Friday, October 18, 2019

Cortical stimulation-induced seizures versus spontaneous seizures for epilepsy surgery planning

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]


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.

To assess whether removal of the seizure-onset zone resulting from cortical stimulation is associated with a good surgical outcome.

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.

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.

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).

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.

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