Abstract Electrical status epilepticus in sleep involves an electroencephalographic pattern where interictal epileptiform activity is potentiated in the transition from wakefulness to sleep. ...Near-continuous spikes and waves that occupy a significant proportion of nonrapid eye movement sleep appear as a result of sleep-potentiated epileptiform activity. This electroencephalographic pattern appears in different electroclinical syndromes that present three common characteristics with different degrees of severity: seizures, sleep-potentiated epileptiform activity, and neuropsychologic regression. Continuous spikes and waves during sleep comprise the severest epileptic encephalopathy in the electroclinical spectrum. Landau-Kleffner syndrome presents with intermediate severity. Some “benign” pediatric focal epileptic syndromes represent the mildest end of this continuum. Based on published data, we provide a framework for clinical and electrical events. The underlying mechanisms leading to sleep potentiation of epileptiform activity in electrical status epilepticus in sleep are incompletely understood. A genetic basis or acquired early developmental insult may disrupt the normal maturation of neuronal networks. These factors may dynamically alter normal processes of brain development, leading to an age-related pattern of electroclinical expression of electrical status epilepticus in sleep.
Abstract A retrospective review of children with epilepsy and obstructive sleep apnea, treated surgically for their obstructive sleep apnea from January 2008-October 2010, was performed for age, sex, ...type of epilepsy, antiseizure medications, sleep-study data, and changes in seizure frequency. Twenty-seven subjects (median age, 5 years) with no adjustment to their medications around their time of surgery were identified. Three months after surgery, 10 (37%) patients became seizure-free, three (11%) demonstrated >50% seizure-reduction, and six (22%) exhibited an amelioration of seizure frequency. Two (7%) demonstrated unchanged seizure-frequency, and six (22%) manifested a worsening of seizure frequency. Median seizure frequency before surgery was 8.5 (interquartile range, 2-90), and after surgery, three (interquartile range, 0-75), with a 53% median seizure reduction. Multivariate analysis demonstrated a trend toward seizure freedom with each percentile increase in body mass index and early age of surgery. We conclude that obstructive sleep apnea surgery may decrease seizure frequency, especially in children with elevated body mass index scores and younger age at time of surgery.
We report our pediatric experience with lacosamide, a new antiepileptic drug, approved by the US Food and Drug Administration as adjunctive therapy in focal epilepsy in patients more than 17 years ...old. We retrospectively reviewed charts for lacosamide use and seizure frequency outcome in patients with focal epilepsy (Wilcoxon signed rank test). Sixteen patients (7 boys) were identified (median dose 275 mg daily, 4.7 mg/kg daily; mean age 14.9 years, range 8-21 years). Patients were receiving a median of 2 antiepileptic drugs (interquartile range IQR 1.7-3) in addition to having undergone previous epilepsy surgery ( n = 3), vagus nerve stimulation ( n = 9), and ketogenic diet ( n = 3). Causes included structural (encephalomalacia and diffuse encephalitis, 1 each; stroke in 2) and genetic abnormalities (Aarskog and Rett syndromes, 1 each) or cause not known ( n = 10). Median seizure frequency at baseline was 57 per month (IQR 7-75), and after a median follow-up of 4 months (range 1-13 months) of receiving lacosamide, it was 12.5 per month (IQR 3-75), ( P < 0.01). Six patients (37.5%; 3 seizure free) were classified as having disease that responded to therapy (≥50% reduction seizure frequency) and 10 as having disease that did not respond to therapy (<50% in 3; increase in 1; unchanged in 6). Adverse events (tics, behavioral disturbance, seizure worsening, and depression with suicidal ideation in 1 patient each) prompted lacosamide discontinuation in 4/16 (25%). This retrospective study of 16 children with drug-resistant focal epilepsy demonstrated good response to adjunctive lacosamide therapy (median seizure reduction of 39.6%; 37.5% with ≥50% seizure reduction) without severe adverse events.
Abstract Background Clobazam has been used in clinical practice as an adjunctive treatment for diverse seizure types and epilepsy syndromes. We evaluated the efficacy and safety of clobazam in a ...large sample of patients with refractory epilepsy at a tertiary pediatric center. Methods We retrospectively reviewed patients treated with clobazam between January 2001 and July 2013 who had a follow-up visit at least one month after starting clobazam. Response was defined as ≥50% reduction in seizure frequency compared with baseline seizure frequency during the 3 months before the introduction of clobazam. We examined the relationship between dose range and response rate. Results Four-hundred twenty-five patients were prescribed clobazam, of whom 300 (median age 9.1 years, interquartile range 4.7-13.3 years) had follow-up data greater than 1 month. Median follow-up was 5 months (interquartile range 3-11 months). Response to treatment with clobazam was observed in 203 of 300 (67.7%) patients, of whom 84 (28%) became seizure-free. The median starting dose was 0.2 (interquartile range 0.13-0.33) mg/kg/day with a target dose of 0.48 (0.26-0.80) mg/kg/day. Twenty-seven (9%) patients discontinued clobazam, 16 (59.3%) because adverse effects, 10 (37%) because of a lack of efficacy, and one (3.7%) because of a combination of adverse effects and lack of efficacy. The most common adverse effects were tiredness in 44 of 300 (14.6%) and mood or behavioral changes in 23 (7.7%). Conclusions Clobazam is a well-tolerated antiepileptic drug with good response rates in pediatric patients with refractory epilepsy.
Rufinamide is a new antiepileptic drug recently approved as adjunctive treatment for generalized seizures in Lennox-Gastaut syndrome. We undertook a retrospective analysis of 77 patients with ...refractory epilepsy and receiving rufinamide to evaluate the drug's efficacy, tolerability, safety, and dosing schedules. It appeared efficacious in diverse epilepsy syndromes, with the highest responder rate in focal cryptogenic epilepsies (81.1% of patients with >50% response rate), and in diverse seizure types, with the highest responder rate in tonic/atonic and partial seizures (48.6% and 46.7% of patients with >50% response rate, respectively). Rufinamide was well tolerated: only 13% of patients developed side effects necessitating drug withdrawal. These findings suggest that rufinamide may possess good efficacy and tolerability, and that its efficacy may extend to epilepsy syndromes beyond Lennox-Gastaut, including both partial and generalized epilepsy syndromes.
Abstract Background This study evaluated whether the reduction in epileptiform activity after treatment with high-dose diazepam in continuous spikes and waves during sleep persists over time. ...Patients Patients aged 1 to 21 years with continuous spikes and waves during sleep who received high-dose nocturnal diazepam and who had electroencephalogram follow-up were included. Twenty-nine patients met the inclusion criteria and underwent a total of 48 high-dose diazepam treatment cycles. Results An overnight reduction of the spike wave percentage of at least 25% (i.e., 75-50%) occurred in 29 cycles (20 patients), and persisted within 6 months in 16 of 29 cycles (12 patients), but returned to baseline in three of 29 cycles (three patients). An overnight reduction of at least 50% (i.e., 75-25%) occurred in 15 cycles (13 patients), and persisted within 6 months in eight of 15 cycles (eight patients), but returned to baseline in three cycles (three patients). Twenty of 29 cycles that responded in the short term had persistent response on follow-up. Thirteen cycles of treatment were associated with mild side effects that did not recur with repeated treatment cycles. Conclusions Treatment with high-dose diazepam reduced epileptiform activity in continuous spikes and waves during sleep in the short term, and improvement persisted for several months in most cycles. Short-term response predicted persistence of this effect on subsequent follow-up.
Surgical treatment emerges as a therapeutic option for refractory status epilepticus (RSE) in children. Surgical approaches for RSE include focal cortical resections, hemispherectomies, multiple ...subpial transections, and rarely corpus callosotomy and vagal nerve stimulator implantation. Resective surgery has shown immediate- and long-term benefits in cases of definite localization of the epileptogenic focus by elecrographic and imaging data. Evidence of focal electrographic activity may not always be available during prolonged status. Nevertheless, resection may be an option in these cases if extensive, and confined pathology is seen on magnetic resonance imaging. On the contrary, electrographic localization may be complemented by intraoperative electrocorticography during multiple subpial transections in cases of nonlesional pathology. The optimal timing of surgery in eligible patients has been determined by concerns about medical intractability weighed against accumulating risks of RSE and the possible appearance of secondary epileptogenic zones caused by ongoing seizures. Overall, preliminary case series suggest that epilepsy surgery may be an alternative treatment option for selected children with RSE. Additional studies are needed to delineate timing and criteria for intervention as well as prognostic factors.
Abstract Background Quality improvement is a major component of the Accreditation Council for Graduate Medical Education core competencies required of all medical trainees. Currently, neither the ...Neurology Residency Review Committee nor the Accreditation Council for Graduate Medical Education defines the process by which this competency should be taught and assessed. We developed a quality improvement curriculum that provides mentorship for resident quality improvement projects and is clinically relevant to pediatric neurologists. Methods Before and after implementation of the quality improvement curriculum, a 14-item survey assessed resident comfort with quality improvement project skills and attitudes about implementation of quality improvement in clinical practice using a 5-point Likert scale. We used the Kruskal-Wallis and Fisher exact tests to evaluate pre to post changes. Results Residents' gained confidence in their abilities to identify measures ( P = 0.02) and perform root cause analysis ( P = 0.02). Overall, 73% of residents were satisfied or very satisfied with the quality improvement curriculum. Conclusions Our child neurology quality improvement curriculum was well accepted by trainees. We report the details of this curriculum and its impact on residents and discuss its potential to meet the Accreditation Council for Graduate Medical Education's Next Accreditation System requirements.
Abstract We describe the short-term effects of high-dose oral diazepam on sleep-potentiated epileptiform activity in patients with electric status epilepticus during sleep. We enrolled patients ...treated with high-dose oral bedtime diazepam from 2001-2009. We defined spike percentage as the percentage of 1-second bins containing at least one spike, and calculated it during three randomly selected 5-minute samples of wakefulness throughout the day and during the first 5 minutes of every hour of non-rapid eye movement sleep at night. In this study, patients were considered to demonstrate sleep-potentiated epileptiform activity when their spike percentage during sleep was increased by ≥50% compared with wakefulness. Twenty-nine children (18 boys) were included (median age, 7.4 years). Twenty-four hours after receiving high-dose diazepam, epileptiform activity was significantly reduced (76.7% at baseline vs 40.8% 24 hours after high-dose diazepam; Wilcoxon signed ranks test, Z = −4.287, P < 0.0001). Seven patients (24.1%) manifested mild, reversible side effects during the first 48 hours after diazepam administration. High-dose oral diazepam effectively and safely reduced epileptiform activity in patients with electric status epilepticus during sleep.
We describe our experience with intraoperative electroencephalography in moyamoya surgery, a method to monitor for ischemic changes during the procedure and to minimize the risk of intraoperative and ...perioperative stroke. Case records and intraoperative electroencephalography recordings of all patients ( n = 220) treated with surgical revascularization for moyamoya (pial synangiosis) performed for 14 years (1994-2008) were reviewed. Electroencephalographic slowing occurred in 100 cases (45.5%), and was persistent in nine cases (9%). Slowing coincided with specific operative manipulations, most commonly while suturing the donor vessel to the pia, and during closure of the craniotomy. Slowing generally occurred bilaterally, independently of the side of intervention. The presence, length, and severity of slowing were not predictive of perioperative ischemic events. We present additional data on intraoperative electroencephalography with a modified montage to accommodate the craniotomy. Although not predictive of perioperative ischemic events in this series, electroencephalographic changes were correlated with specific operative interventions, and revealed global responses to unilateral manipulation. These findings suggest that prospective analyses of this technique may elucidate additional methods of predicting (and possibly preventing) perioperative ischemic events.
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