Seizure clusters in drug‐resistant focal epilepsy

Asadi‐Pooya, Ali A.; Nei, Maromi; Sharan, Ashwini; Sperling, Michael R.

doi:10.1111/epi.13465

Cited by 29 publications

(25 citation statements)

References 13 publications

(20 reference statements)

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“…In addition, changes in therapy including medication, surgeries, devices, and diets were inadequately documented. Furthermore, lack of seizure focus localization information prevents subdividing patients into groups, with region‐specific temporal patterns . Of note, all these biases exist in current clinical practice, and this was the best we could do with available large amount of data.…”

Section: Discussionmentioning

confidence: 99%

Different as night and day: Patterns of isolated seizures, clusters, and status epilepticus

et al. 2018

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Using approximations based on presumed U.S. time zones, we characterized day and nighttime seizure patterns in a patient-reported database, Seizure Tracker. A total of 632 995 seizures (9698 patients) were classified into 4 categories: isolated seizure event (ISE), cluster without status epilepticus (CWOS), cluster including status epilepticus (CIS), and status epilepticus (SE). We used a multinomial mixed-effects logistic regression model to calculate odds ratios (ORs) to determine night/day ratios for the difference between seizure patterns: ISE versus SE, ISE versus CWOS, ISE versus CIS, and CWOS versus CIS. Ranges of OR values were reported across cluster definitions. In adults, ISE was more likely at night compared to CWOS (OR = 1.49, 95% adjusted confidence interval [CI] = 1.36-1.63) and to CIS (OR = 1.61, 95% adjusted CI = 1.34-1.88). The ORs for ISE versus SE and CWOS versus SE were not significantly different regardless of cluster definition. In children, ISE was less likely at night compared to SE (OR = 0.85, 95% adjusted CI = 0.79-0.91). ISE was more likely at night compared to CWOS (OR = 1.35, 95% adjusted CI = 1.26-1.44) and CIS (OR = 1.65, 95% adjusted CI = 1.44-1.86). CWOS was more likely during the night compared to CIS (OR = 1.22, 95% adjusted CI = 1.05-1.39). With the exception of SE in children, our data suggest that more severe patterns favor daytime. This suggests distinct day/night preferences for different seizure patterns in children and adults.

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Section: Discussionmentioning

confidence: 99%

Different as night and day: Patterns of isolated seizures, clusters, and status epilepticus

et al. 2018

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“…Epileptic seizures typically occur as discrete events separated by an intervening interictal period that can range from days to years. Some individuals with epilepsy, however, particularly those with drug‐resistant disease, are likely to experience episodes of increased seizure activity . Such episodes, known as seizure clusters (SCs), or acute repetitive seizures, can be described as a series of seizures with a temporal association that is closer than patients’ usual baseline frequency .…”

Section: Introductionmentioning

confidence: 99%

“…Some individuals with epilepsy, however, particularly those with drug-resistant disease, are likely to experience episodes of increased seizure activity. 1,2 Such episodes, known as seizure clusters (SCs), or acute repetitive seizures, can be described as a series of seizures with a temporal association that is closer than patients' usual baseline frequency. 3,4 Seizures in a cluster may also differ in type, duration, or severity from patients' typical seizures.…”

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confidence: 99%

Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters: An open‐label extension trial

Wheless

Meng²,

Ess³

et al. 2019

Epilepsia

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Objective To evaluate safety‐ and seizure‐related outcomes with repeated intermittent use of a novel formulation of midazolam administered as a single‐dose nasal spray (MDZ‐NS) in the outpatient treatment of patients experiencing seizure clusters (SCs). Methods In this open‐label extension trial (ClinicalTrials.gov NCT01529034), patients aged ≥12 years and on a stable regimen of antiepileptic drugs who completed the original phase III, randomized controlled trial were enrolled. Caregivers administered MDZ‐NS 5 mg when patients experienced SCs; a second dose could be given if seizures did not terminate within 10 minutes or recurred within 10 minutes‐6 hours. Patients were monitored for treatment‐emergent adverse events (TEAEs) throughout, and the main seizure‐related outcome was treatment success, defined as seizure termination within 10 minutes and no recurrence 10 minutes‐6 hours after drug administration. Results Of 175 patients enrolled, 161 (92.0%) received ≥1 MDZ‐NS dose, for a total of 1998 SC episodes. Median time spent by patients in the trial was 16.8 months (range = 1‐55.7 months). TEAEs were experienced by 40.4% of patients within 2 days of drug administration and 57.1% overall. TEAEs reported by most patients (within 2 days and overall) were nasal discomfort (12.4%) and somnolence (9.3%). One patient each discontinued due to treatment‐related nasal discomfort and somnolence. There were no patients with treatment‐related respiratory depression, and none with TEAEs indicative of drug abuse or dependence. Treatment success criteria were met in 55% (1108/1998) of SC episodes after administration of a single 5‐mg dose and in 80.2% (617/769) with the second dose. Treatment success was consistent over treated episode number. Significance Repeated, intermittent, acute treatment of patients experiencing SCs with MDZ‐NS in the outpatient setting was well tolerated over an extended period, with maintenance of efficacy suggesting lack of development of tolerance.

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“…The mechanism(s) underlying the relationship between ISI and seizure duration is unknown but may relate to the long-term memory processes of an epileptic network. 26 In animals and humans, seizures do not occur randomly; they have a tendency to cluster in time [28][29][30][31] and burst in cyclical rhythms, 18,23,32,33 which implies that the epileptic network has an inherent memory of prior events. 23 Individual seizures and clusters have been associated with long periods of seizure freedom, 34 which have been thought to relate to long durations of postictal suppression.…”

Section: Discussionmentioning

confidence: 99%

Evidence for long memory in focal seizure duration

2021

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Objective A major source of disability for people with epilepsy involves uncertainty surrounding seizure timing and severity. Although patients often report that long seizure‐free intervals are followed by more severe seizures, there is little experimental evidence supporting this observation. Optimal characterization of seizure severity is debated; however, seizure duration is associated with seizure type and can be quantified in electrographic recordings as a limited proxy of clinical seizure severity. Here, using chronic intracranial electroencephalography (cEEG), we investigate the relationship between interseizure interval (ISI) and duration of the subsequent seizure. Methods We performed a retrospective analysis of 14 subjects implanted with a responsive neurostimulation device (RNS System) that provides cEEG, including timestamps of electrographic seizures. We determined seizure durations for isolated seizures and for representative seizures from clusters determined through unsupervised methods. For each subject, the median ISI preceding long‐duration seizures, defined as the top quintile of seizure durations, was compared with the median ISI preceding seizures with durations in the residual quintiles. In a group analysis, the mean seizure duration and the proportion of long‐duration seizures were compared across ISI categories representing different lengths. Results For 5 out of 14 subjects (36%), the median ISI preceding long‐duration seizures was significantly greater than the median ISI preceding shorter‐duration seizures. In the group analysis, when ISI was categorized by length, the proportion of long‐duration seizures within the high ISI category was significantly higher than that of the low ISI category (P < 0.001). Significance By leveraging cEEG and accounting for seizure clusters, we found that the likelihood of long‐duration seizures positively correlates with ISI length, in a subset of individuals. These findings corroborate anecdotal clinical observations and support the existence of capacitor‐like long memory processes governing the dynamics of focal seizures.

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Seizure clusters in drug‐resistant focal epilepsy

Cited by 29 publications

References 13 publications

Different as night and day: Patterns of isolated seizures, clusters, and status epilepticus

Different as night and day: Patterns of isolated seizures, clusters, and status epilepticus

Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters: An open‐label extension trial

Evidence for long memory in focal seizure duration

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