Interrater reliability in interpretation of electrocorticographic seizure detections of the responsive neurostimulator
Electrocorticographic (ECoG) recordings from patients with medically intractable partial-onset seizures treated with a responsive neurostimulator system (the RNS System) that detects and stores physician-specified ECoG events provide a new data resource. Interpretation of these recordings has not yet been validated. The purpose was to evaluate the interrater interpretation of chronic ambulatory ECoG recordings obtained by the RNS System.Methods
Five pairs of five experts independently classified 7,221 ECoG recordings obtained from 128 patients with medically intractable partial seizures who participated in a randomized controlled trial of the safety and efficacy of the RNS System. ECoG detections—“long episodes” or “saturations”—were classified as “seizures” or “not seizures” based on a reference definition. Interrater agreement rates and kappa score reliabilities were calculated between rater pairs from the ECoG sample as a whole and within individual patients who had more than the median number of individual ECoG recordings.Results
The overall interrater agreement was 79%, with a reliability κ = 0.57 (moderate agreement). Agreement between pairs of reviewers ranged from 0.69 to 0.85. Agreement rates were 94% or better for 50% of patients. Only 25% of patients had ECoG recordings agreement rates worse than 75%. ECoGs with mixed interpretations (one reviewer “seizure”/the other—“not seizure”) consisted of periods of low amplitude activity that evolved in amplitude or periodic discharges near 2 Hz.Significance
Although reliability as a whole was moderate, for the majority of patients, detections yielded highly reliably interpreted events of either electrographic seizures or nonictal epileptiform activity.
“A journey around the world”: Parent narratives of the journey to pediatric resective epilepsy surgery and beyond
Although shorter time to pediatric resective epilepsy surgery is strongly associated with greater disease severity, other nonclinical diagnostic and sociodemographic factors also play a role. We aimed to examine parent-reported barriers to timely receipt of pediatric epilepsy surgery.Methods
We conducted 37 interviews of parents of children who previously had resective epilepsy surgery at University of California Los Angeles (UCLA; 2006–2011). Interviews were audio-recorded, transcribed, and systematically coded using thematic analysis by two independent coders, and subsequently checked for agreement. Clinical data, including “time to surgery” (age of epilepsy onset to surgery) were abstracted from medical records.Results
The mean time to surgery was 5.3 years (standard deviation [SD] 3.8); surgery types included 32% hemispherectomy, 43% lobar/focal, and 24% multilobar. At surgery, parents were on average 38.4 years (SD 6.6) and children were on average 8.2 years (SD 4.7). The more arduous and longer aspect of the journey to surgery was perceived by parents to be experienced prior to presurgical referral. The time from second antiepileptic drug failure to presurgical referral was ≥1 year in 64% of children. Thematic analysis revealed four themes (with subthemes) along the journey to surgery and beyond: (1) recognition—“something is wrong” (unfamiliarity with epilepsy, identification of medical emergency); (2) searching and finding—“a circuitous journey” (information seeking, finding the right doctors, multiple medications, insurance obstacles, parental stress); (3) surgery is a viable option—“the right spot” (surgery as last resort, surgery as best option, hoping for candidacy); and (4) life now—“we took the steps we needed to” (a new life, giving back).Significance
Multipronged interventions targeting parent-, provider-, and system-based barriers should focus on the critical presurgical referral period; such interventions are needed to remediate delays and improve access to subspecialty care for children with medically refractory epilepsy and potentially eligible for surgery.
A mouse model of Alzheimer's disease displays increased susceptibility to kindling and seizure-associated death
People with Alzheimer's disease (AD) are up to 10 times more likely to develop epilepsy than the age-matched general population. However, given that only a proportion of patients with AD develop epilepsy, it is likely that additional factors may be required for the epilepsy to emerge. This study aimed to better understand the relationship between AD pathology and seizure susceptibility. It also aimed to investigate a “two-hit” hypothesis for seizure susceptibility through amygdala kindling of rodent AD models. Aged AD mice (Tg2576 model) and wild-type (WT) mice underwent electrical amygdala kindling. Compared with WT mice, Tg2576 mice had significantly lower afterdischarge threshold. Significantly fewer stimulations were required for the Tg2576 mice to reach the first class V seizure. Higher death rate was observed with Tg2576 mice in the kindling group. Both sham and kindled Tg2576 animals had increased levels of sprouting in the supragranular layer of the dentate gyrus compared with the WT counterparts. These findings support the “two-hit” hypothesis and represent a potentially novel research model to help better understand the relationship between AD pathology and epilepsy.
To describe the antiepileptic drug (AED) treatment of patients with early infantile epileptic encephalopathy due to KCNQ2 mutations during the neonatal phase and the first year of life.Methods
We identified 15 patients and reviewed the electroclinical, neuroimaging, and AED treatment data.Results
Seizure onset was between 1 and 4 days of age with daily tonic asymmetric, focal and clonic seizures in nine patients and status epilepticus in the remaining six. Electroencephalography (EEG) showed multifocal epileptiform abnormalities in nine patients and a burst-suppression pattern in six. All patients were trialed with adequate daily doses of several AEDs before they reached seizure freedom. Six patients (40%) achieved seizure control within 2 weeks of carbamazepine (CBZ) administration and five (33%) were seizure-free with phenytoin (PHT). The last four patients (27%) were successfully treated with topiramate (TPM) (two patients), levetiracetam (LEV) (one), and a combination of LEV with TPM (one). Most patients reached seizure freedom within the first year of life and remained seizure-free thereafter. Twelve patients had moderate-to-severe developmental delay at follow-up. However, the two patients whose seizures ceased within a few days of onset showed only mild cognitive impairment.Significance
Our findings suggest that drugs acting on sodium channels including CBZ and PHT should be considered as first-line treatment in patients with KCNQ2 encephalopathy. Voltage-gated sodium and potassium channels co-localize at the neuronal membrane. Therefore, the efficacy of drugs acting as sodium-channel blockers could be linked to their modulating effect on both channels. The type of KCNQ2 mutation might influence AED response as well as developmental outcome. Early recognition of KCNQ2 encephalopathy followed by the most appropriate and effective treatment may be important for reducing the neurodevelopmental impairment associated with this disorder.