J Neurosurg 117:864–873, 2012
Gamma Knife surgery in the treatment paradigm for foramen
magnum meningiomas
Clinical article
Georgios Zenonos, M.D.,1 Douglas Kondziolka, M.D.,1,3 John C. Flickinger, M.D.,1,2
Paul Gardner, M.D.,1 and L. Dade Lunsford, M.D.1,3
Departments of 1Neurological Surgery and 2Radiation Oncology, and 3Center for Image-Guided
Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Object. Microsurgical management of foramen magnum meningiomas (FMMs) can be associated with significant morbidity and mortality. Stereotactic radiosurgery may be an efficient and safe alternative treatment modality for
such tumors. The object of this study was to increase the documented experience with Gamma Knife surgery (GKS)
for FMMs and to delineate its role in an overall management paradigm.
Methods. The authors report on their experience with 24 patients harboring FMMs managed with GKS. Twelve
patients had primary symptomatic tumors, 5 had asymptomatic but enlarging primary tumors, and 7 had recurrent or
residual tumors after a prior surgery.
Results. Follow-up clinical and imaging data were available in 21 patients at a median follow-up of 47 months
(range 3–128 months). Ten patients had measurable tumor regression, which was defined as an overall volume reduction > 25%. Eleven patients had no further tumor growth. Two patients died as a result of advanced comorbidities
before follow-up imaging. One patient was living 8 years after GKS but had no clinical evaluation. Ten of 17 symptomatic patients with at least 6 months of follow-up had symptom improvement, and 7 remained clinically stable.
Smaller tumors were more likely to regress. No patient suffered an adverse radiation effect after radiosurgery.
Conclusions. Gamma Knife surgery was a safe management strategy for small, minimally symptomatic, or
growing FMMs as well as for residual tumors following conservative microsurgical removal.
(http://thejns.org/doi/abs/10.3171/2012.8.JNS111554)
Key Words • meningioma • foramen magnum • case series •
Gamma Knife surgery • outcome • oncology • stereotactic radiosurgery
T
umors involving the foramen magnum are rare,
constituting no more than 1% of all intracranial tumors.14,37 Despite their benign nature, FMMs can be
technically challenging to resect, as their usual anterolateral location places them close to osteoarticular structures,
the nervous system, and vascular structures that pose potential morbidity for the patient.1–5,7,10,13,14,17–19,21,24–27,29–32,37
Stereotactic radiosurgery has been proposed as an effective tool that could supplement and complement microsurgery in the treatment of these lesions.6,8,9,15,23,28,33 Although 3 small studies have demonstrated encouraging
results without morbidity or death,9,23,33 additional experience is needed. In the current analysis, we review our experience over the last 21 years with the use of GKS in the
care of FMMs. Based on this experience and a review of
previously published literature, we propose an integrated
treatment paradigm.
Abbreviations used in this paper: FMM = foramen magnum
meningioma; GKS = Gamma Knife surgery.
864
Methods
This retrospective analysis was performed with approval from the University of Pittsburgh institutional review board. Medical records and imaging results were
prospectively collected, and physicians who had not participated in the care of the patients independently retrospectively reviewed the collected data. Clinical follow-up
data were supplemented with a telephone interview, conducted by one of the authors (G.Z.) at the time that this
report was prepared, as well as with outcome data provided by current physicians or family members. For survival statistics, the social security death index was used at
the time that the current paper was prepared to determine
whether patients were still living or to learn the exact date
of death if they had already died.
Review of the Literature
A review of the literature in PubMed was performed
using the MeSH terms “Gamma knife radiosurgery,”
J Neurosurg / Volume 117 / November 2012
Gamma Knife surgery for foramen magnum meningioma
“Meningioma,” “Foramen Magnum,” “Management,”
“Surgery,” “Assessment, patient outcomes.” The reference
lists of reviewed clinical articles were further screened
for available data not included in our initial search.
Statistical Analysis
Microsoft Excel 2010 (Microsoft Corp.) and SPSS
version 16.0 (SPSS, Inc.) were used for data management, descriptive statistics, and statistical comparisons. A
2-tailed Student t-test was used to compare the means of
interval data. The alpha criterion of 0.05 was chosen for
statistical significance.
Results
Diagnosis of Meningioma
The diagnosis of meningioma was based on either
tissue pathology obtained at a prior operation (7 patients)
or characteristic imaging findings of a dura-based mass
located at the foramen magnum (17 patients). These latter findings included uniform contrast enhancement on
CT or MRI, often associated with signal characteristics of
intratumoral calcification. Patients were included in this
study if their tumor was confined to the following anatomical sites: 1) anteriorly, from the lower third of the clivus and upper edge of the body of C-2; 2) laterally, by the
jugular tubercles and superior aspect of the C-2 lamina;
and 3) posteriorly, by the anterior edge of the squamous
occipital bone and C-2 spinous process, according to previous reports.11,13
Patient Population
Between January 1990 and December 2007 at our
center, 24 patients (17 women and 7 men) underwent GKS
for meningiomas involving the foramen magnum. The
median patient age at presentation was 69 years (range
35–83 years). A detailed description of these patients is
featured in Table 1, and patient signs and symptoms are
provided in Table 2. Twelve patients presented neurological signs and symptoms that gradually progressed over
intervals of time ranging from several months to several
years. All 7 patients who had undergone initial microsurgical approaches had one or more postoperative deficits,
including hydrocephalus (2 patients), ataxia (1 patient),
prolonged coma (1 patient), and CSF leakage (1 patient).
Five patients had worsening lower cranial nerve deficits
after an initial surgery, and myelopathy developed in 1
patient.
Five patients had a history of multiple intracranial
tumors. One patient had an acoustic neuroma, 1 had a
pituitary adenoma, and 3 had multiple intracranial meningiomas.
Indications for Radiosurgery
Gamma knife surgery was performed in patients
with residual (2 patients) or recurrent (5 patients) lesions
after previous resections. Twelve had newly diagnosed
symptomatic tumors. Five patients underwent GKS because of progressive tumor growth during observation
(Table 1). Radiosurgery was recommended to patients
J Neurosurg / Volume 117 / November 2012
who had tumor progression despite prior surgery and to
patients whose age or associated medical conditions significantly increased the risk of major postoperative morbidity. Contraindications to radiosurgery included larger
tumor volumes (average diameter > 35 mm) and disabling
symptomatic tumors causing brainstem compression. In
such patients, an initial surgical decompression was recommended. For patients with residual or recurrent tumors
after an initial surgery, the average time between microsurgery and GKS was 85 months (median 35 months,
range 11–170 months).
Radiosurgical Technique
Radiosurgery was performed in a single session after administering a local anesthetic supplemented by
mild intravenous conscious sedation (midazolam and
fentanyl) as necessary. After applying the Leksell stereotactic frame, high-resolution volume-acquisition MR
images were obtained. Before 1991, or in patients with
contraindications for MRI, we performed radiosurgery
using stereotactic CT guidance. Image-integrated isodose
plans were created to enclose the tumor borders (Fig.
1). Given the irregular geometry of the tumors, multiple
isocenters were often used (average 6.7, range 2–14). A
radiosurgery team consisting of a neurosurgeon, a radiation oncologist, and a medical physicist selected maximum and margin radiation doses. Tumor margin isodose
curves of 50% were generally used, delivering a mean 13
Gy of radiation to the tumor margin (median dose 13 Gy,
range 11–15 Gy). The mean maximum dose was 26.5 Gy
(median 26 Gy, range 23–35 Gy), and the mean tumor
volume was 5.7 cm3 (median 4.1 cm3, range 0.7–15.9 cm3).
Dose prescription was individually determined based on
the tumor volume and the goal of keeping spinal cord
and lower brainstem doses at 8–12 Gy. Details regarding
specific Gamma Knife models (U, B, C, and Perfexion,
Elekta Instruments, Inc.) and radiosurgical procedure details for each case are listed in Table 1. Immediately after
radiosurgery, all patients were given a single intravenous
dose of methylprednisolone. All patients not hospitalized
for additional medical comorbidity care were discharged
within 24 hours after GKS.
Clinical Response
Clinical outcome analysis was based on the 23 patients for whom we had follow-up data. The median clinical follow-up to evaluate symptom progression was 62
months. Overall, the last clinical follow-up constituted a
visit to the neurosurgery outpatient offices for 10 patients,
correspondence with the patient (follow-up telephone
calls or letters) in 5 cases, correspondence with other physicians caring for the patient in 6, and clinical evaluation
while in the hospital in the 2 who died shortly after GKS.
The mean follow-up from GKS to the last time that patients were censored with the social security death index
was 106 months (median 107 months; Table 1).
Overall, among 21 patients with at least 6 months of
clinical follow-up after GKS, 10 patients had improvement of at least 1 of their symptoms. Eleven patients remained clinically stable. No asymptomatic patient treated
865
866
70, F
69, F
74, F
80, F
83, F
44, F
62, M
77, F
83, F
80, M
83, F
53, F
58, F
69, M
77, F
67, M
82, M
39, F
35, F
67, M
61, F
72, F
55, F
65, M
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
no
GTR
no
no
no
no
STR
no
STR
STR
no
no
no
no
no
no
no
GTR, STR
no
GTR
no
no
GTR, XRT
no
Prior
Treatment
symptomatic
recurrence
symptomatic
symptomatic
symptomatic
incidental finding
recurrence
symptomatic
recurrence
adjuvant therapy
symptomatic
symptomatic
symptomatic
symptomatic
incidental finding
symptomatic
incidental finding
adjuvant therapy
incidental finding
recurrence
symptomatic
incidental finding
recurrence
symptomatic
Reason For GKS
0.742
11.9
12
5.7
1.9
6.9
9.4
5.8
15.88
3.7
2.5
3.4
2.2
7.9
3.7
4.5
1.9
3
1.4
10.7
7.7
1.3
11.1
1.3
Lesion
Vol
(cm3)
25
22
30
24
30
26
26
26
35
32
26
25
28
25
28
25
26
28
28
24
24
26
24
23
Max
Dose
(Gy)
12.5/50
11/50
12/40
12/50
15/50
13/50
13/50
13/50
14/40
16/50
13/50
12.5/50
14/50
12.5/50
14/50
12.5/50
13/50
14/50
14/50
12/50
12/50
12/50
12/50
11.5/50
2
8
4
10
6
9
7
14
3
6
8
8
4
8
5
11
4
6
5
9
5
5
7
7
No. of
Margin Dose
Isocenters
(Gy)/Isodose (%)
Used
2 × 8, 2 × 14
B
2 × 14, 4 × 8
U
8
B
3 × 14, 6 × 8
B
14
C
8
C
4 × 8, 2 × 14, 1 × 18
U
4 × 8 (8 sectors),
Perfexion
3 × 4 (8 sectors)
2 × 8
C
14
C
2 × 14, 2 × 18
U
2 × 14, 8 × 8
C
2 × 4, 4 × 8
B
4 × 14, 5 × 8
B
4 × 14, 3 × 8
C
12 × 8, 4 × 4
C
3 × 14
U
1 × 14, 5 × 8
B
6 × 8, 2 × 4
B
8
C
3 × 8, 1 × 14
B
4 × 14, 4 × 8
C
2 × 8, 3 × 14
C
8
C
Collimator (mm)
Leksell
GKS
Model
7
NA
44
3
86
49
36
90
73
82
128
6
61
55
78
47
66
10
15
7
NA
NA
26
6
Period From GKS
to Last Imaging
FU (mos)
lesion stable
patient died after 2 wks
lesion stable
lesion stable
lesion regressed
lesion regressed
lesion stable
lesion stable
lesion stable
lesion regressed
lesion regressed
lesion stable
lesion stable
lesion regressed
regressed
regressed
lesion regressed
lesion stable
lesion regressed
lesion stable
patient died after 3 mos
patient lost to FU
lesion stable
lesion regressed
Outcome on FU
Imaging
D (107)
D (0.4)
D (145)
A (63)
A (156)
A (147)
D (107)
A (100)
D (70)
A (186)
A (137)
D (96)
A (163)
A 117)
A (116)
A (88)
D (101)
A (210)
D (42)
D (112)
D (3)
A (92)
A (134)
A (42)
Alive or Dead
(mos of FU)
* Location of FMM in relation to the dentate ligament was anterior in all cases except for Case 6, in which it was posterior. Abbreviations: A = alive; D = dead; FU = follow-up; GTR = gross-total resection; NA = not available; STR = subtotal resection; XRT = fractionated radiation therapy.
Age
(yrs),
Sex
Case
No.
TABLE 1: Demographic, radiosurgical procedure, and imaging outcome details*
G. Zenonos et al.
J Neurosurg / Volume 117 / November 2012
Gamma Knife surgery for foramen magnum meningioma
TABLE 2: Progression of symptoms after GKS in 24 patients*
No. (%)
Immediately After GKS (30 days)
Symptom (total no. of patients for group)
patients w/ primary disease (17)
headaches/neck pain
lower CN deficits
myelopathy
other‡
none
patients w/ residual/recurrent disease (7)
headaches/neck pain
lower CN deficits
myelopathy
other‡
none
all patients (24)
headaches/neck pain
lower CN deficits
myelopathy
other‡
none
≥6 Mos After GKS†
Pre-GKS
Worse
Same
Better
Worse
Same
Better
8 (47)
3 (18)
6 (35)
3 (18)
5 (29)
0
0
0
0
0
8 (47)
3 (18)
6 (35)
3 (18)
0
0
0
0
0
0
0
0
0
0
0
2 (13)
1 (7)
2 (13)
1 (7)
0
6 (40)
1 (7)
3 (20)
1 (7)
0
1 (14)
5 (71)
3 (42)
1 (14)
0
0
0
0
0
0
1 (14)
5 (71)
3 (42)
1 (14)
0
0
0
0
0
0
0
0
0
0
0
0
4 (67)
2 (33)
1 (17)
0
1 (17)
0
1 (17)
0
0
9 (38)
8 (33)
9 (38)
4 (17)
5 (21)
0
0
0
0
0
9 (38)
8 (33)
9 (38)
4 (17)
0
0
0
0
0
0
0
0
0
0
0
2 (10)
5 (24)
4 (19)
2 (10)
0
7 (33)
1 (5)
4 (19)
1 (5)
0
* Some patients presented with more than 1 symptom. Percentages refer to the total percentage of patients in each of the 3
groups (primary disease, residual/recurrent, and total). Abbreviation: CN = cranial nerve.
† Two patients died before the 6-month follow-up time point, and 1 patient was lost to follow-up. These 3 patients are not included
in this column. Therefore, the numbers and percentages of patients in each group are reduced accordingly in this column. For the
primary disease group, the number of patients is 15; for the recurrent or residual disease group, the number of patients is 6; and
the total number of patients is 21.
‡ Other symptoms included vertigo, noncardiogenic syncopal episodes, and ataxia.
for a growing tumor had any new neurological signs
or symptoms after radiosurgery. A detailed analysis of
symptom progression in this series of patients is provided
in Table 2 and Fig. 2.
Among the 17 symptomatic patients with at least 6
months of follow-up, 10 had amelioration of at least 1
symptom, and 9 had improvement in all symptoms. Patients whose condition improved presented, on average,
with smaller tumors (mean 3.7 ± 3.2 cm3, mean ± SD)
than those who remained neurologically stable (mean 9.3
± 3.8 cm3). This difference was statistically significant (p
= 0.0038). An analysis of symptom progression in relation
to initial tumor size is presented in Fig. 2. The mean tumor volume in symptomatic patients was 6.34 ± 4.44 cm3,
whereas in asymptomatic patients it was 3.2 ± 2.5 cm3.
As evident in Table 2, the most common presenting
symptom in primarily treated patients was headache or
neck pain (8 of 17 patients), followed by myelopathy (6
of 17 patients). Conversely, lower cranial deficits were
the most common symptom in residual or recurrent tumor cases (5 of 7 patients). The most common symptom
to resolve after GKS was headache or neck pain (7 of 9
patients), followed by myelopathy (4 of 9 patients). Only
1 of 8 patients with lower cranial deficits experienced improvement after GKS.
J Neurosurg / Volume 117 / November 2012
Imaging Response
Follow-up imaging studies were requested every 6
months for the first 2 years, and then at 4, 8, and 12 years
after radiosurgery. Imaging was performed at other intervals if new neurological signs or symptoms were detected. The median imaging follow-up was 47 months (range
3–128 months). Three patients did not have follow-up imaging data: 2 patients died of intercurrent illness within 6
months of radiosurgery, and 1 patient was lost to followup. Six patients had their last imaging study < 1 year after
GKS, 1 between 1 and 2 years, 6 between 2 and 5 years,
and 8 after 5 years (Tables 1 and 3). Tumor progression,
stability, or regression was based on a review of imaging
studies and the measurement of tumor diameters. Volumes were determined by multiplying measurements in
3 planes and then dividing by 2. Tumor regression was
defined as an overall tumor volume reduction > 25%.
Tumor control was maintained in all 21 evaluable
patients. Ten patients had tumor regression, and all had
stable lesion volumes at a median of 47 months after GKS
(range 3–128 months). Generally, as the duration of follow-up increased, tumor regression was more likely to be
detected. A detailed analysis of the radiographic response
of tumors according to the time to the last imaging fol867
G. Zenonos et al.
Fig. 1. Axial and sagittal MR images with contrast showing a left FMM. Images without (A, 1–6) and with (B, 1–6) the radiosurgical dose plan are shown. This tumor received a margin dose of 11.5 Gy and a maximum dose of 23 Gy.
low-up is provided in Table 3. Tumor progression was not
documented in any evaluable patient.
In a comparison of patients whose tumors had regressed versus those with stable tumors at a minimum of
2 years after radiosurgery, we were unable to detect any
difference in the maximum radiation doses used (27.3 ±
2.5 vs 28.2 ± 3.9 Gy, respectively, p = 0.605), mean tumor
margin doses used (13.6 ± 1.3 vs 13 ± 0.9 Gy, respectively,
p = 0.327), and mean number of isocenters used (7.1 ± 2.3
vs 6.5 ± 4 isocenters, respectively, p = 0.719). However,
the mean tumor volume at presentation was significantly smaller in patients whose tumors had regressed by 2
years (patients with tumor regression, 4.1 ± 2.2 cm3; patients with stable tumors, 9.4 ± 4.8 cm3; p = 0.018; Fig. 2).
All 5 asymptomatic patients with previously untreated but growing tumors had long-term tumor regression.
868
One of the patients with residual tumor after microsurgery had tumor regression, and 1 remained stable.
Patient Survival
Eleven patients still living at the time of the last
follow-up (46% of all patients) were on average 11 years
away from radiosurgery (median 11 years, range 5.2–17.6
years). Average age at the time of GKS in these patients
was 59 years (median 62 years, range 35–77 years), and
average age at the time of this writing was 78 years (median 74 years, range 47–87 years). Of note, the 1 patient
lost to follow-up was still living 8 years after GKS according to the social security death index.
Ten of the 24 patients died during the follow-up interval, that is, the period from treatment to the writing of
this paper. The mean age at death in these patients was 85
J Neurosurg / Volume 117 / November 2012
Gamma Knife surgery for foramen magnum meningioma
TABLE 3: Radiographic tumor progression in relation to the time
to the last follow-up imaging study
No. (% of FU group)
No. of Stable
Tumor
Tumor
Last FU Imaging Study Patients Tumor Regression Progression
Fig. 2. Bar graph demonstrating radiographic tumor progression and
symptom progression in patients with at least 6 months of follow-up
imaging data in relation to the initial tumor size. Tumor regression was
defined as > 25% reduction in tumor volume. The average follow-up
interval was similar in the 3 groups (< 3 cm3 group: 52 months, 3–6 cm3
group: 45 months, > 6 cm3 group: 47 months). Asymptomatic lesions
were not included in the symptom progression analysis. Dark gray bars
represent tumor regression; light gray bars, improved symptoms.
years (median 85 years, range 76–95 years). The mean age
at the time of GKS was 79 years (median 81 years, range
67–84 years), and the mean survival after GKS treatment
was 6.5 years (median 8 years, range 20 days–12 years).
Of note, 2 patients died at 20 days and 3 months, respectively, after GKS. Both of these patients were severely
disabled, nonambulatory octogenarians with multiple comorbidities and initially hospitalized for profound malnutrition (> 40% below ideal body weight) due to a difficulty
in managing secretions. Both patients had multiple lower
cranial nerve deficits, with 1 of the 2 having an absent
gag reflex bilaterally. The other patient also suffered from
advanced Parkinson disease. Despite significant brainstem compression, it was considered highly unlikely that
they would survive surgical decompression. The families
opted for conservative care, and GKS was recommended
as the only reasonable alternative. Excluding these 2 patients, average survival after GKS was 8.5 years (median
9 years, range 3.5–12 years), with a mean age of 86 years
at the time of death (median 87 years, range 76–95 years).
The exact cause of death in the remaining 8 patients is
unknown. Notably, all deceased patients had outlived
their life expectancies calculated at birth according to
United Nations World Population Prospects (75.6 years
for men and 80.8 years for women).34 On average, these
patients were 6.4 years beyond their life expectancy at the
time of death.
Adverse Effects
Although 2 patients died early in the follow-up as
a result of advanced comorbidities, none of the patients
experienced early or late adverse radiation effects. More
specifically, we documented no adverse T2 changes and
no patients requiring the additional use of corticosteroids.
Discussion
Meningiomas of the foramen magnum remain chalJ Neurosurg / Volume 117 / November 2012
none
total
primary
residual/recurrent
<24 mos
total
primary
residual/recurrent
24–60 mos
total
primary
residual/recurrent
>60 mos
total
primary
residual/recurrent
3
1
2
7
5
2
5 (71)
4
2
2 (28)
2
0
0
0
0
6
4
2
3 (50)
1
2
3 (50)
3
0
0
0
0
8
6
2
3 (38)
2
1
5 (62)
4
1
0
0
0
lenging clinical entities. Their rarity adds to the complexity of their management, as most of the information
regarding their treatment comes from case studies with
limited numbers of patients and spanning many decades.1–8,10,13–20,24–32,35,36 Microsurgical removal is considered definitive and the standard of care. However, even
at institutions with highly experienced personnel, surgery
can be associated with significant morbidity, mortality,
and long-term recurrence.1–8,10,13,15–20,24–32,35,36 To date, limited evidence suggests radiosurgery as an alternative tool
that leads to tumor control with a favorable safety profile
in selected cases in which surgery is either contraindicated or declined by the patient.9,23,33 Based on available
microsurgical and radiosurgical data, we propose an integrated treatment paradigm that incorporates radiosurgery
in the armamentarium of neurosurgeons who care for patients with these lesions.
Review of Microsurgical Literature
Over the past century, outcomes of microsurgical
removal of FMMs have improved. Yaşargil and Curcic36
reviewed the published outcomes of 114 patients who had
undergone surgery between 1924 and 1976. Overall mortality was 13%, although it was as high as 45% in some series. Furthermore, classifying survivors in a 3-tiered system, they found that 69% of treated patients had a “good
outcome,” 8% had a “fair outcome,” and 10% had a “poor
outcome.”36 During the past 20 years up to 2011, approximately 400 surgically treated cases of FMM have been
documented in the literature.1–8,10,13,16–20,24–32,35 The various
surgical approaches have included the posterolateral, far
lateral (either retro- or transcondylar),4,5,17,25,28 anterolateral or extreme lateral,3,30,32 transoral and transclival approach,10,19 as well as the lateral and posterior suboccipital
869
G. Zenonos et al.
approaches.5,19,31 Many authors have described variations
in these approaches, such as the transposition of vertebral
arteries,2,3,17,26,28,30,32 resection of the jugular tubercle,3,5,32
or partial mastoidectomy.3,30,32 Overall, advances in microneurosurgical techniques over the last 2 decades have
resulted in an average mortality rate that has decreased
to 6.2% (range 0%–25%), neurological improvement in
70%–100% of patients, neurological stability in 2.5%–
20% of patients, and neurological decline in 7.5%–10%
of patients in published series.1–8,10,13,15–19,24–32,35 Major
morbidity has varied anywhere from 0% to 60% of patients and is mainly associated with lower cranial nerve
deficits leading to aspiration and pneumonia, CSF leaks,
myelopathy, infection, and hydrocephalus.4–24,26,27,29,36,37
Infections and CSF leaks are more commonly reported
with the transoral transclival approach.10,19 The far lateral
approach4,5,17,25,28 seems to be associated with decreased
rates of lower cranial nerve deficits and overall morbidity,
as compared with rates in the extreme lateral and lateral
suboccipital approaches.3,5,19,30–32 Factors associated with
a more challenging surgical procedure and higher procedural morbidity include an anterior tumor location,13,31
tumor extension into the lower clivus,16 small tumor size
(smaller lesions can be more difficult to resect because of
the limited surgical corridor), tumor invasiveness, extradural extension,13 vertebral artery encasement,14 absence
of an arachnoidal sheath,4,12,36 and adherences in recurrent
lesions.3,4,31,32
Complete resection rates have varied from 0% to
100%, while recurrence rates have varied from 0% to 33%
in surgical series published in the last 2 decades.1–5,7,10,
13,17–19,24–27,29–32
The reason behind this wide variability lies
not only in the heterogeneity of the tumors, but also in the
aggressiveness with which these lesions were approached.
Some authors have attempted complete resections even
at the cost of potential morbidity,2 whereas others argue
for a more conservative approach to minimize complications.4,13 Factors associated with incomplete resections
and recurrences include encasement of the vertebral arteries,31 tumor invasiveness (as evident from the extradural component of the tumors),13,22 and adherences to vital
structures, especially in recurrent lesions.2,31,32
Review of Radiosurgery Studies in the Literature
At the time of this review, we found only 3 small
studies specifically addressing the management of FMMs
with radiosurgery via Gamma Knife23,33 or Cyberknife9
technology. Permanent morbidity or mortality after radiosurgery was not observed in any of these studies, and
nearly all patients had long-term tumor control.9,23,33
Muthukumar et al.23 described our early experience
in 1999. In that study, 5 patients with FMMs were treated
with GKS; 3 had newly diagnosed tumors, and 2 had recurrent tumors. Average age at the time of radiosurgery
was 80 years (range 73–84 years). After a mean followup of 36 months (range 12–60 months), 1 patient died
of an intercurrent illness, but all others remained stable.
Follow-up imaging studies revealed a reduction in tumor
volume in 1 patient, and no further lesion growth in the
other 4 patients. Starke et al.33 recently reported their ex870
perience in 5 patients with FMMs. One lesion increased
in size following GKS, requiring a second treatment,
which resulted in size stabilization. By the last followup, all meningiomas demonstrated either no growth (4
patients) or a reduction in size (1 patient). No patients
experienced any postradiotherapy complications. Using
the Cyberknife, Cheshier et al.9 treated 9 patients with
tumors near the foramen magnum. Of these 9 tumors, 6
regressed, 2 remained stable, and 1 increased in size during follow-up.
Indications for Radiosurgery After Reviewing the
Literature and Results of the Current Study
The most important finding in the present study is
that all patients with available follow-up imaging had either tumor regression or tumor control at a median follow-up of 47 months. No patient experienced any permanent morbidity directly attributed to GKS treatment. All
patients with at least 6 months of clinical follow-up either
had improvement of their symptoms or remained clinically stable at their last follow-up. These favorable results
concur with outcomes in the 3 radiosurgery studies described above9,23,33 and further validate the value of radiosurgery in managing these lesions. However, we certainly
believe that further long-term follow-up is necessary in
patients who undergo radiosurgery.
We observed that smaller tumors were more likely
to regress and that patients with smaller tumors were
more likely to have symptom improvement. Patients with
growing but as yet asymptomatic tumors had excellent lesion control and no long-term treatment-related morbidity. These results seem to support a relatively aggressive
approach using GKS for newly diagnosed small asymptomatic or nondisabling symptomatic tumors. Given the
suggested favorable safety profile of GKS, as well as the
technical challenges that accompany the surgical excision
of small FMMs, we recommend close follow-up for stable
asymptomatic lesions and early GKS over surgical excision once the lesions are found to progress on imaging.
Furthermore, we recommend early GKS over surgical
excision for small minimally symptomatic lesions. In patients with significant surgical comorbidities or an older
age or in patients who decline surgery, GKS can be seen
as an alternative to surgery for nondisabling symptomatic
lesions without significant brainstem compression.
Based on our limited experience, we believe that severely disabled or malnourished patients, usually those
with larger tumors causing significant brainstem compression, do not benefit from GKS. Surgical decompression is preferable for disabling symptomatic lesions causing significant brainstem compression if the procedure
seems feasible. In our opinion, the goal of microsurgery
should be to avoid morbidity while achieving the maximal resection that can be safely performed, and GKS can
be used for any residual tumor. Furthermore, given the
increased surgical risk associated with the microsurgical
removal of recurrent tumors, we advocate GKS for recurrent tumors without significant brainstem compression.
Unfortunately, because of their slow-growing nature,
FMMs are not often recognized until they have already
grown significantly, at which point patients have signs or
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Gamma Knife surgery for foramen magnum meningioma
symptoms of mass effect, cranial neuropathy, or myelopathy.1,2,4,6–8,15,16,19,20,25,28,36 For this reason, microsurgery,
which currently represents the standard of care, will likely be the treatment of choice in the majority of patients.
It is possible, however, that the wider availability of MRI
may enable earlier diagnosis of FMM, and thus primary
treatment with GKS may become more feasible.
The inferior location of such tumors in the past has
posed a potential technical difficulty for radiosurgery.
The Leksell Gamma Knife Perfexion unit circumvents
this limitation.
Definition of Goals and Limitations of the Current Study
The goal in the current study was not to directly compare radiosurgery and microsurgery, but rather to propose
an integrated management paradigm that utilizes radiosurgery as a complementary modality for treating the
spectrum of tumors defined as FMMs. In this spectrum,
since the more common lesions are large tumors with
profound brainstem compression, radiosurgery is more
likely to supplement microsurgery and observation rather
than replace them.
This retrospective study has a number of limitations.
As in most retrospective studies, a potential selection
bias should be considered. For example, patients referred
for radiosurgery who had growing tumors but minimal
symptoms may have had lower-grade tumors, which were
less likely to lead to recurrences. Moreover, because of
a referral bias, lesions treated with radiosurgery in this
report are probably different from the average surgically
treated FMM, and thus this study should not be perceived
as a direct comparison of radiosurgery with microsurgery. In addition, although this study currently represents
the largest FMM radiosurgery series, the number of cases
is still relatively small, and therefore the study is probably
underpowered for extensive statistical analyses. Furthermore, even though we elected to present all of our cases
for transparency and completeness, not all cases had significant long-term follow-up. For all of the above reasons,
the proposed management paradigm reflects our personal
understanding and recommendations after interpreting
the presented information, rather than an evidence-based
management algorithm that is substantiated by robust
data. Naturally, given the variety of experiences, preferences, and biases, interpretation of the same data could
lead to different conclusions and recommendations by
different readers. Our proposed management paradigm
has yet to be validated with additional cases or compared
with other proposed paradigms to follow.
We generally prefer radiosurgery to standard or hypofractionated radiotherapy for FMMs, as they are extraaxial tumors in critical locations with a radiobiological
response profile consistent with slow-growing tumors,
for which fractionation may have a lesser response. And
although stereotactic radiosurgery is our personal preference, there are no comparison studies of fractionated
radiotherapy. Furthermore, it is unclear whether a specific
tumor volume, patient age, performance status, or tumor
histology (for example, WHO Grade I, II, or III) would favor one modality over the other, although we recommend
combined radiosurgery and radiotherapy in the setting of
malignant meningiomas.
Proposed Management Algorithm
Despite advances in microneurosurgical techniques,
the surgical removal of FMMs continues to be a challenge. The present study provides additional evidence
that GKS is an effective and safe treatment alternative
that could supplement and complement microsurgery and
Fig. 3. Proposed management algorithm for FMMs.
J Neurosurg / Volume 117 / November 2012
871
G. Zenonos et al.
observation in selected lesions. Based on this evolving
knowledge and our personal understanding of the treatment of these lesions, we suggest the following (Fig. 3):
1) periodic imaging and clinical assessment of patients
with asymptomatic lesions and early GKS once tumor
progression is documented; 2) early GKS rather than
surgical excision for small minimally symptomatic lesions; 3) early GKS for nondisabling symptomatic lesions
without significant brainstem compression; 4) surgical
decompression for disabling symptomatic tumors associated with significant brainstem compression in patients
with a reasonable surgical risk profile, with the goal of a
maximal safe resection; 5) subsequent GKS for tumors
that remain after initial decompression; 6) early GKS for
recurrent tumors without significant brainstem compression; and 7) supportive medical management of elderly
and medically infirm patients with significant brainstem
compression (since the risk profile of surgery is too poor
and the benefit of GKS is unsubstantiated).
Disclosure
Both Drs. Lunsford and Kondziolka are consultants for AB
Elekta, and Dr. Lunsford has direct stock ownership in AB Elekta.
Author contributions to the study and manuscript preparation
include the following. Conception and design: Zenonos. Acquisition of data: Zenonos. Analysis and interpretation of data: Zenonos. Drafting the article: Zenonos. Critically revising the article:
all authors. Reviewed submitted version of manuscript: all authors.
Approved the final version of the manuscript on behalf of all authors:
Zenonos. Statistical analysis: Zenonos. Study supervision: Kondziolka, Lunsford.
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Manuscript submitted September 2, 2011.
Accepted August 7, 2012.
Portions of this work were presented as an electronic poster at the
AANS Annual Scientific Meeting in Miami, Florida, April 14–18,
2012.
Please include this information when citing this paper: published
online September 14, 2012; DOI: 10.3171/2012.8.JNS111554.
Address correspondence to: Georgios Zenonos, M.D., Department of Neurological Surgery, 200 Lothrop Street, Suite B400,
UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania 15213.
email: [email protected].
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