Abstract
The Number of Seizures Needed in the EMU.
Struck AF, Cole AJ, Cash SS, Westover MB. Epilepsia 2015;56:1753–1759.
OBJECTIVE: The purpose of this study was to develop a quantitative framework to estimate the likelihood of multifocal epilepsy based on the number of unifocal seizures observed in the epilepsy monitoring unit (EMU). METHODS: Patient records from the EMU at Massachusetts General Hospital (MGH) from 2012 to 2014 were assessed for the presence of multifocal seizures as well as the presence of multifocal interictal discharges and multifocal structural imaging abnormalities during the course of the EMU admission. Risk factors for multifocal seizures were assessed using sensitivity and specificity analysis. A Kaplan-Meier survival analysis was used to estimate the risk of multifocal epilepsy for a given number of consecutive seizures. To overcome the limits of the Kaplan-Meier analysis, a parametric survival function was fit to the EMU subjects with multifocal seizures and this was used to develop a Bayesian model to estimate the risk of multifocal seizures during an EMU admission. RESULTS: Multifocal interictal discharges were a significant predictor of multifocal seizures within an EMU admission with a p < 0.01, albeit with only modest sensitivity 0.74 and specificity 0.69. Multifocal potentially epileptogenic lesions on MRI were not a significant predictor p = 0.44. Kaplan-Meier analysis was limited by wide confidence intervals secondary to significant patient dropout and concern for informative censoring. The Bayesian framework provided estimates for the number of unifocal seizures needed to predict absence of multifocal seizures. To achieve 90% confidence for the absence of multifocal seizure, three seizures are needed when the pretest probability for multifocal epilepsy is 20%, seven seizures for a pretest probability of 50%, and nine seizures for a pretest probability of 80%. SIGNIFICANCE: These results provide a framework to assist clinicians in determining the utility of trying to capture a specific number of seizures in EMU evaluations of candidates for epilepsy surgery.
Commentary
VideoEEG monitoring is without question one of the most valuable tests for diagnosis in epilepsy. The preadmission diagnosis was altered in 58% of patients and management altered in 73% after admission in one report (1). The number of seizures needed to establish a correct diagnosis has remained a matter of debate. Most recommendations set the number somewhere between 3 and 5 seizures (2, 3). Dr. Struck and the team from Massachusetts General Hospital systematically examined this question in a cohort of 117 patients and found that the number of seizures needed depended on the pretest probability of multifocality. Three seizures may suffice if the suspicion for multifocality is low, while even nine may not be enough if the suspicion for multifocality is high. The authors used two different methods to prove their point to account for drop outs and censoring (Kaplan-Meier Analysis and Bayesian theorem). They report multifocality in 26% of patients, which appears high as compared with other studies (2). Struck et al. define multifocality by seizures originating in different quadrants. Unfortunately, multifocality was not confirmed by intracranial EEG and did not correct for multiple spread patterns of unifocal seizure onset especially in seizures from the posterior quadrant (4).
A previous study recommended to record five unilateral (concordant) seizures to be able to determine with 95% confidence interval that at least 90% of seizures are unilateral. This study allowed for 10% of seizures being bilateral as they felt that surgery is still warranted if 90% of seizures were proven to be unilateral (2).
In the Struck et al. paper it would have been of additional interest whether multifocality was predicted and confirmed more frequently in temporal lobe epilepsy versus other neocortical epilepsies. Laterality is easier to determine in temporal lobe syndromes as compared with frontal lobe syndromes (5). This leads to the question of bilateralism in mesial temporal lobe epilepsy. It has long been known that bilateral interictal discharges are quite prevalent in temporal lobe epilepsy and have been estimated to occur in 30 to 40 percent of presumed unilateral temporal lobe patients (6). Intracranial EEG data obtained with chronically implanted long-term intracranial recording devices (Responsive Neurostimulator, RNS) have demonstrated some surprising results (7). On average, it took 41.6 days (median 13 days) until a contralateral seizure occurred. Unfortunately, it was not recorded in this study how many seizures are sufficient to be recorded to assure unilaterality versus bilaterality. Sixty-four percent (7 of 11) of patients that were thought to be unilateral had bilateral seizure onset and 9% that were thought to be bilateral in onset had only unilateral seizures on electrocorticography. These findings make the following question even more salient: how many seizures are ever enough to be recorded in the EMU to rest assured about unilateral onset and subsequent referral for epilepsy surgery? It also raises the question whether mesial temporal lobe epilepsy is more frequently bilateral than previously assumed or vice versa. Some of those findings may account for some surgical failures.
An equally interesting question is: how many seizures need to be recorded to assure that the patient does not have a dual diagnosis of psychogenic nonepileptic and epileptic seizures? No study has adequately addressed this question, and in an older observational studies at least recording five nonepileptic seizures has been recommended to rule out a concomitant diagnosis of epilepsy (8). Overall the co-occurrence of nonepileptic and epileptic seizures in a careful study has been reported between 5 and 10 percent (9). Pretest probabilities such as risk factors for epilepsy, interictal EEG findings, MRI findings, and history of various seizure types certainly play a role in how many seizures need to be recorded if both diagnoses are suspected.
The authors determined their pretest probability for multifocal epilepsy by interictal EEG and MRI analysis only. It is interesting that multifocal interictal discharges predicted multifocality moderately, while multiple lesions on MRI did not. As epilepsy remains defined by abnormal electrical, synchronized brain activity, this supports that overreliance on anatomical imaging studies is not uniformly warranted and needs to be interpreted in conjunction with electrographic findings.
Additional careful clinical history of different clinical seizure types and other clinical variables would have added to pretest probability and is probably another important factor to determine the number of seizures needed. A clearly defined syndrome such as temporal lobe epilepsy with mesial temporal sclerosis with typical history of febrile seizures and epilepsy due to previous head trauma have certainly varying pretest probability for multifocality. The latter is more commonly associated with multifocality. As it may take quite some time to record up to nine seizures, estimated up to 8 to 12 days in one study (3), a clinician has to weigh risks, benefits, and burden for patient. It still remains up to clinical judgment whether such a prolonged admission is justified.
In summary, the number of seizures required is certainly dependent on the individual's clinical factors, pretest probability for multifocality, and remains the art of medicine. When in doubt record more seizures! In the end it will be to the patient's benefit to be correctly diagnosed, localized, and thoroughly informed about the risks and benefit of epilepsy surgery. Although there is no hard defined number of how many seizures need to be recorded, the above study certainly provides some guidelines.