Cuello Oderiz C, von Ellenrieder N, Dubeau F, Eisenberg A,
Gotman J, Hall J, Hincapié AS, Hoffmann D, Job AS, Khoo HM, Minotti L, Olivier
A, Kahane P, Frauscher B. Association of Cortical Stimulation-Induced Seizure
With Surgical Outcome in Patients With Focal Drug-Resistant Epilepsy. JAMA
Neurol. 2019 Jun 10. doi: 10.1001/jamaneurol.2019.1464. [Epub ahead of print]
Abstract
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 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 (SD) age was 31 (11) years. Fifty-nine patients
(57.3%) 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 of 44 [70.5%] vs 28 of 59
[47.5%]; 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.
_________________________________________________________________________
Some epileptologists already use cortical stimulation to
help define the focal point for surgery, Dr. Frauscher told Neurology Today,
but typically patients are put in an EEG monitoring unit to wait for
spontaneous seizures to happen so that doctors can pinpoint the seizure-onset
zone. She said it may take days, or even weeks, for patients to have a
spontaneous seizure, an approach that may be costlier due to lengthy hospital
stays and riskier because the implanted electrodes need to remain in place
longer.
“These long stays can be inconvenient for patients and
expensive for health care systems,” said Dr. Frauscher. “Using induced seizures
in this way could reduce the length of hospital stays to just 48-72 hours,
which is a game-changer for patients and health care providers.”
The new study was not a randomized trial involving a
head-to-head comparison of the two approaches, but it involved a fairly large
cohort and produced encouraging results.
Several independent epilepsy experts interviewed by
Neurology Today said the new results could cause a shift in the way candidates
for epilepsy surgery are evaluated, though they cautioned that the new study
included only patients with focal drug-resistant epilepsy and among that group,
only those who met the study's strict inclusion criteria. Whether the findings would
apply to a broader patient population remains a question.
“I think it is an intriguing study, and it is an area that
is relatively understudied despite the fact that intracranial monitoring has
been done for years,” said David C. Spencer, MD, FAAN, professor of neurology
at Oregon Health & Science University (OHSU) and director of the OHSU
Epilepsy Center. “If it is further validated, I think that localization by
cortical stimulation could be a very helpful complement to standard
assessments. If we could get the same quality of data in a shorter period, it
could be positive for both the patient and for medical costs and medical care
in general.”…
Seven patients in the total cohort had cortical
stimulation-induced seizures but no spontaneous seizures during their
presurgical workup.
“That surgical outcomes in this group did not differ from
the outcome of the total group suggested that cortical stimulation might be
extremely valuable to obtain induced electroclinical seizures and might be used
as a substitute for the recording of spontaneous seizures,” the researchers
said…
They said that the failure to stimulate seizures in a
sizable portion of the 103 patients may be attributed to the fact that “the
electrodes were probably placed in a cortical area of high neuronal threshold
incapable of sufficiently activating the epileptic network to induce seizures.”
“The absence of cortical-induced seizure might represent a
red flag, suggesting the true epileptic zone was missed or only partially
sampled,” the study authors said…
Joon-Yi Kang, MD, assistant professor of neurology in the
epilepsy center at Johns Hopkins Hospital, said the new report is “very
exciting” because “there has always been this question, ‘Can we incorporate
information about stimulation induced seizures into our surgical plan?” She
said that epilepsy doctors in European epilepsy centers have traditionally been
using the approach longer than doctors in the US, who consider spontaneous seizure
monitoring the gold standard.
Dr. Kang said that while cortical stimulation is frequently
used for functional mapping in epilepsy pre-surgical evaluations, “it hasn't
been clear whether stimulation is as good as monitoring for spontaneous
seizures, when it comes to pre-surgically defining the target for resection.
This paper shows that, yes, it may be as good as passively monitoring patients
for seizures in some cases.”
Chrystal M. Reed, MD, PhD, assistant professor of neurology
at Cedars-Sinai Medical Center in Los Angeles, said a downside to spontaneous
seizure monitoring in an EEG unit is that it may take considerable time for a
seizure to occur and show changes on an EEG, even though the patients has been
tapered off their antiseizure medication.
“A prolonged period of waiting in an EEG monitoring unit is
both time consuming and costly and may increase the risk of infection from
having electrodes implanted in the brain for a long time,” she said.
While most patients tend to have spontaneous seizures rather
quickly, “some patients are in the monitoring unit for weeks or months,” until
a seizure occurs, Dr. Reed said. She said merely taking a patient out of their
normal environment may diminish the likelihood of a seizure because the
everyday stress that can make patients vulnerable to seizures is absent.
https://journals.lww.com/neurotodayonline/Fulltext/2019/10170/Cortical_Stimulation_Induced_Seizures_May_Be_as.8.aspx
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