset of
right arm weakness and difficulty with speech. She denied
headache, neck stiffness, nausea, or vomiting. General
physical examination on admission was unremarkable.
Neurological examination revealed decreased strength in
the right arm and right central facial weakness. A nuclide
brain scan, lumbar puncture, EKG, and EEG were all
within normal limits. The patient’s symptoms cleared
within 36 hours. Angiography revealed two large aneurysms, one o n the left side at the carotid bifurcation, the
other on the right at the junction of the carotid and
ophthalmic arteries. There was evidence of distal intracerebral artery embolization involving two posterior temporal branches of the middle cerebral artery on the left side

368 Annals of Neurology Vol 8 N o 4 October 1980

(Fig 3). N o stenosis or ulceration was observed in the extracranial vasculature. The patient was discharged without
medication and has been symptom free for six years.

Patient 4
A 53-year-old woman was suddenly unable to speak but
could understand words. There was no associated weakness, headache, neck stiffness, nausea, o r vomiting. The
patient had a past history of hypertension. Blood pressure
was 170/110 mm H g but general physical and neurological
examinations were otherwise unremarkable, as were skull
roentgenograms, nuclide brain scan, EEG, EKG, and lumbar puncture. Angiography on the left side revealed a small
dural arteriovenous malformation at the medial end of the
petrous apex and an internal carotid artery aneurysm at the
level of the distal intracavernous portion of the vessel.
There was no evidence of vasospasm o r abnormalities in
the extracranial vessels. The patient was treated with aspirin and has been symptom free for six years.

Patient 5
A 47-year-old man gave a history of several episodes of
numbness and weakness in the right arm and face associated with slurring of speech. There was no associated
nausea, vomiting, headache, or neck stiffness. General
physical examination disclosed a systolic ejection murmur,
but it and the neurological examinations were otherwise
unremarkable, as were an EKG and EEG. Angiography revealed normal extracranial vasculature and bilateral aneurysms at the internal carotid artery bifurcation. The leftsided aneurysm was located within the cavernous sinus and
was 5 mm larger than the lesion on the right side. The patient was started on dipyridamole and aspirin. A recurrent
episode three years later prompted exploration of the left
internal carotid artery, which disclosed no abnormalities.
During the subsequent three years the patient had no recurrences.

Patient 6
A 55-year-old-woman gave a history of several minute
episodes over the preceding two to three years of darken-

F i g I . (Patient 1 ) (A) MagniJed view of left carotid injection,
anteroposterior view, demonstrating a large aneurysm of the
middle cerebral artery with narrowing of the proximal vase1
ufall (arrow). (B) Lateral view of left common carotid artery
injection, demonstrating persistence of the aneurysm and associated vascular narrowing as well as embolic occlusion of several
distal vessels (arrows).

ing of vision in association with right arm and hand weakness and numbness. She gave a history of rheumatic fever
at age 15 and diabetes mellitus treated for three years with
oral hypoglycemic agents. General physical examination
disclosed a grade 2/6 systolic ejection murmur and a loud
bruit over the right carotid and subclavian arteries. A minor
soft bruit was present over the left carotid artery.
Neurological examination showed only decreased pain and
vibratory sensation below the knees and bilaterally decreased Achilles tendon reflexes. CT scan, EEG, EKG, and
lumbar puncture were unremarkable. Angiography revealed a lobulated aneurysm with a broad neck originating
from the supraclinoid portion of the left internal carotid
artery. The right subclavian artery was 50% stenosed

Fisher et al: TIA and Unruptured Aneurysms

369

general physical examination was normal. Neurological examination disclosed mild left central facial weakness, which
cleared within several hours. EEG, EKG, lumbar puncture,
and CT scan were all normal. Angiography revealed an aneurysm at the right middle cerebral artery trifurcation. The
extracranial vessels were normal in appearance. The patient
underwent a craniotomy with ligation of the aneurysm and
has been symptom free for one year.

Fig 2. (Patient 2) Left common carotid injection, demonstrating an internal carotid artery aneurysm (large arrow) and an
area of avascularity with occlusion of a distal arterial branch
(small arrow).

F i g 3. (Patient 3) Left common carotid artery injection, lateral
oiew, demonstrating a large internal carotid artery anearysm
(horizontal arrow) with distal posterior temporal branch abnormalities compatible with embolic activity (vertical arrow).

proximal to the origin of the right vertebral artery, but the
rest of the extracranial vasculature was unremarkable. The
patient was discharged without medication and has had no
recurrence of symptoms during three years of follow-up.

Patient 7
A 43-year-old woman sustained two brief episodes of left
facial weakness and numbness associated with numbness of
the left arm, each episode lasting several hours. There was
no associated headache, nausea, vomiting, or neck stiffness.
She described a similar episode thirteen years earlier. The

370 Annals of Neurology Vol 8 No 4 October 1980

Discussion
The association of TI As with “incidental” saccular
aneurysm in the appropriate vascular distribution in
seven patients over a six-year period strongly suggests a cause-and-effect relationship. The inference is
supported by evidence of arterial emboli in intracranial vessels distal to an aneurysm, without other
obvious sources of embolism, in Patients 1, 2 and 3 .
To test whether coincidence could explain these
findings, we calculated an expected prevalence of cerebral aneurysms for this group over the period in
question.
Our institutional referral base is approximately
350,000 persons. The incidence of TIA in the
general population is estimated to be 30 per
100,000 [31], giving an expected TIA prevalence in
our population of 630 in a six-year period. All our
patients had symptoms referable to the anterior circulation; of the 630 TIAs expected over six years,
2 5 % , or 160 patients, should be excluded as anticipated to have only vertebral-basilar symptoms [61.
The remaining 470 patients would certainly not all
undergo angiography, even if they saw a physician
and were correctly diagnosed. In a recent multicentered study of TIA, only 59% of the patients with a
definite TIA involving the anterior circulation
underwent angiography 1281. Based on this figure,
277 patients in our predicted TIA group would be
expected to undergo angiography. Assuming a 0.8%
incidence of unruptured aneurysm [17, 261, we
would anticipate only 2 patients with incidental aneurysms. Of these 2 , only 4076, or 1 patient, would be
expected to have an aneurysm of the anterior circulation in the appropriate vascular distribution to be
compatible with the symptoms. This expectation that
1 aneurysm would be discovered incidentally during
angiography in patients with TIA symptoms is based
on the highest known figure for the many variables
discussed. In addition, a review of several recent reports of large groups of patients with TIA undergoing angiography fails to mention incidental aneurysm
in any patient [20, 281.
The pathogenesis of the attacks in our TIA population is a matter of speculation. It seems unlikely
that artery-to-artery platelet embolization from an
extracranial arterial source was the cause, because

none of the patients had stenosis or ulceration in
these feeding vessels; neither was a cardiac source,
systemic hypotension, nor underlying conditions
which would predispose to hypercoagulability identified. No evidence of a nonatherosclerotic vasculopathy was present. A cause-and-effect relationship between the aneurysms and the TIA appears
likely.
Completed cerebral infarction is a common complication of aneurysm rupture [25]. Vasospasm has
been cited as the most common cause [24], although
some doubt has been cast on its importance [181.
Crompton [S] has suggested other mechanisms, including atheromatous stenosis of cerebral vessels,
perivascular distention of penetrating arteries by
blood, vascular hypotension, and, rarely, intraluminal
thrombosis of an artery adjacent to the aneurysm. If
one assumed that our patients sustained minor
bleeding of their aneurysms around the time of TIA
symptoms, then any of these mechanisms could be
invoked to explain transient vascular symptoms.
However, their histories and the lack of blood in the
cerebrospinal fluid at the time of their symptoms
make this explanation unlikely.
Thrombosis of a saccular aneurysm is a recognized
pathological phenomenon sometimes demonstrated
by angiography [ 11, 161. Intraarterial embolization
of an aneurysmal sac thrombosis produces a picture
of embolic cerebral infarction in both unruptured
and ruptured aneurysms [2, 10, 231. A similar mechanism could give rise to transient symptoms. Documentation of this hypothesis would require angiographic demonstration of aneurysm thrombosis as well
as evidence of downstream intracerebral vascular occlusion. Such findings have been reported in cases of
ruptured aneurysm [2, 101. Furthermore, Patients
1, 2, and 3 in the present series had angiographic
findings consistent with intracranial arterial embolization distal to an unruptured saccular aneurysm at
a time closely related to their transient symptoms.
In patients with ruptured saccular aneurysm, localized vascular narrowing is often attributed to arterial spasm [3]. It has recently become appreciated
that such narrowing may represent a permanent
change in endothelial structure and not reversible
spasm [22]. These permanent vascular alterations
were found to consist of intimal changes consistent
with granulomatous tissue and were ascribed to early
muscular contraction of the vessel wall with subsequent mechanical or anoxic damage to the intima
[7]. A recent experimental model of these changes
has disclosed that one can induce progressive alterations in the structure of the cerebral arterial wall by
injecting autologous blood into the subarachnoid
space. The intimal changes produced had the poten-

tial to become atheromatous with an atherogenic diet
[ 11. Patient 1 is important because serial angiographic
studies over a six-month period demonstrated permanent vascular narrowing, not reversible spasm.
These changes likely reflect intimal proliferation and
atherogenesis induced by leakage of blood into the
subarachnoid space. A focal area of atherosclerosis in
the middle cerebral artery could serve as a nidus for
platelet thrombus formation, with subsequent embolization producing TIA symptoms.
It is established that unruptured aneurysms may
have focal or generalized seizures as an initial manifestation [15]. Focal seizures can at times mimic
symptoms of TIA [12], and the possibility must be
considered that the transient neurological symptoms
exhibited by our patients could represent focal seizure activity. However, the absence of epileptiform
activity on EEGs makes this possibility remote. Furthermore, the cessation of symptoms following definitive treatment in two patients supports an embolic origin for the symptoms.
What are the implications of this association between unruptured aneurysms and TIA? Since an aneurysm might be present, visualization of the intracranial as well as extracranial vasculature is an
important component, frequently omitted, of the
radiological investigation of patients with TIA [ 13,
281. Detection of an aneurysm as well as other intracranial abnormalities may be crucial in deciding on
the management of individual TIA patients.
The optimal therapeutic approach to patients with
TIA secondary to an unruptured aneurysm has not
been established. Several studies have demonstrated
that transient visual, motor, or sensory symptoms
similar to those of TIA may precede rupture of an
aneurysm [15, 19, 231. The natural history of unruptured aneurysms is unclear, but there appears to be a
risk of subsequent bleeding with its attendant mortality and morbidity [ 4 , 91. Unruptured aneurysms
may embolize and cause a completed infarction. Surgical intervention might be undertaken to prevent
either of these intracranial catastrophies and their
attendant complications. Yet none of our five unoperated patients, who have been followed for up to six
years, has bled or gone on to a completed embolic
infarction. The question of the appropriateness of
medical therapy with anticoagulation o r platelet antiaggregates, surgical intervention, o r no treatment at
all remains unanswered at this time due to the paucity
of recognized cases.
The importance of appreciating the potential
relationship between TIA symptoms and an unsuspected intracranial aneurysm is apparent. The discovery may help to explain cryptogenic TIA symptoms and serve as a mechanism for future evaluation

Fisher et al: TIA and Unruptured Aneurysms

371

of the most appropriate therapeutic modality in these
patients.

Addendum
Stewart et a1 [27] have recently reported on four patients
with unruptured cerebral aneurysms who had transient
symptoms resembling those described in this study. Cessation of symptoms followed aneurysmectomy in three patients, and the authors postulated an ischemic process to
explain the events.
We thank Dr David Drachman for his kind assistance in reviewing the manuscript and Nan Sobel for secretarial assistance.

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