Abstract
Termination of Seizure Clusters is Related to the Duration of Focal Seizures
Ferastraoaru V, Schulze-Bonhage A, Lipton RB, Dümpelmann M, Legatt AD, Blumberg J, Haut SR. Epilepsia 2016;57:889–895.
OBJECTIVE: Clustered seizures are characterized by shorter than usual interseizure intervals and pose increased morbidity risk. This study examines the characteristics of seizures that cluster, with special attention to the final seizure in a cluster. METHODS: This is a retrospective analysis of long-term inpatient monitoring data from the EPILEPSIAE project. Patients underwent presurgical evaluation from 2002 to 2009. Seizure clusters were defined by the occurrence of at least two consecutive seizures with interseizure intervals of <4 h. Other definitions of seizure clustering were examined in a sensitivity analysis. Seizures were classified into three contextually defined groups: isolated seizures (not meeting clustering criteria), terminal seizure (last seizure in a cluster), and intracluster seizures (any other seizures within a cluster). Seizure characteristics were compared among the three groups in terms of duration, type (focal seizures remaining restricted to one hemisphere vs. evolving bilaterally), seizure origin, and localization concordance among pairs of consecutive seizures. RESULTS: Among 92 subjects, 77 (83%) had at least one seizure cluster. The intracluster seizures were significantly shorter than the last seizure in a cluster (p = 0.011), whereas the last seizure in a cluster resembled the isolated seizures in terms of duration. Although focal only (unilateral), seizures were shorter than seizures that evolved bilaterally and there was no correlation between the seizure type and the seizure position in relation to a cluster (p = 0.762). Frontal and temporal lobe seizures were more likely to cluster compared with other localizations (p = 0.009). Seizure pairs that are part of a cluster were more likely to have a concordant origin than were isolated seizures. Results were similar for the 2 h definition of clustering, but not for the 8 h definition of clustering. SIGNIFICANCE: We demonstrated that intracluster seizures are short relative to isolated seizures and terminal seizures. Frontal and temporal lobe seizures are more likely to cluster.
Commentary
Seizures have their “own mind,” but their occurrence is not randomly distributed. Although some triggers can be identified—including, among others, alcohol ingestion, missing antiseizure medication doses, and catamenial epilepsy—seizure clustering can still occur in the absence of triggers and may be associated with major sequelae. During continuous video-EEG monitoring, antiseizure medication dosages are often lowered or discontinued in order to capture seizures, but this is associated with the increased risk of seizure clusters, secondary generalization, and status epilepticus. Seizure clusters are associated with increased morbidity and pose safety issues. This includes the increased likelihood of postictal phenomena, such as psychosis, which is related to increased seizure severity and duration (1). Additionally, seizure clusters are associated with an increased risk of status epilepticus (2).
Ferastraoaru et al. retrospectively studied medically intractable patients who were monitored in the epilepsy monitoring unit for presurgical evaluation, and the authors paid special attention to the last seizure of the cluster, which they termed the “terminal seizure.” They defined cluster as two or more seizures occurring with less than 4 hours between consecutive ones, and, as a sensitivity analysis, tackled the same questions with the clusters redefined as seizures recurring within 2 hours and 8 hours. They compared the characteristics of isolated seizures with those of intracluster seizures and terminal seizures, the latter referring to the last seizure in a cluster. The authors studied 996 seizures in 92 subjects (including some with intracranial recordings) and found seizure clusters in 77 (83%). Perhaps this high percentage of clustering was due to the fact that antiseizure medications are often lowered and discontinued in the video-EEG unit to increase the chances of capturing seizures. The intracluster seizures were of shorter duration than the terminal seizure in a cluster (mean duration 78 seconds vs 95 seconds, p = 0.011), and the terminal seizure had comparable duration to isolated seizures. The explanation for this may be that 1) longer seizures tend to be more effective in depleting excitatory neurotransmitters within the seizure network or 2) activate inhibitory mechanisms that result in longer interseizure intervals. Another finding from this study was that clustering was seen more commonly with seizures of frontal and temporal lobe origins than with ones that originated from other brain regions (p = 0.009). This may be explained by the same reasons that temporal lobe epilepsy is the most common focal epilepsy, followed by frontal lobe epilepsy. One may speculate that the same inherent networking of these lobes that facilitate epileptogenesis also facilitates clustering. Moreover, the authors found that seizures that are part of a cluster tended to originate from the same focus more commonly than are isolated ones. This corroborates the teaching that seizures within a cluster must be counted as one seizure as regards their importance for localization of the seizure focus for presurgical purposes. When the 2-hour, but not the 8-hour, definition of clustering was applied, these results were similar.
Studying seizure clusters is important because it may help identify the critical time for intervening with rescue medications, such as parenteral benzodiazepines. In addition, clinicians need to know which seizure or subset of seizures in a cluster is reliable to draw safe conclusions from regarding localization of the seizure focus for purposes of surgical treatment of intractable epilepsy. This study provided some insight into these matters despite some limitations. The database utilized in this study defined seizure duration as the interval from the electrographic onset to electrographic offset, although clinical onset may precede the EEG onset of some seizures. This is known to occur with both scalp and intracranial monitoring if the implanted electrodes fail to accurately sample the seizure-onset zone. Additionally, this retrospective analysis did not mention medication changes during monitoring and the patients’ reports of clustering at baseline. Even more importantly, the study did not report whether antiseizure medications, including benzodiazepines, were given during the cluster or after the terminal seizure. Despite these limitations, the study is important as it lays the ground for a future prospective study of seizure clustering and its relation to status epilepticus.