Association of Cortical Stimulation-Induced Seziure With Surgical
Outcome in Patients With Focal Drug-Resistant EpilepsyCuello Oderiz C, von Ellenrieder N, Dubeau F, et al. JAMA
Neurol. 2019.
Importance:
Cortical stimulation is used during presurgical epilepsy evaluation
for functional mapping and for defining the cortical area
responsible for seizure generation. Despite wide use of cortical
stimulation, the association between cortical stimulation–induced
seizures and surgical outcome remains unknown.
Objective:
To assess whether the removal of the seizure-onset zone resulting
from cortical stimulation is associated with a good surgical
outcome.
Design, Setting, and Participants:
This cohort study used data from 2 tertiary epilepsy centers:
Montreal Neurological Institute in Montreal, Quebec, Canada, and
Grenoble Alpes University Hospital in Grenoble, France. Participants
included consecutive patients (n = 103) with focal drug-resistant
epilepsy who underwent stereoelectroencephalography between January
1, 2007, and January 1, 2017. Participant selection criteria were
cortical stimulation during implantation, subsequent open surgical
procedure with a follow-up of 1 or more years, and complete
neuroimaging data sets for superimposition between intracranial
electrodes and the resection.
Main Outcomes and Measures:
Cortical stimulation–induced typical electroclinical seizures, the
volume of the surgical resection, and the percentage of resected
electrode contacts inducing a seizure or encompassing the cortical
stimulation–informed and spontaneous seizure-onset zones were
identified. These measures were correlated with good (Engel class I)
and poor (Engel classes II-IV) surgical outcomes. Electroclinical
characteristics associated with cortical stimulation–induced
seizures were analyzed.
Results:
In total, 103 patients were included, of whom 54 (52.4%) were female,
and the mean (standard deviation) age was 31 (11) years. Fifty-nine
(57.3%) patients had cortical stimulation–induced seizures. The
percentage of patients with cortical stimulation–induced
electroclinical seizures was higher in the good outcome group than
in the poor outcome group (31 [70.5%] of 44 vs 28 [47.5%] of 59;
P = .02). The percentage of the resected
contacts encompassing the cortical stimulation–informed
seizure-onset zone correlated with surgical outcome (median [range]
percentage in good vs poor outcome: 63.2% [0%-100%] vs 33.3%
[0%-84.6%]; Spearman ρ = 0.38; P = .003). A similar
result was observed for spontaneous seizures (median [range]
percentage in good vs poor outcome: 57.1% [0%-100%] vs 32.7%
[0%-100%]; Spearman ρ = 0.32; P = .002). Longer
elapsed time since the most recent seizure was associated with a
higher likelihood of inducing seizures (>24 hours: 64.7% vs
<24 hours: 27.3%; P = .04).
Conclusions and Relevance:
Seizure induction by cortical stimulation appears to identify the
epileptic generator as reliably as spontaneous seizures do; this
finding might lead to a more time-efficient intracranial presurgical
investigation of focal epilepsy as the need to record spontaneous
seizures is reduced.
Commentary
Cortical stimulation (CS)–induced seizures were first reported during the early days
of neurosurgery when intraoperative electrical CS elicited patient’s habitual auras.[1,2] Since then CS has been used to delineate the epileptogenic zone (EZ) in
patients undergoing invasive presurgical investigations for pharmacoresistant
epilepsy. The EZ has been defined as the region that produces the complete ictal
electroclinical pattern.[3] Most of the data published on CS-induced seizures are restricted to anecdotal
reports, and what is available relates mostly to stimulation studies using
stereoelectroencephalography (SEEG). Until now the clinical utility of CS-elicited
seizures to delineate the EZ was not well established because it had not been
methodically investigated.Two main schools of thought have been recognized: One born in France where CS-induced
seizures have been routinely used as part of the invasive surgical workup and have
helped define the EZ since the work of Bancaud and Talairach,[3,4] and another born in North America where epileptologists, influenced by
Penfield’s work, do not traditionally rely on the use of CS-induced seizures in the
invasive surgical workup. In the North American approach, CS-induced seizures have
largely been considered the by-product of CS procedures aimed at defining eloquent
cortex, and many centers do not systematically perform CS to elicit seizures due to
concern that symptoms may arise from areas remote to the stimulated site.Cuello Oderiz and colleagues addressed this CS dilemma in the article that is the
subject of this commentary. Their main objective was to assess whether removal of
the seizure-onset zone identified by CS is associated with a good surgical outcome.
This in turn would prove the utility of CS-induced seizures in the identification of
the EZ. They performed a retrospective analysis of a 10-year SEEG data set from the
Montreal Neurological Institute and the Grenoble Alpes University Hospital. A total
of 103 patients who underwent SEEG for presurgical evaluation with >1 year
postsurgical follow-up were included in the study. Both their spontaneous seizures
and the CS-induced seizures were analyzed. All patients underwent CS while receiving
their home antiepileptic medications to decrease the likelihood of inducing atypical
electroclinical seizures, and at least 24 to 48 hours after implant to avoid the
effects of electrode insertion. Atypical seizures were rare in their sample, with
only 7.8% (8/102) and 1.5% (1/66) of patients experiencing them at 50 Hz and 1 Hz
stimulation, respectively. This is important because it is not clear whether
nonhabitual CS-induced seizures have any diagnostic value.[5]Both centers performed CS at 1 Hz and 50 Hz, and both used electrical currents of up
to 5 mA in mesial temporal structures and 8 mA in the neocortex. They were able to
induce electroclinical seizures in 57.3% (59/103) of patients, with a median
response rate of 2 (range: 1-13) CS-induced seizures per patient. Curiously, 3
patients had CS-induced seizures exclusively at 1 Hz. The median current required to
induce electroclinical seizures was 2 mA (range: 0.3-4). A significant difference in
the median current was found between stimulating at 1 Hz and at 50 Hz, with higher
current (3 [2-3] mA) needed when stimulating at lower frequency (vs 2 [0.3-4] mA;
P < .001) in order to induce seizures. However, a potential
benefit of stimulating at low frequency first is the lower occurrence of
after-discharges if high-frequency stimulation is avoided. Previous reports
suggested that not only high-frequency CS had a greater chance of eliciting habitual
seizures but also produced more unexpected clinical responses.[6] The investigators also found a higher likelihood of CS-induced seizures in
patients whose most recent seizure was more than 24 hours before stimulation (63.9%
for patients with >24 hours vs 25.0% for patients with <24 hours;
P = .02).The investigators hypothesized that CS-induced seizures provide similar information
regarding the EZ as spontaneous seizures. They evaluated the performance of the
CS-informed seizure-onset zone for the delineation of the EZ by calculating the
percentage of the induced seizure-onset zone contacts that were resected and
correlating this information with postsurgical seizure outcomes. They analyzed
coregistered magnetic resonance and computer tomography images of electrode contacts
and resection cavities. On the basis of the superposition of the surgical cavity
with the seizure-onset zone electrodes, they calculated the percentage of resected
seizure-onset zone contacts for the spontaneous and CS-informed seizures and the
percentage of resected channels inducing typical electroclinical seizures. The
percentage of patients with a CS-induced seizure was higher in the good outcome
group (Engel class I) compared to the poor outcome group (Engel classes II-IV) with
70.5% (31/44) vs 47.5% (28/59; P = .02), respectively. In addition,
the median percentage of resected CS-informed seizure-onset contacts was higher in
the good than in the poor outcome group (63.2% [0%-100%] vs 33.3% [0%-84.6%];
P = .003). A similar result was observed for spontaneous
seizures with 57.1% (0%-100%) resected seizure-onset contacts in the good and 32.7%
(0%-100%) in the poor outcome groups (P = .002). These data
suggested that inducing a seizure was helpful in defining the EZ and also
corroborated that the electrodes implanted covered the EZ appropriately.This study provides solid evidence about the utility of CS-induced seizures in
identifying the EZ and provides a guide for its CS mapping with SEEG. But there are
some known limitations to this technique. In CS-induced seizures, ideally the
symptoms are generated during the stimulation, and before significant propagation of
the electrical discharge, which ensures close colocalization of the symptomatogenic
area. However, sometimes spontaneous seizures arise in relatively silent areas of
cortex and the initial symptom of the habitual seizures occurs during the
propagation of the ictal activity, thus a CS-induced aura matching typical
symptomatology can falsely localize the noneloquent EZ. In addition,
after-discharges (epileptiform discharges elicited by and outlasting CS) may briefly
propagate to areas functionally connected to the EZ and produce symptoms consistent
with habitual auras by activating areas distant to the stimulated electrodes. In
this case, the CS-induced habitual aura can falsely localize to the stimulated
electrodes. Of note, a previous study on after-discharges did not find any
consistent relationship between the site of stimulus eliciting after-discharges and
that of spontaneously appearing seizures.[6] Although the reader is encouraged to use the aid of CS-induced seizures to
define the EZ, this should always occur after developing a good understanding of the
patient’s habitual ictal symptomatology and in the context of previously captured
spontaneous habitual seizures ideally with SEEG (or with scalp
electroencephalography if the seizures cannot be spontaneously captured on SEEG).
Epileptologists who are in need of capturing seizures within a short time frame due
to the patient-driven factors, such as increased risk of complications, may consider
CS with the purpose of inducing habitual seizures as long as they take into
consideration the limitations of this technique.