Article Title: Factors that Modify the Risk of Intraoperative Seizures Triggered by Electrical Stimulation During Supratentoral Functional Mapping
This paper presents information from a very large retrospective sample (544 cases) and attempts to demonstrate whether intraoperative seizures can be reduced during functional mapping (as the title says). The article also discusses some facts and information about intraoperative seizures caused by direct cortical electrical stimulation previously published by other authors. They begin by discussing the specific risks of intraoperative seizures: 1) “during awake craniotomies… there is no airway,” 2) the state of the neurons in “the post-ictal state… can impede, at least temporarily, the continuation of reliable mapping,” 3) “postictal cortical depression usually results in an increase in the mapping threshold that is hard to predict; this further hinders reliable mapping,” 4) “seizures can spread to eloquent cortical regions distinct from those stimulated resulting in the false localization of eloquent cortex” (pp. 1058-1059).
The goal of this study is to demonstrate “a better way to avoid the complications associated with intraoperative stimulation triggered seizures is to have a means of preventing them that can be broadly applied to all patients undergoing a mapping procedure and which will be effective regardless of the magnitude of the individual risk” (p. 1059).
The authors reviewed 544 cortical mapping cases, “both awake [TIVA] and asleep,” done with either the Penfield method (“repetitive biphasic pulses at 60 Hz, pulse duration of 1 ms, intensities 1–15 mA applied using a bipolar handheld stimulator”) or what has been called the pulse-train method, “multi-pulse train technique,” or “high frequency anodal stimulation”(repetitive trains at 2 Hz, 6 pulses/train, train frequency 250 Hz, pulse duration 0.5 ms, intensity 1–22 mA applied using a monopolar handheld stimulator, with the active electrode connected to the anode (+ positive) and a subdermal needle electrode placed at the margin of the surgical ﬁeld, connected to the cathode (- negative)) (p. 1059).
The variables that were analyzed included data like gender, age, history of anti-epileptic drug (AEDs) use, etc. to see if particular variables would likely affect the likelihood that a patient would have an intraoperative seizure (deﬁned as rhythmic runs of self-propagated stimulation triggered AD with a duration of 10 s or more) (p. 1059). The more pertinent correlational variables were thought to be variable 4 of 12, “pre-operative maintenance treatment with AED” (defined as, “daily oral administration of any AED regimen for at least 3 days prior to surgery”) and variable 5 of 12, “loading with AED (intravenous administration at the beginning of the surgery of: 1–500 mg or more of either levetiracetam, fosphenytoin or valproic acid; or 2–200 mg or more of lacosamide)” (p.1059)
Of the 544 surgical patients reviewed 330 (≈ 61%) had seizures before their surgery. Of the total reviewed 204 (≈ 38%) “were already receiving a maintenance daily AED dose at the time of the surgery.” Also, “356 patients (65.4%) received intravenous loading doses of AED.” Intraoperative seizures occurred 135 (≈ 25%) of patients. (p. 1060)
Of the 12 factors the authors analyzed the ‘factors were found to signiﬁcantly increase the risk of triggering intraoperative seizures’ were:
- Penﬁeld method (OR = 2.16, p = 0.0002) (which in their final analysis increased the likelihood of causing an intraoperative seizure by 2x*)
- awake state (OR = 1.61, p = 0.01)
- diffuse pathology (OR = 2.37, p = 0.002) (in which case the patient was 2.4x* more likely to have an intraoperative seizure)
- stimulation in the temporal lobe (OR = 1.72, p = 0.01)
However, of those four, the authors point out that ‘mapping during awake state was found to be collinear with the use of Penﬁeld paradigm and thus the former was excluded from the ﬁnal model. Also, “the effect of stimulation in the temporal lobe was positively confounded by the use of Penﬁeld paradigm.”
Moreover, they found that “intravenous administration of loading doses of AED decreased the odds of triggering seizures by 45%” while no other factors (including “maintenance AED treatment” and “history of seizures”) were found to statistically affect the likelihood of intraoperative seizures. (p. 1061).
*kitchen sink multivariate logistic regression
Of the patients that received a loading dose of AEDs, “about two thirds (73.3%) of the patients who received intra-venous loading with AED at the beginning of the surgery, had not been previously on maintenance AED” demonstrating that these patients were not receiving the potentially positive effects of maintenance AEDs but still saw a reduction in their intraoperative seizure risk. However, “about a fourth (26.7%)” of the AED loaded patients were on maintenance AEDs but pre-procedure “loading was performed in this… group because of lack of information regarding the effectiveness of the AED maintenance” (p. 1062) which the authors believe may have a “protective effect” for those persons with a ‘positive history of pre-operative seizures’ (p. 1064). In a nutshell the authors can claim, based off of a size case study, “our results show that AED can efﬁciently protect against electrical stimulation triggered seizures in humans and that such protective effect is independent of other risk factors” (pp. 1061-1062). The authors also caution readers that, ‘special attention should be given to cases where map
ping is performed via Penﬁeld method of stimulation and in the presence of diffuse pathology’ (p. 1064).
The authors are comprehensive in the in their presentation of statistical methods and even an additional overview of many of the risk factors they included as they analyzed the information they collected (in the discussion section which I covered very briefly). However, and as the authors acknowledge and promise to address ‘in future prospective studies’ there are certain areas when dealing with seizure history of patients and their use of AEDs prior to surgery that could (and apparently will be) useful to technologists and neurophysiologists when previewing patient information while preparing for the potential risks our soon-to-be-monitored patient might face.
The IONM Big Picture Perspective:
If the information from this study were to be shared with, and implemented by, anesthesiologists and surgeons and the results reliably replicated then surgical teams involved in cortical mapping could potentially cut intraoperative seizures in half. Also, the benefits of avoiding the high costs risks of intraoperative seizures (briefly discussed in the first paragraph) would increase the usefulness and accuracy of intraoperative cortical mapping and thus increase overall safety for these patients. Finally, with the information presented in this article we can be better prepared as technologists and neurophysiologists to anticipate patients that are at the greatest risk for intraoperative seizures and be ready to act regardless of whether other members of the surgical team have converted this information into practice.
- Dineen J, Maus DC, Muzyka I, See RB, Cahill DP, Carter BS, Curry WT, Jones PS, Nahed BV, Peterfreund RA, Simon MV. Factors that modify the risk of intraoperative seizures triggered by electrical stimulation during supratentorial functional mapping. Clin Neurophysiol. 2019 Jun;130(6):1058-1065.
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