CASE REPORTS

Delayed Compressive Angiomatous Degeneration in
a Case of Mesial Temporal Lobe Epilepsy Treated by
Gamma Knife Radiosurgery: Case Report
Patrice Finet, MD
Department of Neurosurgery,
Saint-Luc Hospital,
Brussels, Belgium

Herbert Rooijakkers, MD
Department of Neurosurgery,
Saint-Luc Hospital,
Brussels, Belgium

Catherine Godfraind, MD, PhD
Department of Neuropathology,
Saint-Luc Hospital,
Brussels, Belgium

Christian Raftopoulos, MD, PhD
Department of Neurosurgery,
Saint-Luc Hospital,
Brussels, Belgium
Reprint requests:
Christian Raftopoulos, MD, PhD,
Avenue Hippocrate, 10,
1200 Brussels, Belgium.
E-mail:
Christian.Raftopoulos@uclouvain.be
Received, March 2, 2009.

OBJECTIVE: Mesial temporal lobe epilepsy (MTLE) is one of the most common causes of
intractable partial epilepsy. The conventional treatment of patients with MTLE is surgical
excision. Currently, gamma knife (GK) radiosurgery is being explored as an alternative
treatment. We report the first delayed major complication related to this treatment.
CLINICAL PRESENTATION: A 54-year-old woman with a medical history of a post-viral
encephalitis in childhood was treated in April 2001 by GK radiosurgery for a medically
refractory MTLE. Her right temporomesial area received a dose of 20 Gy at the 50% marginal
isodose line. Unfortunately, the patient continued to experience seizures, although they
were of shorter duration and occurred less frequently. She was seen in our department
on November 8, 2007, for an intracranial hypertensive syndrome. The imaging work-up
showed an expansive hemorrhagic lesion in the right mesiotemporal area. Despite corticosteroid treatment, the patient still complained about headaches on November 13, and
surgery was scheduled for November 22. However, the patient returned to the emergency
department on November 16 with a temporal herniation syndrome requiring an urgent surgical procedure.
INTERVENTION: The expansive lesion was completely removed. Histologic examination
revealed lesions of the gray and white matter consisting of severe gliosis, hemorrhagic
foci, hyalinized vessels, and neovascularization, giving the brain parenchyma an angiomatous aspect.
CONCLUSION: Although reports on GK radiosurgical treatment of MTLE are encouraging,
this case stresses the risk of developing 6 years later an angiomatous degeneration of the
targeted brain with life-threatening intracranial hypertension.

Accepted, February 3, 2010.

KEY WORDS: Degeneration, Epilepsy, Epilepsy surgery, Gamma knife, Medically refractory, Mesial, Radiosurgery,
Temporal lobe

Copyright © 2010 by the
Congress of Neurological Surgeons

Neurosurgery 67:E218-E220, 2010

M

esial temporal lobe epilepsy (MTLE) is one of the bestdefined forms of intractable partial epilepsy, with a good
surgical prognosis. Seizure cessation rates after selective
amygdalohippocampectomy or anterior temporal lobectomy range
from 65% to 90%.1-4An analysis based on the experience of 100
epilepsy surgery centers worldwide showed that 68% of patients
were seizure free after temporal lobe resection.1 In 1982, Wieser
and Yaşargil5 reported preliminary results of selective amygdalohippocampectomy performed in 27 patients with MTLE. Of
these, 22 (81%) were free of seizures, and the postoperative neuropsychological follow-up studies showed better results than in
those patients who underwent large temporal lobe resections. A more
ABBREVIATIONS: GK, gamma knife; MTLE, mesial temporal lobe
epilepsy

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DOI: 10.1227/01.NEU.0000370011.36820.ED

www.neurosurgery- online.com

recent study of a series of 321 patients showed a similar rate: 82%
of patients were seizure free following anterior temporal lobectomy, amygdalohippocampectomy, or lesionectomy, but those
who had undergone amygdalohippocampectomy and lesionectomy had a better postoperative neuropsychological outcome compared to patients who had had anterior temporal lobectomy.6
Another team reported that patients have a greater than 80%
chance of becoming seizure free after selective amygdalohippocampectomy, with a low complication rate. The mortality and severe
morbidity rates associated with temporal lobe surgery for epilepsy
are less than 1% when performed by an experienced surgeon.7
Interest in gamma knife (GK) radiosurgery as an alternative
treatment to open surgery for MTLE has been increasing. Studies
have shown seizure reduction rates after GK radiosurgery comparable to those of conventional open surgery over 2 years of

VOLUME 67 | NUMBER 1 | JULY 2010 | E218

FINET ET AL

as fear with an abnormal increasing epigastric perception. The auras
were followed by partial complex
A
B
seizures, characterized by deterioration of consciousness with automatic movements of the hands and
repetitive swallowing. The epileptic seizures occurred in salvoes,
especially during menstruation (35 seizures per day for several days).
Because her seizures were resistant
to carbamazepine (1100 mg/d) and
lamotrigine (300 mg/d), she was
treated in April 2001 in Erasme
Hospital in Brussels by GK radiosurgery targeting the right temporomesial area with a dose of 20
Gy at the 50% marginal isodose
line (Figure 1).
After GK radiosurgery, the
patient’s seizures increased in freFIGURE 1. Coronal (A) and axial ( B) T2-weighted MRI
quency for several months; they did
images with the target volume. The right amygdale, the hipnot begin to decrease until June
pocampus, the parahippocampic gyrus, and the cortex of
2003. The partial seizures became
the collateral fissure are identified and contoured so as to
rare (<4-5 seizures per month), but
estimate their relation with the target volume. The homolateral hemi-brainstem, the optic tract, the optic chiasm, and
there was a clear increase in the
the optic nerve also are contoured to estimate their risk of irradiation. The radiation beam targets the amygdalohipauras, up to 200 per month. In
pocampic axis so as to cover the major part of the amygdala (with the exception of its superointernal portion, which is
March 2006, gabapentin was added
close to the optical path), the hippocampus, and the entorhinal cortex. The radiation dose is 20 Gy at the 50% isodose (maxto the patient’s treatment, and the
imal dose: 40 Gy). This ensures that 100% of the entorhinal structures are covered by the isodose 17 Gy. The maximal
auras decreased gradually.
punctual doses received by the brainstem and the optic tract are 14.5 Gy and 12.5 Gy, respectively. The time of irradiaOn MRI, changes appeared
tion was 157.65 min.
in July 2002 (15 months posttreatment) with a slight right hippocampic contrast enhancement. This contrast enhancement and the
follow-up.8 The major advantage of GK radiosurgery in comparsurrounding high T2 signal of the white matter of the hippocampic region
ison to open surgery is its very minimal invasive nature with a
gradually expanded. In April of 2007, MRI showed a significant right
very low risk of severe complication, even though the rate of comtemporal edematous reaction with contrast enhancement and also revealed
plication with conventional surgery has been markedly reduced,
2 right internal temporal hemorrhagic spots.
to less than 3%. Another advantage of GK radiosurgery is the posIn November 2007, when the patient came to our department, she still
8
sibility of a better neuropsychological outcome. Limitations conwas experiencing seizures but of shorter duration and significantly less
nected with radiosurgery include the delay of response (about 1
often: 5 seizures per month or less (Engel class IIB). However, she reported
year) and the presence of MRI changes with mass effect for sevabout 1 aura per day (15-40 auras per month). Her treatment consisted
eral months, although with good clinical tolerance and good
of 5 drugs: carbamazepine, gabapentine, topiramate, losartan, and
response to treatment with corticosteroids.8-12 This article reports
amlodipine. Neurologic examination at this stage revealed only 1 instance
a case of a delayed, life-threatening complication of GK radioof minor space-time confusion, with a mini-mental state examination score
of 28/30.
surgery in the treatment of MTLE
The ophthalmologic examination demonstrated normal visual acuity
but with an acute nasal predominant bilateral papilledema with partial
CASE REPORT
obscuration of the small vessels. A cerebral CT scan (Figure 2A) demonA 54-year-old woman presented to our department in November
strated right temporal expansive hemorrhagic lesions associated with
2007, with headaches and nausea. The headaches had started 3 months
edema and a mass effect responsible for subfalcine and temporal cerebral
earlier, but the pain had increased over the preceding several days with
herniations. A cerebral MRI study (Figure 2B and C) showed a right
concomitant nausea. The patient also complained of asthenia and loss
amygdalohippocampic expansive lesion of 27 × 41 mm. It was characof memory. Her past medical history was marked by a post-viral
terized by a heterogeneous signal, mainly hemorrhagic, on all sequences.
encephalitis related to measles at 6 years of age (unfortunately, this
Heterogeneous enhancement with gadolinium also was seen, with sigwas not documented), a benign breast tumor operated when she was
nificant edema with a mass effect on the right ventricle, causing it to be
18, high blood pressure, and right MTLE. She had her first epileptic
partially collapsed, with deviation of the medial line and temporal and subseizure at 7 years of age, and the seizures intensified during adolesfalcine cerebral herniations. These MRI findings were consistent with a
cence. In 2001, her seizures began to be preceded by auras described
hemorrhagic high-grade glioma. A methionine positron emission tomog-

E218 | VOLUME 67 | NUMBER 1 | JULY 2010

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POST-RADIOSURGERY ANGIOMATOUS DEGENERATION

A

B

C

FIGURE 3. Postoperative T1weighted MRI sequences with gadolinium showing complete resection
of the mesiotemporal lesion with
regression of the mass effect.

D
FIGURE 2. Preoperative imaging stud-

ies. A, axial CT scan without contrast
reveals a right mesiotemporal expansive
hemorrhagic lesion associated with edema
and mass effect responsible for a subfalcine
and temporal cerebral herniation. B, T1weighted MRI scan without gadolinium
shows a right amygdalohippocampic lesion
characterized by a heterogeneous signal
(mainly hemorrhagic). Significant edema
with mass effect was seen, causing deviation of the medial line and temporal
and subfalcine cerebral herniation. C,
T1-weighted MRI scan with gadolinium
reveals heterogeneous enhancement of the
irradiated area. D, coregistration of MRI
and methionine positron emission tomography (axial and coronal) indicates a
clear hyperfixation in certain parts of the
right mesiotemporal lesion, especially in
its anterior area.

raphy study (Figure 2D) showed a very clear hyperfixation in certain
parts of the right mesiotemporal lesion, in particular its anterior part,
also consistent with a high-grade glioma.
We contacted the radiosurgical team, which recommended corticosteroid treatment, intravenously at first and thereafter orally, with 64 mg
of methylprednisolone per day for 3 days, followed by 32 mg per day.
The patient improved rapidly, with a partial regression of headaches.
However, due to the persistence of the headaches, which made it impossible for her to lead a normal social life, surgery was scheduled for 14
days after the initiation of her corticosteroid treatment. Unfortunately,
7 days after the procedure was scheduled, the patient developed dizziness, followed by deterioration of consciousness to the point that she had
difficulty waking up, with a Glasgow Coma Scale score of 12 (E3V3M6)
and an areactive right mydriasis on the day she returned to the emergency department (November 16, 2007). An urgent cerebral CT scan

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demonstrated a slight aggravation
of her temporal and subfalcine herniation. An urgent decompressive
surgery was performed through a
standard pterional approach, and
the lesion was macroscopically completely removed.
The patient’s postoperative course
was rapid and favorable, with a normal neurologic examination by the
first postoperative day. There was
no clinical visual field deficit. MRI
performed on the 3rd postoperative day (Figure 3) confirmed the
complete resection of the mesiotemporal lesion with regression of the
mass effect.
More than 1 year later, the patient
complains only of rare (about once
per day) atypical discomforts lasting
a few seconds (Engel IB). These discomforts are different from the auras
and seizures she experienced before
surgery, being much less annoying.
Gabapentine was gradually decreased without seizure recurrence.
Histologic examination (Figure 4) showed no features compatible with
a high-grade glioma, but demonstrated major alterations of the gray and
the white matter consisting of a severe gliosis with hyalinized vessels at different stages, sometimes filled with macrophages. A glial fibrillary acidic
protein analysis showed that gliosis appeared more abundant in the white
matter than in the gray. A neovascularization also was present, giving an
angiomatous aspect associated with hemorrhagic foci to the brain
parenchyma.

DISCUSSION
A recent prospective multicenter study of GK radiosurgical
treatment for MTLE revealed seizure cessation rates (65%) comparable to those obtained with open surgery after a 2-year follow-

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FINET ET AL

A

B

C

FIGURE 4. Three fields of a hematoxylin and eosin preparation showing severe
alterations of both the gray and the white matter. A and B show white matter;
C shows gray matter). +, reactional gliosis; ⇐, hyalinizated vessel; *, macrophages
in the vessel lumen; ←, neovascularization; ←, vessel wall dissection.

E219 | VOLUME 67 | NUMBER 1 | JULY 2010

up.8 Level of safety was good, with transient minor morbidity in
23% of patients, including transient headache, nausea, vomiting,
depression, and dizziness. Only 1 study regarding the long-term
efficacy of GK radiosurgery in MTLE can be found in the literature.13 This study showed, in a population of 15 patients with
follow-up ranging from of 6 to 10 years, a stable rate (60%) of
freedom from seizures. However, all of the patients who were
seizure free experienced a relapse of their seizures in response to drug
reduction, requiring a restoration of their medical treatment.
Although studies on GK radiosurgery in the treatment of MTLE
show encouraging results, with low morbidity rates and rates of
seizure cessation comparable with those of open surgery, significant
side effects have been reported. Edema has appeared on MRI approximately 1 year post treatment, with about 15% of the patients experiencing headaches with nausea and vomiting, but without neurologic
deficit. These symptoms were cleared by administration of corticosteroids, and none of the patients required surgical removal of
the irradiated tissue. The MRI changes usually resolved by the end
of the second year and were replaced by atrophic changes.8,11,14 In
our patient, the volume increase of the targeted area persisted for 6
years after treatment and was accompanied at that time, 6 years
after GK surgery, by the development of an intracranial hypertension syndrome leading to temporal herniation that required an
urgent surgical decompression. Two other side effects also must be
stressed: a 45% rate of visual deficits8 and seizure relapse in all
seizure-free patients during attempts at drug reduction.13
The histologic changes after GK radiosurgery in patients with
MTLE have been only partially described. Prayson and Yoder15
reviewed the clinicopathologic findings of 3 patients with MTLE
who underwent surgical resection for persistent seizures 18, 22, and
20 months post-GK radiosurgery. The results of this small series
demonstrated radiation-induced modifications consisting of foci
of edema with necrosis (3/3), vascular sclerosis (3/3), perivascular chronic inflammation (3/3), reactive astrocytosis (3/3), microglial
proliferation (1/3), and microcalcifications (1/3). House et al16
described 8 histologic examinations of tissue from patients who
underwent surgical resection of the mesial temporal structures
post-GK radiosurgery. Necrotic foci were present in 6 patients (1
with vascular wall thickening), reactive astrocytes with degenerated neurons in another patient, and sclerosis alone, with no other
changes, in the last 1. In our patient’s case, histopathologic analysis also showed a significant angiomatous proliferation, which
might be correlated with an upregulation of vascular endothelial
growth factor due to the presence of hypoxic factors associated
with radiation-induced necrosis. A Korean study showed an upregulation of vascular endothelial growth factor and fibroblast growth
factor in normal rat brain after experimental intraoperative radiation therapy (10 Gy of gamma rays).17
As mentioned in the clinical history, the patient experienced at
6 years of age a post-viral encephalitis, which unfortunately was
not documented. This could mean that her case consists of a very
specific, uncommon combination of factors that led to her abnormal reaction to the radiosurgical treatment. A medical history of
encephalitis could, therefore, be a possible contraindication for

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POST-RADIOSURGERY ANGIOMATOUS DEGENERATION

radiosurgery. However, it is an isolated case and other similar cases
are required before it is possible to confirm this possibility.

CONCLUSION
Even though the studies on MTLE treatment with GK radiosurgery have demonstrated efficacy rates comparable to those of
open surgery, with low morbidity, our case draws attention to the
risk of developing, many years later, the life-threatening adverse
event of a compressive angiomatous degeneration of the targeted
brain. This case stresses the need to evaluate the long-term effects
of GK radiosurgery in the treatment of MTLE in a larger population and to consider a past medical history of encephalitis as a
possible contraindication for radiosurgery.
Disclosure
The authors have no personal financial or institutional interest in any of the
drugs, materials, or devices described in this article.

REFERENCES
1. Engel J Jr. Surgery for seizures. N Engl J Med. 1996;334(10):647-652.
2. Engel J Jr. Finally, a randomized, controlled trial of epilepsy surgery. N Engl J Med.
2001;345(5):365-367.
3. Pilcher WH, Rusyniak WG. Complications of epilepsy surgery. Neurosurg Clin N
Am. 1993;4(2):311-325.
4. Yang I, Barbaro NM. Advances in the radiosurgical treatment of epilepsy. Epilepsy
Curr. 2007;7(2):31-35.
5. Wieser HG, Yaşargil MG. Selective amygdalohippocampectomy as a surgical treatment of mesiobasal limbic epilepsy. Surg Neurol. 1982;17(6):445-457.
6. Clusmann H, Schramm J, Kral T, et al. Prognostic factors and outcome after different types of resection for temporal lobe epilepsy. J Neurosurg. 2002;97(5):11311141.
7. Wieser HG, Ortega M, Friedman A, Yonekawa Y. Long-term seizure outcomes
following amygdalohippocampectomy. J Neurosurg. 2003;98(4):751-763.
8. Régis J, Rey M, Bartolomei F, et al. Gamma knife surgery in mesial temporal lobe
epilepsy: a prospective multicenter study. Epilepsia. 2004;45(5):504-515.
9. Régis Y, Roberts DW. Gamma Knife radiosurgery relative to microsurgery: epilepsy.
Stereotact Funct Neurosurg. 1999;72 Suppl 1:11-21.
10. Régis J, Bartolomei J, Chauvel P. Epilepsy. Prog Neurol Surg. 2007;20:267-278.
11. Régis J, Bartolomei F, Hayashi M, Chauvel P. What role for radiosurgery in mesial
temporal lobe epilepsy. Zentralbl Neurochir. 2002;63(3):101-105.
12. Régis J, Bartolomei F, Hayashi M, Roberts D, Chauvel P, Peragut JC. The role of
gamma knife surgery in the treatment of severe epilepsies. Epileptic Disord.
2000;2(2):113-122.
13. Bartolomei F, Hayashi M, Tamura M, et al. Long-term efficacy of gamma knife
radiosurgery in mesial temporal lobe epilepsy. Neurology. 2008;70(19):1658-1663.
14. Regis J, Semah F, Bryan RN, et al. Early and delayed MR and PET changes after
selective temporomesial radiosurgery in mesial temporal lobe epilepsy. AJNR Am
J Neuroradiol. 1999;20(2):213-216.
15. Prayson RA, Yoder BJ. Clinicopathologic findings in mesial temporal sclerosis
treated with gamma knife radiotherapy. Ann Diagn Pathol. 2007;11(1):22-26.
16. House PA, Kim JH, Lanerolle ND, Barbaro NM. Radiosurgery in epilepsypathological considerations. Prog Neurol Surg. 2007;20:279-288.
17. Kim JH, Chung YG, Kim CY, Kim HK, Lee HK. Upregulation of VEGF and
FGF2 in normal rat brain after experimental intraoperative radiation therapy.
J Korean Med Sci. 2004;19(6):879-886.

COMMENTS

T

his is an interesting case report about a radiosurgical complication as
a result of treatment of a case of mesial temporal lobe epilepsy. The
patient had an excellent outcome following surgical decompression. This

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particular complication illustrates the need to follow patients treated with
radiosurgery for epilepsy, both clinically and radiographically, for an
extended period following their treatment. I suspect that more complications of this type will occur as additional patients with epilepsy proceed with radiosurgery, and it certainly would be helpful to have a better
understanding of the frequency of this type of event.
Steven D. Chang
Stanford, California

R

adiosurgery for mesial temporal epilepsy has been an area of intensive
study in recent years. Two prospective multicenter trials have demonstrated that this technique is effective and safe. The relative merits of
radiosurgery versus open surgical resection continue to be debated. It is
likely, however, that this technique will find greater application in the
coming years, especially for patients with some relative contraindication
to resection. Typical complications described in the literature include
edema and other radiation-related changes requiring corticosteroid therapy, visual field deficits, and headaches. This report discusses a lateappearing complication of angiomatous changes resulting in local mass
effect, which required surgical intervention for relief of the mass effect.
Interestingly, it appears that the seizure disorder improved following the
resection. This report reinforces the need for long-term follow-up of these
patients, because late complications of treatment may present several
years following treatment.
Joseph C. T. Chen
Los Angeles, California

D

elayed radiation-related complications are a rare but real risk of stereotactic radiosurgery. In this case report, the authors describe the clinical course of a patient having radiosurgery for mesial temporal lobe
epilepsy. Six years after the procedure, the patient was symptomatic from
a large hemorrhagic temporal lobe mass at the irradiated site. Resection
of the lesion did not show a high-grade tumor as suspected, but, rather,
necrosis and neovascularization. This case illustrates that continued longterm follow-up is essential when radiosurgery is used for benign tumors,
vascular malformations, and functional disorders. Until the incidence of
such delayed complications is clearly understood, comparison with direct
surgical approaches whose complications typically are realized within the
immediate postoperative period may not be fair or appropriate.
Bruce E. Pollock
Rochester, Minnesota

F

inet et al. are reporting in a 54-year-old patient a post-viral encephalitis epilepsy of the temporal lobe, previously treated by radiosurgery,
presenting with an original long-term complication. Classically, postencephalitis epileptic patients are poor candidates for epilepsy surgery.
Epileptogenic zones have a tendency to be more spread out or even multifocal in post-encephalitis epilepsies, especially with older patients and
a longer history of epilepsy. Thus, proposing the more selective epilepsy
surgery procedure available nowadays, gamma knife (GK) radiosurgery,
based on the assumption that the patient was presenting with a pure
mesial temporal lobe epilepsy (MTLE), is questionable. The fact that the
patient is not completely seizure-free after a resective surgery confirms
the inappropriateness of this initial assumption. Additionally, although
the reaction of a post-encephalitic brain tissue to radiosurgery is unknown,
preliminary data from the literature and vascular effects of encephalitis
are strong arguments against the use of radiosurgery on post-encephalitic

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FINET ET AL

brain tissue. Unfortunately, this case report confirms the well-founded
suspicion. Consequently, the major contribution of this paper is to raise
awareness of the potential risk of the use of radiosurgery on the postencephalitic brain parenchyma.
On the other hand, it is important to mention that such a reaction
has never been reported in patients with MTLE related to hippocampal
sclerosis treated with GK radiosurgery, which has been demonstrated on
medium- and long-term follow-up to be an especially safe procedure,
apparently with the specific advantage of better verbal memory sparing
when performed on the dominant side.
In the current study, the authors describe an angiomatous lesion in
the temporal lobe of a patient who underwent GK radiosurgery for refractory temporal lobe epilepsy. The lesion, located in the cortical gray and
white matter, showed a proliferation of vessels of different calibers, from
telangiectasias to large cavernous-like vascular structures. Some of the
vessels showed typical post-radiation fibrinoid necrosis. The vascular proliferation was accompanied by a severe gliosis, without disruption of the
cortical gray matter.
Radiation-induced lesions are mostly characterized by necrosis that
affects the white matter, a variable degree of gliosis, and vascular changes
including fibrinoid necrosis and hyalinization. Gamma radiation appears
to induce similar lesions. The few reports on patients operated after GK
radiosurgical treatment for medically refractory epilepsy have shown variable degrees of edema, necrosis, and changes in pre-existent vessels, including necrosis and hyalinization.1,2 The current case adds the description
of a GK-induced vascular lesion that presented clinically with severe hemorrhage.
Experimental rodent models have shown that the time course and
extent of cerebral damage induced by gamma irradiation vary as a function of the radiation dose.3-5 Alterations in the cerebral microvasculature are a key component of the structural response to gamma irradiation,
and appear to precede delayed necrosis of the brain neuropil.4 On the
other hand, vascular malformations such as cavernous angiomas have
been described in the brain following conventional radiation therapy,
particularly in the pediatric population.6,7 The mechanism by which
these malformed vascular lesions are created is not well understood. The

E220 | VOLUME 67 | NUMBER 1 | JULY 2010

reaction of endothelial cells and vasculature to radiation changes appears
to be secondary to a direct effect of radiation on blood vessels as well as
hypoxia-driven overexpression of vascular growth factors, including vascular endothelial growth factor.7,8. However, this may depend on the
pathological circumstances. Akakin et al.9 recently have found in a rat
corneal model a decrease of the angiogenic activity of arteriovenous malformations (AVMs) with a reduction of the expression of VEGF after
GKR compared to untreated AVMs or embolized AVMs.1 This most
likely plays a role in the vasculopathies associated with radiation.
Jean Régis
Marseille, France
M. Beatriz S. Lopes
Charlottesville, Virginia

1. House PA, Kim JH, Lanerolle ND, et al. Radiosurgery in epilepsy—pathological
considerations. Prog Neurol Surg. 2007;20:279-288.
2. Prayson R, Yoder B. Clinicopathologic findings in mesial temporal sclerosis treated
with gamma knife radiotherapy. Ann Diagn Pathol 2007;:22-26.
3. Kamiryo T, Kassell NF, Thai QA, et al. Histological changes in the normal rat brain
after gamma irradiation. Acta Neurochir (Wien). 1996;138:451-459.
4. Kamiryo T, Lopes MB, Kassell NF, et al. Radiosurgery-induced microvascular alterations precede necrosis of the brain neuropil. Neurosurgery. 2001;49:409-414; discussion 414-405.
5. Kondziolka D, Lunsford L, Claassen D, et al. Radiobiology of radiosurgery: Part I.
The normal rat brain model. Neurosurgery. 1992;31:271-288.
6. Baumgartner JE, Ater JL, Ha CS, et al. Pathologically proven cavernous angiomas of
the brain following radiation therapy for pediatric brain tumors. Pediatr Neurosurg.
2003;39:201-207.
7. Heckl S, Aschoff A, Kunze S. Radiation-induced cavernous hemangiomas of the
brain: a late effect predominantly in children. Cancer. 2002;94:3285-3291.
8. Tsao MN, Li YQ, Lu G, Xu Y, Wong CS. Upregulation of vascular endothelial growth
factor is associated with radiation-induced blood-spinal cord barrier breakdown.
J Neuropathol Exp Neurol. 1999;58:1051-1060.
9. Akakin A, Ozkan A, Akgun E, et al. Endovascular treatment increases but gamma knife
radiosurgery decreases angiogenic activity of arteriovenous malformations: an in
vivo experimental study using a rat cornea model. Neurosurgery. 2010;66:121-129;
discussion 129-130.

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