Keywords
aneurysm - radiosurgery - de novo
Introduction
Stereotactic radiosurgery is an established treatment option for arteriovenous malformation
(AVM), benign and malignant brain tumors, and neuralgia because of its efficacy and
minimal invasiveness. Conventional radiation-induced late side effects such as tumor
formation and vasculopathy-related lesions are well described.[1]
[2]
[3] However, the occurrence of late complications induced by stereotactic radiosurgery
has not been well documented, and research is ongoing. Stereotactic radiosurgery is
frequently used for patients with nonmalignant diseases who are expected to have long
lifespans, so a radiation-induced problem occurring after radiosurgery is problematic
and increases the amount of care such patients would need. We present a patient who
experienced epilepsy due to progressive enlargement of a pseudoaneurysm that seemed
to have been induced by gamma knife surgery for an AVM.
Case Report
A 65-year-old man had an acute onset of right hemiparesis, aphasia, and consciousness
disturbance at home. After transfer to the hospital, these symptoms improved within
24 hours. Emergent computed tomography (CT) images showed a 1.5-cm diameter ring-like
high-density area in the left Sylvian fissure with a surrounding low-density area
that indicated the probable presence of a brain edema ([Fig. 1A]). Magnetic resonance (MR) images demonstrated that the lesion was hyperintense on
T1- and T2-weighted images with a hypointense rim with surrounding edema ([Fig. 1B]). Angiograms showed an aneurysm on the middle cerebral artery consistent with the
lesion demonstrated on CT and MR images ([Fig. 1C]).
Fig. 1 (A) Computed tomography at admission showed ring-like high density lesion in the
left temporal portion. (B) T2-weighted magnetic resonance image showed a high hyperintensity
mass with hypointensity rim associated with brain edema. (C) Anteroposterior image
of the left carotid angiogram showed a fusiform aneurysm on the left middle cerebral
artery.
This patient had a history of gamma knife treatment for an AVM ([Fig. 2A]) on the left middle cerebral artery 15 years before with a marginal dose of 18 Gy.
Three years later he received a second gamma knife treatment with a marginal dose
of 22 Gy against the residual nidus. Six years after the initial treatment, the obliteration
of the AVM was confirmed by angiograms ([Fig. 2B]), and the patient had no further follow-up.
Fig. 2 (A) The anteroposterior image of the left internal carotid angiogram prior to the
first radiosurgery showed an arteriovenous malformation fed by the middle cerebral
artery and drained into the superior sagittal sinus. (B) The left internal carotid
angiogram 3 years after the second radiosurgery showed complete eradication of the
shunt flow.
The aneurysm was located on the nonbranching portion of the artery in the irradiated
field. From these findings, we diagnosed that this patient had a seizure due to the
mass effect of the radiation-induced de novo aneurysm. We resected the aneurysm under
somatosensory and motor evoked potentials. The arachnoid membrane surrounding the
aneurysm showed thickening and had changed to a white color. The aneurysm was located
in the Sylvian fissure and was a fusiform shape ([Fig. 3A]). He showed no new neurologic deficit after the operation.
Fig. 3 (A) The aneurysm was located on the nonbranching portion of the artery in the Sylvian
fissure. (B, C) The wall of the resected aneurysm showed intimal thickening and fibrous
degeneration with inflammatory cell infiltration and calcification (hematoxylin and
eosin stain). (D) The internal elastic lamina was degenerated and disrupted (Elastica
van Gieson stain). (C, D) Increased magnification of the outlined area in (B). Original
magnification ×12.5 (B), ×40 (C, D).
The resected aneurysm showed that the wall had intimal thickening with inflammatory
cell infiltration and fibrous degeneration. The elastic lamina was degenerated and
disrupted ([Fig. 3B–D]). The seizure was controlled with antiepilepsy medication, and the patient was discharged
without neurologic deficits.
Discussion
Stereotactic radiosurgery is purported to be a less invasive procedure for vascular
malformations and central nervous system tumors. For AVMs, the vessels are the main
target of radiation; for tumors, vessels should be out of the radiation field. Still,
it can induce tumors[4]
[5]
[6] and vasculopathy-related lesions such as cysts,[7]
[8] vessel occlusions,[9] and aneurysms.[10]
[11]
[12]
[13]
[14]
[15]
Sciubba et al reported on 26 patients with conventional radiation-induced aneurysms.[16] For stereotactic radiosurgery, only seven patients including the present patient
have been reported ([Table 1]). The time to discovery of the aneurysm after radiation was from 7 months to 29
years (average: 10.7 years) in the conventional group and 9 months to 15 years (average:
7.8 years) in the radiosurgery group. In the radiosurgery group, the original diseases
were four cases of vestibular schwannomas, one case of cerebellopontine meningioma,
and two cases of AVM. And all of these aneurysms were located in the irradiation field
and nonbranching sites. The radiation doses were 12 or 25 Gy for the schwannomas,
16 Gy for the meningioma, and 20 and 40 Gy for AVMs.
Table 1
Reported cases of de novo intracranial aneurysms following stereotactic radiosurgery
|
Study
|
Age/Sex
|
Original lesion
|
Dose
|
SAH
|
Location
|
Duration[a]
|
|
Huang et al[10]
|
19/F
|
AVM
|
20 Gy
|
−
|
Distal ACA
|
9 mo
|
|
Takao et al[11]
|
63/F
|
Acoustic neuroma
|
12 Gy
|
+
|
Distal AICA
|
6 y
|
|
Akamatsu et al[12]
|
75/F
|
Acoustic neuroma
|
12 Gy
|
+
|
Distal AICA
|
8 y
|
|
Park et al[13]
|
69/F
|
Acoustic neuroma
|
12 Gy
|
+
|
Distal AICA
|
5 y
|
|
Kellner et al[14]
|
58/F
|
Cerebellopontine meningioma
|
16 Gy
|
−
|
Distal SCA
|
10 y
|
|
Sunderland et al[15]
|
50/F
|
Vestibular schwannoma
|
13 + 12 Gy
|
+
|
Distal AICA
|
10 y
|
|
Present case
|
65/M
|
AVM
|
18 + 22 Gy
|
−
|
Distal MCA
|
15 y
|
Abbreviations: ACA, anterior cerebral artery; AICA, anterior inferior cerebellar artery;
AVM, arteriovenous malformation; F, female; M, male; MCA, middle cerebellar artery;
SAH, subarachnoid hemorrhage; SCA, superior cerebellar artery.
a Time to aneurysm discovery after radiation.
For the de novo intracranial aneurysm following stereotactic radiosurgery, only 7
patients including the present patient have been reported. The original diseases were
four cases of acoustic neuroma, two cases of AVM, and one case of meningioma, and
the radiation dose was 12 to 40 Gy. In four patients, the aneurysms were found due
to the rupture. The time to discovery of the aneurysm after radiosurgery was 9 months
to 15 years.
Radiosurgery damages the endothelial cells and causes proliferation of smooth muscle
cells, leading to intimal thickening. It also causes adventitial fibrosis. As the
degeneration progresses, this induces vessel wall hyalinization, calcification, and
necrosis associated with fragmentation of the elastic lamina, resulting in occlusion
of blood vessels.[17]
[18]
[19]
[20]
[21]
In the experimental model, endothelial cell proliferation started at 3 hours after
irradiation, and the endothelial hyperplasia and vessel wall thickening continued
throughout the observation period (90 days after irradiation).[20] Radiation-induced histologic changes of vessels are supposed to be dose related,
and high-dose radiation can induce radionecrosis,[18]
[22] but the radiation dose threshold below which no changes are induced is not yet known.[18]
The reported radiation-induced aneurysm was located on the nonbranching portion,[10]
[11]
[12]
[13]
[14]
[15] and the resected aneurysm wall showed the disruption of the elastic lamina.[12] The histologic findings in our case were consistent with these findings. We do not
know the critical radiation dose that induces an aneurysm formation, but the degeneration
of the elastic lamina may play an important role.
Conclusion
Stereotactic radiosurgery is an established treatment tool for central nervous system
lesions and has been frequently used to treat AVMs and benign tumors. Patients who
are normally expected to have a long lifespan can run risks of aneurysm formation,
vessel occlusion, tumor synthesis, and other unknown late perils. Further research
of these late-occurring health problems is needed to identify unknown long-term risks
and clarify optimal radiation doses and follow-up periods. The current report also
suggests that the treatment procedure be selected prudently, especially among younger
patients.
