American Epilepsy Society
Abstracts presented at the American Epilepsy Society meeting 2012
- The Pediatric Status Epilepticus Research Group (PSERG): Establishment of a Multicenter North American Research Network
- Sleep/Wake and Diurnal Occurrence of Seizures in Relationship to Patient Age and Localization in Pediatric Epilepsy
- Long-Term Outcome After High-Dose Diazepam Treatment for ESES
- Association of Breathing and Cardiac Complications with Epileptic Seizures in Children: A Prelude to Understanding SUDEP
T. Loddenkemper, I. Sánchez Fernández, S. An, N. Abend, S. Agadi, J. Carpenter, K. Chapman, W. Gaillard, H. Goodkin, C. Hahn, M. Mikati, K. Peariso0, S. Ramgopal, R. Arya, M. Ream, J. Riviello, A. Veerapandiyan, K. Williams, T. Glauser
Boston Children's Hospital
Management of refractory convulsive status epilepticus (RCSE) varies at different centers and from patient to patient within a given center. We aimed to establish a North-American multicenter network of tertiary referral hospitals to analyze RCSE management which could provide useful information on outcome and outcome predictors.
Pediatric epileptologists frequently caring for children with RCSE first met at the Child Neurology Society Meeting and American Epilepsy Society meetings in 2010, and subsequently established monthly phone conferences in order to establish a research group on pediatric RCSE. Common inclusion criteria for RCSE included: 1) age 1 month to 21 years; 2) convulsive seizures at onset; and 3) failure of two or more antiepileptic drugs (AEDs) or requirement of any kind of continuous infusion of AEDs to abort seizures. We excluded patients with: 1) non-convulsive SE detected on EEG (without convulsive seizures at onset); and 2) non-convulsive status epilepticus and infrequent myoclonic jerks.
The network began with 8 centers in 2010 and presently comprises 11 tertiary epilepsy centers in the United States and Canada. The group meets monthly in highly-focused 30 minute phone conferences, and biannually in person. These meetings are attended by >75% of participants regularly. IRB approval was obtained from all sites. Funding was obtained from the Epilepsy Foundation of America. Data elements for status epilepticus were developed based on NINDS common data elements. A web-based interface based on the NINDS childhood absence epilepsy trial was developed to permit multi-center anonymized data entry. Data on demographics, comorbidities, semiology of the status epilepticus, AEDs required to stop the seizures, EEG features and complications of the status epilepticus and/or its treatment are being collected for every patient. Since October 2011 we prospectively enrolled 25 children with RCSE. We expect subject recruitment to continue until January 2013 to yield 50 subjects. We plan to perform detailed analysis on the use, timing, efficacy and adverse effects of AEDs in RCSE. Future collaboration may allow for the collection of biologic samples to determine genetic factors and provide data for interventional treatment trials.
We have developed a North-American multicenter network of tertiary hospitals that care for children with RCSE. We are successfully enrolling patients prospectively. With further development and continued enrollment, this registry will allow us to compare differences across the 11 institutions. This will yield valuable data regarding the most effective RCSE treatment and monitoring strategies which can then be studied by the network as interventional treatment trials. Additionally, newly developing consortium links will permit investigation of genetic markers of SE susceptibility and outcome. This study may help in setting up prospective comparative efficacy studies on therapy of status epilepticus.
S. Ramgopal, I. Sánchez Fernández, C. Powell, M. Vendrame, M. Zarowski, A. V. Alexopoulos, S. Kothare, T. Loddenkemper
Boston Children's Hospital
Seizures oftentimes do not occur randomly but present at certain peaks and troughs throughout the day. The propensity to have a seizure at certain times and/or during wake/sleep may be influenced by individual risk factors. We aim to identify risk factors that predict timing of seizures.
We retrospectively reviewed the charts of 955 patients that underwent video-EEG in our center. Patients ≤21 years with recorded seizures were included. Seizures were evaluated based on EEG localization and their occurrence in 3-hour time bins, during the day (6AM-6PM) or night, and out of wakefulness/sleep. Patients were classified according to age: infants (≤3 years), children (3-12 years), and adolescents (>12-21 years). An analysis utilizing generalized estimating equations with a negative binomial distribution was performed. Models were expanded to test for differences in the main effects by age and adjusted for potential confounders (gender, semiology, MRI lesion and medications).
A total of 390 patients (188 girls, mean age 9.2 years, SD 6.0) had 1,754 recorded seizures. Generalized seizures (109 patients, 490 seizures) occurred more out of wakefulness (p<0.001) and more during the day (p<0.001). Infants had more seizures between 6AM-3PM (p<0.05). Children had more seizures between 6-9AM and 12-3PM (p<0.05). Adolescents had more seizures between 6-9AM and 6-9PM (p<0.05). Modeling revealed a greater occurrence of seizures at night with increasing age (p=0.046). Temporal lobe seizures (62 patients, 271 seizures) occurred overall more out of wakefulness (p=0.03). This was specifically observed in children (p<0.05) and adolescents (p<0.01). In infants, seizures were more common between 3-6AM (p<0.05). In the >12 age group, seizures occurred more between 12-3PM (p<0.01). There was no evidence of sleep/wake or day/night seizure variation based on age or age groups in temporal lobe seizures. Frontal lobe seizures (41 patients, 184 seizures) occurred more out of wakefulness in infants (P<0.05) and more out of sleep in adolescents (p<0.0001). Children had more seizures between 9PM-12AM (p<0.01) and 12-3AM (p<0.05) and adolescents had more seizures between 6AM-12PM (p<0.05). Adolescents were 3.6 times more likely to have seizures during sleep compared to other children with frontal lobe seizures (95% confidence interval: 1.8-7.2). Modeling revealed a gradual increase in seizures during sleep with each unit increase in age (p=0.02). This was not affected by potential confounders. All occipital lobe seizures (2 patients, 13 seizures) occurred during wakefulness. Parietal lobe seizures (11 patients, 50 seizures) did not occur in a specific pattern in relation to the sleep/wake or day/night state.
Seizures occur in different sleep/wake and diurnal patterns depending on patient age and EEG location. These findings are suggestive of maturational changes in circadian rhythmicity that may alter seizure susceptibility in different age groups. Results may assist in age related and EEG localization based prediction of times of greatest seizure propensity.
I. Sánchez Fernández, S. V. Kothare, S. Hadjiloizou, A. Bergin, A. Rotenberg, J. M. Peters, I. Abdelmoumen, S. An, S. Ramgopal, M. Takeoka, J. Riviello, B. Bourgeois, T. Loddenkemper
Boston Children's Hospital
Treatment strategies in patients with the electroencephalographic (EEG) pattern of electrical status epilepticus in sleep (ESES) are based on expert opinions and small case series. The objective of this study was to review our long-term experience with high-dose diazepam treatment.
We retrospectively reviewed patients who were monitored by overnight inpatient video-EEG at Boston Children's Hospital with: 1) presence of ESES considered as at least 50% of the non-REM sleep tracing occupied by spike-waves, 2) on high-dose diazepam treatment (1mg/Kg the first night, followed by 0.5 mg/Kg/day for a variable time subsequently and eventually a tapering schedule), 3) during the period from 2000 to 2007, and 4) had at least 4 years of clinical and EEG follow-up data after the last treatment with high-dose diazepam. We investigated their electro-clinical features and recorded the age of occurrence of the significant clinical events. Per patient, we recorded the number and timing of treatments with highdose diazepam, any adverse effects associated with this treatment protocol, and the timing of any other anti-epileptic treatments needed after the last high-dose diazepam treatment.
25 patients were identified. Demographic features are presented in Table 1. Treatment with high-dose diazepam led to improvement in clinical (seizure frequency and severity, cognitive and behavioral function) and EEG features in all patients, but its effect slowly wore off over time. Five patients received two trials of high-dose diazepam treatment and four patients received three trials of high-dose diazepam (Table 2). 20/25 patients required other antiepileptic treatments after high-dose diazepam, including epilepsy surgery (functional hemispherectomy and corpus callosotomy) in two cases. Adverse effects of the high-dose diazepam treatment protocol included daytime somnolence (two patients), agitation (two patients), and ataxia (two patients); these adverse effects led to treatment discontinuation in one patient. There were no respiratory complications related to the treatment administration.
Children with ESES experienced improvement in clinical and EEG features after high-dose diazepam treatment. Beneficial effects dissipated and further trials of high-dose diazepam and/or other treatments were needed. Infrequent and mild adverse effects were found with the high-dose diazepam treatment protocol. No patients suffered from respiratory complications related to the treatment.
K. Singh, E. Katz, M. Zarowski, T. Loddenkemper, N. Llewellyn, S. Manganaro, M. Gregas, M. Pavlova, S. Kothare.
Massachusetts General Hospital, Boston Children's Hospital
Sudden Unexpected Death in Epilepsy Patients (SUDEP) is an important cause of death in epilepsy patients. Role of cardio-pulmonary abnormalities in SUDEP is unclear in pediatric population. This study was done to assess cardio-pulmonary abnormalities during epileptic seizures in children, with the long-term goal of identifying potential mechanisms of SUDEP.
We prospectively recorded and analyzed cardio-pulmonary abnormalities by pulseoximetry, EKG and respiratory-inductance-plethysmography (RIP) during 101 seizures in 26 children. Logistic regression was done to evaluate association of these abnormalities with patient characteristics.
RIP provided data in 78% and pulse-oximetry in 63% seizures. Ictal-apnea increased with younger-age (p=0.01), male-gender (p=0.08) temporal-lobe (p=0.0005), left-sided (p=0.003), symptomatic-generalized (vs. primary-generalized and complex-partial) (p=0.01 and 0.08), complex-partial (vs. primary-generalized) (p=0.08), longer-duration seizures (p=0.0002), desaturation (p<0.0001), ictalbradycardia (p=0.02), more antiepileptic-drugs (AEDs) (p=0.006) and decreased in frontal-lobe seizures (p=0.004). Ictal-bradypnea increased in temporal-lobe (p=0.07), left-sided (p=0.04), lesional (on MRI-brain) (p=0.09), symptomaticgeneralized seizures (vs. complex-partial and primary-generalized) (p=0.005, 0.005), desaturation (p=0.07), more AEDs (p=0.07) and decreased in frontal-lobe seizures (p=0.07). Ictal-tachypnea increased in older-age (p=0.01), female-gender (p=0.05), frontal-lobe (vs. temporal and other foci) (p=0.09, 0.02), right-sided seizures (p=0.0008) less AEDs (p=0.005) and decreased in lesional (p=0.03) symptomatic-generalized seizures (vs. complex-partial and primary-generalized) (p=0.02, 0.03). Ictal-bradycardia increased in younger-age (p=0.09) male-gender (p=0.03) longer-duration seizures (p=0.03), desaturation (p=0.001), more AEDs (p=0.04), and decreased in frontal-lobe seizures (p=0.01). Ictal and post-ictal bradycardia were directly correlated (p=0.02). Ictal tachycardia increased in olderage (p=0.08), female-gender (p=0.001), frontal-lobe (p=0.06) seizures, and decreased with lesional-seizures (p=0.01) and more AEDs (p=0.02). Desaturation increased with longer-duration seizures (p<0.0001), ictal-apnea (p<0.0001), ictalbradycardia (p=0.001), and more AEDs (p=0.001).
Potentially life-threatening cardio-pulmonary abnormalities like bradycardia, apnea and hypoxemia in pediatric epileptic seizures are associated with predictable patient and seizure characteristics, including seizure sub-type and duration. Understanding epidemiology of cardio-pulmonary compromise in epilepsy patients may lead to preventative strategies for patients at high-risk for SUDEP.