ARTICLE
Auteur(s) : Ajay
Gupta
Section of Pediatric Epilepsy, Department of Neurology,
Cleveland Clinic Foundation, Cleveland OH, USA
The challenge of defining and localizing the epileptogenic zone is
a key step in selecting patients for surgical treatment of
epilepsy. Several general principles from two major approaches, the
North American and French/Italian schools, guide us in evaluating
epilepsy patients for surgery (Talairach et al. 1974, Rosenow and
Luders 2001). However, the application of tests, their
interpretation, and how they complement each other in defining the
epileptogenic zone remains unique for each individual patient. We
present an illustrative case with a seizure-free outcome after
surgery in order to discuss the complex interplay of a variety of
techniques that were used to localize and define the epileptogenic
zone in this case. Whenever possible, we also discuss the
similarities and differences in approach to this patient’s
pre-surgical evaluation using the North American and French/Italian
schools of thought.
Case report
History
A 25-year-old, right-handed male presented for management of
intractable seizures that had begun at the age of seven years. He
had no prior illness or identifiable risk factors for epilepsy. The
patient reported a consistent aura before most of his seizures,
which was characterized by hallucinatory distortion of familiar
sounds such as ringing, human crying or television sounds. Sounds
were perceived in both ears. A few seconds later, he would lose
awareness, and witnesses reported the patient to be restless,
moving and stiffening his trunk, and unresponsiveness for 1-2
minutes. He had 2-3 seizures a day; 25% of the episodes being
followed by a generalized tonic-clonic seizure for an additional
2-3 minutes. After regaining awareness, he had marked difficulty in
finding his words. He also usually felt exhausted and reported
headache (no post-ictal deficit?). He had tried unsuccessfully
several medications including phenytoin, carbamazepine, gabapentin,
valproate, lamotrigine and levatiracetam as monotherapy or in
various combinations. His physical and neurological examination
results were within normal limits. He was a high school graduate,
previously employed as a non-skilled factory worker. He sought
disability services a year prior to our seeing him, and had stopped
working because of the daily seizures.
Scalp-video EEG and pre-surgical work-up
Typical auras followed by complex partial seizures and secondarily
generalized, tonic-clonic seizures were recorded. In one seizure,
he was noted to have right-hand dystonia (before secondary
generalization) and post-ictal aphasia (naming, comprehension, and
repetition). Interictal EEG using scalp and sphenoidal electrodes,
showed sharp waves in the left anterior temporal region ( (figure 1) ) Ictal EEG
showed a 6-7Hz, left temporal sharp rhythm that developed and
evolved 8-17 seconds after the patient announced his aura
(figures 2, 3). A high resolution brain MRI, including
three dimensional, T1-weighted, thin coronal volume acquisition
images, T2-weighted and FLAIR (fluid attenuated inversion recovery)
coronal sequences were normal. Brain FDG-PET (fluorodeoxyglucose
positron emission tomography) showed significant hypometabolism in
the left temporal pole, mesial temporal structures, and extending
up to the mid-lateral temporal region ( (figure 4) ). Ictal SPECT
(single photon emission computed tomography) was attempted
unsuccessfully. Speech and memory lateralization by intra-carotid
amobarbital injection revealed left hemispheric speech and equal,
bilateral memory representation. Neuropsychological evaluation
showed an average, full scale IQ (FSIQ) score of 101 with average
verbal (immediate verbal score 97, delayed verbal score 97) and
visual (immediate visual score 102, delayed visual score 108)
memory scores. The patient was presented in the epilepsy management
conference. A diagnosis of left temporal epilepsy was agreed upon.
It was thought that the possibility of lateral neocortical epilepsy
could not be ruled out because of the auditory aura and atypical
seizure semiology for mesial temporal seizures. Invasive monitoring
over the left mesial and lateral temporal regions was suggested to
further define and localize the epileptogenic zone.
Invasive video EEG evaluation with sub-dural arrays
To further define the location of the epileptogenic zone in the
left temporal region, the patient underwent left craniotomy for
placement of sub-dural arrays. Sub-dural arrays (( figure 5 ), see inset brain
cartoon) were placed over the left lateral temporal region (plate
A, 4x11 electrodes), peri-rolandic and upper sylvian bank (plate B,
5x8 electrodes), left frontal opercular region (plate C, 4x4
electrodes), orbito-frontal region (plate D, 4x4 electrodes), and
basal temporal regions extending from the mesial to lateral surface
covering the anterior (plate E, 1x6 electrodes), mid- (plate F, 1x6
electrodes), and posterior (plate G, 1x6 electrodes) basal temporal
regions. Sub-dural arrays were co-registered with three dimensional
brain MRI images to localize accurately the relationship of the
electrodes to the major anatomical surface landmarks.
Video EEG recording identified a much wider area of interictal
and ictal onset as shown in figures 5-11. Interictal
epileptiform discharges were noted independently over the left
lateral anterior and mid temporal regions ( (figure 5) ) and the
parahippocampal gyrus overlying the mesial structures (( figure 6 )). Ictal
onset was diffuse over the lateral surface of the left temporal
lobe during typical complex partial seizures
(figures 7, 8). During two auditory auras that lasted for
1 minute without evolving into a motor seizure, ictal EEG seizures
began and remain localized over the left para-hippocampal gyrus
(figures 9, 10). Cortical mapping was also done by
electric stimulation (Grass stimulator, 50Hz, 1-15mamp, bipolar and
biphasic stimulation) over the A and C plate and eloquent areas for
speech and language were identified ( (figure 11) ). During brain
mapping, patient reported his typical auditory auras at two
electrodes and had a complex partial seizure at one electrode
(stimulation intensity = 5-6 mamp) over the mid-portion of the
superior temporal gyrus ( (figure 11) ). The patient
was discussed again in the epilepsy surgery management conference.
After discussion of benefits, risks and alternatives with the
patient and family (see discussion) it was decided to proceed with
the resection of the anterior and mid-left superior temporal gyrus
avoiding of Wernicke’s areas ( (figure 12) ).
Post-operative evaluation
Histopathology of the resected brain tissue showed findings of
neuronal heterotopia, architectural disorganization, neuronal
cytomegaly and dysmorphic neurons. Post-operative brain MRI
performed six months after surgery ( (figure 12) ) showed
surgical resection with no new findings of concern. The patient
reported no change in his memory, speech and language function for
routine activities. Neuropsychological testing at six months showed
no significant change in visual (immediate score 121, delayed score
129) and verbal (immediate score 102, delayed score 105) memory
scores. The patient reported no auras or seizures at his two year
follow-up visit. He was able to come off two medications and is
currently on carbamazepine monotherapy.
Discussion
This patient illustrates some of the many challenges in the
accurate localization of the epileptogenic zone. Using the North
American approach (refer to article by Lüders et al. 2006), table
1( Table 1 ) summarizes the contribution
of each test in the localization of various cortical zones in this
patient. The patient’s history, video EEG evaluation combined with
scalp EEG and brain PET suggested the location of the epileptogenic
zone to be in the left temporal lobe, most likely in the mesial
temporal regions. However, there were several unusual findings in
this patient, which meant that this was not a straightforward,
surgical treatment of mesial temporal lobe epilepsy. The unusual
findings included a consistent auditory aura, absence of mesial
temporal sclerosis or any other structural abnormality in the
mesial structures on brain MRI, average memory scores with no
neuropsychological deficits suggesting dominant hippocampal
dysfunction, and suggestion of dominance (memory and language) in
the left hemisphere based on his right-handedness, post-ictal
aphasia, and intracarotid amobarbital test. Sometimes,
differentiation between mesial temporal lobe epilepsy (MTLE) and
neocortical lateral temporal lobe epilepsy (NTLE) is not easy
(Andermann 2003, Burgerman et al. 1995) This is especially true in
patients like ours, where the brain MRI fails to show a structural
lesion. Brain FDG-PET is known to show a much wider region of
hypometabolism, but may not help in the differentiation of MTLE and
NTLE as in our patient, where FDG-PET showed global, left, temporal
hypometabolism.(Hajek et al. 1993) Although in our patient, the
eventual resection (after invasive subdural evaluation) was a
subset of the area that was hypometabolic on the FDG-PET, the
standard anterior temporal lobe resection including the mesial
structures as suggested by FDG-PET, would have posed an
unacceptably high risk of post-operative, verbal memory deficits,
and the posterior margins of a standard resection may not have
reached the final resection. The mesial temporal lobe contains
certain highly epileptogenic structures, and it is well known that
scalp-recorded epileptogenic discharges and seizures may appear
falsely to be originating from the temporal lobe even though they
are due to lesions located outside the temporal lobe in the
lateral, mid-to-posterior lateral temporal lobe, parieto-occipital
regions or even the frontal lobe (Lee et al. 2003, Andermann 2003,
Pacia et al. 1996).
Subsequent evaluation in our patient by subdural arrays
suggested a wider area of irritative and ictal-onset zone in the
left mesial and lateral temporal lobe extending from the anterior
pole to the mid-posterior temporal regions over the superior and
middle temporal gyrus. Using the North American concept of defining
the irritative and actual seizure-onset zones with the subdural
evaluation, the best estimate of the epileptogenic zone was that it
was located somewhere in the left temporal lobe. The patient did
not undergo the three dimensional stereotactic EEG, but applying
the French/Italian view point to the subdural evaluation, left
mesial temporal structures were at least the part of early seizure
spread and were in the epileptogenic zone. It is possible that
invasive recording from three dimensional stereotatically-placed
electrodes at various points in the left temporal lobe could have
better defined the ictal-onset zone. Notably in this particular
case, the only way to record Heschl’s gyrus was to place a depth
electrode inside it. Similarly, the only way to record the T1-T2
sulcus was to use depth electrodes rather than grids or strips that
only record the cortical surface and cannot give access to the
depths of the sulcus. During electrical stimulation of the brain
for mapping eloquent cortex, the patient had a typical auditory
aura and seizure over the mid-superior temporal gyrus close to the
anatomical location of Heschl’s gyrus. Although this finding was
not incorporated in the localization of the epileptogenic zone, it
implies a close relationship of the epileptogenic zone with the
surface area being stimulated under the electrode. A similar
analogy was used by Sir Victor Horsley and his colleagues when
epilepsy surgery was first performed in 1886 (refer to article by
Lüders et al. 2006). After discussion with the patient of the two
surgical alternatives of standard, left temporal lobe resection
versus a limited resection of the mid-portion of the superior
temporal gyrus, it was decided to perform a limited resection of
the superior temporal gyrus including the area under the electrodes
that had led to the stimulation-induced seizures.
Table 1 Contribution of each test in the localization
of various cortical zone in a patient.
|
Tests/observations used
|
Cortical Zones Defined in the Presurgical Evaluation
|
|
|
Irritative zone
|
Ictal onset zone
|
Symptomatogenic zone
|
Functional Deficit Zone
|
Epileptogenic Lesion
|
|
Seizure history/video evaluation
|
|
Aura
|
-
|
-
|
STG (auditory) or temporal (psychic) aura
|
-
|
-
|
|
Right hand dystonia
|
-
|
-
|
Left hemisphere
|
-
|
-
|
|
Post ictal aphasia
|
-
|
-
|
Dominant language hemisphere
|
-
|
-
|
|
Examination
|
|
Clinical exam
|
-
|
-
|
-
|
None
|
-
|
|
Neuropsychological
|
-
|
-
|
-
|
None
|
-
|
|
Neuroimaging
|
|
Brain MRI
|
-
|
-
|
-
|
-
|
None
|
|
Brain PET
|
-
|
-
|
-
|
Left temporal (mesial and lateral)
|
-
|
|
Scalp EEG
|
|
Interictal
|
Left temporal
|
-
|
-
|
-
|
-
|
|
Ictal
|
-
|
Left temporal (likely mesial)
|
-
|
-
|
-
|
|
Electrocorticography
|
|
(subdural arrays)
|
Interictal
|
Left mesial and lateral temporal
|
|
-
|
-
|
-
|
|
Ictal
|
-
|
Left mesial and lateral temporal
|
-
|
-
|
-
|
|
Aura/seizures on electrical stimulation
|
-
|
Left mid superior temporal gyrus
|
-
|
-
|
-
|
Conclusion
The epileptogenic zone is a useful theoretical concept in the
evaluation of patients for surgical treatment. Accurate definition
and localization of the epileptogenic zone should be individualized
in each patient based on the critical interpretation of all
available data.
References
Andermann, 2003 Andermann F. Pseudotemporal versus neocortical
temporal epilepsy: things aren’t always where they seem to be.
Neurology 2003; 61: 732-3.
Burgerman et al 1995 Burgerman RS, Sperling MR,
French JA, et al. Comparison of mesial versus neocortical
onset temporal lobe seizures: neurodiagnostic findings and surgical
outcome. Epilepsia 1995; 36: 662-70.
Hajek et al 1993 Hajek M, Antonini A,
Leenders KL, et al. Mesiobasal versus lateral temporal
lobe epilepsy: metabolic differences in the temporal lobe shown by
interictal 18F-FDG positron emission tomography. Neurology 1993;
43: 79-86.
Lee et al 2003 Lee SK, Yun CH, Oh JB, et al.
Intracranial ictal onset zone in nonlesional lateral temporal lobe
epilepsy on scalp ictal EEG. Neurology 2003; 61: 757-64.
Lüders et al 2006 Lüders HO, Najm I, Nair D,
Widdess-Walsh P, Bingman W. The epileptogenic zone:
general principles. Epileptic Disord 2006; 8(Suppl. 2): S1-S9.
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epilepsy. Ann Neurol 1996; 40: 724-30.
Rosenow et Luders, 2001 Rosenow F, Luders H.
Presurgical evaluation of epilepsy. Brain 2001; 124: 1683-700.
Talairach et al 1974 Talairach J, Bancaud J,
Szikla G, et al. New approach to the neurosurgery of
epilepsy. Stereotaxic methodology and therapeutic results. 1.
Introduction and history. Neurochirurgie 1974; 20: 1-240.
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