Cavernous Malformations Presenting with Seizures:

Therapeutic Options and Outcome

Kris A. S m i t h , M D , S a m J a v e d a n ,

MD, Joseph

M. Zabramski,

M D , D a v i d E. B l u m , M D , a n d

R o b e r t F. S p e t z l e r , M D

Controversies exist regarding the appropriate initial management

of patients with cavernous malformations associated with a
seizure disorder. We retrospectively reviewed our experience
with simple lesionectomy in the treatment of 82 patients with
supratentorial cortical cavernous malformations who presented
with seizures. Fifty-five patients had adequate follow up (at least
1 year; mean, 52 months) to assess outcome related to seizure
control. Forty (73%)patients had single and 15 (27%) had
multiple cavernous malformations. Eighteen (33%) patients underwent surgery within the first 2 months of their initial seizure.
Thirty-seven (67%) patients had seizures for more than 6 months
before their lesionectomy. All patients were treated with lesionectomy alone as their initial management. Outcomes were
evaluated based on Engel's criteria. Seizure outcome was based
on the number of seizures pre- and postoperatively, lesion location, and number of lesions. Of the 55 patients with adequate
follow up, 69% were seizure free (grade 1) and 13% were almost
seizure free (grade II). All 18 patients who were operated on
within 2 months of their initial seizure have remained seizure free.
Of the patients with chronic epilepsy before surgery, 57% are
seizure free, and 17% are almost seizure free. Patients with
multiple cavernous malformations and well-localized seizure activity on preoperative testing responded well to lesionectomy.
Lesion location was not significant in predicting seizure outcome
after surgery. Lesionectomy is a valuable treatment for patients
with cavernous malformations associated with epilepsy and represents the best initial treatment option. Patients with chronic
epilepsy who fail to become seizure free after lesionectomy may
require further epilepsy monitoring and resection. Initial lesionectomy, however, will avoid unnecessary epilepsy surgery in most
of these patients.
Copyright 2002, Elsevier Science (USA). All rights reserved.

n clinical studies, 34 to 81% of patients with cavernous

I malformations present with seizures. >~2 Because the risk of

hemorrhage is small in patients who present with seizures (less
than 1%/lesion/yr), 2,1~ some authors question the need to treat
lesions in this population surgically unless their epilepsy cannot be controlled with medications. 2,5 However, numerous reports document improved seizure control after the removal of
cavernous malformations "lesionectomy" in patients with epilepsy. 1.3.4,6,8-1o.13-15

From the Divisions of Neurological Surgery and Neurology, Barrow

Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ
Address reprint requests to Kris A. Smith, MD, c/o Neuroscience
Publications; Barrow Neurological Institute, 350 West Thomas Road;
Phoenix, AZ 85013-4496; neuropub@chw.edu
Copyright 2002, Elsevier Science (USA). All rights reserved.
doi:l 0.1053/otns.2002.32483

In patients with epilepsy, health-related quality of life is most

closely related to degree of seizure control. ~6 Surgery should
maximize seizure control while minimizing the risks of the
procedure. Lesion location may be a critical factor in determining which lesions are best treated by lesionectomy rather than
by more aggressive epilepsy operations. 6,z3a7 Cavernous malformations in the temporal lobe may kindle seizure loci in
nearby limbic structures and thus reqmre a more aggressive
surgical approach. 4,~Ba7 Because lesionectomy is less likely to
be successful at seizure control when there is "dual pathology, "2-~8it is important to rule out other causes of seizures (i.e.,
coexistence of mesial temporal sclerosis) before recommending
a procedure:
In this study, we reviewed our experience with lesionectomy
for seizure control in pauents with supratentorial cavernous
malformations. 19-22

Methods
The clinical records of all patients who underwent resection of
supratentorial cavernous malformations at the authors' institution between 1984 and 1998 were retrospectively reviewed. We
identified 82 patients who underwent resection lesionectomy
of a supratentorial cortical cavernous malformation associated
with at least one preoperative seizure. Of these 82 patients, 55
(22 males and 23 females) had adequate follow up (more than
1 year; median, 45 months; mean, 52 months) to assess outcome related to seizure control. All patients had histopathologically confirmed cavernous malformations. Their mean age and
median age were 30 and 32 years, respectively (range, 1 to 67
years).
The location of all resected lesions was recorded to assess
differences in outcome. Two patients had lesions in the occipital lobe, 12 had lesions in the parietal lobe, 17 had lesions in
the temporal lobe, and 24 had lesions in the frontal lobe.
Of the 55 patients, 40 (73%) had single cavernous malformations and 15 (27%) had more than one lesion. Eighteen (33%)
patients presented with a acute history of new seizures onset
and underwent surgery within 2 months of their first seizure.
Thirty-seven (67%) patients had more than a 6-month history
of seizures before undergoing resection. No patients fell between these two categories. Overall, patients had experienced
seizures before surgery for a mean of 72 months (median, 12
months; range, 1 to 576 months).
Initially, all patients underwent simple lesionectomy of their
cavernous malformation without extra-lesional cortical resection or any attempt at electrocorticography (ECoG) to guide
the resection. Hemosiderin-stained cortex adjacent to the lesion was removed although such tissue was removed more
judiciously in eloquent locations. The value of removing all

Operative Techniques in Neurosurgery, Vol 5, No 3 (September), 2002: pp 161-165

161

TABLE 1. Engers Classification of Postoperative

Outcome

TABLE 3. Outcome of Lesionectomy as a Function of

Number of Cavernous Malformations

Class

Description

No. lesions

Class I

Class II

Class III

Class IV

I
II
III
IV

Free of disabling seizures*

Rare disabling seizures "almost seizure-free"
Worthwhile improvement-iNo worthwhile improvement1-

1
>1

29
10

5
1

3
2

3
2

*Excludes early postoperative seizures (first few weeks).

-i-Determination of "worthwhile improvement" will require quantitative
analyses of additional data such as percent seizure reduction, cognitive
function, and quality of life.
Modified from Engel J Jr: Surgical Treatment of the Epilepsies, 2nd
edition, New York, Raven Press, 1993. With permission from LippincottRaven.

hemosiderin-stained tissue is unclear. 23 Since 1992, all cases

have been performed with the assistance of frameless stereotactic guidance. The goal has been to minimize the size of the
craniotomy directly over the lesion and to operate through
cortical incisions that were as small as possible while safely and
completely resecting the entire lesion. When possible, the lesion was resected through an approach using an adjacent or
overlying sulcus to minimize cortical trauma.
Clinical follow up of seizure control was obtained by reviewing the office charts of the treating neurosurgeons and referring
neurologists. Phone interviews with patients and family members were conducted to determine the patients' status in terms
of seizure occurrence and anticonvulsant medication usage, if
any. Seizure outcomes were categorized according to Engel's
criteria (Table 1).24 Outcomes based on chronicity of epilepsy,
number of lesions, and lesion location were subjected to twosided chi-square analysis.

patients who presented with one or two seizures and were

operated on within 2 months of presentation were seizure-free
at last follow up (Table 2). One had seizures in the initial
postoperative period but now has rare auras 'only. Only two
patients remain on antiepileptic medications. Of the 37 patients
with chronic epilepsy ( > 6 months) before lesionectomy, 21
(57%) were grade 1, 6 (17%) were grade 2, 5 (14%) were grade
3, and 5 (14%) were grade 4 after surgery.
Of the 5 patients who failed lesionectomy (Engel grade 4),
one required subdural grid mapping and underwent further
epilepsy surgery and had a good outcome. One patient remained seizure-free for 10 years after a lesionectomy of a right
temporal malformation only to become symptomatic from a
new lesion that developed in the left frontal Rolandic area. She
continues to have focal motor seizures after lesionectomy of the
second malformation. The remaining three patientg continue to
be treated medically. There were no significant differences in
outcome as a function of number of malformations (P =
0.7508, Table 3). Nor did outcome differ significantly (P =
0.4855) as a function of lesion location (Table 4) although
patients with temporal and parietal lesions tended to have less
favorable outcomes than patients with frontal or occipital lesions.

Discussion

Results
Of the 55 patients available for follow up, 38 (69%) were seizure-free (grade 1), 7 (13%)Were almost seizure-free (grade 2),
5 (9%) improved (grade 3), and 5 (9%) were unchanged (grade
4) after surgery (Table 2). No patients died in the perioperative
period, and no major perioperative complications such as reoperation for hematoma or infection were encountered. One patient required reoperadon after the lesion Could not be localized
at the initial surgery.
The difference in outcome between patients with acute and
chronic epilepsy was statistically significant (P < 0.01). All 18

TABLE 2. Seizure Outcome after Lesionectomy in 55

Patients:
Outcomes

No. (%)

All patients
Seizure-free (Engel 1)
Rare seizures (Engel 2)
Improved: frequency (Engel 3)
No improvement (Engel 4)
Sporadic seizures*
Seizure:free
Off antiepileptic drugs
Chronic epi!epsyl
Seizure~free
Rare seiZure
improved'frequency
No improvement
* = <2' months before Surgery, 18 patients;
1 = >6,rnohths before surgery, 37 patients.

162

38 (69)
7 (13)
5 (9)
5 (9)
18 (100)
16 (89)
21
6
5
5

(57)
(17)
(14)
(14)

Although cavernous ,malformations often manifest with seizures, their natural history is not well established. Recent articles have focused primarily on mode of presentation, the risk ot
hemorrhage, and subsequent complications associated with
cavernous malformations as diagnosed by MRI. 2,r,~I Some authors have differentiated between the risks of future hemorrhage in patients whose lesions manifest with hemorrhagic
events and those who present with seizures or whose lesions are
discovered incidentally. 2,5,r The risk of hemorrhage in the
former group appears to be substantially higher than in the
latter two groups, at least in the first year or tWO after hemorrhage. 2,5,r Moriarty and coworkers 25 found that the overall annual risk of seizures was 4.8%/patient-year and 2.4%/patientyear in patients with no previous history of seizures at
presentation.
Several articles on the management of cavernous malformations associated with seizures have been published. 1,3-6,8-1~
The extent of surgical resection needed to afford the best
chance of curing epilepsy caused by cavernous malformations

TABLE 4. Outcome of Lesionectomy as a Function of

Lesion Location in 55 Patients
Location

Class I

Class II

Class III

Class IV

Frontal
Temporal
Parietal
Occipital

20
10
6
2

3
2
2
0

0
3
2
0

1
2
2
0

SMITH ET AL

Fig 1. (A) T2-weighted coronal and Tl-weighted (B) coronal and (C) sagittal enhanced magnetic resonance (MR) images of a
frontal cavernous malformation in a 17-year-old girl who presented with a secondarily generalized seizure. The patient also
had a large posterior fossa cavernous malformation as seen in (D) coronal T2-weighted and (E) Tl-weighted (MR) images, Both
lesions were treated under a single anesthetic using frameless stereotactic microsurgery, The patient has remained
seizure-free and neurologically normal and needed no anticonvulsant medications at a 4-year follow up,

is controversial. Some authors propose that in most cases simple lesionectomy is effective and associated with less risk of
neurologic morbidity than more extensive epilepsy operations
that resect adjacent cortex based on ECoG. 4 In contrast, simple
CAVERNOUS MALFORMATIONS PRESENTING WITH SEIZURES

lesionectomy to control seizures with loci in cortex adjacent to

or at sites distant from the cavernous malformations is unlikely
to be successful. 1Bar
Robinson and coworkers 1~ reported 21 patients with intrac-

163

table epilepsy and cavernous malformations who underwent

video-EEG telemetry. Ictal onset localized to the lesion's location in only three cases. Ictal onset localized to the lesion and
surrounding areas in seven cases and was indeterminate or
bilateral in 7 cases, The authors concluded that lesion removal
often improved seizure control but recommended that patients
undergo the same extensive preoperative evaluation as other
patients undergoing epilepsy surgery. They also suggested that
removal of an extralesional "epileptogenic zone" may be necessary in many cases.
Acciarri and coworkers ~ reported a cure or reduction in the
use of antiepileptic medication in 20 of 36 patients (55%) who
underwent lesionectomy and improved seizure control on a
preexisting medical regimen in the remainder (16 of 36). Their
surgical approach, similar to ours, involved lesionectomy with
removal of surrounding gliosis when possible but did not involve corticography or preoperative ictal localization. The same
group has since reported 100~ improved seizure control in
children undergoing lesionectomy for epilepsy. They have postulated that lesionectomy may help prevent the adjacent tissue
from converting to an autonomous epileptogenic focus.
More recently, Casazza and coworkers 4 reported seizure-free
outcomes in 23 of 26 patients who presented with sporadic
seizures and in 13 of 21 patients who presented with chronic
epilepsy. They used simple lesionectomy and found no, relationship between residual hemosiderin on postoperat{ve MRI
and the likelihood of a seizure relapse. Results improved if
lesion location correlated with electroclinical data. Cohen and
coworkers 6 found lesionectomy to be most successful in patients with few preoperative seizures and short intervals between seizure onset and surgery. They recommended lesionectomy as a reasonable strategy for patients with a brief history of
seizures but suggested that patients with a longer preoperative
history undergo more extensive evaluation before surgical
treatment is pursued.
In our series, seizures were eliminated in all patients whose
history of seizures was brief and in 57% of patients with chronic
epilepsy treated with lesionectomy alone. Seizure control improved after lesionectomy in an additional 31~ of patients with
chronic epilepsy. Results of lesionectomy were poorest in patients with a history of intractable chronic epilepsy before surgery. None of our patients developed recurrent seizures after
undergoing early lesionectomy. There were no deaths and no
permanent neurological morbidity attributable to lesionectomy.
The results in this series suggest that lesionectomy for a
cavernous malformation that presents with a the new onset of
seizure a~tivity may be a reasonable alternative to medical management to prevent epilepsy as long as the lesion is in a readily
accessible-location and can be removed with minimal morbidity. It is unknown, however, how many of these patients would
have become seizure-flee if they had received medical management alone. Extrapolating from clinical trials of anticonvulsants in new or recent onset epilepsy suggests this number
would be between 40 and 60%. 2~ More importantly, prophylactic lesionectomy for epilepsy may reduce these patients' need
for long-term antiepileptic drugs and their associated side effects. Of the 18 patients with medically controlled seizures
before surgery, 16 (89%) were free of seizures and medications
after surgery, and an attempt at weaning the other 2 patients
from antiepileptic drugs is planned.
For patients with chronically uncontrolled epilepsy associ-

164

ated with cavernous malformations, lesionectomy alone helped

most patients. Fifty-seven percent became seizure-flee and an
additional 13% were almost seizure-flee after lesionectomy.
Overall, these results are inferior to those reported for epilepsy
surgery compared with lesionectomy. In many recent epilepsy
surgery series, the seizure-flee outcome rates approximate
80%. 27'28 These outcomes suggest that patients with longstanding epilepsy, poorly controlled seizures, and/or a temporal
lobe lesion should be evaluated in a more comprehensive fashion. If necessary, surgery should be planned to include more
extensive resection than the limited lesionectomy used in our
series. In particular, our study supports previous studies that
patients with dual pathology should not undergo a simple lesionectomy. However, a prospective, randomized, controlled
trial would be needed to answer this question. A reasonable
approach is to offer lesionectomy as the initial treatment to all
patients with the realization that a significant minority will later
require further investigation and resection of extralesional tissue for complete seizure control. However, more than 50% of
the patients will have been rendered seizure-free without an
invasive evaluation or, more importantly, unnecessary tissue
resection.

Conclusion
Lesionectomy is a valuable treatment option for patients with
cavernous malformations associated with epilepsy, successful
control of seizures is greatest in patients who undergo resection
soon after the onset of symptoms. Patients with chronic epilepsy who fail to become seizure free after lesionectomy may
require further epilepsy monitoring and resection. Initial lesionectomy, however, will avoid unnecessary epilepsy surgery
in most of these patients.

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165