Safety and Usefulness of Insular Depth Electrodes Implanted Via an Oblique Approach in Patients with Epilepsy

Abstract

This study investigates the feasibility, safety, and usefulness of depth electrodes stereotactically implanted within the insular cortex.
Thirty patients with suspected insular involvement during epileptic seizure underwent presurgical stereotactic electroencephalographic recordings using 10 to 16 depth electrodes per patient. Among these, one or two electrodes were implanted via an oblique approach to widely sample the insular cortex.
Thirty-five insular electrodes were implanted in the 30 patients without morbidity. A total of 226 recording contacts (mean, 7.5 contacts/patient) explored the insular cortex. Stereotactic electroencephalographic recordings of seizures allowed the differentiation into groups: Group 1, 10 patients with no insular involvement; Group 2, 15 patients with secondary insular involvement; and Group 3, five patients with an initial insular involvement. In temporal epilepsy (n = 17), the insula was never involved at the seizure onset but was frequently involved during the seizures (11 out of 17). In frontotemporal or frontal epilepsy, the insula was involved at the onset of seizure in five out of 13 patients. All patients in Groups 1 and 2 underwent surgery, with a seizure-free outcome in 76.2% of patients. In Group 3, only two of the five patients underwent surgery, with a poor outcome. In temporal lobe epilepsy, surgical outcome tended to be better in Group 1 compared with Group 2 in this small series: results were good in 83.3% (Engel I) versus 72.7%.
Insula can be safely explored with oblique electrodes. In temporal lobe epilepsy, insular involvement does not significantly modify the short-term postoperative outcome. Future larger studies are necessary to clarify the long-term prognostic value of insular spread.

Full text

S
AFETY AND
U
SEFULNESS OF
I
NSULAR
D
EPTH
E
LECTRODES
I
MPLANTED
U
SING AN
O
BLIQUE
A
PPROACH IN
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ATIENTS WITH
E
PILEPSY
OBJECTIVE: This study investigates the feasibility, safety, and usefulness of depth elec-
trodes stereotactically implanted within the insular cortex.
METHODS: Thirty patients with suspected insular involvement during epileptic seizure
underwent presurgical stereotactic electroencephalographic recordings using 10 to 16
depth electrodes per patient. Among these, one or two electrodes were implanted using
an oblique approach to widely sample the insular cortex.
RESULTS: Thirty-five insular electrodes were implanted in the 30 patients without mor-
bidity. A total of 226 recording contacts (mean, 7.5 contacts/patient) explored the insu-
lar cortex. Stereotactic electroencephalographic recordings of seizures allowed the dif-
ferentiation into groups: Group 1, 10 patients with no insular involvement; Group 2, 15
patients with secondary insular involvement; and Group 3, five patients with an initial
insular involvement. In temporal epilepsy (n ⫽17), the insula was never involved at
the seizure onset but was frequently involved during the seizures (11 of 17). In fron-
totemporal or frontal epilepsy, the insula was involved at the onset of seizure in five of
13 patients. All patients in Groups 1 and 2 were operated on with a seizure-free outcome
in 76.2% of patients. In Group 3, only two of the five patients underwent surgery with
a poor outcome. In temporal lobe epilepsy, surgical outcome tended to be better in
Group 1 compared with Group 2 in this small series: 83.3% (Engel I) versus 72.7%.
CONCLUSION: Insula can be safely explored using oblique electrodes. In temporal
lobe epilepsy, insular involvement does not significantly modify the short-term post-
operative outcome. Future larger studies are necessary to clarify the long-term prog-
nostic value of insular spread.
KEY WORDS: Depth electrode, Epilepsy surgery, Frontal lobe, Insula, Oblique electrode, Stereotactic elec-
troencephalographic, Temporal lobe epilepsy.
Neurosurgery 00:000-000, 2008
DOI: 00-0000/00.NEU.0000000000.00000 www.neurosurgery-online.com
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SPECIAL TECHNIQUE APPLICATION
Afif Afif, M.D.
Department of Neurosurgery,
Grenoble University Hospital,
Grenoble, France
Stephan Chabardes, M.D.
Department of Neurological Surgery, and
INSERM U836,
Grenoble University Hospital,
Grenoble, France
Lorella Minotti, M.D.
Department of Neurology, and
INSERM U704,
Grenoble University Hospital,
Grenoble, France
Philippe Kahane, M.D., Ph.D.
Department of Neurology, and
INSERM U704,
Grenoble University Hospital,
Grenoble, France, and
CTRS-IDEE,
Lyon University Hospital,
Lyon, France
Dominique Hoffmann, M.D.
Department of Neurosurgery,
Grenoble University Hospital,
Grenoble, France
Reprint requests:
Dominique Hoffmann, M.D.,
Service de Neurochirurgie,
CHU de Grenoble,
BP 217,
38043 Grenoble,
Cedex 9, France.
Email: DHoffmann@chu-grenoble.fr
Received, November 16, 2006.
Accepted, November 14, 2007.
Arole of the insular cortex in temporal
lobe epilepsy was first suggested 50
years ago after perioperative electrocor-
ticography and the analysis of interictal spik-
ing activity as well as the clinical effects of cor-
tical electrical stimulation (12, 13, 18). How-
ever, Silfvenius et al. (25) pointed out the poor
postoperative outcome and the high rate of
surgical complications after insular resection
in patients with electrocorticography-recorded
spikes in the insular cortex. Since this initial
discovery, only a few studies have reported on
the benefit of insular surgical resection in cases
of partial epilepsy associated with insular
lesions (7, 9, 23).
The insular cortex has not been investigated
using depth electrodes because of its anatomic
location in the depth of the sylvian fissure and
its close anatomic relationship with segments
of the middle cerebral artery constituting a
“vascular screen” at the surface of the insula
(30, 31). Recently, however, new developments
in stereo-electroencephalography (SEEG) such
as multimodal imaging techniques and new
smaller electrode designs opened up the possi-
bility of exploring the insula in temporal lobe
epilepsy (14, 15) and frontal lobe epilepsy (24).
These studies have mainly been performed
with implanted transopercular electrodes per-
pendicular to the sagittal plane. However, the
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vascular environment and the shape of the insula could explain
the insufficient sampling of this structure achieved by this
approach. To overcome this limitation, since 1998, we have
developed an oblique trajectory for implantation of insular
depth electrodes in patients with drug-refractory partial tempo-
ral and/or frontal seizures with suspected insular involvement.
This retrospective study aimed to evaluate the feasibility,
safety, and usefulness of oblique insular electrodes in a popu-
lation of 30 consecutive patients who underwent a SEEG study
between June 1998 and January 2005. This oblique approach
has allowed a wide sampling of the insular cortex, which may
prove useful when analyzing epileptogenic networks or when
considering the large surface of the insular lobe and the com-
plexity of its connections with other cortical regions and sub-
cortical structures.
PATIENTS AND METHODS
Between 1998 and 2005, 119 patients underwent invasive recordings
at Grenoble University Hospital using the SEEG methodology for
presurgical evaluation of their epilepsy. Of these 119 patients, 101 were
operated on. During the same period, surgery was performed without
SEEG recording in 48 patients. Schematically, SEEG recordings were
judged necessary when noninvasively obtained data were insufficiently
concordant, discordant, inconclusive, and/or suggested an early
involvement of highly eloquent areas.
The noninvasive presurgical evaluation included in all cases high-
resolution magnetic resonance imaging (MRI) (with coronal T1-weighted
images perpendicular to the hippocampal axis and T2-weighted images
parallel to the hippocampal plane), neuropsychological tests, and pro-
longed electroencephalographic (EEG) video monitoring. Of this pop-
ulation, we selected those patients in whom at least one oblique trans-
frontal or transparietal intracerebral electrode was implanted within
the insular cortex during the SEEG evaluation. The choice to perform
a transfrontal or transparietal approach depended on anatomic char-
acteristics of the area of entry with the frontal approach generally the
most appropriate choice. Postoperative follow up was at least 24
months and Engel’s classification was used to evaluate the postoper-
ative outcome (10).
Population Studied
Among the total population of 119 patients studied by SEEG, we
uncovered 30 patients meeting the inclusion criteria (Table 1). These
included 18 men (60%) and 12 women (40%), ages between 9 and 53
years old (mean ⫽28 yr ⫾13.2; maximum, 53 yr; minimum, 7 yr). The
mean duration of epilepsy was 20 ⫾11 years. Four patients were left-
handed (13.3%) and 26 patients right-handed (86.7%). MRI scan
showed a unilateral hippocampal sclerosis in 17 patients (56.6%), a
cortical dysplasia in five patients (16.7%), and a cavernoma in two
patients (6.7%). Six patients (20%) were considered cryptogenic. Two
patients harbored a dysplastic tissue within the insular cortex.
Before SEEG, 10 patients were suspected as having temporal
epilepsy, 14 from temporofrontal epilepsy, and six from frontal lobe
epilepsy. The number and targets of intracerebral electrodes were
designed to address one or more of the following: 1) the demonstration
that brain regions suspected to be involved in seizure onset and early
propagation showed the expected ictal pattern; 2) the consideration
that this pattern might in fact reflect the propagation of an ictal dis-
charge generated elsewhere; 3) the delineation of the border of the
epileptogenic zone to perform minimal cortical resection; 4) to assess
the possibility of removing cortical areas involved in seizure generation
without unacceptable functional deficit; and 5) the evaluation of the
precise relationships between an anatomic lesion (when present) and
the epileptogenic zone (17).
More specifically, the electrode implantation of the insular lobe was
decided in all 30 patients because ictal clinical symptoms (gustatory
hallucination, laryngeal discomfort or throat tightening, paresthesias or
tonic–clonic movements of the face, unpleasant paresthesias affecting
large somatic territories, hypersalivation) or scalp video-EEG data sug-
gested an early spread of seizures to the suprasylvian opercular cortex
and insula (14, 15).
Implantation of Intracerebral Electrodes
The implantation of intracerebral electrodes was performed accord-
ing to the classical approach described by Talairach et al. (27) and
elaborated more recently by several groups (3, 14, 17). First, a stereo-
tactic digital cerebral tele-angiography (Pixray; Bioscan System,
Switzerland) was performed under general anesthesia and a three-
dimensional cerebral contrasted T1-weighted MRI scan obtained in
stereotactic conditions. The targeting of the insular cortex was planned
on the basis of the three-dimensional MRI scan and the trajectory com-
puted with stereotactic software (Voxim; IVS Solutions, Chemnitz,
Germany). Each trajectory was plotted onto the stereotactic digital
cerebral tele-angiography to assess the presence of any vessels cross-
ing the trajectory. Electrode implantation was performed in a second
surgical step in the same stereotactic conditions using a robotized arm
(Neuromate; ISS, France) connected to the stereotactic frame and
driven by stereotactic planning software (Voxim; Iversus Solution).
More specifically, intrainsular electrodes were implanted using either
an anterior (transfrontal) approach passing through the middle frontal
gyrus and/or a posterior (transparietal) trajectory passing through the
inferior parietal cortex. The number and the trajectory of insular
oblique electrodes were chosen according to the working hypothesis on
the location of the epileptogenic zone. Thus, most patients were
explored by means of at least one transfrontal insular electrode,
whereas the choice to use one additional transparietal electrode was
decided for patients showing rapid posterior spreading of the seizures
on EEG recordings.
The electrodes (DIXI; Besançon, France) had a diameter of 0.8 mm
and comprised 10 to 18 leads 2 mm in length and 1.5 mm apart
depending on the targeted region. One single electrode, therefore,
sampled different regions along its trajectory and, with respect to
insular electrodes, a wider sampling of insular cortex could be eval-
uated (Fig. 1).
Anatomic Location of Insular Recording Sites
For each patient, the contact positions of all insular leads were plot-
ted onto the Talairach and Tournoux stereotactic atlas (28). Moreover,
the contacts of the insular electrodes were localized using postoperative
three-dimensional computed tomographic (CT) scan and matched with
the preoperative MRI scan performed in the same stereotactic refer-
enced system (Fig. 2). It was thus possible to localize with high
anatomic precision the position of all insular contacts according to dif-
ferent insular sulci and gyri.
SEEG Recordings
SEEG recordings were performed extraoperatively over 1 to 3 weeks
using an audio–video-EEG monitoring system (Micromed, Treviso,
Italy) allowing the simultaneous recording of up to 96-depth EEG chan-
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nels in each patient. Patients were continuously observed by a member
of the epilepsy team to obtain a precise description of patient subjective
experience at seizure onset as well as to test awareness, language, mus-
cle tone, and sensorimotor functions. At least one seizure was recorded
in each patient. The ictal (or seizure) onset zone was defined as the
“area of cortex initiating clinical seizure” (22) or, more precisely, the cor-
tical area(s) from which the first clear ictal electrical change was
recorded, providing 1) that this change occurred before the clinical
onset of the seizure and 2) that it manifested by a fast synchronizing
discharge (low-voltage fast activity or recruiting fast discharge of
spikes). Interictal depth EEG activity and ictal electroclinical data were
stored in a computerized support for easy retrospective review.
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TABLE 1. General data concerning the population of patients
a
Patient Age Lat. Age at EZ hy- EZ after Out-
no. (yr)/sex R/L History first seizure MRI pothesis SEEG Group Surgery come
b
1 15/F R 6 yr HcS R T (i) R T 1 T Discon Ia
2 28/M R HT 20 yr Normal R T (i) R T 1 T Discon Ia
3 19/F R FC (6 mo) 6 mo HcS L T (i) L T 1 T Lobect Ia
4 35/F R FC (1 yr) 12 yr HcS L T (i) L T 1 T Lobect Ib
5 37/M R HT (18 yr) 23 yr T dysplasia R T (i) R T 1 T Lobect Ic
6 11/M L 1 yr TP dysplasia. L TF (i) L T 1 T Lobect III
7 13/M L 6 yr Normal L TF (i) L F 1 F Lobect Ia
8 20/F R 11 mo F dysplasia L F (i) L F 1 F Lobect Ia
9 22/F R HT (4 yr) 14 yr FP dysplasia R F (i) R F 1 F Lobect Ia
10 34 /F R 3 yr Normal R F (i) R F 1 F Lobect IV
11 38/M R HT (14 yr) 14 yr HcS R T (i) R T (I*) 2 T Discon Ia
12 41/F R Meningitis (3 yr) 12 yr HcS R T (i) R T (I*) 2 T Discon Ia
13 18/M R 15 yr HcS L T (i) L T (I*) 2 T Lobect Ia
14 44/M L Meningitis (2 yr) 6 yr HcS L TF (i) L T (I*) 2 T Discon Ia
⫹FC (3 yr)
15 42/M R 10 yr HcS R TF (i) R T (I*) 2 T Discon Ia
16 41/F R 13 yr HcS R TF (i) R T (I*) 2 T Lobect Ia
17 40/M R FC (10 mo) 2 yr HcS L TF (i) L T (I*) 2 T Lobect Ia
18 18/F R FC (2.5 yr) 9 yr HcS R T (i) R T (I*) 2 T Lobect Ib
19 42/M R 14 yr HcS L TF (i) L T (I*) 2 T Lobect IIb
20 26/F R FC (18 mo) 18 yr HcS L TF (i) L T (I*) 2 T Lobect IIb
21 52/M R HT (20 yr) 20 yr Amygdala L T (i) L T (I*) 2 T Lobect IId
cavernoma
22 18/M R FC (16 mo) 3 yr HcS, F caver- R TF (i) R TF (I*) 2 T Lobect ⫹Ia
noma F lesionect
23 27/M R HT (9 mo) 16 yr HcS R TF (i) R TF (I*) 2 F T lobect Ia
24 26/F L FC (20 mo) 10 yr HcS R TF (i) R TF (I*) 2 T Lobect ⫹Ia
F discon
25 13/M R West syndrome 18 mo F ⫹insular cort- R TF (i) R TF (I*) 2 T + F + insula Ia
(10 mo) ical dysplasia lobect
26 9/M R 1 yr Orbito-insular R TF (i) R ITF 3 T ⫹F ⫹anterior III
cortical dysplasia insula lobect
27 37/M R HT (3 mo) ⫹3 yr HcS R TF (i) R ITF 3 T ⫹F ⫹anterior IV
FC (9 mo) insula lobect
28 53/M R HT (5 yr) 9 yr Normal L F (i) L IF 3 No surgery NA
29 14/M R 5 yr Normal L F (i) LIF 3 No surgery NA
30 7/F R 2.5 yr Normal R F (i) RIF 3 No surgery NA
a
Lat, hemispheric dominance for language; R, right; L, left; MRI, magnetic resonance imaging; EZ, epileptogenic zone; SEEG, stereotactic electro-encephalography; F,
female; M, male; HT, head trauma ; FC, febrile convulsion; HcS, hippocampal sclerosis; TP, temporopolar; FP, frontopolar; T, temporal; F: frontal; TF, temporofrontal; (i), insular
involvement was suspected during seizures before SEEG; (I*), secondary insular involvement demonstrated after SEEG evaluation; ITF, insulotemporofrontal; IF, insulofrontal;
Discon, disconnection; Lobect, lobectomy; Lesionect, lesionectomy; NA , .
b
Outcome according to Engel’s classification with at least 2-year follow up.
TQ:1

RESULTS
A total of 411 intracerebral electrodes were implanted (mean,
13.7 electrodes/patient), unilaterally in 25 cases and bilaterally
in the remaining five patients, using either an orthogonal (n ⫽
337) or oblique (n ⫽74) trajectory. The insular cortex was
explored by 35 oblique electrodes, 19 on the right side (54.3%)
and 16 on the left side (45.7%). Three patients had two elec-
trodes implanted within the same insula. A total of 226 contacts
(mean, 7.5/patient) was used for insular recording.
No morbidity was directly related to insular electrodes.
Concerning the SEEG procedure, one complication occurred in
one patient (Patient 30) who presented intracerebral posterior
temporal bleeding during electrode removal at the end of the
SEEG recording step (lateral electrode exploring the posterior
part of the s. temporal gyrus). The hematoma was surgically
removed with no postoperative neurological damage.
SEEG Data
A total number of 177 seizures were recorded in the 30 patients
studied (mean, 6 seizures/patient; range, 1–13). Three groups
of patients were identified
according to insular involve-
ment during SEEG-recorded
seizures (Table 2). Group 1
comprised 10 patients (33.3%)
showing no insula involve-
ment during seizures (Fig. 3).
In this group, six patients had
temporal lobe epilepsy (TE)
and four patients had frontal
lobe epilepsy (FE). Group 2
comprised 15 patients (50%)
with no insular involvement at
seizure onset but involvement
after a short delay during sei-
zure evolution (Fig. 4). Eleven
patients in this group had TE
and four had temporofrontal
lobe epilepsy (TFE). Group 3
comprised five patients (16.6%)
with insular involvement at
seizure onset (Fig. 5). Three of
these five patients had hyper-
motor seizures, either crypto-
genic (Patients 30 and 28) or
genetically determined (Pa-
tient 29; autosomal-dominant
nocturnal frontal lobe epi-
lepsy). Seizures arose from the
insula alone in two patients
(Patients 30 and 28) and from
both the insula and the frontal
operculum in the other patient
(Patient 29). These seizures
then propagated in all three patients to the ipsilateral frontal
lobe. In the remaining two patients, the ictal onset zone was
widely extended, involving simultaneously the insula, the
fronto-orbital cortex, and the anterior temporal lobe region.
One of these two patients had an orbitoinsular cortical dyspla-
sia (Patient 26) and the other a hippocampal sclerosis (Patient
27) (Table 1).
Compared with the initial hypothesis, SEEG changed the
final location of the diagnosed epileptogenic zone in 13 of 30
patients (43.3%; Table 2). Three patients out of six with an ini-
tial hypothesis as having FE were finally considered as having
insulofrontal epilepsy. Ten of 14 patients with an initial
hypothesis of TFE were finally considered as TE in seven
patients, FE with secondary propagation to insula in one
patient, and insulotemporofrontal epilepsy in the remaining
two patients. Thus, the SEEG data reduced the proposed sur-
gical resection or disconnection zone in eight of 14 patients
(57.1%) in whom the initial hypothesis was TFE, and the
epileptic zone was changed before undergoing surgery in
eight of 10 (80%) patients (Table 1).
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FIGURE 1. Anatomic localization of insular cortex electrodes. Frontal (A) and lateral (B) x-rays of the patient’s head
in the operating room are shown after implantation of intracerebral electrodes. Yⴕ,anterior oblique electrode targeting
anterior and middle short gyrus of the insula; Xⴕ, posterior oblique electrode targeting the postcentral gyrus of the insula.
C,individual, lateral, and anatomic stereotactic scheme of the patient contain anatomic structures and the implanted
electrodes (lower case letters on the scheme). This scheme is built on the basis of the postimplantation x-ray and pre-
operative magnetic resonance imaging (MRI) scan. Both neuroradiological explorations are plotted in an individual,
bicommissural stereotactic referenced system. D,image fusion with Voxim stereotactic software (IVS Solutions,
Chemnitz, Germany) between preoperative MRI and postoperative computed tomographic (CT) scans. Slices (a) frontal
and (b) lateral are coplanar to electrode Yⴕ. E,image fusion with Voxim stereotactic software between preoperative MRI
and postoperative CT scans is shown. Slices (a) lateral and (b) frontal are coplanar to electrode Xⴕ. This anatomic pro-
cedure associated with the electrophysiological data obtained during postoperative recordings gives very high definition
of real electrode positioning. On Eb, we can see the frontal reconstruction of electrode T (lateral orthogonal implanted
electrode in the middle portion of the superior temporal gyrus), its inner extremity touching the insular cortex with only
one lead. This is a good example of the limitations experienced using this type of electrode to explore the thin layer insu-
lar cortex. In fact, the part of the insular cortex available for recording is restricted to only one lead of electrode, T.
T2
F3
F4
F5

Surgical Treatment and Outcome
On the basis of SEEG data analysis, 27 patients underwent a
tailored surgical resection or disconnection. Temporal lobe sur-
gery was performed in 17 patients, frontal lobe surgery in four
patients, temporofrontal resection in three patients, tempo-
rofrontal resection associated with removal of the anterior part
of the insula in two patients, and total insulectomy in one
patient (Patient 25, Group 2) who was seizure-free (Engel’s
Class I). Three patients, all in
Group 3, were not operated
on; one died suddenly from
unexplained causes while
awaiting the decision to oper-
ate (Patient 28), one having
had a temporal lobe bleed after
electrode removal refused sur-
gery (see previously, Patient
30), and one could not be oper-
ated on because of the initial
involvement of the insulo-
opercular region of the domi-
nant hemisphere for language
(Patient 29).
Overall (Table 1), 20 of the
27 operated patients (74%)
were seizure-free (Engel’s
Class I) after surgery, three
had rare seizures (Engel’s
Class II), two had a worth-
while improvement (Engel’s
Class III), and two showed no
improvement. With respect to
insular involvement, eight of
the 10 operated patients in
Group 1 were seizure-free
(80%), one was classified in
Engel’s Class III, and one in
Engel’s Class IV. In Group 2,
surgery relieved seizures in 12
of 15 patients (80%), whereas the remaining three patients had
rare seizures. Surgery was unsuccessful in those patients in
Group 3 who underwent surgery (one in Engel’s Class III, one
in Engel’s Class IV).
Considering the epileptogenic zone assessed by SEEG, 13
patients out of 17 were seizure-free in TE, three were classified
as Engel’s Class II, and one as Engel’s Class III. In FE, three of
four patients were classified as Engel’s Class I and one as
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FIGURE 2. Example showing one insular electrode. Lateral (A) and axial (B) reconstruction of an oblique electrode
insertion into the anterior insula is demonstrated. This document is obtained after preoperative MRI and postoper-
ative CT scan image fusion computed by our stereotactic software (Voxim). This particular electrode clearly demon-
strates how an oblique implantation enables the exploration of a large part of the insular cortex. In this case, 10 leads
of the same electrode are located in the insular cortex covering from the anterior short gyri to the posterior long gyri
of the insula. C, The frontal sections perpendicular to the electrode, corresponding for each image to the lines cross-
ing the electrode trajectory in Aand B.
TABLE 2. Summary of the localization of the epileptogenic zone before and after SEEG and case grouping relative to insular involvement
a
Before SEEG After SEEG
EZ hypothesis No. of patients EZ No. of patients Group 1 Group 2 Group 3
T (i) 10 ■T 17 6 = (5 ■+ 1▲) 11 = (5 ■+ 6▲)
F (i) 6 ●F 4 4 = (3 ●+ 1▲)
TF (i) 14 ▲TF 4 4 ▲
Total 30 ITF 2 2 ▲
IF 3 3 ●
Total 30 10 15 5
a
SEEG, stereotactic electroencephalography; EZ, epileptogenic zone; Group 1, no insular involvement; Group 2, secondary insular involvement; Group 3, epileptogenic onset
zone involving the insula T, temporal; (i), insular involvement was suspected during seizures; F, frontal; TF, temporofrontal; ITF. insulotemporofrontal; IF, insulofrontal; ■, patients
with initial hypothesis of temporal lobe epilepsy; ●, patients with initial hypothesis of frontal lobe epilepsy; ▲, patients with initial hypothesis of temporofrontal lobe epilepsy.

Engel’s Class IV. In TFE, all four
patients were classified as
Engel’s Class I. Neither of the
two patients with initial insular
involvement became seizure-
free after surgery (Table 1).
DISCUSSION
Evidence for Insular
Involvement during
Epileptic Seizure
The central situation of the
insular cortex, linking the
frontal, temporal, and parietal
cortex in a paralimbic net-
work (16), puts the insula in a
pivotal position when consid-
ering the epileptogenic net-
work involved during TE, FE,
or TFE. The involvement of
the insula during epileptic
seizure with suspected tem-
poral origin has been advo-
cated for several decades
(7, 9, 12, 13, 18, 21, 25).
Recently, studies using pos-
itron emission tomography
have strengthened this
hypothesis, showing a high
rate of insular hypometabo-
lism or a decrease in benzodi-
azepine receptors in the in-
sula of patients with TE (2, 4).
Such metabolic changes may
vary according to the type of
TE (4) and do not seem of
postoperative prognostic sig-
nificance (2). In addition,
direct recordings of insular
EEG activity during SEEG
procedures have shown a
common involvement of the
insula in the course of tempo-
ral lobe seizures. Tailored
temporal lobe resection spar-
ing the insula has been of no
postoperative prognostic val-
ue, and conversely, temporal
lobe surgery has proven inef-
fective when the insular cor-
tex was involved at seizure
onset (14). This was the case
in two of 21 patients (9%) in
this earlier study, and such an
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FIGURE 3. No insular involvement is shown in Patient 8 (Group 1; stereo-electroencephalography [SEEG] trace and
individual implantation lateral and frontal scheme). The ictal discharge (fast activity) begins (first arrow) in the
lesion frontal cortical dysplasia (Lⴕ) and the anterior cingulate gyrus (Hⴕ)and then (s arrow) becoming more evi-
dent later. Five seconds later (arrowheads), the ictal discharge propagates to the mesial prefrontal cortex (Pⴕand
Fⴕ). Other regions are less involved with no involvement of the insular cortex. SMA, supplementary motor area;
DLPF, dorsolateral prefrontal; DLPM, dorsolateral premotor. Small arrow on implantation schemes represents the
recorded contacts of the insular electrode.
FIGURE 4. Clear insular spread in Patient 15 (Group 2; SEEG trace and individual implantation lateral and
frontal scheme). The ictal discharge (fast spikes) begins in the hippocampus (first arrow) and then involves the tem-
poral pole and the amygdala (*fast activity) in less than 5 seconds. The insula becomes involved 3 seconds later and
the cingulate gyrus 2 seconds later (arrowheads). Different parts of the insula are successively involved. The dis-
charge then propagates over other territories, mainly the suprasylvian operculum and the orbitofrontal cortex. Note
how the insular discharge is first recorded at different levels along the axis of the insular oblique electrode (Ya and
Yb) before becoming visible over the recording contacts of the perpendicular insular electrode (Q). T, temporal; P, pari-
etal; F, frontal; C, central; Cing, cingulate; DLPF, dorsolateral prefrontal. Letters refer to the recording electrodes.
*Amplitude ⫻2; **amplitude: 2.
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insular onset was found in six of 50 patients (12%) in another
study conducted by the same group (15).
Complications Resulting from Oblique
Insular Electrodes
The safety of stereotactic depth electrode implantation has
been addressed in numerous studies with severe morbidity
with permanent deficit related to electrode implantation rang-
ing from 1 to 2% in these series (1, 11, 26, 29). Recently, De
Almeida et al. (8) reported a higher risk of hematoma (2.9% per
hemisphere) in cases in which SEEG was performed in frontal
epilepsy and when four or more electrodes were implanted.
The surgical procedure described in this previous study
included no more digital substraction angiography, but was
substituted by double-dose gadolinium magnetic resonance
angiography. Computed angiography provides additional
information necessary to minimize the incidence of bleeding,
although a positive role for stereotactic computed angiogra-
phy in avoiding hematoma will be difficult to assess as a result
of the globally low morbidity rate observed in centers perform-
ing SEEG worldwide.
Cossu et al. (5, 6) recently reported the oblique implantation
of electrodes in stereotactic conditions in adults and in children.
For these authors, this procedure was mandatory in targeting
the frontal or parietal mesial regions, the orbitobasal region, the
amygdala, and the hippocampus. The oblique approach has
also been used to record epileptic activity (19, 20) from the basal
ganglia. In our institution, we believe that a safe implantation of
electrodes within the insula can be achieved using an oblique
stereotactic approach coupled with preoperative MRI scanning
and stereotactic angiography.
Above all, it offers a better
sampling of insular EEG activ-
ity compared with the more
classical lateral transopercu-
lar approach. In the present
study, we observed no mor-
bidity related to the surgical
implantation.
Contribution of Insular
Electrodes in Presurgical
Evaluation
Our data suggest that three
groups can be identified
among patients suspected as
having TE, FE, or TFE: a first
group (Group 1) without any
involvement of the insula, a
second group (Group 2) with
a spread of ictal discharge to
the insula and finally, a third
group (Group 3) with an ictal
onset zone involving the
insula.
TLE
Among 10 patients suspected as having temporal lobe sei-
zure, five (50%) showed no insular involvement at the electri-
cal onset of seizure and in the remaining 50%, the insula was
involved later. According to our data, insular seizure in TE is
less frequent compared with that found in other studies (14,
15). However, the insula is frequently part of the epileptogenic
network as shown by late involvement during TE seizure in
half of the patients.
This is in agreement with studies using positron emission
tomography showing approximately 60% of patients with TE
presenting interictal hypometabolism of the insula. Our study
raises the question of the significance of early or late spreading
of seizure to the insula as seen in half of the patients in our
series. We did not systematically measure the delay between
insular involvement and onset of seizure. This may, however,
be of major importance with the postoperative control of
seizure seeming to vary in Group 2 and will be addressed in a
future study. Considering the temporal epileptogenic zone as
proven by SEEG data analysis, 17 patients instead of 10 had to
be considered as having TLE rather than TFE as initially
hypothesized. Eleven of these patients (64.7%) had secondary
involvement of insular structures (Table 2).
Furthermore, postoperative outcome decreased from Group
1 to Group 2 in TE, achieving 83.3% good results (Engel’s
Class I) in Group 1 compared with 72.7% in Group 2. The dif-
ference was not significant possibly as a result of the small
number of patients in each group. According to our data, the
insular cortex is not part of the ictal onset or epileptogenic
zone in most of patients, but more likely forms part of the
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FIGURE 5. Insular onset in Patient 30 (Group 3; SEEG trace and individual implantation lateral and frontal
scheme). The ictal discharge (fast activity) begins in the insula (arrow) involving part of the mesial frontal cortex a
few seconds later followed by the dorsolateral frontal cortex and the parietal cortex (arrowheads). Note that only the
anterosuperior portion of the insula is involved at seziure onset. T, temporal; F, frontal; P, parietal; Cing, cingulate;
SMA, supplementary motor area; DLPF, dorsolateral prefrontal; DLPM, dorsolateral premotor; G, gyrus. Letters
refer to the recording electrodes. *Amplitude ⫻2.

“potential epileptogenic zone.” Further larger studies are nec-
essary to address this issue.
FE
In our department, most patients suspected as having FE
based on presurgical investigation undergo SEEG evaluation.
Most of these generally do not have insular electrodes as a
result of the absence of clinical or scalp EEG evidence suggest-
ing insular involvement during seizure. For this reason, only
selected patients were included in this study explaining the
small number of patients with FE and eventual insular explo-
ration performed. However, in accordance with a recent study
(24), insular recording helped us confirm the initial involve-
ment of the insular cortex (Group 3) in 42.8% of patients (three
patients with insulofrontal lobe epilepsy out of seven consid-
ered after SEEG to have FE) and helped exonerate it in the
remaining 52.7% (four of seven patients) in which no insular
onset or late insular spread (Group 1) was observed (Table 2).
Two patients from Group 3 had left insulofrontal epilepsy and
were not considered for resective surgery (Table 1). According to
our data, insula involvement was confirmed in half of the
patients suspected as having FE (Table 2). Interestingly, they all
had nocturnal hypermotor seizures and were all cryptogenic
cases. In such cases, depth insular recordings gave clear infor-
mation necessary to decide on resective surgery.
TFE
The role of the insula in TFE has not been well documented
in the literature and in this respect, our study provides original
data. Of 14 patients previously hypothesized as having TFE
with implication of the insular cortex: 1) 12 (85.7%) had an
insular involvement as proven by SEEG (Table 2); 2) only four
patients were considered as having TFE after SEEG (all of them
having secondary insular involvement); 3) two patients had
initial insular involvement with simultaneous ictal discharge in
both frontal and temporal lobes; 4) seven patients had SEEG-
proven TE with insular involvement in six patients; and 5) one
patient had pure FE (Table 2). These observed data highlight the
gap in our knowledge on the clinical expression of insular
structures involved in the ictal discharge. In fact, the insular
involvement in the potential epileptogenic zone may be mis-
leading in initial hypotheses of this zone. It is noteworthy that
all cases of TFE in this series had secondary involvement of the
insular cortex. The small number of patients does not allow
powerful statistical analysis, but our data provide new land-
marks in this field. In this respect, our data strongly suggest the
usefulness of insular recording to better predict the postopera-
tive outcome and tailor the cortical resection when surgery is
planned in TFE.
Advantages of Oblique versus Lateral Trajectory
for Placement of Insular Electrodes
The sampling of the insula with intracranial electrodes might
be an issue when using a lateral trajectory. Indeed, the insula
represents a thin layer of gray matter with a width usually less
than 5 mm, which consequently allows the placement of a max-
imum of two contacts for each electrode implanted orthogo-
nally (Fig. 1, [E]b) compared with a mean of 7.5 leads for each
electrode implanted with an oblique approach. First, our
methodology to target the insula using an oblique approach
allows the electrode to cover a larger surface of insula (Fig. 1)
and thus explore all anatomic parts of the insular cortex (Fig. 2)
without limits in contrast to an orthogonal, trans-opercular
approach. Second, the orthogonal approach may distort any
data collected resulting from anatomic limitations not permit-
ting access to the greatest part of the insula largely covered by
the sylvian arterial branches, especially the antero-inferior part
(30, 31). The insular involvement observed in TE in some stud-
ies (14, 15) may be overestimated as a result of electrical activ-
ity originating in the supra or infrasylvian opercular cortex
(sites easier to target) interfering with insular gyri recordings.
Third, as shown in Figure 2, our trajectory enabled the explo-
ration of between two and three distinct insular gyri or even
the anterior and posterior insula with one single electrode. This
should prove useful when delineating the epileptogenic zone
and enable precise tailoring of resection when necessary. Our
study provides new arguments in favor of the use of a stereo-
tactic procedure to insert depth recording electrodes in diffi-
cult-to-reach areas such as the insula.
CONCLUSION
Oblique electrodes implanted in the insular cortex permit
the safe exploration of different insular regions and limit poten-
tial electrical contamination from adjacent areas, especially the
opercular cortex. Insular recordings provide additional presur-
gical information to allow a tailored surgical approach when
necessary and avoid surgery in cases of insular seizure where
the insula cannot be removed. Insula recordings using oblique
electrodes should be considered when the decision is made to
explore FE or TFE with intracranial electrodes and whenever
clinical or scalp EEG points to a possible insular involvement or
propagation during seizure. In cases of TE with suspected insu-
lar involvement, our study clearly indicates no insular involve-
ment in the epileptogenic zone, but that the seizure frequently
propagates to the insula later. The prognostic value of this late
propagation to the insula in the long-term postoperative out-
come needs to be clarified.
We are not yet able to target one specific part of the insular
cortex related to clinical data. Consequently, wider sampling of
the different sulci and convolutions of the insular lobe seems
necessary to gather enough information to either exonerate or
implicate the insula in a patient’s epileptic network. The asso-
ciation of lateral electrodes in the temporal or frontal lobe and
oblique electrodes in the insula seems at present to be a good
compromise to study multilobar epilepsy.
REFERENCES
1. Binnie CD, Elwes RD, Polkey CE, Volans A: Utility of stereoelectroen-
cephalography in preoperative assessment of temporal lobe epilepsy.
J Neurol Neurosurg Psychiatry 57:58–65, 1994.
8| VOLUME 62 | NUMBER 2 | FEBRUARY 2008
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2. Bouilleret V, Dupont S, Spelle L, Baulac M, Samson Y, Semah F: Insular cor-
tex involvement in mesiotemporal lobe epilepsy: A positron emission tomog-
raphy study. Ann Neurol 51:202–208, 2002.
3. Chabardès S, Kahane P, Minotti L, Tassi L, Grand S, Hoffmann D, Benabid
AL: The temporopolar cortex plays a pivotal role in temporal lobe seizures.
Brain 128:1818–1831, 2005.
4. Chassoux F, Semah F, Bouilleret V, Landre E, Devaux B, Turak B, Nataf F,
Roux FX: Metabolic changes and electro-clinical patterns in mesio-temporal
lobe epilepsy: A correlative study. Brain 127:164–174, 2004.
5. Cossu M, Cardinale F, Castana L, Citterio A, Francione S, Tassi L, Benabid AL,
Lo Russo G: Stereoelectroencephalography in the presurgical evaluation of
focal epilepsy: A retrospective analysis of 215 procedures. Neurosurgery
57:706–718, 2005.
6. Cossu M, Cardinale F, Colombo N, Mai R, Nobili L, Sartori I, Lo Russo G:
Stereoelectroencephalography in the presurgical evaluation of children with
drug-resistant focal epilepsy. J Neurosurg 103:333–343, 2005.
7. Cukiert A, Forster C, Andrioli MS, Frayman L: Insular epilepsy. Similarities
to temporal lobe epilepsy. Case report. Arq Neuropsiquiatr 56:126–128, 1998.
8. De Almeida AN, Olivier A, Quesney F, Dubeau F, Savard G, Anderman F:
Efficacy of and morbidity associated with stereoelectroencephalography
using computerized tomography- or magnetic resonance imaging-guided
electrode implantation. J Neurosurg 104:483–487, 2006.
9. Duffau H, Capelle L, Lopes M, Bitar A, Sichez JP, van Effenterre R: Medically
intractable epilepsy from insular low-grade gliomas: Improvement after an
extended lesionectomy. Acta Neurochir (Wien) 144:563–573, 2002.
10. Engel JJr VNPC, Rasmussen TB, Ojemann LM: Outcome with respect to
epileptic seizures, in J Jr E (ed): Surgical Treatment of the Epilepsies. New York,
Raven Press, 1993, pp 609–621.
11. Guenot M, Isnard J, Ryvlin P, Fischer C, Ostrowsky K, Mauguiere F, Sindou
M: Neurophysiological monitoring for epilepsy surgery: The Talairach SEEG
method. StereoElectroEncephaloGraphy. Indications, results, complications
and therapeutic applications in a series of 100 consecutive cases. Stereotact
Funct Neurosurg 77:29–32, 2001.
12. Guillaume MM, Mazars G: Cinq cas de foyers epileptogènes insulaires
opérés. Soc Française de Neurol:766–769, 1949.
13. Guillaume MM, Mazars G, Mazars Y: Surgical indications in so-called tempo-
ral epilepsy. Rev Neurol 88:461–501, 1953.
14. Isnard J, Guenot M, Ostrowsky K, Sindou M, Mauguière F: The role of the
insular cortex in temporal lobe epilepsy. Ann Neurol 48:614–623, 2000.
15. Isnard J, Guenot M, Sindou M, Mauguière F: Clinical manifestations of
insular lobe seizures: A stereo-electroencephalographic study. Epilepsia
45:1079–1090, 2004.
16. Mesulam M, Mufson E: The Insula of Reil in Man and Monkey. Architectonics,
Connectivity, and Function. New York, Plenum Press, 1985, vol 4.
17. Munari C, Hoffmann D, Francione S, Kahane P, Tassi L, Lo Russo G, Benabid
AL: Stereo-electroencephalography methodology: Advantages and limits.
Acta Neurol Scand Suppl 152:56–69, 1994.
18. Penfield W, Faulk ME J.: The insula; further observations on its function.
Brain 78:445–470, 1955.
19. Rektor I, Kaiiovsky P, Bares M, Brázdil M, Streitová H, Klajblová H, Kuba R,
Daniel P: A SEEG study of ERP in motor and premotor cortices and in the
basal ganglia. Clin Neurophysiol 114:463–471, 2003.
20. Rektor I, Kuba R, Brázdil M: Interictal and ictal EEG activity in the basal gan-
glia: An SEEG study in patients with temporal lobe epilepsy. Epilepsia
43:253–262, 2002.
21. Roper SN, Lévesque MF, Sutherling WW, Engel J Jr: Surgical treatment of par-
tial epilepsy arising from the insular cortex. Report of two cases. J Neurosurg
79:266–269, 1993.
22. Rosenow F, Lüders H: Presurgical evaluation of epilepsy. Brain 124:
1683–1700, 2001.
23. Rossetti AO, Mortati KA, Black PM, Bromfield EB: Simple partial seizures
with hemisensory phenomena and dysgeusia: An insular pattern. Epilepsia
46:590–591, 2005.
24. Ryvlin P, Minotti L, Demarquay G, Hirsch E, Arzimanoglou A, Hoffman D,
Guénot M, Picard F, Rheims S, Kahane P: Nocturnal hypermotor seizures,
suggesting frontal lobe epilepsy, can originate in the insula. Epilepsia
47:755–765, 2006.
25. Silfvenius H, Gloor P, Rasmussen T: Evaluation of insular ablation in surgi-
cal treatment of temporal lobe epilepsy. Epilepsia 5:307–320, 1964.
26. Sindou M, Guenot M, Isnard J, Ryvlin P, Fischer C, Mauguière F: Temporo-
mesial epilepsy surgery: Outcome and complications in 100 consecutive adult
patients. Acta Neurochir (Wien) 148:39–45, 2006.
27. Talairach J, Bancaud J: Stereotaxic approach to epilepsy. Methodology of
anatomo-functional stereotaxic investigations. Progr Neurol Surg 5:297–354,
1973.
28. Talairach J, Tournoux P: Co-Planar Stereotaxic Atlas of the Human Brain, 3-
dimensional Proportional System: An Approach to Cerebral Imaging. Stuttgart,
New York, Georg Thieme Verlag, 1988.
29. Tassi L, Colombo N, Cossu M, Mai R, Francione S, Lo Russo G, Galli C,
Bramerio M, Battaglia G, Garbelli R, Meroni A, Spreafico R: Electroclinical,
MRI and neuropathological study of 10 patients with nodular heterotopia,
with surgical outcomes. Brain 128:321–337, 2005.
30. Türe U, Yas¸argil DC, Al-Mefty O, Yas¸argil MG: Topographic anatomy of the
insular region. J Neurosurg 90:720–733, 1999.
31. Varnavas GG, Grand W: The insular cortex: Morphological and vascular
anatomic characteristics. Neurosurgery 44:127–138, 1999.
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AQ:7
AQ:8

Author Query
AQ 1: Please spell out/translate “INSERM U836,” if appropriate.
AQ 2: Please spell out/translate “CTRS-IDEE,” if appropriate.
AQ 3: Callout for Table 1 ok here? It was moved from the subhead per journal style.
AQ 4: Is Bioscan the name of the manufacturer? City where they’re located?
AQ 5: City in France where ISS is located?
AQ 6: City in France where Besancon is located?
AQ 7: Please clarify first author ’s name in reference 10 and provide editor’s last name.
AQ 8: For reference 12, provide English translation of article title and state what language this was
published in.
AQ 9: Please provide sharper images for Figs. 3-5.
Table Query
TQ 1: Is NA not available or not applicable?
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