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EDITED BY
Chloe Dumot,
Hospices Civils de Lyon, France
REVIEWED BY
Steve M. Cordina,
University of South Alabama, United States
Ashish Kulhari,
HCA Midwest Health, United States
*CORRESPONDENCE
Michael T. Lawton
neuropub@barrowneuro.org
SPECIALTY SECTION
This article was submitted to Neurosurgery, a
section of the journal Frontiers in Surgery
RECEIVED 19 January 2023
ACCEPTED 29 March 2023
PUBLISHED 21 April 2023
CITATION
Hackett AM, Koester SW, Rhodenhiser EG,
Scherschinski L, Rulney JD, Naik A, Nico E,
Eberle AT, Hartke JN, Fox BM, Winkler EA,
Catapano JS and Lawton MT (2023) A
comprehensive assessment of self-reported
symptoms among patients harboring an
unruptured intracranial aneurysm.
Front. Surg. 10:1148274.
doi: 10.3389/fsurg.2023.1148274
COPYRIGHT
© 2023 Hackett, Koester, Rhodenhiser,
Scherschinski, Rulney, Naik, Nico, Eberle,
Hartke, Fox, Winkler, Catapano and Lawton.
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the terms of the Creative Commons Attribution
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permitted which does not comply with these
terms.
A comprehensive assessment of
self-reported symptoms among
patients harboring an unruptured
intracranial aneurysm
Ashia M. Hackett, Stefan W. Koester, Emmajane G. Rhodenhiser,
Lea Scherschinski, Jarrod D. Rulney, Anant Naik, Elsa Nico,
Adam T. Eberle, Joelle N. Hartke, Brandon M. Fox,
Ethan A. Winkler, Joshua S. Catapano and Michael T. Lawton*
Department of Neurosurgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center,
Phoenix, AZ, United States
Background: Approximately 3.2%–6% of the general population harbor an
unruptured intracranial aneurysm (UIA). Ruptured aneurysms represent a
significant healthcare burden, and preventing rupture relies on early detection
and treatment. Most patients with UIAs are asymptomatic, and many of the
symptoms associated with UIAs are nonspecific, which makes diagnosis
challenging. This study explored symptoms associated with UIAs, the rate of
resolution of such symptoms after microsurgical treatment, and the likely
pathophysiology.
Methods: A retrospective review of patients with UIAs who underwent
microsurgical treatment from January 1, 2014, to December 31, 2020, at a
single quaternary center were identified. Analyses included the prevalence of
nonspecific symptoms upon clinical presentation and postoperative follow-up;
comparisons of symptomatology by aneurysmal location; and comparisons of
patient demographics, aneurysmal characteristics, and poor neurologic outcome
at postoperative follow-up stratified by symptomatic versus asymptomatic
presentation.
Results: The analysis included 454 patients; 350 (77%) were symptomatic. The
most common presenting symptom among all 454 patients was headache
(n= 211 [46%]), followed by vertigo (n= 94 [21%]), cognitive disturbance
(n= 68 [15%]), and visual disturbance (n= 64 [14%]). Among 328 patients
assessed for postoperative symptoms, 258 (79%) experienced symptom
resolution or improvement.
Conclusion: This cohort demonstrates that the clinical presentation of patients
with UIAs can be associated with vague and nonspecific symptoms. Early
detection is crucial to prevent aneurysmal subarachnoid hemorrhage. It is
imperative that physicians not rule out aneurysms in the setting of nonspecific
neurologic symptoms.
KEYWORDS
cerebrovascular, microsurgical treatment, retrospective analysis, symptoms, unruptured
intracranial aneurysms
Abbreviations
aSAH, aneurysmal subarachnoid hemorrhage; ICA, internal carotid artery; ISUIA, International Study of
Unruptured Intracranial Aneurysms; SAH, subarachnoid hemorrhage; SD, standard deviation; UIA,
unruptured intracranial aneurysm.
TYPE Original Research
PUBLISHED 21 April 2023
|
DOI 10.3389/fsurg.2023.1148274
Frontiers in Surgery 01 frontiersin.org
1. Introduction
Approximately 3.2%–6% of the general population harbor an
unruptured intracranial aneurysm (UIA). UIAs are increasingly
found among women and are often detected between the fourth
and sixth decades of life (1,2). More than 91% of UIAs are
asymptomatic and are only incidentally discovered when imaging
is performed for unrelated reasons (3). Rupture of intracranial
aneurysms represents a significant healthcare burden, with nearly
50% of cases resulting in death within 3 months of presentation.
Of those patients who undergo life-saving treatment, 66% will
experience varying degrees of permanent neurologic disability
(4). Prevention of rupture, therefore, relies on early detection and
treatment of aneurysms, although the clinical presentation is
often nonspecific, and UIAs are frequently misdiagnosed on
initial evaluation (5,6). As such, recognition of symptoms related
to UIAs and early detection are pertinent.
The International Study of Unruptured Intracranial Aneurysms
(ISUIA) trial reported that the most common presenting symptoms
are headache, ischemic cerebrovascular events, and cranial nerve
deficits (7). Although headache is the most common reason for
diagnostic imaging that leads to the detection of UIAs, it is
unclear in most cases whether a headache is directly related to
the aneurysm in the absence of subarachnoid hemorrhage (SAH)
(2). Aneurysmal characteristics, such as size and location, can
influence symptomatology and are likely responsible for
compression of adjacent structures (1,8). The pathophysiology
associated with many of the vague symptoms reported in the
presence of a UIA is not well understood. Additionally, many
other nonspecific symptoms are associated with UIAs, which
makes their diagnosis challenging. This study explores various
symptoms associated with UIAs, the rate of resolution of such
symptoms after microsurgical treatment, and the likely
pathophysiology.
2. Methods
This retrospective observational cohort study was approved by
the St. Joseph’s Hospital and Medical Center Institutional Review
Board (Phoenix, AZ) and complied with the Health Insurance
Portability and Accountability Act. The need for patient consent
was waived by the institutional review board due to the
retrospective nature of the study.
All patients with a UIA who underwent microsurgical
treatment between January 1, 2014, and December 31, 2020, at a
single quaternary center were identified using a retrospective
research database. Inclusion criteria were the availability of
treatment data, adequate follow-up (≥6 weeks), and adequate
symptom assessment. Patients who experienced recent
(<6 months before surgery) SAH of an unrelated aneurysm were
excluded from the analyses. Analyses included assessment of the
prevalence of nonspecific symptoms upon clinical presentation
and postoperative follow-up; comparisons of symptomatology by
aneurysmal location; and a comparison of patient demographics,
aneurysm characteristics, and poor neurologic outcome (defined
as a modified Rankin Scale score greater than 2) at follow-up,
with patients stratified by symptomatic versus asymptomatic
presentation. Electronic medical records were analyzed for
demographic information (age, sex, comorbidities), preoperative
life expectancy, and Charlson Comorbidities Index. Aneurysm
characteristics from computed tomography angiography were
collected to assess each aneurysm’s maximum diameter, neck
diameter, perpendicular height (defined as the largest
perpendicular distance from the neck of the aneurysm to the
dome of the aneurysm), maximum height, aneurysm
calcification, aneurysm type, location on critical perforating or
branch vessels, intraluminal thrombosis, and size and aspect
ratios. The size ratio was calculated as the maximum height
divided by the mean vessel diameter of all branches associated
with the aneurysm. The aspect ratio was calculated as the
maximum perpendicular height divided by the neck diameter.
Statistical analyses included data aggregation, exploratory
analysis, and multivariate analysis using R, version 4.0.1 (R
Foundation for Statistical Computing). Demographic and clinical
characteristics of patients were analyzed using a Wilcoxon rank
sum test for interval variables, Pearson chi-square test for
categorical variables, or Kruskal-Wallis rank sum test for
nonparametric comparisons for multiple comparators. Fisher
exact test was used for categorical variables to evaluate
differences in asymptomatic and symptomatic patients and to
compare symptoms based on aneurysm location. Significance was
defined as pless than 0.05. Results are reported as mean
(standard deviation [SD]) or as number (percentage) of patients.
3. Results
A total of 454 patients treated during the 7-year study period
were included in the final analyses (Table 1). The mean (SD) age
of all patients was 58 (12) years; 335 (74%) were women, and
119 (26%) were men. Most patients had a preoperative life
expectancy of greater than 10 years (298 of 416 [72%]). The
vascular categories involved included 152 (33%) middle cerebral
artery, 116 (26%) anterior cerebral artery, 97 (21%) internal
carotid artery (ICA), and 89 (20%) posterior circulation
aneurysms. The mean (SD) aspect ratio was 1.72 (1.53) for 419
aneurysms, and 32 (7%) of 434 aneurysms had calcification.
Overall, 90% (n= 408) aneurysms were saccular and the
remaining 10% (n= 46) were nonsaccular. Additionally, 126
(29%) of 431 UIAs were found on critical perforating vessels or
vessel branches.
Overall, 350 (77%) of the 454 patients were symptomatic; some
patients had more than 1 symptom. The most common presenting
symptom was headache, occurring in 211 (46%) patients, followed
by vertigo (94 [21%]), cognitive disturbance (68 [15%]), and visual
disturbance (64 [14%]) (Table 2). Of 328 patients for whom
symptom resolution or improvement was assessed, 258 (79%)
experienced full symptom resolution or improvement (Table 3).
Of 204 patients assessed for headache resolution, 58 (28%)
experienced residual headache at follow-up. Of these 58 patients,
Hackett et al. 10.3389/fsurg.2023.1148274
Frontiers in Surgery 02 frontiersin.org
32 (55%) reported an ability to control headache with over-the-
counter pain medication. Of 23 patients assessed for cranial
nerve recovery, 4 (17%) experienced residual cranial nerve deficits.
Overall, 104 (23%) patients were asymptomatic and 350 (77%)
were symptomatic at presentation (Table 4). The proportion of
patients with symptomatic presentation was greater among
women (266/335 [79%]) than among men (84/119 [71%]).
Compared with asymptomatic presentation, symptomatic
presentation was associated with a greater prevalence of
hypertension (65% [228/350] vs. 51% [53/104]; p= 0.009),
clinically diagnosed anxiety (8% [29/350] vs. 1% [1/104]; p=
0.008], and diabetes mellitus (18% [62/350] vs. 9% [9/104]; p=
0.03). A significantly greater proportion of patients with
asymptomatic presentations than patients with symptomatic
presentations had an SAH >6 months before microsurgical
treatment of a UIA (21% [22/104] vs. 8% [28/350]; p≤0.001).
The mean (SD) maximum aneurysm diameter was significantly
greater in the symptomatic cohort than in the asymptomatic
cohort (6.54 [4.98] mm vs. 5.46 [3.06] mm, p= 0.004). The
proportion of patients with poor neurologic outcome (modified
Rankin Scale score >2) at postoperative follow-up was not
significantly different between the symptomatic and
asymptomatic cohorts (14% [50/350] vs. 10% [10/104]; p= 0.15).
Table 5 reports symptoms by vascular territory. The
proportion of patients with intracranial internal carotid artery
aneurysms who were symptomatic (85 of 97 [88%]) was
significantly greater than the proportion of patients with
aneurysms in other locations who were symptomatic (p= 0.03).
Gait imbalance (19 of 97 [20%]; p= 0.04) and limb weakness (13
of 97 [13%]; p= 0.01) were both significantly more prevalent in
patients harboring an intracranial ICA aneurysm, compared with
patients with aneurysms in other vascular locations. The
TABLE 3 Symptoms reported at postoperative follow-up among 454
patients with microsurgical treatment of unruptured intracranial
aneurysms.
Characteristic No. of patients with symptom/no.
of observations (%)
Symptoms completely resolved
and/or improved
258/328 (79)
Residual headache 58/204 (28)
Headache controlled by over-the-
counter medication
32/58 (55)
Residual vertigo 17/94 (18)
Residual visual disturbance 10/64 (16)
Residual cognitive disturbance 10/62 (16)
Residual cranial nerve deficit 4/23 (17)
TABLE 1 Patient demographics and aneurysm characteristics among 454
patients with unruptured intracranial aneurysms.
Characteristic Value, N= 454
a
Sex
Female 335 (74)
Male 119 (26)
Age, mean (SD), years 58 (12)
Symptomatic 350 (77)
Prior SAH 50 (11)
Preoperative life expectancy (n= 416)
>10 years 298/416 (72)
5–10 years 114/416 (27)
<5 years 4/416 (1)
Comorbidities
Anxiety 30 (7)
Depression 42 (9)
Diabetes mellitus 71 (16)
Hypercholesterolemia 140 (31)
Hyperlipidemia 41 (9)
Hypertension 281 (62)
Charlson Comorbidity Index
0 97 (21)
1 85 (19)
2 115 (25)
3 94 (21)
4 42 (9)
5 16 (4)
6 4 (1)
7 0 (0)
8 1 (0.2)
Vasculature location
ACA 116 (26)
ICA 97 (21)
MCA 152 (33)
Posterior circulation 89 (20)
Aneurysm measurements, mean (SD)
Maximum diameter, mm (n= 446) 6.29 (4.63)
Maximum perpendicular height, mm 5.12 (3.38)
Maximum height, mm 5.48 (3.55)
Maximum neck diameter, mm 3.66 (1.37)
Aspect ratio (n= 419) 1.72 (1.53)
Size ratio 2.52 (1.39)
Aneurysm characteristics
Calcification (n= 434) 32 (7)
Complex saccular 60 (13)
Critical or perforating branch vessels (n= 431) 126 (29)
Intraluminal thrombosis on imaging (n= 433) 18 (4)
Nonsaccular 46 (10)
Saccular 408 (90)
ACA, anterior cerebral artery; ICA, internal carotid artery; MCA, middle cerebral
artery; SAH, subarachnoid hemorrhage; SD, standard deviation.
a
Data are presented as number (%) of 454 observations unless otherwise noted.
TABLE 2 Presenting symptoms among 454 patients with unruptured
intracranial aneurysms.
Characteristic No. (%) of patients, N= 454
Cognitive disturbance 68 (15)
Cranial nerve deficit 25 (6)
Gait imbalance 58 (13)
Headache 211 (46)
Hearing disturbance 9 (2)
Ischemic event 17 (4)
Limb weakness 29 (6)
Nausea and/or vomiting 22 (5)
Paresthesia 35 (8)
Seizure 10 (2)
Syncope/near syncope 24 (5)
Tinnitus 3 (1)
Vertigo 94 (21)
Visual disturbance 64 (14)
Other 15 (3)
Hackett et al. 10.3389/fsurg.2023.1148274
Frontiers in Surgery 03 frontiersin.org
prevalence of cranial nerve deficit was comparable in patients with
ICA aneurysms (11 of 97 [11%]) and patients with posterior
circulation aneurysms (11 of 97 [11%]); the prevalence of cranial
nerve deficit among these patients was significantly greater than
the prevalence among patients with aneurysms at other locations
(p≤0.001). The highest burden of cognitive changes was found
among patients with aneurysms in the middle cerebral artery
territory (29 of 152 [19%]; p= 0.04).
4. Discussion
In our retrospective cohort, 77% (350/454) of patients
presented with symptoms; often, aneurysms were discovered
during evaluation for unrelated issues. It is unclear whether
symptoms were a direct result of the aneurysms, yet 79% of the
patients who had follow-up of 6 weeks or greater reported either
improvement or complete resolution of presenting symptoms
TABLE 4 Comparison of demographic and clinical characteristics of 104 asymptomatic and 350 symptomatic patients with unruptured intracranial
aneurysms.
Characteristic
a
Asymptomatic, N= 104 Symptomatic, N= 350 pvalue*
Sex 0.049
Female 69 (66) 266 (76)
Male 35 (34) 84 (24)
Age, mean (SD), years 59 (13) 58 (12) 0.09
Prior SAH 22 (21) 28 (8) <0.001
Preoperative life expectancy (n= 416) 0.51
>10 years 73/96 (76) 225/320 (70)
5–10 years 22/96 (23) 92/320 (29)
<5 years 1/96 (1) 3/320 (1)
Comorbidities
Anxiety 1 (1) 29 (8) 0.008
Depression 6 (6) 36 (10) 0.16
Diabetes mellitus 9 (9) 62 (18) 0.03
Hypercholesterolemia 33 (32) 107 (31) 0.82
Hyperlipidemia 9 (9) 32 (9) 0.88
Hypertension 53 (51) 228 (65) 0.009
Vasculature location 0.03
ICA 12 (12) 85 (24)
ACA 34 (33) 82 (23)
MCA 37 (36) 115 (33)
Posterior circulation 21 (20) 68 (19)
Maximum diameter, mean (SD), mm (n= 446) 5.46 (3.06) 6.54 (4.98) 0.004
Aspect ratio, mean (SD) (n= 419) 1.56 (0.61) 1.76 (1.71) 0.11
Aneurysm calcification (n= 434) 7 (7) 25 (8) 0.85
Nonsaccular 5 (5) 41 (12) 0.04
Saccular 99 (95) 309 (88) 0.04
Complex saccular 16 (15) 44 (13) 0.46
Critical or perforating branch vessels (n= 431) 24 (24) 102 (31) 0.21
Intraluminal thrombosis on imaging (n= 433) 4 (4) 14 (4) >0.99
Death 3 (3) 12 (3) >0.99
Discharge mRS score (n= 452) 0.83
1 37/103 (36) 106/349 (30)
2 23/103 (22) 92/349 (26)
3 37/103 (36) 131/349 (38)
4 6/103 (6) 17/349 (5)
5 0/103 (0) 2/349 (1)
6 0/103 (0) 1/349 (0.3)
Follow-up mRS score 0.048
0 27/104 (26) 63/350 (18)
1 51/104 (49) 181/350 (52)
2 16/104 (15) 56/350 (16)
3 1/104 (1) 27/350 (8)
4 6/104 (6) 12/350 (3)
5 0 (0) 0 (0)
6 3/104 (3) 11/350 (3)
Follow-up mRS score >2 10 (10) 50 (14) 0.15
ACA, anterior cerebral artery; ICA, internal carotid artery; MCA, middlecerebral artery; mRS, modified Rankin Scale; SAH, subarachnoid hemorrhage; SD, standard deviation.
a
Data are presented as number (%) of patients unless otherwise noted.
*Pearson chi-square test, Wilcoxon rank sum test, or Fisher exact test used to compare groups.
Hackett et al. 10.3389/fsurg.2023.1148274
Frontiers in Surgery 04 frontiersin.org
after microsurgical treatment. Although the general population of
patients with UIAs tends to be asymptomatic, our institution
often receives referrals of patients with complex or atypical
presentations, which may account for the high percentage of
patients who presented with symptoms. Patients with prior SAH
(>6 months prior) were significantly more likely than other
patients to have an asymptomatic presentation associated with
their unruptured aneurysm diagnosis, likely due to recommended
follow-up imaging after experiencing an aneurysmal SAH
(aSAH). Interestingly, the presence of a clinically diagnosed
anxiety disorder, prior to aneurysm diagnosis, was associated
with a symptomatic UIA. Although the relationship between
anxiety and aneurysms after SAH and treatment has been
explored, the relationship between anxiety and symptomatic
UIAs has not been discussed in literature (9). A possible
explanation for this association is that patients with nonspecific
symptoms who experience anxiety may be more persistent with
follow-up and request further investigation, leading to higher
rates of incidental UIA findings.
Headaches are the most frequently reported symptom of UIAs
in the literature (10,11) and were reported in 46% (211/454) of
patients in our cohort. In these patients, the presence of an
aneurysm is often missed due to nonspecificity and the varied
characterization of headaches associated with UIA. Headaches
can present as chronic with variable characterization in two-
thirds of cases, but they may also present acutely as a sudden
onset headache in one-third of cases (11). Although acute
“thunderclap”headaches are typical of aSAH, less severe and
more chronic headaches may be associated with UIAs. For
example, a “sentinel headache”is well-described in the literature
and is thought to be associated with local thrombosis (12).
Chronic headaches may have variable presentations but most
frequently resemble migraines (13). In 2013, Lebedeva et al. (14)
conducted a prospective case-control study of 199 patients and
found that migraine-like headaches without aura were
significantly associated with saccular aneurysms up to 1 year
before rupture (odds ratio [OR], 6.7; 95% confidence interval
[CI], 3.8–11.9; p≤0.001). Another examination of 172 patients
found that a history of migraines was significantly associated
with UIAs (OR, 1.9; 95% CI, 1.1–3.5) but no other headache
types (15). Although the pathophysiology of headaches among
patients with UIAs is a topic of ongoing research, headaches
most likely arise from local inflammatory processes involving the
meninges or cranial nerves, pulsation of the aneurysm itself, or
local thrombosis (11). Intriguingly, headaches have been found to
resolve in the majority of patients after treatment (11,16,17).
Although headache was the most common residual symptom at
follow-up in our analysis, 55% (32/58) of those patients reported
an ability to control the pain with over-the-counter medications.
Only patients with a clear diagnosis of a cranial nerve palsy
were categorized into the cranial nerve deficit cohort in this
analysis. However, patients reporting hearing or visual
disturbances could be experiencing a cranial nerve deficit as well.
Specifically, aneurysms of the anterior inferior cerebellar artery
have been implicated in patients presenting with symptoms of
hearing loss and tinnitus, likely due to the close approximation
of the artery to the internal auditory canal as well as cranial
nerves VII and VIII (18,19). In our study, 3 patients presented
with an aneurysm of the anterior inferior cerebellar artery, and 1
of these patients had a cranial nerve deficit.
A range of visual deficits were reported in our patient cohort
(14% [64/454]). Aneurysm-related visual changes commonly
reported in the literature may include diplopia, ptosis, pupillary
dilation, and lateral deviation of the affected eye, likely secondary
to oculomotor palsy. Decreased visual acuity as a result of optic
pathway compression has also been reported. In fact, 2 of the
most common causes of non–pupil-sparing oculomotor nerve
palsy are posterior communicating artery aneurysms and distal
basilar artery aneurysms (20). Less commonly, aneurysms of the
cavernous portion of the ICA have been reported to cause third
TABLE 5 Symptoms among 454 patients with unruptured intracranial aneurysms, by aneurysm location.
Characteristic
No. (%) of patients
pvalue*ICA, N= 97 ACA, N= 116 MCA, N= 152 Posterior circulation, N=89
Cognitive disturbance 17 (18) 17 (15) 29 (19) 5 (6) 0.04
Cranial nerve deficit 11 (11) 2 (2) 2 (1) 10 (11) <0.001
Gait imbalance 19 (20) 13 (11) 21 (14) 5 (6) 0.04
Headache 54 (56) 47 (41) 74 (49) 36 (40) 0.09
Hearing disturbance 4 (4) 1 (1) 3 (2) 1 (1) 0.44
Ischemic event 7 (7) 3 (3) 6 (4) 1 (1) 0.17
Limb weakness 13 (13) 3 (3) 9 (6) 4 (5) 0.01
Nausea and/or vomiting 4 (4) 6 (5) 6 (4) 6 (7) 0.76
Paresthesia 9 (9) 9 (8) 10 (7) 7 (8) 0.89
Tinnitus 1 (1) 0 (0) 2 (1) 0 (0) 0.62
Seizure 2 (2) 3 (3) 5 (3) 0 (0) 0.40
Symptomatic 85 (88) 82 (71) 115 (76) 68 (76) 0.03
Syncope or near syncope 6 (6) 6 (5) 8 (5) 4 (5) 0.97
Vertigo 20 (21) 21 (18) 32 (21) 21 (24) 0.82
Visual disturbance 20 (21) 17 (15) 13 (9) 14 (16) 0.06
Other 5 (5) 2 (2) 4 (3) 4 (5) 0.44
ACA, anterior cerebral artery; ICA, internal carotid artery; MCA, middle cerebral artery.
*Pearson chi-square test, Kruskal-Wallis rank sum test, or Fisher exact test used to compare groups.
Hackett et al. 10.3389/fsurg.2023.1148274
Frontiers in Surgery 05 frontiersin.org
cranial nerve palsy (21). Although the pathophysiology behind
oculomotor nerve palsy is thought to be due to pulsatility and
compressive mass effect of large aneurysms, there are reports of
small aneurysms causing third cranial nerve palsy, refuting the idea
that these deficits are strictly related to aneurysm size (21–23). Any
aneurysm of the circle of Willis can cause anterior optic pathway
compression and result in visual deficits; however, the most
common locations include the ICA, specifically the paraclinoid
region. In a study conducted by Park et al. (8), the most common
aneurysms causing visual deficits arose from the ophthalmic
segment of the ICA (31 of 33 cases). The close approximation of
the ICA to the optic nerve and optic chiasm may yield
compression from UIAs and is likely the cause of visual
disturbances. Direct compression is thought to be the most
common etiology; however, other causes include diminished blood
supply due to compromise of the ophthalmic artery or small
arterial branches in the parasellar and suprasellar regions (24–26).
In the ISUIA trial, the second most common symptom reported
among patients presenting with UIAs was an ischemic
cerebrovascular event (2). In our cohort of 454 patients, 17 (4%)
presented with signs and symptoms of either a transient ischemic
attack or cerebrovascular infarction, and an aneurysm was
discovered upon further investigation. Both hemodynamic and
biological factors of aneurysms contribute to the prothrombotic
environment within the aneurysmal sac, which may result in
subsequent thrombosis of the parent vessel or dislodged emboli
from the thrombus (27). Compression of nearby vasculature can
also result in ischemic events. In a retrospective study of 3,202
patients, reported by Calviere et al. (28), 15 patients (0.47%) were
found to have stroke or transient ischemic attack solely caused by
UIAs, among whom 10 had evidence of aneurysmal thrombosis.
Aneurysmal thrombosis was significantly associated with ischemic
stroke (p= 0.02) in that study. Additionally, cases of large vessel
occlusion caused by a thrombus formed in the aneurysmal sac have
been documented in the literature (29–31). Although aneurysms
can be an exclusive cause of ischemia, a UIA discovered in the
presence of an ischemic event is usually thought to be an incidental
finding due to the overlapping risk factors of both strokes and
aneurysms, which include hypertension, diabetes, hyperlipidemia,
and smoking (28,32). As such, UIAs are more commonly found in
patients who have experienced an ischemic stroke than in the
general population. In our cohort, among patients with
hypertension and patients with diabetes, the proportion who were
symptomatic at presentation was greater than the proportion who
were asymptomatic at presentation.
Vertigo was the second most common presenting symptom
(21% [94/454]) in our UIA cohort. In 1 case reported by Oh
et al. (33), a patient who was later found to have a large left
vertebral artery aneurysm had a clinical presentation consisting
of positional vertigo and vomiting, which resolved after
aneurysm resection. The likely cause of this patient’s clinical
presentation was presumed to be secondary to mass effect on the
inferior cerebellum around the fourth ventricle and compression
of the area postrema. In another case, a patient presented with
headache, nausea, vomiting, and vertigo; an unruptured
aneurysm, partially eroding the floor of the sella and causing
hydrocephalus, was identified (34). Cerebral aneurysms of the
ICA and anterior communicating artery can mimic sellar lesions;
in the reported case, cerebral angiography identified an aneurysm
of the right carotid artery at the intracavernous tract.
The functional disability of people with seizures often prompts
further workup, yet it is unclear whether seizures are a direct result
of aneurysms or incidental findings. In our analysis, only 2% (10/
454) of the patients had an aneurysm that was discovered upon
workup for seizures. However, a series of articles have reported
seizure as a primary presenting symptom of UIA (12,35–38). Of
662 surgically managed unruptured intracranial aneurysms, Patil
et al. (38) reported a total of 3 patients with unruptured anterior
communicating artery aneurysms who presented with seizures as
the only symptom. In a separate study, Hanggi et al. (39)
assessed 347 UIA patients, and 9 presented with seizures, all of
which resolved after aneurysm treatment. In the same study, a
comprehensive review of seizures secondary to aneurysms
suggested direct or intermittent cortical compression can cause
cortical gliosis and resultant epileptogenesis. The authors
concluded that surgical resection of the surrounding gliosis leads
to a seizure-free postoperative course (39).
Additional and extremely vague symptoms displayed in our
analysis of 454 patients included syncope and near syncope (24
[5%]), limb weakness (29 [6%]), paresthesia (35 [8%]), gait
imbalance (58 [13%]), and cognitive-related impairments (68
[15%]). Many of these symptoms are nonspecific, and reports of
them in the literature are limited to case studies. Syncope was
identified in 1 other case of a woman with transient syncopal
episodes prompting presentation to the emergency department, at
which time an unruptured fusiform mid-basilar artery aneurysm
was incidentally found (40). A case report published in 2021 details
a patient with a giant thrombosed middle cerebral artery aneurysm,
with gait disturbance as the sole presenting symptom (41). A case
series published in 1980 described 3 patients with episodic weakness
and numbness of the arms and legs and 1 patient with confusion
spells leading to incidental findings of UIAs; 3 of the 4 patients
reported symptom resolution after treatment (42). It is unclear
whether these extremely vague symptoms are a direct result of the
aneurysms, and a direct correlation remains difficult to assess.
Limitations of this study include its retrospective design and an
inability to account for all confounding variables. Additionally, the
external validity of this study was limited because it was conducted
at a single institution that receives high volumes of patient referrals
with atypical and complex clinical presentations. Furthermore, it is
difficult to ascertain whether clinical symptoms upon presentation
are related to the aneurysm or whether the aneurysm is an
incidental finding.
5. Conclusion
The clinical presentation of patients with UIAs can consist of
vague and nonspecific symptoms. In the setting of nonspecific
neurologic symptoms, such as headache, cranial nerve deficits,
ischemic events, and even seizures, UIAs should be considered as
a potential etiology. In many cases, it is unclear whether
Hackett et al. 10.3389/fsurg.2023.1148274
Frontiers in Surgery 06 frontiersin.org
aneurysms cause these symptoms or are simply an incidental
finding. However, a substantial proportion of patients with UIAs
experience resolution of nonspecific symptoms after aneurysm
treatment. Aneurysms may therefore be the origin of these
symptoms through varied pathogenesis. Because early detection
is crucial to prevent aSAH, it is imperative that physicians not
rule out aneurysms in the setting of nonspecific neurologic
symptoms.
Data availability statement
The raw data supporting the conclusions of this article will be
made available by the authors, without undue reservation.
Ethics statement
Ethical review and approval was not required for the study on
human participants in accordance with the local legislation and
institutional requirements. The ethics committee waived the
requirement of written informed consent for participation.
Author contributions
Conception and design: AH, SK, and JC. Acquisition of data:
ER and LS. Analysis and interpretation of data: SK and AN.
Drafting the article: AH, JR, EN, and AE. Critically revising the
article: JC, JH, BF, EW, and ML. Statistical analysis: SK and AN.
Study supervision: JC and ML. All authors contributed to the
article and approved the submitted version.
Acknowledgments
We thank the staff of Neuroscience Publications at Barrow
Neurological Institute for assistance with manuscript preparation.
Conflict of interest
The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could
be construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the
authors and do not necessarily represent those of their affiliated
organizations, or those of the publisher, the editors and the
reviewers. Any product that may be evaluated in this article, or
claim that may be made by its manufacturer, is not guaranteed
or endorsed by the publisher.
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