Summary Gamma Knife Radiosurgery for Arteriovenous Malformations serval.unil.ch
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Gamma knife radiosurgery is a medical procedure that treats abnormal blood vessel tangles called arteriovenous malformations, which can lead to intracranial hemorrhage.
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Slide Presentation (9 slides)
Key Points
- Gamma Knife radiosurgery (GKR) is used for the treatment of arteriovenous malformations (AVMs).
- AVMs are vascular malformations characterized by abnormal connections between arteries and veins.
- The therapeutic role and outcomes of GKR for AVMs were evaluated over a period of 5 years in a single center.
- Follow-up evaluations, including medical consultations and radiological assessments, were conducted after GKR.
- GKR has a low rate of complications, with each complication occurring in only one patient out of the 63 patients studied.
- Surgery for AVMs carries a mortality rate of 3.3% and morbidity rate of 8.6%.
- Advances in radiosurgery for AVMs have been made since the late 1980s.
- The ARUBA trial investigated the effectiveness of medical management with or without interventional therapy for unruptured AVMs.
Summaries
21 word summary
Gamma knife radiosurgery (GKR) is used to treat arteriovenous malformations (AVMs), abnormal tangles of blood vessels that can cause intracranial hemorrhage.
30 word summary
This summary discusses the use of gamma knife radiosurgery (GKR) for treating arteriovenous malformations (AVMs). AVMs are abnormal tangles of blood vessels that can lead to intracranial hemorrhage. The study
285 word summary
This article discusses the use of gamma knife radiosurgery (GKR) for the treatment of arteriovenous malformations (AVMs). AVMs are vascular malformations characterized by abnormal connections between arteries and veins, which can lead to
This summary evaluates the therapeutic role and outcomes of gamma knife radiosurgery (GKR) for arteriovenous malformations (AVMs) over a period of 5 years in a single center. AVMs are abnormal tangles of blood
Patients underwent follow-up evaluations at specific time points after Gamma Knife Radiosurgery (GKR), including medical consultations and radiological assessments. The gold standard for confirming complete arteriovenous malformation (AVM) obliteration was cerebral DSA,
The study evaluated the obliteration rates of arteriovenous malformations (AVMs) treated with Gamma Knife radiosurgery. The overall obliteration rates at various time points were presented. The study found that for a Pollock-Flickinger score
Gamma Knife Radiosurgery (GKR) for arteriovenous malformations (AVMs) has a low rate of complications, with each complication occurring in only one patient out of the 63 patients studied. Complications included ischaemic
Surgery for arteriovenous malformations (AVMs) carries a mortality rate of 3.3% and morbidity rate of 8.6%. Endovascular treatment has become more common, with a fatality rate of
Gamma Knife radiosurgery is a safe and effective treatment for arteriovenous malformations (AVMs) in the brain. Case illustrations demonstrate successful obliteration of AVMs and disappearance of seizures following treatment. The overall obliteration rate by surgery
Advances in radiosurgery for arteriovenous malformations (AVMs) of the brain have been made since the late 1980s. Intracranial hemorrhage is a common morbidity associated with AVMs. The need
Gamma Knife radiosurgery is a treatment option for arteriovenous malformations (AVMs) in the brain. The ARUBA trial, a randomized trial, investigated the effectiveness of medical management with or without interventional therapy for unruptured
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Original article | Published 03 April 2018 | doi:10.4414/smw.2018.14602
Cite this as: Swiss Med Wkly. 2018;148:w14602
Gamma knife radiosurgery for arteriovenous
malformations: general principles and
preliminary results in a Swiss cohort
Raboud Matthieu a , Tuleasca Constantin abc , Maeder Philippe ad , Schiappacasse Luis e , Marguet Maud f , Daniel Roy Thomas ab ,
Levivier Marc ab
a
b
c
d
e
f
University of Lausanne, Faculty of Biology and Medicine, Lausanne, Switzerland
Department of Clinical Neurosciences, Neurosurgery Service and Gamma Knife Centre, Lausanne University Hospital (CHUV), Lausanne, Switzerland
Swiss Federal Institute of Technology (EPFL), Laboratory of Transmission Signal (LTS-5), Lausanne, Switzerland
Radiology Department, CHUV, Lausanne, Switzerland
Radiotherapy Department, CHUV, Lausanne, Switzerland
Institute of Radiation Physics, Lausanne, Switzerland
Summary
INTRODUCTION: Arteriovenous malformations (AVMs)
are a type of vascular malformation characterised by an
abnormal connection between arteries and veins, bypass-
ing the capillary system. This absence of capillaries gen-
erates an elevated pressure (hyperdebit), in both the AVM
and the venous drainage, increasing the risk of rupture.
Management modalities are: observation, microsurgical
clipping, endovascular treatment and radiosurgery. The
former can be used alone or in the frame of a multidisci-
plinary approach. We review our single-institution experi-
ence with gamma knife radiosurgery (GKR) over a period
of 5 years.
MATERIALS AND METHODS: The study was open-label,
prospective and nonrandomised. Fifty-seven consecutive
patients, benefitting from 64 GKR treatments, were includ-
ed. All were treated with Leksell Gamma Knife Perfex-
ion (Elekta Instruments, AB, Sweden) between July 2010
and August 2015. All underwent stereotactic multimodal
imaging: standard digital subtraction angiography, mag-
netic resonance imaging and computed tomography an-
giography. We report obliteration rates, radiation-induced
complications and haemorrhages during follow-up course.
Author contributions
Matthieu Raboud and Con-
stantin Tuleasca contributed
equally to the study.
Correspondence:
Constantin Tuleasca, MD,
CHUV, Neurosurgery Ser-
vice and Gamma Knife
Centre, Rue du Bugnon
44-46, BH-08, CH-1011,
Lausanne, constan-
tin.tuleasca[at]gmail.com
RESULTS: The mean age was 46 years (range 13–79
years). The mean follow-up period was 36.4 months (me-
dian 38, range 12–75 months). Most common prethera-
peutic clinical presentation was haemorrhage (50%). The
most common Pollock-Flickinger score was between 1.01
and 1.5 (46%) and Spetzler-Martin grade III (46%). In 39
(60.1%) of cases, GKR was performed as upfront thera-
peutic option. The mean gross target volume (GTV) was
2.3 ml (median 1.2, range 0.03–11.3 ml). Mean marginal
dose was 22.4 Gy (median 24, range 18–24 Gy). The
mean prescription isodose volume (PIV) was 2.9 ml (me-
dian 1.8, range 0.065–14.6 ml). The overall obliteration
rates (all treatments combined) at 12, 24, 36, 48 and 60
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months were 4.8, 16.9%, 37.4, 63.6 and 78.4%, respec-
tively. The main predictive factors for complete oblitera-
tion were: higher mean marginal dose (23.3 vs 21.0 Gy),
lower GTV (mean 1.5 vs 3.5 ml) and absence of previ-
ous embolisation (at 60 months 61.8% prior embolisation
compared with 82.4% without prior embolisation) (for all
p <0.05). Eight (14%) patients experienced complications
after GKR. Overall definitive morbidity rate was 3.1%. No
patient died from causes related to GKR. However, during
the obliteration period, one case of extremely rare fatal
haemorrhage occurred.
CONCLUSION: Radiosurgery is a safe and effective treat-
ment modality for intracranial AVMs in selected cases. It
can be used as upfront therapy or in the frame of a com-
bined management. Obliteration rates are high, with min-
imal morbidity. The treatment effect is progressive and
subsequent and regular clinical and radiological follow-up
is needed to evaluate this effect.
Key words: gamma knife, stereotactic radiosurgery, arte-
riovenous malformation, obliteration, complication
Introduction
Arteriovenous malformations (AVMs) are a type of vas-
cular malformation characterised by abnormal connections
between arteries and veins, bypassing the capillary system.
The draining veins are dilated because of the arteriovenous
shunt. Absence of capillaries generates an elevated pres-
sure (hyperdebit), inside both the AVM and the venous
drainage [1]. The high pressure transmitted to the venous
system increases the risk of rupture and, in consequence,
the risk of haemorrhagic events, as the vascular walls are
not adapted to this type of blood flow. The hyperdebit can
also create “blood steal phenomenon”, which can in turn
generate additional clinical manifestations (epilepsy, oth-
er neurological deficits, etc.) [2]. Chronic high blood flow
in arterial feeders may induce stenotic or dilated vessel
Page 1 of 10Original article
Swiss Med Wkly. 2018;148:w14602
changes with endothelial thickening, abnormal or absence
media and elastic lamina, as well as intimal hyperplasia
[3]. They are usually solitary, but can also occur as multi-
ple lesions, within the frame of a syndrome, such as Ren-
du-Osler-Weber, Wyburn-Mason or Wyburn-Mason [4, 5]
The natural history and prevalence of AVMs are not com-
pletely understood. The estimated prevalence ranges be-
tween 14 and 18 cases per 100,000 [6, 7]. The main loca-
tion is supratentorial (90%). The feeding artery is usually
the middle cerebral artery, followed by the anterior and
posterior cerebral arteries. Over time, AVMs may vary in
size, increasing, decreasing or even disappearing unexpect-
edly [8]. The risk of spontaneous brain haemorrhage is 2 to
4% per year [9]. Moreover, ruptured AVMs are responsible
for 38% of intracranial haemorrhages in patients aged be-
tween 15 and 45 years [10]. Morbidity rates vary, depend-
ing on the study, between 4 and 30% [11]. Clinical man-
ifestations include haemorrhage (the most frequent, more
than 50% of cases), epilepsy, symptomatic mass effect, is-
chaemia, neurological deficit or headaches [9, 12, 13].
Management of intracranial AVMs includes observation,
microsurgical excision, endovascular treatment and radio-
surgery. These treatment modalities can be used alone, or
in the frame of multimodal management [9, 14]. Micro-
surgery directly approaches the AVM, coagulates and clip-
pers the arterial pedicle, followed further by nidus ablation
and exclusion of the abnormal drainage vein [15]. En-
dovascular treatment is based upon injection of embolisa-
tion agents (coils, glue, onyx) into the AVM. Radiosurgery
is a noninvasive approach, which is being increasingly
used and which results in progressive obliteration over a
mean period of 2 years. The ideal radiosurgery targets are
small to medium size, and for these it represents a safe pri-
mary treatment option. The adverse radiation effects are
considered low. Five-year obliteration rates vary between
70 and80% [16–19]. A multidisciplinary approach is con-
sidered the key for optimal patient management.
The present report evaluates the therapeutic role and the
outcomes (both clinical and radiological) of gamma knife
radiosurgery (GKR), as primary or combined treatment for
intracranial AVMs, during a period of 5 years in a single
centre. We report the three main standard outcomes after
GKR: obliteration rate, radiation-related complications and
postherapeutic GKR haemorrhages.
Materials and methods
Study design
The study was prospective, open-label and nonran-
domised. A case report form was created for the first treat-
ed case and prospectively filled in for each patient. It in-
cluded both baseline (pretherapeutic) and follow-up data.
Overall information encompassed demographic and dosi-
metric data, related to the radiosurgical approach.
Patients
All GKR treatments were performed during the period July
2010 and August 2015, in a single centre, Lausanne Uni-
versity Hospital (CHUV). The database was considered
closed for new information in October 2017.
Fifty-seven consecutive patients (64 GKR treatments)
were included, with variety of AVM stages (see classifi-
cation below) and locations. The choice of radiosurgery
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was made after discussion within the interdisciplinary neu-
rovascular board in the CHUV.
Inclusion criteria were: AVM documented by MRI, further
and confirmed with digital subtraction arteriography
(DSA); patient able to give free and informed consent; cas-
es who benefitted from previous radiosurgery and/or other
treatments, regardless of the techniques used (GK or other
radiosurgery devices (ex. linear accelerator), microsurgical
resection, endovascular approach)
Exclusion criteria were: patients who were not able to give
an informed consent and cases lost for follow-up (only one
case; taken into consideration for baseline pretherapeutic
data only).
Gamma knife radiosurgery procedure
After application of the Leksell Model G stereotactic frame
(Elekta Instruments AB, Sweden) under local anaesthesia,
all patients underwent stereotactic imaging on the day of
GKR. In our Gamma Knife Centre in Lausanne, we always
use multimodal imaging for target definition. For AVMs,
digital subtraction angiography (DSA), magnetic reso-
nance imaging (MRI) and computed tomography (CT) an-
giography were used. MRI sequences routinely used Rou-
tinely used to better identify the AVM, were time of flight
(TOF, 0.6 mm slices) and T1 without and with contrast-
enhanced (1 mm thickness). Additional sequences, such as
T2 star were employed if necessary to visualise possible
previous haemorrhages. CT angiography with bolus con-
trast injection routinely supplemented the neuroimaging
investigation in order to correct for any distortion errors on
the MRI and to have complementary information for better
targeting (e.g., nidus and complete angioarchitecture) defi-
nition (fig. 1).
All patients underwent Leksell Gamma Knife Perfexion™
(Elekta Instruments AB, Sweden) by the same operators
(ML, CT) within the specified timeframe. Leksell Gamma
Plan (LGP version 10.0 and 11.0, Elekta Instruments AB,
Sweden) was used for dosimetry planning.
Basic dosimetric data
The mean marginal prescribed dose was 22.4 Gy (median
24, range 18–24 Gy). The delivered dose was established
mainly on the basis of the AVM volume and anatomical lo-
cation. We usually prescribe 24 Gy if possible, based on
the published literature within the past three decades, and
on the safety and efficacy of radiosurgery in this indication
[20].
Follow-up procedures
Data were collected between July 2010 and October 2017.
Patients were seen in person at baseline (before therapy)
and at 6, 12, 24, 36, 48 and 60 months after GKR, except
for cases with clinical and/or radiological complications
before these time-points.
Follow-up investigations included a medical consultation
and radiological assessment with MRI angiography. If
MRI suggested complete obliteration, cerebral DSA was
performed. This represents the gold standard, in our set-
ting, for formally confirming complete AVM obliteration.
However, in some instances, in both Lausanne and in other
Swiss referral hospitals that referred cases for GKR, in rare
instances DSA was not done because the patient refused (a
Page 2 of 10Original article
Swiss Med Wkly. 2018;148:w14602
total of seven cases had MRI only without DSA for confir-
mation of complete obliteration).
Reported outcomes
We report the main following three outcomes after GKR:
obliteration rate; radiation-induced complications, includ-
ing new or worsened confirmation clinical symptomatol-
ogy and/or new radiological findings (cerebral oedema, ra-
dionecrosis, cysts, etc.); post-GKR haemorrhages.
Standard classifications for pre- and post-therapeutic
evaluations
The most common radiosurgical grading system for brain
AVMs is the Pollock-Flickinger score [21]. It is based on
three main factors: patient age, AVM volume and AVM lo-
cation. The score is calculated with the following formula:
(0.1 × volume in ml) + (0.02 ×age in years) + (0.5 × loca-
tion [hemisphere / corpus callosum / cerebellum = 0; basal
ganglia / thalamus / brain stem = 1]). The score predicts the
success rate, mainly the potential for obliteration without
secondary effects after GKR treatment.
The most common surgical grading system is the Spetzler-
Martin score. The score takes into account the AVM size
(small <3 cm; medium 3–6 cm; large >6 cm; 1, 2, 3 points,
respectively), location (eloquent adjacent brain 1 point;
non-eloquent 0 points) and the venous drainage pattern
(superficial 0 points; deep 1 point). Eloquent brain areas
include sensory, motor and visual cortex, language-ded-
icated areas (Broca and Wernicke areas), hypothalamus,
thalamus, internal capsule, cerebral stem, cerebellar pe-
duncles and nodes. The score predicts the surgical success
rate and also evaluates other possible modalities of treat-
ment (embolisation and radiosurgery).
Statistical analysis
Stata software (STATA version 11; STATA Corp., Texas,
USA) was used for the statistical analysis. Kaplan-Meier
analysis was used to evaluate the time-to-event for oblit-
eration and complication rates. Patients’ data were cen-
sored at the last follow-up for those who did not have these
events. For cases with an event, either obliteration or a
complication, the date of the event was recorded and was
considered as reference. An acceptable type I error was de-
termined at 0.05 for all statistical tests. Univariate analyses
included the two-sample t-test and the log-rank test.
Results
Basic clinical and demographic data
The median age was 46 years (range 13–79 years). The
mean follow-up period was 38.2 months (median 38, range
12–75 months). The most common clinical presentation
was haemorrhage (50%). The Pollock-Flickinger score
was most commonly between 1.01 and 1.5 (46%) and the
Spetzler-Martin grade III (46%). In 39 (60.1%) instances,
there was no previous treatment and GKR was used as up-
front therapy. Other basic demographic data can be found
in table 1 and table 2.
Basic dosimetric data
The mean gross target volume was 2.295 ml (median 1.2,
range 0.032–11.3 ml). Mean marginal dose was 22.4 Gy
(median 24, range 18–24 Gy). The mean prescription iso-
dose volume was 2.984 ml (median 1.77, range 0.065–14.6
Gy). Other basic dosimetric data, including standard radio-
surgical indexes, can be found in table 3.
Figure 1: Example of multimodal imaging for gamma knife radiosurgery (GKR) purposes; all the MRI and CT examinations are done after
stereotactic frame placement, the day of GKR; from left to right, DSA, MR time-of-flight (TOF) sequence and CT angiography (the former two
in coronal-up, axial-middle, and sagittal-bottom reconstruction).
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Page 3 of 10Original article
Swiss Med Wkly. 2018;148:w14602
Obliteration rates after GKR
For 39 (61%) GKR treatments, there was complete obliter-
ation after a mean period of 32.9 months (median 35, range
8–56 months). The mean follow-up period in the partially
obliterated AVM group was higher, at 40.7 ± 8.5 months
(range 12–71 months), as compared with complete oblit-
eration 32.9 ± 3.7 months (range 8–56 months). Howev-
er, the partially obliterated group included more complicat-
ed cases, including previous embolisation, larger size with
staged-treatments, etc.
The overall obliteration rates at 12, 24, 36, 48 and 60
months were 4.8, 16.9, 37.4, 63.6 and 78.4%, respectively
(figs 2 and 3a). DSA confirmed complete obliteration in 30
(76.9%) out of the 39 cases. Two patients will have DSA
evaluation in the next 3 months. The other seven had only
MRI angiography confirmation, because they refused DSA
evaluation for various reasons.
The overall obliteration rates, by Pollock-Flickinger scores
at 12, 24, 36 and 48 months, respectively, (see fig. 3b)
were:
– for a score of 1: 0, 7.7, 16.9, 44.6%, staying stable up to
60 months (mean follow-up period 31.2 months, range
12–51 months, mean obliteration time 29.5 months;
range 12–51 months);
– for a score of 2: 10.3, 24.1, 54.5 and 71.4%, reaching
80.9% at 60 months (mean follow-up period 37.9
months, range 12–66 months, mean obliteration time
34.7 months, range 21–50 months);
– for a score of 3: 0, 27.3, 45.4 and, 89.1%, reaching
100% at 56 months (mean follow-up period 46.2
months, range 13–75, mean obliteration time 35 months
range 26–56 months);
– for a score of 4: 0, 20 and 40%, reaching 100% at 49
months (mean follow-up period 50.4 months, range
35–65 months, mean obliteration time 40.7 months,
range 35–52 months).
Table 1: Demographic and clinical data before gamma knife radiosurgery treatment.
Variable
Sex (n = 64)
n (%)
Man
32 (50.0)
Woman
32 (50.0)
Age (years), median (range)
46 (13–79)
Follow-up (months), median (range)
Side (n = 64)
Clinical presentation (n = 64)
38 (12–75)
Right 32 (50.0)
Left 32 (50.0)
Haemorrhage 32 (50.0)
Epilepsy 12 (18.8)
Headaches 6 (9.4)
Vertigo 6 (9.4)
Incidental 6 (9.4)
Hemisyndrome 4 (6.2)
Tinnitus
2 (3.1)
Trigeminal neuralgia, behavioural prob-
lems, transient neurological deficits, oph-
thalmological symptoms, aphasia, neck
pain
Spetzler-Martin grade (n = 63)
Modified Pollock-Flickinger score (n = 63)
each with 1 (1.6)
I 9 (14.3)
II 14 (22.2)
III 29 (46.0)
IV 7 (11)
V 4 (6.3)
<1.0 17 (27.0)
1.01–1.5 29 (46.0)
1.51–2.0 11 (17.5)
>2.0
Vascularisation territory (n = 64, more than one possible)
6 (9.5)
Right internal carotid 25 (39.1)
Left internal carotid 16 (25.0)
Right vertebrobasilar 22 (34.4)
Left vertebrobasilar 17 (26.6)
Right external carotid
Arterial pedicle (n = 64, more than one possible)
0 (0.0)
Left external carotid 1 (1.6%)
Anterior cerebral artery 15 (23.4)
Middle cerebral artery 34 (53.1)
Posterior vascularisation 33 (51.6)
Extracranial
Previous treatment (n = 64, more than one possible)
1 (1.6)
None
39 (60.1%)
Surgery
1 (1.6)
Embolization
Radiosurgery: gamma knife
Radiosurgery: linear accelerator
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16 (25.0)
2 (3.1)
7 (10.9)
Page 4 of 10Original article
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The main predictive factors for complete obliteration were:
higher mean marginal dose (23.3 vs 21.0 Gy), lower gross
target volume (1.5 ml, range 0.03–5.55 ml vs 3.5 ml, range
0.06–11.3ml) and no previous embolisation (at 60 months
61.8 vs 82.4%) (p<0.05 for all; fig. 3c).
Previous other radiosurgical treatment was not a statis-
tically significant factor with regard to final obliteration
rates (at 60 months, 82.9 compared with 84.9%, p >0.05;
fig. 3d). Five of the seven cases (71.4%) were obliterated
(mean follow-up time 44 months, range 24–71 months
compared with 37.5 months, range 12–75 months).
Table 2: Demographic and clinical data after gamma knife treatment: obliterated versus non-obliterated arteriovenous malformations.
Variable
Sex
Obliterated
n (%) Non- obliterated
n (%)
(n total = 39) (n total = 25)
Man 16 (41.0) 16 (64.0)
Woman 23 (59.0) 9 (36.0)
Age (years), median (range) 47 (18–79) 34 (13–76)
Follow-up (months), median (range) 38 (12–60) 41.5 (12–71)
Obliteration time (months), median (range) 35 (8–56) –
Side (n total= 39) Right 21 (53.8) 11 (44.0)
Left 18 (46.2) 14 (56.0)
(n total = 38) (n total = 25)
I 7 (18.4) 2 (8.0)
II 13 (34.2) 1 (4.0)
III 17 (44.7) 12 (48.0)
IV 1 (2.6) 6 (24.0)
V 0 (0) 4 (16.0)
(n total = 38) (n total = 25)
<1.0 12 (31.6) 5 (20.0)
1.01–1.5 18 (47.4) 11 (44.0)
1.51–2.0 5 (13.2) 6 (24.0)
>2.0 3 (7.9) 3 (12.0)
(n = 39) (n = 25)
Haemorrhage 16 (41.0) 16 (64.0)
Headaches 6 (15.4) –
Incidental 6 (15.4) –
Epilepsy 5 (12.8) 7 (28.0)
Vertigo 5 (12.8) 1 (4.0)
Tinnitus 2 (5.1) –
Behavioural problems 1 (2.6) –
Hemisyndrome 1 (2.6) 2 (8.0)
Trigeminal neuralgia 1 (2.6) –
Neck pain 1 (2.6) –
Ophthalmological symptoms 1 (2.6) –
Aphasia 1 (2.6) –
Transient neurological deficits – 1 (4.0)
(n total = 39) (n total = 25)
Right internal carotid 14 (35.9) 11 (44.0)
Left internal carotid 10 (25.6) 6 (24.0)
Right vertebrobasilar 14 (35.9) 8 (32.0)
Left vertebrobasilar 8 (20.5) 9 (36.0)
Right external carotid 0 (0) 0 (0)
Left external carotid 1 (2.6) 0 (0)
(n = 39) (n = 25)
Anterior cerebral artery 8 (20.5) 7 (28.0)
Middle cerebral artery 20 (51.3) 14 (56.0)
Posterior vascularisation 17 (43.6) 16 (64.0)
Extracranial 1 (2.6) 0 (0)
(n total = 39) (n total = 25)
None 28 (71.8) 11 (44.0)
Surgery 6 (15.4) 0 (0)
Embolisation 1 (2.6) 10 (40.0)
Radiosurgery: gamma knife 0 (0) 2 (8.0)
Radiosurgery: linear accelerator 5 (12.8) 2 (8.0)
Spetzler-Martin Grade
Modified Pollock-Flickinger score
Clinical presentation (more than one possible)
Vascularisation territory (more than one possible)
Arterial pedicle (more than one possible)
Previous treatment (more than one possible)
Radiosurgery
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Clinical and/or radiological complications (including
haemorrhage) after GKR
Nine (14%) patients experienced complications after GKR
(see table 4). The actuarial complication rate was 8% at 1
year and was 9% at 16 months, remaining stable over time
until last follow-up.
Three cases (4.7%) had haemorrhage during the follow-
up period after GKR. One died, one presented few symp-
toms and was followed-up with serial MRI (progressive re-
sorption) and one underwent microsurgical resection with
a slowly favourable clinical outcome.
The following complications occurred, each in one patient
(1.6%): ischaemic stroke; ventriculo-peritoneal shunt
placement for high intracranial pressure (12 months after
GKR); volumetric growth of a previous asymptomatic
cyst; important perilesional oedema; and superior sagittal
sinus partial thrombosis. The ischaemic thalamic stroke
occurred in a young patient, was clinically symptomatic,
and was treated with embolisation, followed by decom-
pression craniectomy and further right partial temporal
lobectomy. One case had benefitted previously from a Lin-
ear Accelerator (Linac) radiosurgery treatment, 4 years be-
fore GKR, with incomplete obliteration. This patient had
a transient asymptomatic increase of cysts present after
Linac radiosurgery, at 6, 12 and 18 months after GKR;
their volume decreased at 24 months, when the AVM was
completely obliterated. In one case, there was major per-
ilesional oedema at 6 and 12 months, which disappeared
at 24 months, and the patient showed progressive clinical
improvement on prolonged corticosteroid therapy. The pa-
tient with an asymptomatic partial thrombosis of the supe-
rior sagittal sinus was given anticoagulant therapy; 2 years
after GKR and 12 months after the start of this therapy,
there was complete resolution.
Discussion
Our study analysed the place of GKR, as an upfront or ad-
juvant treatment, in the upfront and/or multimodal man-
agement of brain AVMs. We reported overall obliteration
rates at 12, 24, 36, 48 and 60 months of 4.8, 16.9, 37.4,
63.6 and 78.4%, respectively. Furthermore, in the cases
without prior embolisation, the 5-year obliteration rate was
as high as 82.4%. Eight (14%) patients experienced com-
plications after GKR, most of them transient. Three cases
(5.2%) experienced haemorrhage during the follow-up pe-
riod after GKR, of whom one died. These reported out-
comes are in perfect alignment with the current literature.
An important consideration in the decision-making process
is the natural history of the AVM. The choice of obser-
vation or medical management needs to take into account
several factors. Without any treatment, haemorrhage risk is
estimated to be approximately 3 to 4% per year; this in-
creases substantially if the venous drainage is exclusively
deep, in presence of venous stenosis, or if there is an in-
tranidal aneurysm. Morbidity rate is approximately 2.7%
per year and mortality rates at approximately 1%. Over-
all assessment in the form of the Spetzler-Martin grade in-
dicates surgery for grades I to IIIA, radiosurgery for IIIB
to V and combined management for giant AVMs (vol-
ume >25 cc). In a recent meta-analysis, which included
observational studies, severe complications were observed
in 5.1 to 7.4% of patients and median obliteration rates
were 13 to 96% [22]. The ARUBA study, designed to an-
swer the question of observation and medical management
alone versus medical management plus prophylactic inter-
ventional therapy, was stopped because of increased com-
plications rates in the treatment arm compared with the
medical management group [23, 24]. Typically, observa-
tion and medical management is considered for asympto-
matic patients and those without previous haemorrhage.
Treatment strategies may be used alone or in the frame of
multimodal therapy. They include microsurgery, endovas-
cular treatment and GKR.
Surgery requires craniotomy and dural opening. Overall
mortality rates are approximately 3.3% and morbidity
8.6% (increasing with increase of the Spetzler-Martin
grade) [25].
Endovascular treatment has become increasingly used with
the advances in this technology, including new micro-
catheter designs and the development of solid and liquid
embolic agents. In a recent meta-analysis, the fatality rate
was estimated to be 0.96 per 100 person years and haem-
orrhage rates 1.7 per 100 person years [22]. Complications
leading to permanent neurological deficits or death were
seen in 6.6% of cases [22].
Table 3: Gamma knife radiosurgery dosimetric data (n total = 64).
Target volume (cm 3 )
Prescription isodose volume (cm 3 )
Conformity index
Selectivity
Gradient index
Marginal dose (Gy)
Mean 2.295
Median 1.2
Range 0.032–11.3
Mean 2.984
Median 1.770
Range 0.065–14.6
Mean 0.979
Median 0.991
Range 0.660–1.000
Mean 0.677
Median 0.718
Range 0.118–0.969
Mean 2.718
Median 2.695
Range 0.270–4.351
Mean 22.406
Median 24
Range 18–24
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AVMs were among the first GKR indications, with a first
treatment in Sweden in the early 1970s. This was directed
by use of the standard imaging technique, DSA, which al-
ready allowed optimal targeting, even before the appear-
ance of MRI in the early 1980s [26]. The physiopatholog-
ical mechanisms of obliteration after GKR are related to
structural changes within the endothelial cells, followed by
myofibroblast proliferation, expansion of the extracellular
matrix into the intima and further hyaline transformation
of the wall of the irradiated vessels. This occurs mainly in
two steps, one related to degeneration/proliferation of the
vascular wall and the second involving changes within the
connective tissue [27, 28].
The crucial factor for successful obliteration with GKR is
targeting. This is based upon multimodal imaging, which
should include, in our opinion and experience, cranial DSA
in addition to the widely used MRI and CT angiography.
The definition of the nidus, even in experienced hands, is
still sometimes difficult and should be done in collabora-
tion with an experienced neuroradiologist. It is nowadays
considered that the foot of the vein should be included in
the dosimetry [29]. However, this does not apply to the en-
tire trajectory of the draining vein. In particular, irradiating
large parts of the former should be avoided, as this might
provoke a collapse of this anatomical structure before the
nidus itself has been entirely obliterated, leading to high-
er blood pressure on the nidus wall and ultimately result-
ing in accidental haemorrhage. Moreover, in clinical prac-
tice, even with use of multimodal imaging (DSA included),
draining veins are complicated in their structure, making
Figure 2: Case illustration 1 (single fraction radiosurgery 24 Gy at the 50% isodose line; images a1 and a2): 50-year-old patient with a right
temporal AVM, Spetzler-Martin grade II, fed by temporal branches of the inferior sylvian trunk, with both superficial and deep venous drainage;
clinical discovery after initial seizure; (a1) initial DSA, and (a2) DSA 3 years after treatment, showing complete obliteration; clinically, disap-
pearance of seizures.Case illustration 2 (“staged-volume” radiosurgery, 20 Gy at the 50% isodose line, at 9 months interval; images b1 and
b2): 52-year-old patient, presenting with large right temporo-insular AVM, Spetzler-Martin grade III, fed both by the middle and posterior cere-
bral arteries, with an important afferent component by the anterior choroid artery, with both superficial and deep venous drainage; clinical dis-
covery after initial seizure; (b1) initial DSA, and (b2) DSA 2 years after treatment, showing complete obliteration; clinically, disappearance of
seizures.
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an accurate delineation and further separation from the tar-
get volume difficult [30].
For all Spetzler-Martin grades combined, the overall oblit-
eration rate by surgery is 97%, with a mortality of around
3.3% and a morbidity of 8.6% [31]. Microsurgical treat-
ment completely obliterates high-grade AVMs in 57 to
100% of cases, with non-negligible mortality rates of be-
tween 0 and 11% and higher morbidity rates of between 4
and 85% (higher for higher Spetzler-Martin grades III–V)
[32]. Combined endovascular and surgical treatment al-
lows higher obliteration rates, of between 83 and 100%,
with a complication rate of 15.4% [33, 34].
With embolisation alone, AVM volume reduction is
achieved in 79.5% and complete obliteration in 20% of
cases, with a complication rate of 12% (range 8–40%)
[35]. It is estimated that 40% of AVMs can be treated with
embolisation alone, with a morbidity and mortality rate of
1.3% (range 2–7%), depending on the AVM characteristics
[36].
With radiosurgery and surgery combined, the overall oblit-
eration rate is 33%. It is nowadays considered that treat-
ment with radiosurgery alone, without prior embolisation,
gives a higher probability of obliteration [20]. This is relat-
ed to several factors, including that combined treatment is
used for more complex AVMs, difficult to cure by only one
treatment modality. In this context, multimodal manage-
ment offers a real possibility for cure. Furthermore, there
are more radio-induced changes in previously embolised
AVMs than in those having had an upfront radiosurgical
treatment (43 vs 33%). On the other hand, radiation-in-
duced clinical deficits are lower for the AVMs not previ-
ously embolised [20].
In our experience, 70.6% of AVMs with a modified Pol-
lock-Flickinger score equal to or less than 1.0 were oblit-
erated (mean follow-up time 31.2 months, median 27
months, range 12–51 months); obliteration rates were
62.1% for scores between 1.01 and 1.5 (mean follow-
up time 34.7 months, median 39 months, range 12–66
months), 45.5% for scores between 1.51 and 2.0 (mean fol-
low-up time 46.2 months, median 47 months, range 13–75
months), and 50% for scores more than 2.01 (mean fol-
low-up time 50.4 months, median 52 months, range 35–65
Figure 3: Kaplan-Meier curves showing: (a) the overall probability of obliteration over time; (b) the overall probability of obliteration by Pollock-
Flickinger score; (c) the overall probability of obliteration by prior embolisation versus no prior embolisation (p <0.05); (d) the overall probability
of obliteration by prior radiosurgery versus no prior radiosurgery (p >0.05).
Table 4: Complications related to gamma knife radiosurgery treatment (including haemorrhages during the preobliteration period).
Type of complication n total = 9/64 (14%)
n (%)
Haemorrhage 3 (4.7)
Ischaemic stroke 1 (1.6)
Ventriculo-peritoneal shunt placement for high intracranial pressure 1 (1.6)
Growth of previous cyst 1 (1.6)
Important perilesional oedema 1 (1.6)
Superior sagittal sinus partial thrombosis 1 (1.6)
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Swiss Med Wkly. 2018;148:w14602
months). The obliteration rates were higher for low-score
AVMs, which was expected and in accordance with pre-
viously published data. The mean obliteration time was
29.5 months for low scores, less than or equal to 1.0 (me-
dian 28, range 12–51 months). For scores between 1.01
and 1.5, this time increased to 34.7 months (median 38,
range 21–50 months) and it further increased for scores be-
tween 1.51 and 2.0 at 35 months (median 28, range 26–56
months). Moreover, for scores more than 2.0, the mean
obliteration time was even higher, at 40.7 months (median
35, range 35–52 months).
For Spetzler-Martin grades I and II, our obliteration rates
were high, at 77.9% (mean follow-up time 33.3, median
34, range 12–56 months) and 92.7%, respectively, (mean
follow-up time 36.4, median 39.5, range 12–52 months).
The mean obliteration times were quite similar (33.3 vs
36.4 months). For higher Spetzler-Martin grades, obliter-
ation rates decreased to 58.6% for grade III, 14.3% for
grade IV and 0.0% for grade V. The mean follow-up peri-
ods for these grades were 39.6 months (median 38.5, range
15–75), 45 months (median 44, range 12–67 months) and
39.5 months (median 39.5, range 24–54 months), respec-
tively. The mean obliteration times were 31.1 months for
grade III (median 35, range 12–41 months) and 37 months
for grade IV (only one case obliterated). No grade V AVM
was obliterated.
Our study has several potential limitations. The first is the
low number of cases. The second is the relatively short fol-
low-up period, if the mean delay of obliteration after radio-
surgery is taken into account; this varies across the studies,
but is generally considered to be 2 to 3 years for small to
medium size AVMs. The third is the retrospective design.
Radiosurgery is safe and effective as part of a multimodal
management of intracranial AVMs, as upfront treatment,
or in the frame of combined treatment associated with oth-
er modalities (e.g., microsurgical clipping, endovascular).
Overall obliteration rates were as high as 80% at 5 years
in the present study, in close agreement with what has al-
ready been described in the literature. Complications were
rare, up to 14% at 5 years, and were transient in the vast
majority of cases. The mortality due to radiosurgery itself
is 0%. However, during the obliteration period, haemor-
rhages may still occur until complete AVM cure.
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Acknowledgements
Lausanne University Hospital and University of Lausanne
19
Financial disclosure
Lausanne University Hospital.
20
Potential competing interests
No potential conflict of interest relevant to this article was reported.
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