Abstract 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.
Developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (D/EE-SWAS), also referred to as electrical status epilepticus during sleep (ESES) or epileptic encephalopathy ...with continuous spike-and-wave during sleep (CSWS or EE-CSWS), is a spectrum of rare childhood epileptic encephalopathies that can lead to long-term cognitive impairment. Despite the importance of early diagnosis and intervention for D/EE-SWAS, there is a paucity of well-controlled clinical trial data to inform treatment, and no approved treatments are available. To assess correlations between diagnosis, treatment, and outcomes in D/EE-SWAS, we carried out a systematic review of the literature.
In August 2020, we conducted comprehensive database searches using search terms including "electrical status epilepticus," "ESES," "CSWS," and "Landau-Kleffner syndrome." Two or more independent reviewers screened titles, abstracts, and full-text articles for those that met the following criteria: prospective studies (randomized controlled trials RCTs or open-label trials), retrospective studies (drug evaluations or observational studies/chart reviews), and case series with ≥ 10 participants. Both interventional and non-interventional studies were included (i.e., drug intervention was not an inclusion criterion). Articles published before 2012, review articles, animal studies, and studies of surgical or dietary interventions were excluded. Standardized data extraction templates were used to capture data on study design, patient characteristics, interventions, and outcomes from each of the selected publications. Study quality was assessed using the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale (NOS) or the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for retrospective, observational studies.
A total of 34 studies were included for full data extraction, most of which were uncontrolled and observational. Interpretation of study outcomes was limited by small study populations, variability in inclusion criteria, and inconsistency in methods of assessment and reporting of outcomes, which resulted in large heterogeneity in patients and their presenting symptoms. Despite these limitations, some patterns could be discerned. Several studies found that longer duration of ESES and younger age at onset were correlated with more severe language and cognitive deficits. In addition, several studies reported an association between improvement in cognitive outcomes and reduction in electroencephalogram (EEG) abnormalities and/or seizure frequency. In the 16 prospective or retrospective studies that evaluated drug treatments (e.g., antiseizure medications, corticosteroids, and high-dose diazepam), there was some improvement in EEG, seizure, and/or cognitive outcomes, although the specific outcomes and rates of improvement reported varied from study to study.
Long-term cognitive deficits remain common in D/EE-SWAS, and data gaps exist in the literature that preclude an evidence-based approach to managing this complex epilepsy indication. Early intervention with more effective medications is needed to optimize long-term outcomes. Sufficiently powered, randomized, double-blind, controlled trials with standardized methods and predefined primary and secondary outcomes are needed.
Our objective was to summarize and evaluate the rapidly expanding body of literature studying functional connectivity in childhood epilepsy. In the self‐limited childhood epilepsies, awareness of ...cognitive comorbidities has been steadily increasing, and recent advances in our understanding of the network effects of these disorders promise insights into the underlying neurobiology. We reviewed publications addressing functional connectivity in children with epilepsy with an emphasis on studies of children with self‐limited childhood epilepsies. The majority of studies have been published in the past 10 years and predominantly examine childhood epilepsy with centrotemporal spikes and childhood absence epilepsy. Cognitive network alterations are commonly observed across the childhood epilepsies. Some of these effects appear to be nonspecific to epilepsy syndrome or even to category of neurological disorder. Other patterns, such as changes in the connectivity of cortical language areas in childhood epilepsy with centrotemporal spikes, provide clues to the underlying cognitive deficits seen in affected children. The literature to date is dominated by general observations of connectivity patterns without a priori hypotheses. These data‐driven studies build an important foundation for hypothesis generation and are already providing useful insights into the neuropathology of the childhood epilepsies. Future work should emphasize hypothesis‐driven approaches and rigorous clinical correlations to better understand how the knowledge of network alterations can be applied to guidance and treatment for the children in our clinics.
Summary
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.
Critical Care Continuous EEG (CCEEG) is a common procedure to monitor brain function in patients with altered mental status in intensive care units. There is significant variability in patient ...populations undergoing CCEEG and in technical specifications for CCEEG performance.
The Critical Care Continuous EEG Task Force of the American Clinical Neurophysiology Society developed expert consensus recommendations on the use of CCEEG in critically ill adults and children.
The consensus panel recommends CCEEG for diagnosis of nonconvulsive seizures, nonconvulsive status epilepticus, and other paroxysmal events, and for assessment of the efficacy of therapy for seizures and status epilepticus. The consensus panel suggests CCEEG for identification of ischemia in patients at high risk for cerebral ischemia; for assessment of level of consciousness in patients receiving intravenous sedation or pharmacologically induced coma; and for prognostication in patients after cardiac arrest. For each indication, the consensus panel describes the patient populations for which CCEEG is indicated, evidence supporting use of CCEEG, utility of video and quantitative EEG trends, suggested timing and duration of CCEEG, and suggested frequency of review and interpretation.
CCEEG has an important role in detection of secondary injuries such as seizures and ischemia in critically ill adults and children with altered mental status.
•Outcome in pediatric status epilepticus is highly related to underlying etiology.•Mortality in pediatric SE is relatively low, while morbidity poses more challenges.•Greater use of objective, valid, ...and reliable outcome measures should be utilized.
To summarize different aspects of short and long-term outcomes associated with SE, including mortality, recurrence, subsequent epilepsy, neurocognitive dysfunction, imaging abnormalities, and health-related quality of life.
We searched MEDLINE for studies that assessed the short-term and long-term outcome of status epilepticus in pediatric population, including mortality, recurrence of seizure and status epilepticus, neurological, cognitive, or behavioral impairment, and health-related quality of life. We excluded studies that exclusively assessed the adult population.
Mortality in pediatric SE is relatively low, while morbidity poses more challenges. The underlying cause of SE has been shown to be a major determinant in the outcome after SE. However, it is difficult to establish the net effect of SE on outcome due to the heterogeneity of the studies. Notably, this review highlights that health-related quality of life, an important aspect of long-term outcome in pediatric SE, is under-addressed and merits further investigation.
There is a need to acquire high-quality long-term data evaluating QoL, neuroimaging, use of continuous infusions, and cognitive and behavioral outcome of children who experience SE.
Highlights ► A review of North American randomized clinical trials was conducted from 1993 to 2010. ► Of 47 trials identified, 21 reported ethnic/racial minority demographic information. ► Only 4.9% ...were African American, 3.4% were Hispanic, and 1.1% were Asian American. ► Minorities are greatly underrepresented in panic disorder studies. ► Findings of panic studies may not generalize to diverse populations.
Up to half of the children undergoing epilepsy surgery will continue to have seizures (szs) despite a cortical resection or ablation. Functional connectivity has shown promise in better identifying ...the epileptogenic zone. We hypothesized that cortical areas showing high information outflow during interictal epileptiform discharges are part of the epileptogenic zone.
We identified 22 children with focal epilepsy who had undergone stereo electroencephalography, surgical resection or ablation, and had ≥1 year of postsurgical follow-up. The mean phase slope index, a directed measure of functional connectivity, was calculated for each electrode contact during interictal epileptiform discharges. The positive predictive value and negative predictive value for a sz-free outcome were calculated based on whether high information outflow brain regions were resected.
Resection of high outflow (z-score ≥ 1) and very high outflow (z-score ≥ 2) electrode contacts was associated with higher sz freedom (high outflow: χ 2 statistic = 59.1; P < 0.001; very high outflow: χ 2 statistic = 31.3; P < 0.001). The positive predictive value and negative predictive value for sz freedom based on resection at the electrode level increased at higher z-score thresholds with a peak positive predictive value of 0.86 and a peak negative predictive value of 0.9.
Better identification of the epileptogenic zone has the potential to improve epilepsy surgery outcomes. If the surgical plan can be modified to include these very high outflow areas, more children might achieve sz freedom. Conversely, if deficits from resecting these areas are unacceptable, ineffective surgeries could be avoided and alternative therapies offered.
Summary
In epileptic encephalopathy, the seizures and interictal epileptiform activity create additional neurocognitive dysfunction beyond that due to the underlying etiology. Treatment leading to a ...reduction in seizures or interictal abnormalities may help improve neurocognitive function in these situations. The focus of our discussion is reviewing data that support the concept that treatment can impact outcome independent of the etiology in some cases.
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