TOPIC REVIEW

Bradley A. Gross, M.D. CAVERNOUS MALFORMATIONS OF THE BASAL

Department of Neurological Surgery,
Feinberg School of Medicine and GANGLIA AND THALAMUS
McGaw Medical Center,
Northwestern University,
Chicago, Illinois, and CAVERNOUS MALFORMATIONS OF the basal ganglia and thalamus present a unique
Division of Neurosurgery,
Evanston Northwestern Healthcare,
therapeutic challenge to the neurosurgeon given their unclear natural history, the risk
Evanston, Illinois of surgical treatment, and the unproven efficacy of radiosurgical therapy. Via a PubMed
search of the English and French literature, we have systematically reviewed the natu-
H. Hunt Batjer, M.D. ral history and surgical and radiosurgical management of these lesions reported through
Department of Neurological Surgery, April 2008. Including rates cited for “deep” cavernous malformations, annual bleeding
Feinberg School of Medicine and
McGaw Medical Center,
rates for these lesions varied from 2.8% to 4.1% in the natural history studies. Across
Northwestern University, surgical series providing postoperative or long-term outcome data on 103 patients, we
Chicago, Illinois, and found an 89% resection rate, a 10% risk of long-term surgical morbidity, and a 1.9%
Division of Neurosurgery,
Evanston Northwestern Healthcare,
risk of surgical mortality. The decrease in hemorrhage risk reported 2 years after radio-
Evanston, Illinois surgery might be a result of natural hemorrhage clustering, underscoring the unproven
efficacy of this therapeutic modality. Given the compounded risks of radiation-induced
Issam A. Awad, M.D. injury and post-radiosurgical rebleeding, radiosurgery at modest dosimetry (12–14 Gy
Department of Neurological Surgery, marginal doses) is only an option for patients with surgically inaccessible, aggressive lesions.
Feinberg School of Medicine and
McGaw Medical Center, KEY WORDS: Angioma, Basal ganglia, Cavernous malformation, Natural history, Radiosurgery, Surgery,
Northwestern University, Surgical approach, Thalamus
Chicago, Illinois, and
Division of Neurosurgery, Neurosurgery 65:7–19, 2009 DOI: 10.1227/01.NEU.0000347009.32480.D8 www.neurosurgery-online.com
Evanston Northwestern Healthcare,
Evanston, Illinois

Bernard R. Bendok, M.D.
Department of Neurological Surgery,
Feinberg School of Medicine and
McGaw Medical Center,
Northwestern University,
Chicago, Illinois, and
Division of Neurosurgery,
Evanston Northwestern Healthcare,
Evanston, Illinois
Reprint requests:
H. Hunt Batjer, M.D.,
Department of Neurological Surgery,
Feinberg School of Medicine,
Northwestern University,
676 N. St. Clair Street,
Suite 2210,
Chicago, IL 60611.
Email: h-batjer@northwestern.edu
Received, June 18, 2008.
Accepted, January 9, 2009.
Copyright © 2009 by the
Congress of Neurological Surgeons
C
avernous malformations (CMs) are
clusters of sinusoidal channels filled
with blood at various stages of evolu-
tion (54, 55). Vessel walls comprise a flattened
endothelium and a thin fibrous adventitia,
lacking elastin and smooth muscle (54, 55).
Although these are low-pressure lesions (46),
they are remarkably dynamic with a potential
to both enlarge and diminish in size (17, 37,
43, 69). Although the latter is often attributed
to hematoma absorption (17, 37), a variety of
mechanisms of enlargement have been pro-
posed. These include hemosiderin deposition
with reactive gliosis (69, 82, 95), sinusoidal
proliferation (75, 82, 83), neovascularization
into an environment of local coagulopathy
(24, 69, 78), recanalization after intraluminal
thrombosis (78, 91, 97), cystic enlargement via
osmosis with reactive neocapillary network-
ing (86), or the activation of angiogenic fac-
tors by microhemorrhage (69, 97). Either local
mass effect from lesion enlargement or
extralesional bleeding can cause neurological
ABBREVIATIONS: CM, cavernous malformation;
DVA, developmental venous anomaly
deficits (1, 37, 67), with a particular sensitivity
of highly eloquent tissue to even minor mor-
phological changes (67). A prime example is
CMs of the basal ganglia or thalamus, rela-
tively rare lesions with the potential to cause
significant, devastating neurological deficits
(13, 28, 31, 35, 68, 90). Their rarity has limited
descriptions of their natural history and sur-
gical and radiosurgical management to pri-
marily case reports (13, 28, 35, 40, 49, 73, 76,
82, 90) and larger, broad series (51, 87). This
has obscured the unique challenge these
lesions present from a management stand-
point. In comprehensively reviewing the nat-
ural history and surgical and radiosurgical lit-
erature on these lesions, we synthesized a
management algorithm while highlighting
the nuances of particular surgical approaches
and radiosurgical therapy.
PATIENTS AND METHODS
A literature search of the PubMed database for
English and French language articles published from
January 1970 to April 2008 was performed. The
search terms, “cavernoma,” “cavernous malforma-
tion,” “cavernous angioma,” “basal ganglia,” “thal-

NEUROSURGERY VOLUME 65 | NUMBER 1 | JULY 2009 | 7

GROSS ET AL.
amus,” “deep,” “natural history,” “surgery,” and “radiosurgery” were
used. We further reviewed all references provided in our identified
articles, incorporating all relevant cited articles. Publications or partic-
ular patients within our reviewed series without specific postoperative
or long-term outcome data for CMs of the basal ganglia or thalamus
were excluded (53 patients) (24, 50, 51, 53, 57, 60, 87, 97). Because of the
rarity of CMs of the basal ganglia and thalamus, we incorporated case
reports into our analysis of surgical treatment, adding reporter and
publication bias but also affording a more comprehensive picture of
these lesions.
Natural History
The prevalence of CMs has been reported to range from 0.4% to
0.6% across several natural history and autopsy studies (37, 63, 72, 76),
with 5% to 17% (average of 9% across natural history studies) occuring
in the basal ganglia or thalamus (1, 11, 37, 41, 59, 67, 72). Prospective
natural history studies have reported CM annual bleeding rates rang-
ing from 0.7% to 3.1% (41, 59, 67, 72). Whereas lesion size does not seem
to affect hemorrhage rates (59, 72), female sex (59, 72) and previous
bleeds (1, 41) have been proposed as risk factors for hemorrhage.
Although not seen in the study by Moriarity et al. (59), the prospective
natural history studies of Kondziolka et al. (41) and Aiba et al. (1)
demonstrated a significantly increased risk of rebleeding, citing annual
rebleed rates of 4.5% and 22.9%, respectively. Variability in rebleeding
rates may be attributed in part to hemorrhage clustering, a phenome-
non elegantly demonstrated in the study by Barker et al. (6).
Deep CM location is a controversial risk factor for hemorrhage.
Using a rigorous definition of symptomatic extralesional hemorrhage,
Moriarity et al. (59) demonstrated no significant difference in hemor-
rhage rates between superficial and deep lesions. The annual bleeding
rate for deep lesions in this study was 3.1%. In a prospective study,
Kondziolka et al. (41) also reported no significant effect of location on
hemorrhage rates, citing an overall annual bleeding rate of 2.9% for
CMs of the basal ganglia and thalamus. Tew et al. (89) observed 8
patients with CMs of the basal ganglia and thalamus over a mean
period of 5.1 years. Two patients rebled and 2 patients experienced
progressive neurological deficits. Among patients experiencing hemor-
rhage from a thalamic CM in the study by Pozzati (68), 1 patient
remained severely disabled, 3 patients had mild nondisabling dysesthe-
sias, and 3 patients recovered, although 2 underwent surgical interven-
tion. This study cited a 6.1% annual rebleed rate for thalamic CMs, not-
ing that all rebleeds occurred within 2 years. Aiba et al. (1) reported an
annual rebleed rate of 11% over a mean follow-up period of 6.51 years
for CMs of the basal ganglia and thalamus, citing no significant relation
of lesion location and rebleed rates.
In a retrospective study, Cantu et al. (11) reported an annual bleed-
ing rate of 2.82% for deep hemispheric lesions, significantly greater
than the 1.22% annual rate for lobar CMs in this study. Porter et al.
(67) reported a 4.1% annual hemorrhage rate and a 10.6% annual clin-
ical event rate for deep lesions, a significant contrast to the 0% rate
reported for superficial lesions. Fifteen clinical events occurred in
patients with lesions in the brainstem, whereas 1 occurred in a patient
with a thalamic CM. The sensitivity of highly eloquent parenchyma
in the basal ganglia, thalamus, and brainstem to minor morphologi-
cal changes likely explains the increased aggressiveness of deep CMs
reported in such studies. In contrast, hemorrhage in a noneloquent
location can go undetected, further inflating relative bleeding rates of
deeper lesions. Importantly, however, Porter et al. reported no signif-
icant difference in the degree of recovery between hemorrhagic and
nonhemorrhagic clinical events (67). Approximately one-third of
patients did not improve after a clinical event, which, taken together
8 | VOLUME 65 | NUMBER 1 | JULY 2009
with the results from Pozzati’s (68) series of thalamic CMs, results in
an approximate significant long-term morbidity rate of 15% to 33%
from deep CM hemorrhage. Overall, natural history studies have
reported annual bleeding rates ranging from 3.1% to 4.1% for deep
CMs and from 2.82% to 2.9% for CMs of the basal ganglia and thala-
mus specifically.
Clinical Presentation
CMs of the basal ganglia and thalamus traditionally present with
contralateral sensorimotor deficits when symptomatic (9, 8, 22, 29, 31,
45, 51, 62, 68). Severe headache (31, 45, 77) and seizures (20, 68, 90,
101) are less common presentations. Although any large CM hemor-
rhage can cause hydrocephalus (28, 35), medial or dorsal thalamic
lesions abutting the ventricular system intuitively have a greater
probability of causing obstructive hydrocephalus after a bleed (44, 51,
68). Twenty-five percent of thalamic CMs presented with hydro-
cephalus in the series by Pozzati (68); 15% of thalamic CMs in the
series by Mathiesen et al. (51) presented with hydrocephalus.
Thalamic lesions can also present with hemianopsia (19, 68), thalamic
pain syndromes (62), or oculomotor paresis as a result of extension
into the mesencephalon (62, 68). Parkinsonism (23) and extrapyrami-
dal symptoms have also been reported for CMs of the basal ganglia
and thalamus (2, 10, 13, 21, 30, 42, 87, 99).
Several cases of ganglionic lesions causing hemichorea are described
in the literature (10, 13, 21, 42, 99). In 1 case report in which a patient
with hemichorea and a putaminal CM declined surgery, sodium val-
proate was effectively used to improve, but not eliminate, the sympto-
matology (21). Yakinci et al. (99) reported alleviation of symptoms in a
child with a caudostriatal CM and hemichorea with pimozide. Another
patient with hemichorea and a caudate CM had complete resolution of
symptoms after surgical excision (13). The authors proposed a mecha-
nism of release phenomena caused by interruption of striatal neurons
projecting to the globus pallidus externa. Hidaka et al. (30) proposed a
similar mechanism to explain hemiballismus caused by a putaminal
CM. After biopsy of the lesion, symptoms transiently ceased, poten-
tially because of interruption of excitatory fibers from the thalamus
and cortex projecting to the striatum by a postoperative hematoma. As
the hematoma resolved, symptoms returned.
A B
FIGURE 1. A, this multiloculated, thalamic cavernous malformation
(CM) demonstrates the classic appearance of these lesions on T2-
weighted imaging: a reticulated mixed signal core with a surrounding
hypointense hemosiderin halo. B, after recurrent bleeding, this CM with
ample lateral extension was successfully resected via a distal transsyl-
vian approach.
www.neurosurgery-online.com
 CAVERNOUS MALFORMATIONS OF THE BASAL GANGLIA AND THALAMUS

TABLE 1. Approaches to cavernous malformations of the basal ganglia and thalamus

Location/approach Comments
Caudate
Interhemispheric transcallosal
Contralateral interhemispheric Added lateral exposure
transcallosal (44, 45)
Transcortical Most direct route
Best used with stereotaxy if hematoma cavity extends close to cortical surface
Risk of postoperative seizures (81) and neuropsychological deficits (14, 96)
Transsylvian For lesions with large hematoma cavities with ample lateral extent
Lentiform
Transsylvian, transinsular Approach of choice
Transcortical Transsulcal with stereotaxy (49) if hematoma cavity extends close to cortical surface
Dorsal/medial thalamus
Interhemispheric transcallosal Risk of forniceal injury
Contralateral interhemispheric Approach of choice
transcallosal (44, 45) Risk of forniceal injury
Added lateral exposure
Transparietal transventricular Potential damage to optic radiations
Added lateral exposure
Posterior thalamus
Occipital interhemispheric subcallosal Wider exposure
Extensive dissection of deep venous system
Supracerebellar infratentorial Dependent on slope of tentorium, limited superior and lateral exposure
Paraculminar supracerebellar infratentorial/ Tentorium can be cut to extend field superolaterally
transtentorial (62)
No need to retract culmen downward
Lateral thalamus/significant lateral
extension of hematoma
Posterior transsylvian transinsular

Dystonia is another less common presentation of both thalamic (68,
87) and ganglionic CMs (2, 49). Akbostanci et al. (2) reported improve-
ment of symptoms with biperiden. Lorenzana et al. (49) reported a
focal hand dystonia as the exclusive presentation of a lentiform CM.
Symptoms resolved after surgical excision. The authors proposed dis-
ruption of striatopallidothalamic projections to the premotor cortex as
the mechanism of the symptomatology.
Surgical Approaches and Results
After diagnosis of a thalamic or ganglionic CM via its pathogno-
monic appearance on magnetic resonance imaging (Fig. 1A), surgery is
often considered for symptomatic patients with aggressive lesions with
a noneloquent corridor of access. Surgical approaches are summarized
in Table 1. We have chronologically tabulated results from case reports
and surgical series reported through June 2008 (Tables 2–5).
A total of 103 CMs were reviewed. Using data from series provid-
ing specific information on lesion resection rates, 71 of 80 lesions
(89%) were completely resected. Two recurrences were noted 2 and 8
years after radiographically confirmed complete surgical resection
(62, 87). Two of 9 partially resected lesions rebled, leading to poor out-
comes in both cases (9, 78). Another partially resected CM regrew,
requiring reoperation (83).
Early postoperative and long-term morbidity is difficult to calculate
given variable surgical selection criteria, outcome reporting, and fol-
low-up. Steinberg et al. (87) reported common transient hemiparesis
after resection of 15 CMs of the basal ganglia and thalamus. Across our
reviewed surgical series and case reports, 10 of 103 patients (10%) were
worse at the time of the long-term follow-up evaluation. Two of 103
patients (1.9%) died from surgery, 1 of them from a postoperative thal-
amic infarct after resection of a CM with an associated developmental
venous anomaly (DVA) (68).
Caudate CMs
Fourteen caudate CMs are reviewed in Table 3. Eleven of 12 (92%)
were completely resected. Four patients (33%) were worse postopera-
tively, and 1 neonate had moderate mental retardation at the time
of follow-up (28). One patient developed debilitating obsessive-
compulsive disorder, potentially from frontal deafferentation leading to

NEUROSURGERY VOLUME 65 | NUMBER 1 | JULY 2009 | 9

GROSS ET AL.

TABLE 2. General surgical series and case reports of cavernous malformations of the basal gangliaa
No. of Preoperative Resection Early postoperative
Series (ref. no.) Long-term outcome
patients condition rate morbidity
Aiba et al., 1995 (1) b 5 All bled at least 3 excellent/good;
once 2 moderate disability from
surgery
Attar et al., 2001 (5) 1 HP bled None
Bertalanffy et al., 2002 (8) 8 8/8 No permanent complications
Di Rocco et al., 1996 (20) 2 1 seizure, both bled 2/2 None Both improved/same
Koukkari et al., 1996 (42) 1 Hemichorea No surgical Improved, hemichorea
complicationsc resolved without medication
Lobato et al., 1988 (48) 1 Progressive HP 1/1 Same
Matz et al., 1995 (52) 1 Intact 1/1 Intact
Scott et al., 1992 (78) 1 Symptomatic 1/1 None
Tomlinson et al., 1994 (91) 3 Symptomatic None All with focal deficits and/or
headaches improved
Vaquero et al., 1983 (93) 1 HP 0/1 Same
Winkler et al., 2006 (98) 1 Symptomatic 1/1 Same
Zamorano et al., 1997 (101) 1 Seizures 1/1 Transient HP Improved
Zhao et al., 2007 (102) b 11 11/11 1 transient HP; All improved/same
1 transient facial paresis

a
HP, hemiparesis.
b
Series include both ganglionic and thalamic cavernous malformations.
c
Patient was transiently worse from phenytoin.

dysfunction of frontostriatal loops and a loss of inhibition of automatic
behavior (90).
The interhemispheric transcallosal approach is the common approach
of choice, given the ability to avoid incising cortex and decreasing the
risk of postoperative seizures (81) and neuropsychological deficits (14,
96). A contralateral approach adds lateral exposure and may be particu-
larly attractive for dominant hemisphere lesions (45); it was successfully
used for 4 CMs, as shown in Table 2. All were excised completely with-
out reported complications (3, 45). Although transcortical approaches
with intraoperative stereotaxy provide a more direct route to the CM,
they are best used exclusively for lesions with large hematoma cavities
that allow for minimization of cortical transgression.
Lentiform CMs
Eight lentiform CMs are reviewed in Table 4. All but 1 patient had
a preoperative hemiparesis, making these results less applicable to
asymptomatic or minimally symptomatic patients. Overall, 7 of 8
CMs (88%) were completely resected, and 2 of 8 patients (25%) expe-
rienced transient worsening of their hemiparesis, although all
patients were ultimately in improved condition at the time of follow-
up. The transsylvian approach with intraoperative stereotaxy is the
common approach of choice, with larger hematoma cavities facilitat-
ing dissection and minimizing the amount of transgressed cortex.
Additionally, Duffau (22) used subcortical stimulation and somato-
topically mapped the internal capsule, noting 4 mm of brain shift.
Lorenzana et al. (49) described an interesting case of a lentiform CM
presenting exclusively with a focal hand dystonia. The lesion was
resected stereotactically via the second frontal sulcus without com-
plication. Such an approach is generally only considered when the
hematoma cavity closely abuts the sulcus.
Thalamic CMs
Thirty-three thalamic CMs are reviewed in Table 5. Twenty-seven of
33 (82%) were completely resected; 2 lesions recurred at 2 and 8 years
after ostensibly successful complete surgical resection (62, 87). Thirteen
patients (39%) were reported as transiently worse postoperatively, and
2 patients (6%) died from surgery, 1 from a thalamic infarct after resec-
tion of a lesion with an associated DVA (68). Long-term surgical morbid-
ity was observed in 6 patients (18%), attributed to capsular damage in
2 patients as a result of attempts to remove perilesional gliotic tissue (9).
CMs presenting to the ependymal surface of the dorsal or medial
thalamus are best approached via either an ipsilateral or contralateral
interhemispheric transcallosal approach. The contralateral transcallosal
approach, popularized by Lanzino et al. (44) and Lawton et al. (45), pro-
vides added lateral exposure. With the sagittal suture parallel to the
floor, retraction of the lesion-containing hemisphere is facilitated by the
falx while gravity retracts the contralateral hemisphere downward and
brings the lesion down into view. The interhemispheric dissection is per-
formed on the contralateral side, an advantage for dominant hemisphere
lesions. Using this approach, Lawton et al. (45) completely resected 3
thalamic CMs without complication. A transparietal, transventricular
approach provides added lateral exposure (7, 68, 77, 89), although it is
less frequently used and less appealing because of the need for a corti-
cal incision and the risk of damage to the optic radiations. Lesions with
ample lateral extension of their hematoma cavity may also be removed
via a posterior transsylvian approach (19, 39) (Fig. 1).

10 | VOLUME 65 | NUMBER 1 | JULY 2009 www.neurosurgery-online.com

 CAVERNOUS MALFORMATIONS OF THE BASAL GANGLIA AND THALAMUS

TABLE 3. Surgical series and case reports of cavernous malformations of the caudate nucleusa
Early
No. of Preoperative Resection Long-term
Series (ref. no.) Approach postoperative
patients condition rate outcome
morbidity
Alves de Sousa, 2007 (3) 3 Contralateral, 3/3 None All in good
interhemispheric condition
transcallosal
Bicknell et al., 1978 (10) 1 Arm monoparesis, 1/1 Same
choreoathetoid
movements
Carpay et al., 1994 (13) 1 Worsening hemichorea Stereotactic, 1/1 None ASx after 0.2 y
deteriorating to transfrontal
hemiballismus
Multiple bleeds
Hashimoto et al., 1997 (28) 1 Neonate 1/1 HCP, VPS Moderate mental
retardation
IPH, IVH 1 seizure
Houtteville, 1995 (31) 2 Both severe HA 1 transparietal 2/2 1 transient Both ASx
leg paresis
Both no focal deficit 1 transsylvian
Both bled
1 SAH
Kerchner et al., 2006 (35) 1 HCP Anterior 1/1 Transient Improved
cognitive
Multiple bleeds Interhemispheric Impairment
Lawton et al., 1996 (45) 1 HA Contralateral anterior 1/1 None
Bled Interhemispheric
Transcallosal
Pozzati et al., 1996 (69) 2 1 seizure Both same/
improved
1 progressive HP
Both bled
Both growing
Stacey et al., 2000 (83) 1 HP, dysphasia 0/1 Regrew Improved
then resected long term
completely
Multiple bleeds
Thobois et al., 2004 (90) 1 Comatose 1/1 Total recovery OCD
R HP Otherwise ASx
a
ASx, asymptomatic; HCP, hydrocephalus; VPS, ventriculoperitoneal shunt; IPH, intraparenchymal hemorrhage; IVH, intraventricular hemorrhage; HA, headache; SAH, subarachnoid
hemorrhage; OCD, obsessive-compulsive disorder; R, right; HP, hemiparesis.

CMs of the posterior thalamus may be approached via an occipital
interhemispheric subcallosal or supracerebellar infratentorial approach.
Although the former is encumbered by requisite dissection of the deep
galenic venous system, it provides a wider exposure. Chi and Lawton
(16) noted improved visual outcomes and decreased need for manual
retraction, less blood loss, and less postoperative edema for patients
positioned laterally (as compared with supine) for posterior interhemi-
spheric approaches. They attributed this, in part, to the decreased need
for manual occipital lobe retraction. They successfully removed 1 poste-
rior thalamic CM without complication. The occipital interhemispheric
approach was specifically described for 3 additional thalamic CMs (Table
5) (3, 51, 68). Although 2 patients experienced transient worsening of sen-
sorimotor symptoms, all 3 CMs were completely removed, and all
patients were ultimately in improved condition. Otani et al. (62) used a
paraculminar supracerebellar approach with selective tentorial incision
to give added superolateral exposure in the resection of 6 thalamic CMs.

NEUROSURGERY VOLUME 65 | NUMBER 1 | JULY 2009 | 11

GROSS ET AL.

TABLE 4. Surgical series and case reports of cavernous malformations of the lentiform nucleusa
Early
No. of Preoperative Resection Long-term
Series (ref. no.) Approach postoperative
patients condition rate outcome
morbidity
Duffau, 2000 (22) 1 HP 3 bleeds Stereotactic distal 1/1 Transient Improved
transsylvianb worse HP
Heffez, 1997 (29)c 4 All HP, 3 HS Stereotactic pterional 4/4 1 transient All improved
transsylvian transinsulard worse HP, HS
Kon et al., 2007 (40) 1 HP growing Transsylvian 0/1e Improvedf
Lorenzana et al., 1992 (49) 1 Focal hand Stereotactic via second 1/1 None Improved
dystonia frontal sulcus
Yamasaki et al., 1986 (100) 1 HP, HS bled 1/1 None Improved
a
HP, hemiparesis; HS, hemisensory deficits.
b
Adjunctive subcortical stimulation of internal capsule.
c
Cavernous malformations were described as 0.5 to 2 cm deep to the insular cortex.
d
Adjunctive somatosensory evoked potentials did not change any procedures; however, changes were observed in patients with postoperative hemisensory deficit worsening.
e
Limited by profuse intraoperative bleeding.
f
Underwent postoperative radiotherapy.

This approach averted the need for downward retraction of the culmen.
Mild transient morbidity was reported in 2 of 6 patients, and 5 of 6
patients ultimately improved from their preoperative condition.
Radiosurgery
Radiosurgical treatment of CMs has been regarded with a consider-
able amount of skepticism (71, 80). Given the known proclivity for
CMs to naturally decrease in size with hematoma resorption (17, 37),
and the lack of imaging modalities to demonstrate lesion obliteration,
we have relied on post-radiosurgical hemorrhage rates as an indicator
of radiosurgical efficacy. Although an indirect measure of lesion oblit-
eration, hemorrhage rates more directly reflect clinical outcome.
Larger radiosurgical series have reported annual hemorrhage rates
of 6.3% to 22.4% in the first 2 years after radiosurgery, decreasing to
0.8% to 4.5% after this “latency period” (4, 15, 27, 33, 36, 47, 65). The
startling early post-radiosurgical hemorrhage rates were generally
comparable or even improved compared with pre-radiosurgical hem-
orrhage rates, underscoring the fact that most radiosurgical data in
surgical series is for highly aggressive CMs. However, many lesions
ultimately underwent surgical resection, deflating reported hemor-
rhage rates with time (15, 27, 33).
For CMs of the basal ganglia and thalamus in particular, Amin-
Hanjani et al. (4) demonstrated a notable decrease in annual hemorrhage
rate from 16.4% to 2.2% (including the first 2 years) after radiosurgical
treatment of 16 lesions. This improvement was markedly better than
that observed for brainstem CMs in this series. In contrast, Karlsson
et al. (33) reported no significant impact of CM location on hemorrhage
rate, reporting an overall post-radiosurgical hemorrhage rate of 11% for
the first 4 years after radiosurgery decreasing to 6% thereafter. Seven of
22 CMs in this series were in the basal ganglia or thalamus. Mitchell et al.
(58) reported 2 rebleeds after radiosurgical treatment of 7 CMs of the
basal ganglia and thalamus. Across the series by García-Muñoz et al. (25)
(follow-up duration, 6.3 years), Kayali et al. (34) (median follow-up dura-
tion, 2.5 years), Huang et al. (32) (mean follow-up duration, 5 years), Kim
et al. (38) (mean follow-up duration, 2.5 years), and Stea et al. (85) (mean
follow-up duration, 3 years), 0 of 19 CMs of the basal ganglia or thala-
mus rebled after radiosurgery.
The striking parallel between post-radiosurgical hemorrhage rates
and the natural history of aggressive CMs further reinforces the need
for a prospective, randomized trial of radiosurgery compared with
observation. As mentioned previously, Barker et al. (6) reported a sig-
nificant decrease in hemorrhage rates after 2 years among aggressive
CMs, and Pozzati (68) reported no rebleeds after 2 years in a smaller
series of 12 thalamic CMs. The series by Pozzati (68) and Pozzati et al.
(69) and Tung et al. (92) also demonstrated a proclivity toward hemor-
rhage clustering among aggressive lesions; however, it should be noted
that the data from these studies were collected retrospectively.
In addition to the unclear therapeutic effects of radiosurgery in the
treatment of CMs, multiple series have demonstrated an increased risk
of radiation-induced deficits compared with radiosurgery of arteriove-
nous malformations (33, 65), potentially from the radiosensitizing
effects of iron and/or radiation of associated DVAs (68, 88).
Nonetheless, experienced centers have demonstrated waning radio-
surgical morbidity rates with accumulating experience (27). Across
larger radiosurgical series, radiation-induced early morbidity varied
widely from 2.5% to 59% (4, 15, 27, 33, 36, 47, 65), likely related to
operator experience, available imaging and radiosurgical technology,
and dosimetry (4, 33, 36, 47, 65). In a radiosurgical series of 125 patients
(14 with CM in the basal ganglia or thalamus), Liu et al. (47) used the
lowest mean marginal dose (12.1 Gy) and reported the lowest radia-
tion-induced early complication rate of 2.5%.
Among series with specific morbidity data on CMs of the basal gan-
glia and thalamus, permanent radiation-induced complication rates
have ranged from 0% to 75% (Table 6). In most cases, dosimetry and
follow-up was not specified for this subset of patients, although taken
together, 11 of 50 patients (22%) in these series experienced radiation-
induced complications that were permanent in 7 of 50 cases (14%).
DISCUSSION
CMs of the basal ganglia and thalamus present a unique
therapeutic challenge. In contradistinction to arteriovenous
malformations of these locations that are oftentimes “reflex-

12 | VOLUME 65 | NUMBER 1 | JULY 2009 www.neurosurgery-online.com

 CAVERNOUS MALFORMATIONS OF THE BASAL GANGLIA AND THALAMUS
ively” treated radiosurgically, the neurosurgeon, faced with a
paucity of information on the natural history and surgical and
radiosurgical treatment of these lesions must often rely on
anecdotal data and intuition, affording a “best guess.”
Our review of natural history studies demonstrated an
annual bleed risk ranging from 2.8% to 4.1%, with some stud-
ies reporting elevated annual rebleed rates of 6.1% to 11% (1,
68), a striking parallel to modern natural history data for arte-
riovenous malformations (84). However, these annual bleed
and rebleed rates are based on the false assumption of a con-
stant, linear risk. They are likely overestimates for initially
asymptomatic lesions that are often underrepresented in nat-
ural history studies. Several reports have demonstrated the
potential benign course deep CMs can follow (12, 68, 69, 73).
Thus, we believe that asymptomatic or minimally sympto-
matic lesions should be observed. Our 10% long-term mor-
bidity rate from surgery comes from the most experienced
hands operating on primarily symptomatic lesions; it is
undoubtedly an underestimate for asymptomatic or minimally
symptomatic lesions. We think it outweighs the 15% to 33%
risk of significant, long-term morbidity from deep CM hemor-
rhage, should it even occur.
Conversely, a significant, fixed neurological deficit can serve
as a convincing factor to the patient and surgeon that opera-
tive intervention is less likely to add further disability, but
may prevent further deterioration from future bleeding. Thus,
surgical intervention after a single hemorrhage is only a con-
sideration for patients with: 1) fixed, significant, or progressive
neurological deficits, and 2) convincing pial/ependymal rep-
resentation of their CM or hematoma cavity on T1-weighted
imaging. “Bloom effect” leading to overestimation of the prox-
imity of the CM to an accessible surface makes T2-weighted
imaging merely an initial, sensitive diagnostic tool for CMs
(87). In Pozzati’s (68) surgical series of 4 thalamic CMs, all
lesions protruded into the lateral ventricle or posterior inci-
sural space. Although we concur with Steinberg et al. (87) that
small incisions of the pulvinar portion of the thalamus may be
tolerated, we are only inclined to perform such incisions with
intraoperative stereotaxy and hemosiderin staining of the sur-
face of the thalamus.
After a second clinically significant hemorrhage, the possibil-
ity of further hemorrhage clustering (6, 69) and escalating mor-
bidity (69, 92) compel us to forego our first inclusion criterion
for surgery. Two exceptions are patients with multiple lesions
and those with lentiform CM, given the decreased likelihood of
surgical cure in the former case and significant risk of postoper-
ative motor weakness in the latter. As mentioned previously, the
vast majority of patients with lentiform CM undergoing surgery
were hemiparetic preoperatively. Similar to Houtteville (31), we
are hesitant to operate on patients who have fully recovered
after 2 clinically symptomatic hemorrhages from their lentiform
CM. In addition, given the rarity of mortality from CM hemor-
rhage, the potential benefit of surgery for patients with complete
preoperative motor loss is questionable, even though the risk of
intervention is seemingly decreased.
NEUROSURGERY
Once surgery has been selected, an anatomic (Table 1) or
hematoma-produced surgical approach is selected. DVAs can
be a particular source of postoperative morbidity and mortal-
ity (9, 66, 68). Their benign natural history (0.15%–0.34% symp-
tomatic annual hemorrhage rate) (26, 56, 61), coupled with their
role in draining normal parenchyma (66, 79), make them an
important influence on the selected surgical approach. Their
disruption must be avoided to prevent potentially fatal venous
infarction (9, 68, 66, 79). Thus, they may contraindicate surgery
because of their size or if they lie between the requisite corridor
of access and the lesion. Intraoperative ultrasound is a useful
adjunct to facilitate detection of the DVA (98).
Although minimally invasive or endoscopic approaches for
the successful management of 3 deep CMs have been reported
(64), we are less inclined to use these, advocating the premise
of “more is more” when it comes to fashioning our craniotomy
for deep-seated lesions. Even though CMs are low-flow lesions,
the potential for intraoperative bleeding, and, more impor-
tantly, incomplete surgical excision, demand a more generous
exposure. Intraoperative stereotaxy, motor evoked potentials,
and somatosensory evoked potentials are requisite adjuncts (8,
16, 29, 78, 87, 101, 102). We are inclined to account for brain
shift via intraoperative ultrasound (29, 102) or subcortical stim-
ulation mapping (22) as opposed to catheter implantation (50).
The potential for intraoperative diffusion-weighted imaging is
an exciting area of study that might further reduce potential
surgical morbidity (18). One report of diffusion-weighted imag-
ing used to guide the resection of 4 lesions (including 1 occip-
ital CM) in close proximity to the optic radiations demonstrated
no persistent postoperative visual field deficits (18).
Persistently symptomatic lesions that have hemorrhaged twice
without a surgical corridor of access may undergo radiosurgery
at modest dosimetry (12–14 Gy to the margin). Notwithstanding
the confounding factors of natural CM hemorrhage clustering (6)
and of selecting patients for surgery after radiotherapy, there
does seem to be a decrease in rebleed rates after radiosurgery,
particularly after 2 years (4, 15, 27, 33, 36, 47, 65). However, these
data come from series of predominantly aggressive CMs. It is
therefore not applicable to minimally symptomatic CMs or those
that have bled once with stable or improving neurological
deficits. These patients should be observed.
Our review of radiosurgical series suggests a potentially
decreased risk of radiosurgical morbidity for these lesions as
compared with brainstem lesions (4, 27, 85). The overall 14%
risk of permanent morbidity we cite is further compounded by
the known risk of rebleeding and its associated morbidity.
Overall, this modality therefore poses a greater risk of morbid-
ity than surgery for accessible lesions. Thus, it is only an alter-
native to observation for clinically aggressive, surgically inac-
cessible lesions, particularly lentiform, capsular, and ventral
thalamic lesions (Fig. 2).
CONCLUSIONS
Natural history studies of CMs of the basal ganglia and thal-
amus cite annual bleed rates of 2.8% to 4.1%. CMs of the basal
VOLUME 65 | NUMBER 1 | JULY 2009 | 13
GROSS ET AL.

TABLE 5. Surgical series and case reports of cavernous malformations of the thalamusa
Early
No. of Preoperative Resection Long-term
Series (ref. no.) Approach postoperative
patients condition rate outcome
morbidity
Alves de Sousa, 1 Occipital interhemispheric 1/1 Transient HP Good outcome
2007 (3) transventricular
Becker et al., 1 HP, HS Transparietal transventricular 1/1 Transient dysphasia Persistent HP
1979 (7) Bled Incised posteromedial thal
Bertalanffy et al., 2 Both mild HP Anterior interhemispheric 1/2 1 residual Both worse HP
1991 (9) transcallosal rebleed
1 venous infarctb 1 new memory deficit
Bertalanffy et al., 4 1 frontal interhemispheric 4/4 1 long-term memory
2002 (8) transcallosal worsening
3 supracerebellar infratentorial
Chi and Lawton, 1 HP, HS Contralateral interhemispheric 1/1 None mRS 1
2006 (16) occipital transfalcinec
Multiple bleeds
Cohen et al., 1982 (19) 1 HP, HS Posterior transsylvian, 1/1 Thal pain Improving with thal
transinsular syndrome pain syndrome
Hemianopsia
2 bleeds
Houtteville, 1995 (31) 1 Progressive HP, HS Interhemispheric transcallosal 0/1 Asymptomatic
Severe bleed
Kobata et al., 1999 (39) 1 HP Transsylvian (large hematoma) Improved
Multiple bleeds
Lawton et al., 1996 (45) 3 1 HA Contralateral interhemispheric 3/3 None
transcallosal
2 HP, HS
All bled
Mathiesen et al., 1 HP Contralateral transcallosal 1/1 Transient worse Improved
2003 (51)d HP, mutism
Mathiesen et al., 1 Bled twice Occipital interhemispheric 1/1 Transient worse HS Improved
2003 (51)d
Subcallosal transpulvinar
Otani et al., 6 5 oculomotor def Paraculminar supracerebellar 5/6 1 transient 4 improved
2008 (62) infratentorial/transtentorial hemianopsia
4 sensorimotor def 1 transient vertical 1 same
gaze paresis
1 thal pain 1 improved after repeat
syndrome surgery for recurrence
4 bled (3 IVH) 3 independent
2 progressive def
Pannek et al., 3 Retroauricular bur hole with None
1999 (64) stereotaxy with sleeve
Pozzati, 2000 (68) 1 Thal hand, diplopia Occipital interhemispheric subsplenial 1/1 Improved
4 bleeds
Pozzati, 2000 (68)e 3 2 HCP 1 transcallosal 2/3 1 death from thal 1 asymptomatic
infarctf
1 progressive HP, HS 2 transcortical transventricular 1 same
1 dead

Continues

14 | VOLUME 65 | NUMBER 1 | JULY 2009 www.neurosurgery-online.com

 CAVERNOUS MALFORMATIONS OF THE BASAL GANGLIA AND THALAMUS

TABLE 5. Continued
Early
No. of Preoperative Resection Long-term
Series (ref. no.) Approach postoperative
patients condition rate outcome
morbidity
Roda et al., 1990 (74) 1 HP Interhemispheric 1/1 New motor aphasia, Worse
worse HP
Bled Transcallosal
Sato and Kubota, 1995 (77) 1 HA Transcortical 1/1 Asymptomatic
Transventricular
Scott et al., 1992 (78) 1 HP Transcallosal 0/1 Worse—III, VII, HP Worse, rebled
Steinberg et al., 2000 (87)g 2 Both HP 1 transcallosal 1/2 Both worse HP Both HP improved
transpulvinar to baseline
1 hemidystonia 1 interhemispheric 1 recurred
transcallosal
1 worse after SRS
Tew et al., 1995 (89) 6 4 transcortical 4 improved
2 transcallosal 1 same
1 worse
Tung et al., 1990 (92) 1 HP, seizure 1/1 Same/improved
4 episodes
Vaquero et al., 1987 (94) 1 Progressive HP, Died Died
dysphasia
Zamorano et al., 1997 (101) 1 Seizures 1/1 None

a
HP, hemiparesis; HS, hemisensory deficit; thal, thalamic; mRS, modified Rankin Scale; HA, headache; def, deficit; IVH, intraventricular hemorrhage; HCP, hydrocephalus;
SRS, stereotactic radiosurgery; III, third nerve palsy; VII, seventh nerve palsy; CM, cavernous malformation.
b
Possible damage to draining vein/developmental venous anomaly.
c
The falx was sectioned; the tentorium was not.
d
This series included a total of 13 CMs of the basal ganglia or thalamus. Our data are from detailed explanations provided for 2 thalamic cases in figure captions. Only patients
with postoperative CM rebleeding had permanent morbidity in this series. Twenty-five of 29 CMs of the basal ganglia, thalamus, or brainstem were completely resected in
this series with a 69% early morbidity rate. At a mean follow-up duration of 4.6 years, 69% of patients were improved, 10% were the same, 17% were worse (mainly from
rebleeding), and 3% were dead.
e
This series provided long-term follow-up data on patients in the earlier report of Pozzati et al. (70).
f
This lesion had an associated developmental venous anomaly.
g
This series included a total of 15 CMs of the basal ganglia or thalamus. Our data are from detailed explanations provided for 2 thalamic cases in figure captions. Fifty-two
of 56 CMs of the basal ganglia, thalamus, or brainstem were completely resected in this series with a 29% early morbidity rate. At a mean follow-up of 4.7 years, 52% of
patients were improved, 43% were the same, and 5% were worse.

TABLE 6. Radiosurgical morbidity rates among series providing data specifically on cavernous malformations of the basal ganglia and thalamusa
Early radiation- Permanent radiation-
Series (ref. no.) No. of patients Radiation source
induced morbidity induced morbidity
Amin-Hanjani et al., 1998 (4) 16 Proton beam 4/16 4/16
Kayali et al., 2004 (34) 5 LA 0/5 0/5
Hasegawa et al., 2002 (27) 13 GK 2/13 0/13
Mitchell et al., 2000 (58) 7 GK 1/7 0/7
Pollock et al., 2000 (65) 4 3/4
Stea et al., 1994 (85) 5 LA 1/5 0/5
a
LA, linear accelerator; GK, gamma knife.

ganglia and thalamus most often present with sensorimotor Across a review of 103 CMs in surgical series, 71 of 80 CMs
deficits. Other, less common presentations include headache, (89%) were documented as completely resected, 10 of 103
hydrocephalus, seizures, and extrapyramidal symptoms. patients (10%) experienced permanent, long-term morbidity

NEUROSURGERY VOLUME 65 | NUMBER 1 | JULY 2009 | 15

GROSS ET AL.
A B
FIGURE 2. A and B, after 3 successive, symptomatic hemorrhages over the
course of 1 year, these 2 thalamic CMs, lacking pial or ependymal represen-
tation, were successfully radiated at moderate dosimetry. A, after radiosur-
gical treatment with a marginal dose of 13 Gy, this small, deep thalamic CM
with a prominent, associated developmental venous anomaly did not demon-
strate any further bleeding at 2 years’ follow-up. B, after treatment with 20
from surgery, and 2 of 103 patients (1.9%) died as a result of
surgery. These impressive morbidity rates are from experienced
neurosurgeons operating on primarily symptomatic CMs,
thereby having “less to lose.”
Radiosurgery is only an option at modest dosimetry (12–14
Gy) for surgically inaccessible, aggressive CMs. An approxi-
mate 14% risk of permanent morbidity from radiation must be
further compounded to morbidity from rebleeding after radio-
surgery, although rebleeding rates seem to decrease, particu-
larly 2 years after treatment.
Disclosure
The authors have no personal financial or institutional interest in any of the
drugs, materials, or devices described in this article.
REFERENCES
1. Aiba T, Tanaka R, Koike T, Kameyama S, Takeda N, Komata T: Natural his-
tory of intracranial cavernous malformations. J Neurosurg 83:56–59, 1995.
2. Akbostanci MC, Yiğit A, Ulkatan S: Cavernous angioma presenting with
hemidystonia. Clin Neurol Neurosurg 100:234–237, 1998.
3. Alves de Sousa A: Deep-seated (corpus callosum, intraventricular, basal
ganglia and insula) and brain stem cavernous angiomas. Experience in Brazil
[in French]. Neurochirurgie 53:182–191, 2007.
4. Amin-Hanjani S, Ogilvy CS, Candia GJ, Lyons S, Chapman PH: Stereotactic
radiosurgery for cavernous malformations: Kjellberg’s experience with pro-
16 | VOLUME 65 | NUMBER 1 | JULY 2009
Gy in 5 hypofractionated doses (equivalent single marginal dose of approx-
imately 12 Gy), this large CM did not demonstrate any further bleeding at
the time of the 3-year follow-up evaluation. Fractionated radiosurgery was
used to limit radiation exposure to the hypothalamus and optic pathways.
Both patients demonstrated near-complete recovery at the time of the most
recent follow-up evaluation.
ton beam therapy in 98 cases at the Harvard Cyclotron. Neurosurgery
42:1229–1238, 1998.
5. Attar A, Ugur HC, Savas A, Yüceer N, Egemen N: Surgical treatment of
intracranial cavernous angiomas. J Clin Neurosci 8:235–239, 2001.
6. Barker FG 2nd, Amin-Hanjani S, Butler WE, Lyons S, Ojemann RG,
Chap man PH, Ogilvy CS: Temporal clustering of hemorrhages from
untreated cavernous malformations of the central nervous system.
Neurosurgery 49:15–25, 2001.
7. Becker DH, Townsend JJ, Kramer RA, Newton TH: Occult cerebrovascular
malformations. A series of 18 histologically verified cases with negative
angiography. Brain 102:249–287, 1979.
8. Bertalanffy H, Benes L, Miyazawa T, Alberti O, Siegel AM, Sure U: Cerebral
cavernomas in the adult. Review of the literature and analysis of 72 surgi-
cally treated patients. Neurosurg Rev 25:1–55, 2002.
9. Bertalanffy H, Gilsbach JM, Eggert HR, Seeger W: Microsurgery of deep-
seated cavernous angiomas: Report of 26 cases. Acta Neurochir (Wien)
108:91–99, 1991.
10. Bicknell JM, Carlow TJ, Kornfeld M, Stovring J, Turner P: Familial cavernous
angiomas. Arch Neurol 35:746–749, 1978.
11. Cantu C, Murillo-Bonilla L, Arauz A, Higuera J, Padilla J, Barinagar-
rementeria F: Predictive factors for intracerebral hemorrhage in patients
with cavernous angiomas. Neurol Res 27:314–318, 2005.
12. Cappabianca P, Spaziante R, de Divitiis E, Villanacci R: Thalamic cavernous
malformations. J Neurosurg 75:169–171, 1991.
13. Carpay HA, Arts WF, Kloet A, Hoogland PH, Van Duinen SG: Hemichorea
reversible after operation in a boy with cavernous angioma in the head of
caudate nucleus. J Neurol Neurosurg Psychiatry 57:1547–1548, 1994.
14. Carton CA, Hickey WC: Arteriovenous malformation of the head of the
caudate nucleus; report of a case with total removal. J Neurosurg 12:414–418,
1955.
www.neurosurgery-online.com
 CAVERNOUS MALFORMATIONS OF THE BASAL GANGLIA AND THALAMUS
15. Chang SD, Levy RP, Adler JR Jr, Martin DP, Krakovitz PR, Steinberg GK:
Stereotactic radiosurgery of angiographically occult vascular malformations:
14-year experience. Neurosurgery 43:213–221, 1998.
16. Chi JH, Lawton MT: Posterior interhemispheric approach: Surgical tech-
nique, application to vascular lesions, and benefits of gravity retraction.
Neurosurgery 59 [Suppl 1]:ONS41–ONS49, 2006.
17. Clatterbuck RE, Moriarity JL, Elmaci I, Lee RR, Breiter SN, Rigamonti D:
Dynamic nature of cavernous malformations: A prospective magnetic reso-
nance imaging study with volumetric analysis. J Neurosurg 93:981–986,
2000.
18. Coenen VA, Huber KK, Krings T, Weidemann J, Gilsbach JM, Rohde V:
Diffusion-weighted imaging-guided resection of intracerebral lesions involv-
ing the optic radiation. Neurosurg Rev 28:188–195, 2005.
19. Cohen HC, Tucker WS, Humphreys RP, Perrin RJ: Angiographically cryptic
histologically verified cerebrovascular malformations. Neurosurgery 10:704–
714, 1982.
20. Di Rocco C, Iannelli A, Tamburrini G: Cavernomas of the central nervous
system in children. A report of 22 cases. Acta Neurochir (Wien) 138:1267–
1274, 1996.
21. Donmez B, Cakmur R, Uysal U, Men S: Putaminal cavernous angioma pre-
senting with hemichorea. Mov Disord 19:1379–1380, 2004.
22. Duffau H: Intraoperative direct subcortical stimulation for identification of
the internal capsule, combined with an image-guided stereotactic system
during surgery for basal ganglia lesions. Surg Neurol 53:250–254, 2000.
23. Ertan S, Benbir G, Tanriverdi T, Alver I, Uzan M: Parkinsonism caused by
cavernoma located in the basal ganglion. Parkinsonism Relat Disord
11:517–519, 2005.
24. Frim DM, Scott RM: Management of cavernous malformations in the pedi-
atric population. Neurosurg Clin N Am 10:513–518, 1999.
25. García-Muñoz L, Velasco-Campos F, Lujan-Castilla P, Enriquez-Barrera M,
Cervantes-Martínez A, Carrillo-Ruiz J: Radiosurgery in the treatment of
brain cavernomas. Experience with 17 lesions treated in 15 patients [in
French]. Neurochirurgie 53:243–250, 2007.
26. Garner TB, Del Curling O Jr, Kelly DL Jr, Laster DW: The natural history of
intracranial venous angiomas. J Neurosurg 75:715–722, 1991.
27. Hasegawa T, McInerney J, Kondziolka D, Lee JY, Flickinger JC, Lunsford LD:
Long-term results after stereotactic radiosurgery for patients with cavernous
malformations. Neurosurgery 50:1190–1198, 2002.
28. Hashimoto H, Sakaki T, Ishida Y, Shimokawara T: Fetal cavernous
angioma—Case report. Neurol Med Chir (Tokyo) 37:346–349, 1997.
29. Heffez DS: Stereotactic transsylvian transinsular approach for deep-seated
lesions. Surg Neurol 48:113–124, 1997.
30. Hidaka M, Shimoda M, Sato O, Watabe T, Tsugane R, Ohsuga H, Araki G:
Case report: Hemiballism due to a putaminal cavernous hemangioma [in
Japanese]. No To Shinkei 41:1135–1139, 1989.
31. Houtteville JP: The surgery of cavernomas both supra-tentorial and infra-
tentorial. Adv Tech Stand Neurosurg 22:185–259, 1995.
32. Huang YC, Tseng CK, Chang CN, Wei KC, Liao CC, Hsu PW: LINAC radio-
surgery for intracranial cavernous malformation: 10-year experience. Clin
Neurol Neurosurg 108:750–756, 2006.
33. Karlsson B, Kihlström L, Lindquist C, Ericson K, Steiner L: Radiosurgery for
cavernous malformations. J Neurosurg 88:293–297, 1998.
34. Kayali H, Sait S, Serdar K, Kaan O, Ilker S, Erdener T: Intracranial caver-
nomas: analysis of 37 cases and literature review. Neurol India 52:439–442,
2004.
35. Kerchner GA, Smith W, Lawton MT, Singh V: Co-occurrence of a cavernous
malformation and contralateral moyamoya. Neurology 66:1601–1602, 2006.
36. Kida Y, Kobayashi T, Mori Y: Radiosurgery of angiographically occult vas-
cular malformations. Neurosurg Clin N Am 10:291–303, 1999.
37. Kim DS, Park YG, Choi JU, Chung SS, Lee KC: An analysis of the natural his-
tory of cavernous malformations. Surg Neurol 48:9–18, 1997.
38. Kim MS, Pyo SY, Jeong YG, Lee SI, Jung YT, Sim JH: Gamma knife surgery
for intracranial cavernous hemangioma. J Neurosurg 102 [Suppl]:102–106,
2005.
NEUROSURGERY
39. Kobata H, Kondo A, Iwasaki K, Hattori I: Massive subependymal hemor-
rhage caused by an occult vascular malformation—Two case reports. Neurol
Med Chir (Tokyo) 39:302–307, 1999.
40. Kon T, Mori H, Hasegawa K, Nishiyama K, Tanaka R, Takahashi H:
Neonatal cavernous angioma located in the basal ganglia with profuse intra-
operative bleeding. Childs Nerv Syst 23:449–453, 2007.
41. Kondziolka D, Lunsford LD, Kestle JR: The natural history of cerebral cav-
ernous malformations. J Neurosurg 83:820–824, 1995.
42. Koukkari MW, Vanefsky MA, Steinberg GK, Hahn JS: Phenytoin-related
chorea in children with deep hemispheric vascular malformations. J Child
Neurol 11:490–491, 1996.
43. Labauge P, Brunereau L, Lévy C, Laberge S, Houtteville JP: The natural his-
tory of familial cerebral cavernomas: A retrospective MRI study of 40
patients. Neuroradiology 42:327–332, 2000.
44. Lanzino G, Wanebo JE, Spetzler RF: Contralateral interhemispheric resection
of thalamic cavernous malformations with frameless stereotaxy. Oper Tech
Neurosurg 5:191–197, 2002.
45. Lawton MT, Golfinos JG, Spetzler RF: The contralateral transcallosal
approach: Experience with 32 patients. Neurosurgery 39:729–735, 1996.
46. Little JR, Awad IA, Jones SC, Ebrahim ZY: Vascular pressures and cortical
blood flow in cavernous angioma of the brain. J Neurosurg 73:555–559, 1990.
47. Liu KD, Chung WY, Wu HM, Shiau CY, Wang LW, Guo WY, Pan DH:
Gamma knife surgery for cavernous hemangiomas: An analysis of 125
patients. J Neurosurg 102 [Suppl]:81–86, 2005.
48. Lobato RD, Perez C, Rivas JJ, Cordobes F: Clinical, radiological, and patho-
logical spectrum of angiographically occult intracranial vascular malforma-
tions. Analysis of 21 cases and review of the literature. J Neurosurg
68:518–531, 1988.
49. Lorenzana L, Cabezudo JM, Porras LF, Polaina M, Rodriguez-Sanchez JA,
Garcia-Yagüe LM: Focal dystonia secondary to cavernous angioma of the
basal ganglia: Case report and review of the literature. Neurosurgery
31:1108–1112, 1992.
50. Mao Y, Zhou L, Du G, Chen L: Image-guided resection of cerebral cavernous
malformations. Chin Med J (Engl) 116:1480–1483, 2003.
51. Mathiesen T, Edner G, Kihlström L: Deep and brainstem cavernomas: A
consecutive 8-year series. J Neurosurg 99:31–37, 2003.
52. Matz P, McDermott M, Gutin P, Dillon W, Wilson C: Cavernous malforma-
tions: Results of image-guided resection. J Image Guid Surg 1:273–279, 1995.
53. Mazza C, Scienza R, Beltramello A, Da Pian R: Cerebral cavernous malfor-
mations (cavernomas) in the pediatric age-group. Childs Nerv Syst
7:139–146, 1991.
54. McCormick WF: The pathology of vascular (“arteriovenous”) malforma-
tions. J Neurosurg 24:807–816, 1966.
55. McCormick WF, Nofzinger JD: “Cryptic” vascular malformations of the cen-
tral nervous system. J Neurosurg 24:865–875, 1966.
56. McLaughlin MR, Kondziolka D, Flickinger JC, Lunsford S, Lunsford LD: The
prospective natural history of cerebral venous malformations. Neurosurgery
43:195–201, 1998.
57. Mehdorn HM, Barth H, Buhl R, Nabavi A, Weinert D: Intracranial caver-
nomas: Indications for and results of surgery. Neurol Med Chir Suppl
(Tokyo) 38:245–249, 1998.
58. Mitchell P, Hodgson TJ, Seaman S, Kemeny AA, Forster DM: Stereotactic
radiosurgery and the risk of haemorrhage from cavernous malformations. Br
J Neurosurg 14:96–100, 2000.
59. Moriarity JL, Wetzel M, Clatterbuck RE, Javedan S, Sheppard JM, Hoenig-
Rigamonti K, Crone NE, Breiter SN, Lee RR, Rigamonti D: The natural his-
tory of cavernous malformations. A prospective study of 68 patients.
Neurosurgery 44:1166–1173, 1999.
60. Mottolese C, Hermier M, Stan H, Jouvet A, Saint-Pierre G, Froment JC, Bret
P, Lapras C: Central nervous system cavernomas in the pediatric age group.
Neurosurg Rev 24:55–73, 2001.
61. Naff NJ, Wemmer J, Hoenig-Rigamonti K, Rigamonti DR: A longitudinal
study of patients with venous malformations: Documentation of a negligible
hemorrhage risk and benign natural history. Neurology 50:1709–1714, 1998.
62. Otani N, Fujioka M, Oracioglu B, Muroi C, Khan N, Roth P, Yonekawa Y:
Thalamic cavernous angioma: Paraculminar supracerebellar infratentorial
VOLUME 65 | NUMBER 1 | JULY 2009 | 17
GROSS ET AL.
transtentorial approach for the safe and complete surgical removal. Acta
Neurochir Suppl 103:29–36, 2008.
63. Otten P, Pizzolato GP, Rilliet B, Berney J: 131 cases of cavernous angiomas
(cavernomas) of the CNS, discovered by a retrospective analysis of 24,535
autopsies [in French]. Neurochirurgie 35:82–83, 128–131, 1989.
64. Pannek HW, Oppel F: Minimally invasive lesionectomies through a stereo-
tactically guided working sleeve. Neurol Res 21:51–59, 1999.
65. Pollock BE, Garces YI, Stafford SL, Foote RL, Schomberg PJ, Link MJ:
Stereotactic radiosurgery for cavernous malformations. J Neurosurg
93:987–991, 2000.
66. Porter RW, Detwiler PW, Spetzler RF, Lawton MT, Baskin JJ, Derksen PT,
Zabramski JM: Cavernous malformations of the brainstem: Experience with
100 patients. J Neurosurg 90:50–58, 1999.
67. Porter PJ, Willinsky RA, Harper W, Wallace MC: Cerebral cavernous malfor-
mations: Natural history and prognosis after clinical deterioration with or
without hemorrhage. J Neurosurg 87:190–197, 1997.
68. Pozzati E: Thalamic cavernous malformations. Surg Neurol 53:30–40, 2000.
69. Pozzati E, Acciarri N, Tognetti F, Marliani F, Giangaspero F: Growth, subse-
quent bleeding, and de novo appearance of cerebral cavernous angiomas.
Neurosurgery 38:662–670, 1996.
70. Pozzati E, Gaist G, Poppi M, Morrone B, Padovani R: Microsurgical removal
of paraventricular cavernous angiomas. J Neurosurg 55:308–311, 1981.
71. Robinson JR, Spetzler RF: An analysis of the natural history of cavernous
malformations. Surg Neurol 48:17–18, 1997 (comment).
72. Robinson JR, Awad IA, Little JR: Natural history of the cavernous angioma.
J Neurosurg 75:709–714, 1991.
73. Roda JM, Alvarez F, Isla A: Thalamic cavernous malformations. J Neurosurg
75:169–170, 1991 (letter).
74. Roda JM, Alvarez F, Isla A, Blázquez MG: Thalamic cavernous malforma-
tion: Case report. J Neurosurg 72:647–649, 1990.
75. Rothbart D, Awad IA, Lee J, Kim J, Harbaugh R, Criscuolo GR: Expression
of angiogenic factors and structural proteins in central nervous system vas-
cular malformations. Neurosurgery 38:915–925, 1996.
76. Sarwar M, McCormick WF: Intracerebral venous angioma. Case report and
review. Arch Neurol 35:323–325, 1978.
77. Sato K, Kubota T: Large calcified cystic cavernous angioma in the thala-
mus—Case report. Neurol Med Chir (Tokyo) 35:100–103, 1995.
78. Scott RM, Barnes P, Kupsky W, Adelman LS: Cavernous angiomas of the
central nervous system in children. J Neurosurg 76:38–46, 1992.
79. Senegor M, Dohrmann GJ, Wollmann RL: Venous angiomas of the posterior
fossa should be considered as anomalous venous drainage. Surg Neurol
19:26–32, 1983.
80. Seo Y, Fukuoka S, Takanashi M, Nakagawara J, Suematsu K, Nakamura J,
Nagashima K: Gamma knife surgery for angiographically occult vascular
malformations. Stereotact Funct Neurosurg 64 [Suppl 1]:98–109, 1995.
81. Shucart WA, Stein BM: Transcallosal approach to the anterior ventricular
system. Neurosurgery 3:339–343, 1978.
82. Simard JM, Garcia-Bengochea F, Ballinger WE Jr, Mickle JP, Quisling RG:
Cavernous angioma: A review of 126 collected and 12 new clinical cases.
Neurosurgery 18:162–172, 1986.
83. Stacey RJ, Ashkan K, Edwards JM: Rapid growth in a cavernoma. Br J
Neurosurg 14:585–588, 2000.
84. Stapf C, Mast H, Sciacca RR, Choi JH, Khaw AV, Connolly ES, Pile-Spellman
J, Mohr JP: Predictors of hemorrhage in patients with untreated brain arte-
riovenous malformation. Neurology 66:1350–1355, 2006.
85. Stea RA, Schicker L, King GA, Winfield JA: Stereotactic linear radiosurgery
for cavernous angiomas. Stereotact Funct Neurosurg 63:255–265, 1994.
86. Steiger HJ, Markwalder TM, Reulen HJ: Clinicopathological relations of cere-
bral angiomas: Observations in eleven cases. Neurosurgery 21:879–884, 1987.
87. Steinberg GK, Chang SD, Gewirtz RJ, Lopez JR: Microsurgical resection of
brainstem, thalamic and basal ganglia angiographically occult vascular mal-
formations. Neurosurgery 46:260–271, 2000.
88. St George EJ, Perks J, Plowman PN: Stereotactic radiosurgery XIV: The role
of the haemosiderin ‘ring’ in the development of adverse reactions follow-
ing radiosurgery for intracranial cavernous malformations: A sustainable
hypothesis. Br J Neurosurg 16:385–391, 2002.
18 | VOLUME 65 | NUMBER 1 | JULY 2009
89. Tew JM Jr, Lewis AI, Reichert KW: Management strategies and surgical
techniques for deep-seated supratentorial arteriovenous malformations.
Neurosurgery 36:1065–1072, 1995.
90. Thobois S, Jouanneau E, Bouvard M, Sindou M: Obsessive-compulsive dis-
order after unilateral caudate nucleus bleeding. Acta Neurochir (Wien)
146:1027–1031, 2004.
91. Tomlinson FH, Houser OW, Scheithauer BW, Sundt TM Jr, Okazaki H, Parisi
JE: Angiographically occult vascular malformations: A correlative study of
features on magnetic resonance imaging and histological examination.
Neurosurgery 34:792–800, 1994.
92. Tung H, Giannotta SL, Chandrasoma PT, Zee CS: Recurrent intraparenchy-
mal hemorrhages from angiographically occult vascular malformations.
J Neurosurg 73:174–180, 1990.
93. Deleted in proof.
94. Vaquero J, Salazar J, Martínez R, Martínez P, Bravo G: Cavernomas of the cen-
tral nervous system: Clinical syndromes, CT scan diagnosis, and prognosis
after surgical treatment in 25 cases. Acta Neurochir (Wien) 85:29–33, 1987.
95. Voigt K, Yaşargil MG: Cerebral cavernous haemangiomas or cavernomas.
Incidence, pathology, localization, diagnosis, clinical features and treatment.
Review of the literature and report of an unusual case. Neurochirurgia
19:59–68, 1976.
96. Waga S: Surgical treatment of arteriovenous malformations in the lateral
ventricle. Neurol Res 8:18–24, 1986.
97. Wilson CB: Cryptic vascular malformations. Clin Neurosurg 38:49–84, 1992.
98. Winkler D, Lindner D, Strauss G, Richter A, Schober R, Meixensberger J:
Surgery of cavernous malformations with and without navigational sup-
port—A comparative study. Minim Invasive Neurosurg 49:15–19, 2006.
99. Yakinci C, Durmaz Y, Korkut M, Aladag A, Onal C, Aydinli M: Cavernous
hemangioma in a child presenting with hemichorea: Response to pimozide.
J Child Neurol 16:685–688, 2001.
100. Yamasaki T, Handa H, Yamashita J, Paine JT, Tashiro Y, Uno A, Ishikawa M,
Asato R: Intracranial and orbital cavernous angiomas. A review of 30 cases.
J Neurosurg 64:197–208, 1986.
101. Zamorano L, Matter A, Saenz A, Buciuc R, Diaz F: Interactive image-guided
resection of cerebral cavernous malformations. Comput Aided Surg
2:327–332, 1997.
102. Zhao J, Wang Y, Kang S, Wang S, Wang J, Wang R, Zhao Y: The benefit of
neuronavigation for the treatment of patients with intracerebral cavernous
malformations. Neurosurg Rev 30:313–319, 2007.
COMMENTS
T his research article is important. Gross et al. have not only dis-
cussed their own experience within the difficult field of cavernous
malformations of the basal ganglia and thalamus but have researched
the available literature and have drawn some conclusions. The review
is an excellent condensed summary formulated from the collection of
literature published in French and English during the past 38 years.
The findings of this study are what neurosurgeons involved in this
specialized area need to know.
Albino Bricolo
Verona, Italy
T
he outcome of management of cavernous malformations is still less
then optimal. On the other hand, they are relatively rare, and only
a multicenter study can provide any statistically sound data. Despite
the limitations of a meta-analysis, it is currently the best option avail-
able. This is an extensive and very well-written meta-analysis of the
natural history and surgical and radiosurgical management of cav-
ernous malformations of the basal ganglia and thalamus.
The natural history, clinical presentation, and surgical treatment,
including the alternative operative approaches, are discussed in detail.
Published data showed that in natural history studies, the annual
bleeding rates for these lesions was found to vary from 2.8% to 4.1%.
www.neurosurgery-online.com
 CAVERNOUS MALFORMATIONS OF THE BASAL GANGLIA AND THALAMUS
Surgical series provided outcome data on 103 patients; the resection
rate was 89%, the risk of long-term surgical morbidity was 10%, and
the risk of surgical mortality was 1.9%. After radiosurgery, the risk of
hemorrhage declines in 2 years; however, it remains an option for
patients with surgically inaccessible, aggressive lesions.
Venelin M. Gerganov
Madjid Samii
Hannover, Germany
T his literature review is an excellent analysis of the current knowl-
edge base regarding cavernous malformations of the basal ganglia
and thalamus. These lesions are so rare that the only method for under-
standing their natural history and treatment options is to pool the
available clinical information. I completely agree with the conclusions
of this study.
However, as the authors note, several biases are introduced in this
type of report and should be highlighted. Most of the lesions reported
in the literature will have presented with significant symptoms and/or
hemorrhage. Therefore, natural history information might not be rele-
vant for incidental or minimally symptomatic lesions. Similarly, the
surgical outcome data carry a publication bias, i.e., from surgeons with
extensive experience and relatively good outcomes. As well, for the
most part, surgeons have only performed resection on malformations
in these critical areas in patients with significant neurological deficits,
and the potential morbidity for a minimally symptomatic patient is
vastly underestimated.
I have been very reluctant to operate on patients with cavernous
malformations in the basal ganglia, thalamus, internal capsule, and
brainstem unless there is a clear path of progressive and devastating
neurological decline. The great majority of patients who present with
acute symptoms from these lesions will make a complete or near-com-
plete recovery with conservative management and will not have recur-
rent problems.
Robert A. Solomon
New York, New York
T he Northwestern University group presents their review of out-
comes related to various modalities for management of cavernous
malformations of the basal ganglia and thalamus. They emphasize sev-
eral points that we fully agree with: 1) only patients with 2 or more
bleeding events (documented by new neurological signs or symptoms
and imaging confirmation of new blood products) warrant considera-
tion of a surgical or radiosurgical strategy; 2) malformations that pres-
ent on a pial or ependymal surface are more amenable to surgical
approaches with less risk. The morbidity of removal of a cavernous
malformation that is located in an area of deep or critical brain function
NEUROSURGERY
does not lie in the actual removal. The morbidity lies in the access cor-
ridor necessary to reach the cavernous malformation. Lesions that pres-
ent on pial or ependymal surfaces are more amenable to surgical extir-
pation because the access to the “real estate” is less morbid; 3)
radiosurgical management is an option for those patients who have
high-risk cavernous malformations with 2 or more bleeding episodes
and who do not have a reasonable surgical corridor that can be used by
experienced surgeons working in a center of excellence. In our experi-
ence of 102 solitary cavernous malformations located in deep areas of
critical brain function, the risk of bleeding in that group of patients
decreases from 32% per year (after 2 prior bleeds) to 1% per year or less
after a latency interval of 2 years.
I believe that the doses described in this report are not correct. Doses
vary, but it is unlikely that marginal doses of 12 Gy are therapeutic. We
believe that doses in the range of 13 to 16 Gy at the edge are more likely
to be effective. However, dose at the edge is only 1 factor. Highly con-
formal and selective radiosurgery is critical. Modalities that are unable
to provide this degree of sharp dose falloff or selectivity in areas of crit-
ical brain function are much more likely to sustain radiosurgically
related morbidity. This is in part related to the hemosiderin stain sur-
rounding brain (well seen on T2-weighted magnetic resonance imaging
and dramatic on a gradient series which detects blood pigment).
Because this iron-sensitized brain is more likely to be affected by radio-
surgical doses, we have emphasized radiosurgical dose conformality.
Patients with multiple cavernous malformations, again, should be
observed. Only those lesions that have had more than 2 bleeding events
should be considered for some form of surgical or radiosurgical man-
agement. Clustering of bleeding events from a cavernous malformation
has been hypothesized, as noted within this article. However, this tem-
poral clustering phenomenon appears to be noted only in small series
and has not been verified in our experience (1, 2).
We believe that this report provides additional data that support
several options for cavernous malformation management. Perhaps a
multicenter trial would be feasible. Patients with 2 or more bleeds
could be randomized to observation or radiosurgery, provided that a
microsurgical option is declined by the patient or is not feasible. Such
a prospective study might be performed by centers participating in
the North American Gamma Knife Consortium.
L. Dade Lunsford
Pittsburgh, Pennsylvania
1. Hasegawa T, McInerney J, Kondziolka D, Lee JYK, Flickinger JC, Lunsford LD:
Long-term results after stereotactic radiosurgery for patients with cavernous
malformations. Neurosurgery 50:1190–1198, 2002.
2. Kondziolka D, Lunsford LD, Kestle JRW: The natural history of cerebral cav-
ernous malformations. J Neurosurg 83:820–824, 1995.
VOLUME 65 | NUMBER 1 | JULY 2009 | 19