New-onset seizure survey of epilepsy centers in the United States.

OBJECTIVES: Children presenting with new-onset seizures have variable access to resources and may not receive timely and adequate treatment. Some may experience adverse consequences when not evaluated in a timely manner by appropriate medical providers. Consequences can be especially severe for children under the age of two and for children who have psychiatric, cognitive, and behavioral comorbidities. There are no published data on how children with new-onset seizure are evaluated and treated across the US. Our goal was to gain insight into how different epilepsy centers across the country evaluate and treat children with new-onset seizures. METHODS: We conducted a survey of Epilepsy Centers in the US that are part of the Pediatric Epilepsy Research Consortium (PERC) and focused on children presenting with new-onset seizures; PERC is a group of pediatric epilepsy providers and researchers who participate in collaborative multicenter research in pediatric epilepsy with the goal of improving outcomes in children with pediatric epilepsy. The questionnaire was developed by the authors of this study. It was designed to provide a descriptive assessment of the consistency and variability in how patients with new-onset seizure are evaluated and treated at epilepsy sites across the country. The questionnaire was designed to assure all points of interest were explored. The questions were aimed at describing access to care, how care is delivered, whether centers prioritize based on clinical presentation and/or age, and availability of resources. The survey was sent to 80 epileptologists at 42 different Epilepsy Centers that are part of PERC. RESULTS: Respondents included 29 pediatric epileptologists representing 24 unique centers. In the cases where there were multiple respondents from each center, response of the most senior epileptologist was used. It is possible that the senior epileptologist may have not known about the center as much as a junior epileptologist, but this was used to establish consistencies among centers with multiple respondents. Results showed that 30% of centers had a dedicated new-onset seizure clinic. The median time for children to be seen was two to four weeks, and 12% reported that it takes more than five weeks until the patient is seen. There was a trend toward centers with new-onset seizure clinic having less wait times. Most centers identified lack of adequate care based on insurance coverage, resources, long wait times, and long travel times. SIGNIFICANCE: Most centers (70%) do not have a dedicated new-onset seizure clinic. Children presenting with new-onset seizures often do not receive timely and comprehensive care because of limitations in resources and lack of established standard of care. Standardizing care for patients presenting with new-onset seizures has not yet occurred in the US. Many centers do not have a screening process and employ staff other than physicians or nurses for screening and triaging patients. This study shows that having a neurologist or epileptologist in charge of triaging does not reduce wait times. This survey revealed that there is substantial variability in how these patients are evaluated. Although this study shows a trend for epilepsy centers with new-onset seizure clinic having less wait times, even when there is a new-onset seizure clinic, wait times can be greater than five weeks. Overall, however, a new-onset seizure clinic may be an effective way to improve access to timely and efficient care for these patients.

Prospective evaluation of oral cannabis extracts in children with epilepsy.

PURPOSE: Interest in the use of artisanal cannabinoids in pediatric epilepsy has increased but safety and utility data are lacking. Our aim was to prospectively characterize the use of oral cannabis extracts (OCE) in a refractory pediatric epilepsy population. METHODS: Families considering the use of an OCE were enrolled in a prospective observational study. Baseline seizure frequency was assessed over a period of 4 weeks. Seizure frequency, CBD and THC-COOH levels were assessed every 4 weeks during a 12-week treatment period. Response was defined as at least a 50% reduction in seizure frequency over the final 8 weeks of the study relative to baseline. RESULTS: Consent was obtained in 32 children; 11 were excluded from analysis (3 failed to complete baseline data, 3 started OCE before completing baseline period and 5 did not start OCE) leaving 21 to be included in subsequent analyses. Median age was 10.3 years (IQR 6.8-12.6), 13 (62%) were male and median seizure frequency was 2.7 seizures/day during the baseline period. The median of the high dose of CBD that was administered during the observation period was of 0.9 (0.6-2.2) mg/kg/day. Of the 21 subjects who were included in the analysis, 5 (24%) were responders. OCE was stopped early in 3 subjects (14%) due to a perceived increase in seizures. THC-COOH and CBD blood levels did not have a significant association with response status (p = 0.95 CBD, p = 0.53 THC-COOH, N = 14). CONCLUSION: The observed response rate in this study is similar to placebo rates in prospective randomized trials of pharmaceutical grade products and the withdrawal rate is greater than rates obtained with retrospective methods. Doses of OCE administered were lower than doses used in randomized trials.

Duration of use of oral cannabis extract in a cohort of pediatric epilepsy patients.

OBJECTIVE: Oral cannabis extracts (OCEs) are being used in the treatment of epilepsy with increasing rates in the United States following product legalization; however, no studies demonstrate clear efficacy. We evaluated the duration of use of OCEs as a measure of perceived benefit in a cohort of patients with pediatric epilepsy. METHODS: Retrospective chart review was performed of children and adolescents who were given OCEs for treatment of epilepsy. RESULTS: Of the 119 patients included in the analysis, 71% terminated use of their OCE product during the study period. The average length of use of OCE was 11.7 months (range 0.3-57 months). Perceived seizure benefit was the only factor associated with longer duration of treatment with OCE (p < 0.01). Relocation to Colorado was associated with perceived benefit of OCEs for seizures (65% vs. 38%, p = 0.01), but was not independently associated with longer OCE use. Factors associated with shorter use included adverse effects (p = 0.03) and a diagnosis of Dravet syndrome (p = 0.02). Twenty-four percent of patients were considered OCE responders, which was defined by a parent's report of a > 50% reduction in seizures while on this therapy. Adverse events (AEs) were reported in 19% of patients, with the most common side effects being somnolence and worsening of seizures. SIGNIFICANCE: Parental report of OCE use in refractory pediatric epilepsy suggests that some families perceive benefit from this therapy; however, discontinuation of these products is common. Duration appears to be affected by logical factors, such as perceived benefit and side effect profile. Surprisingly, families of patients with Dravet syndrome terminated use of OCEs more quickly than patients with other epilepsy syndromes. Results from this study highlight the need for rigorous clinical studies to characterize the efficacy and safety of OCEs, which can inform discussions with patients and families.

Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy.

OBJECTIVE: Oral cannabis extracts (OCEs) have been used in the treatment of epilepsy; however, no studies demonstrate clear efficacy. We report on a cohort of pediatric patients with epilepsy who were given OCE and followed in a single tertiary epilepsy center. METHODS: A retrospective chart review of children and adolescents who were given OCE for treatment of their epilepsy was performed. RESULTS: Seventy-five patients were identified of which 57% reported any improvement in seizure control and 33% reported a >50% reduction in seizures (responders). If the family had moved to CO for OCE treatment, the responder rate was 47% vs. 22% for children who already were in CO. The responder rate varied based on epilepsy syndrome: Dravet 23%, Doose 0%, and Lennox-Gastaut syndrome (LGS) 88.9%. The background EEG of the 8 responders where EEG data were available was not improved. Additional benefits reported included: improved behavior/alertness (33%), improved language (10%), and improved motor skills (10%). Adverse events (AEs) occurred in 44% of patients including increased seizures (13%) and somnolence/fatigue (12%). Rare adverse events included developmental regression, abnormal movements, status epilepticus requiring intubation, and death. SIGNIFICANCE: Our retrospective study of OCE use in pediatric patients with epilepsy demonstrates that some families reported patient improvement with treatment; however, we also found a variety of challenges and possible confounding factors in studying OCE retrospectively in an open-labeled fashion. We strongly support the need for controlled, blinded studies to evaluate the efficacy and safety of OCE for treatment of pediatric epilepsies using accurate seizure counts, formal neurocognitive assessments, as well as EEG as a biomarker. This study provides Class III evidence that OCE is well tolerated by children and adolescents with epilepsy.