ISRN Neurology

Volume 2013 (2013), Article ID 148519, 7 pages

http://dx.doi.org/10.1155/2013/148519

Clinical Study

Somatosensory and Pharyngolaryngeal Auras in Temporal Lobe Epilepsy Surgeries

Alexander G. Weil,¹ Werner Surbeck,¹ Ralph Rahme,¹ Alain Bouthillier,¹ Adil Harroud,¹ and Dang Khoa Nguyen²

¹Division of Neurosurgery, Notre Dame Hospital, University of Montreal Medical Center (CHUM), Montreal, QC, Canada

²Division of Neurology, Notre Dame Hospital, University of Montreal Medical Center (CHUM), 1560 Rue Sherbrooke Est, Montreal, QC, Canada, H2L 4M1

Received 18 April 2013; Accepted 8 May 2013

Academic Editors: C.-M. Chen, C.-Y. Hsu, K. W. Lange, L. Manni, T. Mezaki, and K. R. Pennypacker

Copyright © 2013 Alexander G. Weil et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

Purpose. Somatosensory (SSA) and pharyngolaryngeal auras (PLA) may suggest an extratemporal onset (e.g., insula, second somatosensory area). We sought to determine the prognostic significance of SSA and PLA in temporal lobe epilepsy (TLE) patients undergoing epilepsy surgery. Methods. Retrospective review of all patients operated for refractory TLE at our institution between January 1980 and July 2007 comparing outcome between patients with SSA/PLA to those without. Results. 158 patients underwent surgery for pharmacoresistant TLE in our institution. Eleven (7%) experienced SSA/PLA as part of their seizures. All but one had lesional (including hippocampal atrophy/sclerosis) TLE. Compared to patients without SSA or PLA, these patients were older , had a higher prevalence of early ictal motor symptoms and prior CNS infection , and were less likely to have a localizing SPECT study . A favorable outcome was achieved in 81.8% of patients with SSA and/or PLA and 90.4% of those without SSA or PLA . Conclusion. Most patients with pharmacoresistant lesional TLE appear to have a favorable outcome following temporal lobectomy, even in the presence of SSA and PLA.

1. Introduction

Recent evidence suggests that failure to recognize insular cortex seizures could be responsible for some cases of surgical failure in patients with temporal lobe epilepsy (TLE) [1–5]. Insular seizures may mimic TLE or may coexist with temporal seizures, an entity referred to as temporal plus epilepsy [6–8]. Clinical observation of patients with insular seizures proven by depth recordings and after cortical stimulation using insular contacts has revealed a high prevalence of somatosensory and pharyngolaryngeal auras (SSA and PLA, resp.), including a characteristic sensation of laryngeal constriction (LC) [1–3, 9–15]. In this study, we sought to determine the prevalence and prognostic significance of SSA and PLA in TLE patients undergoing epilepsy surgery.

2. Materials and Methods

We performed a retrospective chart review of all patients who underwent surgery for refractory TLE at our institution between January 1980 and July 2007. All patients underwent a comprehensive epilepsy surgical workup, including complete anamnesis and neurological examination, neuropsychological evaluation, and video-electroencephalographic (VEEG) monitoring with scalp electrodes. Magnetic resonance imaging (MRI) were performed in all patients after 1992. Single photon emission computed tomography (SPECT) and ¹⁸F fluorodeoxyglucose positron emission tomography (PET) was performed in more recent cases. Invasive VEEG recordings were obtained in the majority of patients before the availability of MRI. Since then, electrode implantation has been performed only in well-selected cases following evaluation by our epilepsy multidisciplinary team.

Collected data included patient demographics, cause of epilepsy and risk factors, seizure type and clinical features, presence and characteristics of SSA and/or PLA, number of antiepileptic drugs tried, type of resective surgery, histopathological findings, and final outcome in seizure control. SSAs were defined as a perceptual experience of tingling, numbness, electric-shock sensation or pain, occurring in isolation as a simple partial seizure or as an early manifestation (i.e., aura) of a complex partial seizure [16–18]. PLAs were defined as ictal pharyngolaryngeal symptoms of paresthesia (tingling or burning), discomfort, or sensation of throat constriction of varying intensity [1–3, 19–22]. Other early ictal symptoms suggestive of operculoinsular involvement were also documented, including motor, epigastric viscerosensory, cephalic, auditory, and dysphasic symptoms. Outcome was classified using the Engel classification system [23]. A favorable outcome was defined as Engel I or II. The study protocol was approved by the institutional review board.

We compared subgroups of patients with SSA/PLA to those without SSA/PLA. Categorical (binomial) variables were compared using Boschloo exact unconditional test and continuous variables using the Wilcoxon rank sum test. Statistical analysis was performed using R [24, 25] and PASW Statistics 18 (SPSS Inc., Chicago, IL, USA). A value <0.05 was considered to be statistically significant.

3. Results

3.1. Study Population and Patient Characteristics

During the study period, a total of 158 patients underwent surgery for pharmacoresistant TLE in our institution. This patient population consisted of 74 women (47%) and 84 men (53%) with an average age of 33.9 years (range 13–62) and an average duration of epilepsy of 21 years (range 1–46). Risk factors for epilepsy included CNS infection in 20 (12.7%), head trauma in 12 (5%), positive family history for epilepsy in 33 (21%), febrile seizures in 34 (22%), perinatal complications in 10 (6%), and developmental delay in 10 (6%). MRI was obtained in 114 (72%) of these patients, revealing abnormalities in most cases (87%), hippocampal atrophy (HA) without sclerosis in 22 (19%), hippocampal sclerosis (HS) in 54 (47%) and other temporal lobe abnormalities in 51 patients (32%). Ictal scalp EEG suggested unilateral temporal lobe origin in 88 (58%) cases. Intracranial electrodes were implanted in 76 patients (48%). Sixty-five (67%) ictal SPECT scans localized the seizure focus to one temporal lobe. FDG PET was only obtained in 15 patients, and it localized the seizure focus to the temporal lobe in 13 of these patients (87%). Patients had tried 4.4 AEDs (range 2–12) on average prior to surgery. Twenty-seven underwent selective amygdalo-hippocampectomy (SAH) (17%), 75% underwent anterior medial temporal lobectomy (AMTL) (), 4% AMTL and lesionectomy (), and 4% lesionectomy (). AMTL involved resection of 3.5–7 cm T2, T3, most (two-thirds) of the amygdala, and a radical hippocampectomy. Pathology confirmed HS in 69 (44%), HS and another pathology in 9 (5.7%), ganglioglioma in 6 (3.8%), glioma in 5 (3.2%), cavernoma in 4 (3%), focal cortical dysplasia in 4 (3%), gliosis in 3 (2%), dysembryoplastic neuroepithelial tumor in 2 (1%), was normal in 24 (15%), and was inconclusive in 16 (10%).

3.2. Subgroup Analysis: Patients with SSA and/or PLA

A-General Characteristics. Of all patients, only 11 (7%) experienced symptoms of SSA and/or PLA as part of their seizures: SSA (, 5%), PLA (, 1.2%), or both (, 0.6%) (Table 1). This group of patients was composed of 3 men and 8 women with mean epilepsy duration of 27 years (range 2–46) and mean age at surgery of 40 years (range 21–55). Risk factors for epilepsy included central nervous system (CNS) infections in 4 patients, perinatal anoxia in 1, febrile seizures in 1, and family history of epilepsy in 1 (Table 2). No risk factors were identified in 4 patients. MRI was obtained in 10 patients, revealing HS in 6, HA in 2, a posterior temporal cavernous malformation in 1, and a fusiform gyrus pilocytic astrocytoma in 1. Scalp EEG recordings localized the seizure focus to the temporal lobe in 7 patients (64%), lateralized the focus to the hemisphere ipsilateral to the resection side in 3 (27%), and were non-localizing in 1 (9%) patient. Seven patients underwent preoperative ictal SPECT, which localized the seizure focus to the temporal lobe in 2 and was nonlocalizing in 5 cases. Intracranial electrodes were implanted in 6 patients, enabling localization of seizure focus to the mesial temporal lobe in all of them. Patients were on an average of 4.8 antiepileptic medications (range 2–9). Surgical procedures included AMTL in 7 patients, SAH in 2, lesionectomy and temporal corticectomy in 1, and simple lesionectomy in 1. Three patients underwent a second operation during the study period (before outcome assessment). One patient with previous cavernoma lesionectomy and corticectomy underwent second operation with electrocorticography (ECoG) guided further perilesional corticectomy. Two patients with initial SAH underwent a second resective surgery consisting of radical temporal lobectomy, including the superior temporal gyrus. Pathology demonstrated HS either alone () or with another pathology () in 8 patients, a cavernous malformation in 1, a pilocytic astrocytoma in 1, and was inconclusive in 1.

Table 1: Demographics and clinical features in 11 patients with SSA and/or PVA.

Pt
Sex, age (yr)
Duration of epilepsy (yr)
Seizure characteristics

Aura
Late manifestations

1
F, 47
24
L hand SS, cephalic
L hand dystonic, R versive, oroalimentary automatisms, L versive, gestural automatisms

2
F, 21
2
bilateral forearm SS
oroalimentary and manual automatisms

3
M, 46
26
olfactory, gustatory, epigastric VS, hypersalivation, R palpebral myoclonic, R leg SS, mnemonic déja vu
oroalimentary and manual automatism, affective (psychomotor agitation)

4
F, 55
15
L hemibody SS, epigastric VS, face myoclonic,
R versive, oroalimentary automatism, L hand dystonic

5
F, 36
35
R hand SS, LC, R arm SM
R arm dystonic, R arm, and R hemiface myoclonic

6
F, 47
27
2 types: 1, L hemiface then L hemitongue, then L arm, then L leg SS, cephalic; 2:affective (fear)
type 2: affective (fear), L arm manual and oroalimentary automatisms, verbal (jargon) automatisms, thrusting, then L motor tonic L versive then L hemiface myoclonic

7
M, 39
38
2 types: 1, LC and laryngeal pain; 2, epigastric VS
LOC, oroalimentary automatisms, dyspraxia

8
F, 43
37
LC, epigastric VS, then mnesic (déjà vu, deja vecu), generalized warmth
2 types, 1, aura only; 2, LOC, gestural automatisms

9
F, 34
17
2 types: 1, epigastric VS, olfactory, déjà vu; 2, R hemiface SS
oroalimentary automatisms, manual automatisms, vocal, R face myoclonic, generalization

10
F, 26
19
2 types: 1, epigastric VS, affective; 2, bilateral leg SS
auditory (remote noise/vice), LOC, oroalimentary automatisms, manual automatisms, hypersalivation, verbal

11
M, 48
46
2 types: 1, dysgeusia, affective; 2, L hemibody SS
LOC, oroalimentary automatisms, hypermotor agitation, R versive, R arm dystonia, generalization

Pt: patient; M: male; F: female; yr: years; L: left; R: right; SS: somatosensory; LC: laryngeal constriction; SM: somatomotor; LOC: loss of contact; VS: viscerosensory.

Table 2: Findings of presurgical work-up, surgical procedures performed, pathology results, and final outcomes in 11 patients with SSA and/or PVA.

Pt
Risk factor
MRI
Ictal SPECT
sEEG
Intracranial electrode study
First surgery
Second surgery
FU

(yrs)
Outcome
Re-investigation
Third surgery
Final outcome

Performed

(y/n)
Coverage
Focus

1
None
R PT Cavernoma
NL
Loc
N
—
—
R cavernoma resection, corticectomy
ECoG, perilesional corticectomy
4
IIIa
R post T, R T et lat inf, R H, R I
R ATL
Ia

2
Fam
L T pilocytic astrocytoma
NL
Loc
N
—
—
L tumor resection
—
1
Ia (Rx)
—
—
—

3
None
R HS
—
Loc
N
—
—
R SAH
R ATL including TO
1
IIIa
R I, residual TL, FPO, OF
R insulectomy
Ia

4
None
R HS
NL
Loc
Y
R F, T, Pd, A, H
R MT
R ATL
—
7
IIb

—
—

5
Encephalitis (6 months) residual R hemiparesis, mental retardation
L HS, L hemisph atrophia
L
Lat
Y
L H, L A, L subtemp ant post, L FT
L MT
L ATL
—
9
Ib

—
—

6
None
R HS
L
Loc
N
—
—
R ATL
—
8
Ia (Rx)
—
—
—

7
Viral encephalitis (8 months)
L HA
—
Loc
N
—
—
L ATL
—
13
Ia (No Rx)
—
—
—

8
Encephalitis (8 months)
R HA
NL
Loc
Y
R H, R A, L H
R MT
R ATL
—
13
IIc
—
—
—

9
Meningitis (12 months)
L F, L T atrophia, L T gliosis
—
NL
Y
NA
L MT
L ATL
—
4
Ib
—
—
—

10
None
—
—
Lat
Y
R A, R H, R PT, R cingular gyrus ant, R SMA, L H, L cingular gyrus ant
R MT
R ATL
—
10
Ia (No Rx)
—
—
—

11
None
L HS
NL
Lat
N
—
—
L SAH
L ATL (4 cm T1, 5 cm T2, 7 cm T3)
1
IIb
—
—
—

MRI: magnetic resonance imaging; sEEG: scalp EEG; Y: yes; N: no; SSA: somatosensory aura; F: frontal; T: temporal; P: parietal; O: occipital; A: amygdala; H: hippocampus; R: right; L: left; MT: mesial temporal lobe; FU: followup; Fam: family history of epilepsy; PT: posterior temporal; HS: hippocampal sclerosis; HA: hippocampal atrophy; Loc: localized; Lat: lateralized to hemisphere; SAH: selective amygdalohippocampectomy; ATL: anterior temporal lobectomy; ECoG: electrocorticography; TO: temporal operculum; TFG: temporal fusiform gyrus; I: insula; NL: nonlocalizing; hemisph: hemisphere; Rx: medication.

Compared to patients without SSA or PLA, those with SSA and/or PLA were older at surgery (), had a higher prevalence of early ictal motor symptoms (), had a higher rate of CNS infections (), and were less likely to have a localizing SPECT study () (Table 3).

Table 3: Baseline characteristics of patients in the SSA/PVSA group and controls.

Variable
SSA/PVSA ( = 11)
Controls ( = 147)
-value

Demographic

Female sex
8 (72.7%)
66 (44.9%)
0.095

Age at surgery (yrs)
40.18
33.44
0.049

Duration of epilepsy (yrs)
26.91
20.84
0.086

Seizure characteristics

Daily seizures or worse
2 (18.2%)
38 (25.9%)
0.649

Early ictal symptoms suggestive of insular involvement

    Epigastric symptoms
6 (54.5%)
54 (36.7%)
0.280

    Motor symptoms
4 (36.4%)
16 (10.9%)
0.022

    Auditory symptoms
0 (0%)
7 (4.8%)
1.000

    Cephalic symptoms
1 (9.1%)
27 (18.4%)
0.572

    Dysphasic symptoms
0 (0%)
7 (4.8%)
1.000

Generalized seizures
7 (63.6%)
94 (63.9%)
1.000

Status epilepticus
1 (9.1%)
6 (4.1%)
0.296

Number of AEDs tried
5.00
4.36 ( = 144)
0.280

Left side
5 (45.5%)
91 (61.9%)
0.292

Etiology

    History of CNS infection
4 (36.4%)
16 (10.9%)
0.022

    History of head trauma
0 (0%)
12 (8.2%)
1.000

    Family history
1 (9.1%)
32 (21.8%)
0.406

    Febrile seizures
1 (9.1%)
33 (22.4%)
0.405

    Perinatal complications
1 (9.1%)
9 (6.1%)
0.374

    Developmental delay
1 (9.1%)
9 (6.1%)
0.374

imaging

    Normal MRI
0/10 (0%)
15/104 (14.4%)
0.301

    Hippocampal atrophy
2/10 (20%)
20/104 (19.2%)
1.000

    Hippocampal atrophy and sclerosis
6/10 (60%)
48/104 (46.2%)
0.466

Other temporal lesion
5 (45.5%)
46 (31.3%)
0.270

Scalp EEG

    Localizing to TL
7 (63.6%)
81/144 (56.3%)
0.690

    Lateralizing
3 (27.3%)
34/144 (23.6%)
0.641

    Nonlateralizing
1 (9.1%)
29/144 (20.1%)
0.615

SPECT localizing to TL
2/7 (28.6%)
63/89 (70.8%)
0.025

FDG PET

    Normal
0/0 (?)
2/15 (13.3%)
N/A

    Temporal focus
0/0 (?)
13/15 (86.7%)
N/A

Intracranial electrode implantation
6 (54.5%)
70 (47.6%)
0.692

Surgery

    SAH
2 (18.2%)
25 (17%)
0.839

    ATL
7 (63.6%)
111 (75.5%)
0.417

    ATL and lesionectomy
0 (0%)
6 (4.1%)
1.000

    Lesionectomy
2 (18.2%)
5 (3.4%)
0.039

    ECOG
0 (0%)
4 (2.7%)
0.610

Pathology

    Sclerosis
7 (63.6%)
62 (42.2%)
0.179

    Cavernoma
1 (9.1%)
3 (2%)
0.162

    Glioma
1 (9.1%)
4 (2.7%)
0.199

    Ganglioglioma
0 (0%)
6 (4.1%)
1.000

    Focal cortical dysplasia
0 (0%)
4 (2.7%)
0.610

    DNET
0 (0%)
2 (1.4%)
1.000

    Gliosis
0 (0%)
3 (2%)
0.572

    Normal
0 (0%)
24 (16.3%)
0.172

B-Seizure Characteristics. Eight patients had only SSA, 2 had only PLA, and 1 had both SSA and PLA. Of the 9 SSA patients, 7 (77.8%) had strictly unilateral symptoms involving the contralateral hemiface in 2, the contralateral hand in 2, the contralateral hemibody in 1, the ipsilateral leg in 1, and the ipsilateral hemibody in 1. In 1 patient with contralateral hemiface SSA, symptoms progressed in a somatotopic Jacksonian march to the ipsilateral hemitongue, arm, and leg. In 2 patients (22.2%), SSAs were strictly bilateral, involving the legs in 1 and the forearms in the other. In the 3 patients with PLA, symptoms were described as a sensation of pharyngo-laryngeal constriction (), with occasional pharyngeal pain in 1 patient.

C-Surgical Outcomes. Outcomes were assessed in all but 1 patient who was lost to followup in the no SSA/PLA group (). The mean followup was 7.2 years. A favorable outcome (Engel I or II) was achieved in 81.8% (9/11) of patients with SSA and/or PLA and 90.4% (132/146) of those without SSA or PLA () (Table 4). A complete seizure-free outcome (Engel Ia) was observed in 36.4% (4/11) of patients with SSA and/or PLA and 32.2% (47/146) of those without SSA or PVA ().

Table 4: Impact of somatosensory auras (SSA) and pharyngeal viscerosensory auras (PVSA) on surgical outcome.

SSA and/or PVSA
Surgical outcome
Total ()

Engel class I or II ()
Engel class III or IV ()

Yes
9
2
11

No
132
14
146

141
16
157

= 0.244 (Boschloo unconditional exact test).

Since the study period, two patients of the SSA/PLA cohort have undergone invasive reinvestigation for persistent disabling seizures (Table 2). Both have obtained seizure-freedom following a third resection of the temporal lobe and anterior insular cortex, respectively.

4. Discussion

Insular epilepsy should be suspected whenever TLE-like seizures are accompanied by early-occurring LC and/or somatosensory symptoms (SSS), especially those described as unpleasant paresthesias or warmth affecting the perioral region or extending to a large somatic territory, either bilateral or ipsilateral to the seizure focus [1–3, 5]. Although some studies have suggested that patients with pharmacoresistant TLE who exhibit SSA and PLA have a favorable prognosis following temporal lobe surgery [8, 21, 26, 27], others have reported a poor outcome in this patient population [28–30]. The purpose of this study was to determine the prevalence and prognostic significance of SSA/PLA as a potential marker of insular epilepsy and thus a predictor of poor response to surgery in TLE patients.

4.1. Prevalence of SSA and PLA in Surgical TLE Patients

The 5% rate of SSA among surgical TLE patients in the present series is comparable to the 1.7%–14% rates reported in the literature [26, 29, 31–35]. Unlike prospective studies [26] that have reported an 11% incidence of SSA in TLE surgery patients, retrospective series may actually underestimate the real prevalence of SSA, mainly as a result of recall bias. Although viscerosensory auras are frequent (45%) in patients with pharmacoresistant TLE [33], the prevalence of PLA is less well known. Pharyngeal auras have been reported to occur in up to 16.9% of pharmacoresistant TLE and 13% of temporal plus epilepsy cases [8]. The higher prevalence in the series of Barba et al. compared to ours may either reflect a difference in the definition of PLA or a selection bias since all patients in their study had undergone intracranial electrode implantation [8].

4.2. Failure of SSA and PLA to Predict Worse Surgical Outcomes: Significance and Implications

In this study, SSA and/or PLA were not found to be negative prognostic factors in TLE patients undergoing surgery. Our findings are in line with previous reports suggesting that SSA [8, 26, 27] and PLA [21, 22] do not necessarily indicate an extratemporal seizure onset or an independent extratemporal seizure focus in patients with pharmacoresistant temporal lobe-like epilepsy. Our findings would suggest that for the majority of our patients, SSA or PLA was the result of rapid spread of epileptic activity to perisylvian somatosensory structures such as the insular cortex and second somatosensory cortex (SII) [1, 2, 5, 6, 22, 26, 35–37] rather than from an extratemporal seizure focus.

Because almost all of the patients in the SSA/PLA cohort had lesional TLE, it is not possible to draw any conclusion about the prognosis of SSA/PLA in nonlesional TLE surgery patients. For the latter, it would remain prudent to perform an intracranial study to rule out an extratemporal focus. For the former, however, temporal lobe surgery without preoperative invasive investigation would appear to result in a good outcome for most. Although independent insular seizures have been known to coexist with temporal lobe seizures and HA/HS (i.e., the hippocampal MRI abnormality may represent only the tip of the iceberg of a larger pathological substrate), it may be that this is a rare occurrence which does not necessarily warrant systematic invasive investigation in the presence of SSA/PLA. In our series, this situation was encountered in only one subject (patient 3). Isnard et al. [2] sampled the insula in 50 consecutive patients with TLE on the basis of ictal symptoms or scalp VEEG data suggesting an early spread of seizures either to the suprasylvian opercular cortex (e.g., lip and face paresthesiae, tonic-clonic movements of the face, dysarthria, motor aphasia, gustatory illusions, hypersalivation, and postictal facial paresis) or the infrasylvian opercular cortex (e.g., auditory hallucinations, early sensory aphasia). Only five patients (10%) had seizures originating from the insular cortex while in 43 patients (86%), they propagated to the insula after a temporal onset. Hopefully, further clinical observations and imaging techniques (e.g., magnetoencephalography) will allow us to better identify the small subset of patients who will most benefit from an implantation prior to surgery [38, 39].

4.3. Study Limitations

The retrospective nature of this study may be associated with a recall bias for the incidence and characteristics of SSA/PLA. These auras are very subjective and are very much dependent on the history taking skills and detailed attention of the examiner. Furthermore, because they were not assessed in a standardized way, the timing of these auras during a seizure may not always be clear with regards to other subjective symptoms patients may have felt at seizure onset. Whether SSA/PLA occurs as the initial or only aura may be important [28, 29]. Many of the patients in this report had multiple auras, some more typical of mesial temporal lobe epilepsy (déjà vu, epigastric). Finally, as mentioned previously, our data does not allow drawing conclusions about the prognosis of SSA/PLA in non-lesional temporal lobe-like epilepsy as numbers are too small. It is possible that these patients have been selected out already by careful presurgical evaluation and found to have extratemporal or temporal plus epilepsy.

5. Conclusion

Most patients with pharmacoresistant lesional TLE appear to have a favorable outcome following temporal lobectomy, even in the presence of SSA and PLA.

References

J. Isnard, M. Guenot, K. Ostrowsky, M. Sindou, and F. Mauguiere, “The role of the insular cortex in temporal lobe epilepsy,” Annals of Neurology, vol. 48, no. 4, pp. 614–623, 2000.

J. Isnard, M. Guénot, M. Sindou, and F. Mauguière, “Clinical manifestations of insular lobe seizures: a stereo-electroencephalographic study,” Epilepsia, vol. 45, no. 9, pp. 1079–1090, 2004.

D. K. Nguyen, D. B. Nguyen, R. Malak et al., “Revisiting the role of the insula in refractory partial epilepsy,” Epilepsia, vol. 50, no. 3, pp. 510–520, 2009.

R. Malak, A. Bouthillier, L. Carmant et al., “Microsurgery of epileptic foci in the insular region: clinical article,” Journal of Neurosurgery, vol. 110, no. 6, pp. 1153–1163, 2009.

A. Desai, B. C. Jobst, V. M. Thadani et al., “Stereotactic depth electrode investigation of the insula in the evaluation of medically intractable epilepsy: clinical article,” Journal of Neurosurgery, vol. 114, no. 4, pp. 1176–1186, 2011.

P. Kahane, D. Hoffmann, G. Lo Russo, A. L. Benabid, and C. Munari, “Perisylvian cortex involvement in seizures affecting the temporal lobe,” in Limbic Seizures in Children, G. Avanzini, A. Beaumanoir, and L. Mira, Eds., pp. 115–127, John Libbey, London, UK, 2001.

P. Ryvlin and P. Kahane, “The hidden causes of surgery-resistant temporal lobe epilepsy: extratemporal or temporal plus?” Current Opinion in Neurology, vol. 18, no. 2, pp. 125–127, 2005.

C. Barba, G. Barbati, L. Minotti, D. Hoffmann, and P. Kahane, “Ictal clinical and scalp-EEG findings differentiating temporal lobe epilepsies from temporal “plus” epilepsies,” Brain, vol. 130, no. 7, pp. 1957–1967, 2007.

W. Penfield and M. E. Faulk, “The insula: further observations on its function,” Brain, vol. 78, no. 4, pp. 445–470, 1955.

J. Isnard, “Insular epilepsy: a model of cryptic epilepsy. The Lyon experience,” Revue Neurologique, vol. 165, no. 10, pp. 746–749, 2009.

A. O. Rossetti, K. A. Mortati, P. M. Black, and E. B. Bromfield, “Simple partial seizures with hemisensory phenomena and dysgeusia: an insular pattern,” Epilepsia, vol. 46, no. 4, pp. 590–591, 2005.

S. Gil Robles, P. Gelisse, H. El Fertit et al., “Parasagittal transinsular electrodes for stereo-EEG in temporal and insular lobe epilepsies,” Stereotactic and Functional Neurosurgery, vol. 87, no. 6, pp. 368–378, 2009.

C. Stephani, G. Fernandez-Baca Vaca, R. MacIunas, M. Koubeissi, and H. O. Lüders, “Functional neuroanatomy of the insular lobe,” Brain Structure and Function, vol. 216, no. 2, pp. 137–149, 2011.

A. Afif, L. Minotti, P. Kahane, and D. Hoffmann, “Anatomofunctional organization of the insular cortex: a study using intracerebral electrical stimulation in epileptic patients,” Epilepsia, vol. 51, no. 11, pp. 2305–2315, 2010.

M. Pugnaghi, S. Meletti, L. Castana, et al., “Features of somatosensory manifestations induced by intracranial electrical stimulations of the human insula,” Clinical Neurophysiology, vol. 122, no. 10, pp. 2049–2058, 2011.

F. Mauguiere and J. Courjon, “Somatosensory epilepsy. A review of 127 cases,” Brain, vol. 101, no. 2, pp. 307–332, 1978.

W. T. Blume, H. O. Lüders, E. Mizrahi, C. Tassinari, W. Van Emde Boas, and J. Engel, “Glossary of descriptive terminology for ictal semiology: report of the ILAE Task Force on classification and terminology,” Epilepsia, vol. 42, no. 9, pp. 1212–1218, 2001.

I. E. B. Tuxhorn, “Somatosensory auras in focal epilepsy: a clinical, video EEG and MRI study,” Seizure, vol. 14, no. 4, pp. 262–268, 2005.

W. Penfield and H. Jasper, Epilepsy and the Functional Anatomy of the Human Brain, Little Brown, Boston, Mass, USA, 1954.

W. T. Blume, D. C. Jones, G. B. Young, J. P. Girvin, and R. S. McLachlan, “Seizures involving secondary sensory and related areas,” Brain, vol. 115, no. 5, pp. 1509–1520, 1992.

L. Carmant, E. Carrazana, U. Kramer et al., “Pharyngeal dysesthesia as an aura in temporal lobe epilepsy,” Epilepsia, vol. 37, no. 9, pp. 911–913, 1996.

K. Garganis, C. Papadimitriou, K. Gymnopoulos, and J. Milonas, “Pharyngeal dysesthesias as an aura in temporal lobe epilepsy associated with amygdalar pathology,” Epilepsia, vol. 42, no. 4, pp. 565–571, 2001.

J. Engel Jr., P. Van Ness, T. Rasmussen, and L. Ojemann, “Outcome with respect to epileptic seizures,” in Surgical Treatment of the Epilepsies, J. Engel Jr., Ed., pp. 609–621, Raven Press, New York, NY, USA, 1993.

R Development Core Team, R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing, Vienna, Austria, 2012.

C. Peter, “Exact: Unconditional Exact Tests,” R package version 1.1, http://CRAN.R-project.org/package=Exact, 2012

J. C. Erickson, L. E. Clapp, G. Ford, and B. Jabbari, “Somatosensory auras in refractory temporal lobe epilepsy,” Epilepsia, vol. 47, no. 1, pp. 202–206, 2006.

M. A. Rahal, G. M. De Araújo Filho, L. O. S. F. Caboclo et al., “Somatosensory aura in mesial temporal lobe epilepsy: semiologic characteristics, MRI findings and differential diagnosis with parietal lobe epilepsy,” Journal of Epilepsy and Clinical Neurophysiology, vol. 12, no. 3, pp. 155–160, 2006.

Y. Aghakhani, A. Rosati, F. Dubeau, A. Olivier, and F. Andermann, “Patients with temporoparietal ictal symptoms and inferomesial EEG do not benefit from anterior temporal resection,” Epilepsia, vol. 45, no. 3, pp. 230–236, 2004.

A. E. Elsharkawy, A. H. Alabbasi, H. Pannek et al., “Long-term outcome after temporal lobe epilepsy surgery in 434 consecutive adult patients: clinical article,” Journal of Neurosurgery, vol. 110, no. 6, pp. 1135–1146, 2009.

M. J. Hennessy, R. D. C. Elwes, C. D. Binnie, and C. E. Polkey, “Failed surgery for epilepsy: a study of persistence and recurrence of seizures following temporal resection,” Brain, vol. 123, no. 12, pp. 2445–2466, 2000.

J. A. French, P. D. Williamson, V. M. Thadani et al., “Characteristics of medial temporal lobe epilepsy: I. Results of history and physical examination,” Annals of Neurology, vol. 34, no. 6, pp. 774–780, 1993.

A. K. Gupta, P. M. Jeavons, R. C. Hughes, and A. Covanis, “Aura in temporal lobe epilepsy: clinical and electroencephalographic correlation,” Journal of Neurology Neurosurgery and Psychiatry, vol. 46, no. 12, pp. 1079–1083, 1983.

A. Palmini and P. Gloor, “The localizing value of auras in partial seizures: a prospective and retrospective study,” Neurology, vol. 42, no. 4, pp. 801–808, 1992.

A. Gil-Nagel and M. W. Risinger, “Ictal semiology in hippocampal versus extrahippocampal temporal lobe epilepsy,” Brain, vol. 120, no. 1, pp. 183–192, 1997.

P. Kotagal, H. O. Luders, G. Williams, T. R. Nichols, and J. McPherson, “Psychomotor seizures of temporal lobe onset: analysis of symptom clusters and sequences,” Epilepsy Research, vol. 20, no. 1, pp. 49–67, 1995.

M. Guillaume and G. Mazars, “Cinq cas de foyers épileptogènes insulaires opérés,” Société Française De Neurologie, pp. 766–769, 1949.

H. Lüders and I. Awad, “Conceptual considerations,” in Epilepsy Surgery, H. Lüders, Ed., pp. 51–63, Raven Press, New Yorks, NY, USA, 1991.

M. Heers, S. Rampp, H. Stefan, et al., “MEG-based identification of the epileptogenic zone in occult peri-insular epilepsy,” Seizure, vol. 21, no. 2, pp. 128–133, 2012.

H. M. Park, N. Nakasato, and T. Tominaga, “Localization of abnormal discharges causing insular epilepsy by magnetoencephalography,” Tohoku Journal of Experimental Medicine, vol. 226, no. 3, pp. 207–211, 2012.