Early Clinical Variables Associated With Refractory Convulsive Status Epilepticus in Children.

BACKGROUND AND OBJECTIVES: The objective of this study was to determine patient-specific factors known proximate to the presentation to emergency care associated with the development of refractory convulsive status epilepticus (RSE) in children. METHODS: An observational case-control study was conducted comparing pediatric patients (1 month-21 years) with convulsive SE whose seizures stopped after benzodiazepine (BZD) and a single second-line antiseizure medication (ASM) (responsive established status epilepticus [rESE]) with patients requiring more than a BZD and a single second-line ASM to stop their seizures (RSE). These subpopulations were obtained from the pediatric Status Epilepticus Research Group study cohort. We explored clinical variables that could be acquired early after presentation to emergency medical services with univariate analysis of the raw data. Variables with p < 0.1 were retained for univariable and multivariable regression analyses. Multivariable logistic regression models were fit to age-matched and sex-matched data to obtain variables associated with RSE. RESULTS: We compared data from a total of 595 episodes of pediatric SE. Univariate analysis demonstrated no differences in time to the first BZD (RSE 16 minutes [IQR 5-45]; rESE 18 minutes [IQR 6-44], p = 0.068). Time to second-line ASM was shorter in patients with RSE (RSE 65 minutes; rESE 70 minutes; p = 0.021). Both univariable and multivariable regression analyses revealed a family history of seizures (OR 0.37; 95% CI 0.20-0.70, p = 0.0022) or a prescription for rectal diazepam (OR 0.21; 95% CI 0.078-0.53, p = 0.0012) was associated with decreased odds of RSE. DISCUSSION: Time to initial BZD or second-line ASM was not associated with progression to RSE in our cohort of patients with rESE. A family history of seizures and a prescription for rectal diazepam were associated with a decreased likelihood of progression to RSE. Early attainment of these variables may help care for pediatric rESE in a more patient-tailored manner. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that patient and clinical factors may predict RSE in children with convulsive seizures.

Treatment Practices and Outcomes in Continuous Spike and Wave during Slow Wave Sleep: A Multicenter Collaboration.

OBJECTIVES: To determine how continuous spike and wave during slow wave sleep (CSWS) is currently managed and to compare the effectiveness of current treatment strategies using a database from 11 pediatric epilepsy centers in the US. STUDY DESIGN: This retrospective study gathered information on baseline clinical characteristics, CSWS etiology, and treatment(s) in consecutive patients seen between 2014 and 2016 at 11 epilepsy referral centers. Treatments were categorized as benzodiazepines, steroids, other antiseizure medications (ASMs), or other therapies. Two measures of treatment response (clinical improvement as noted by the treating physician; and electroencephalography improvement) were compared across therapies, controlling for baseline variables. RESULTS: Eighty-one children underwent 153 treatment trials during the study period (68 trials of benzodiazepines, 25 of steroids, 45 of ASMs, 14 of other therapies). Children most frequently received benzodiazepines (62%) or ASMs (27%) as first line therapy. Treatment choice did not differ based on baseline clinical variables, nor did these variables correlate with outcome. After adjusting for baseline variables, children had a greater odds of clinical improvement with benzodiazepines (OR 3.32, 95%CI 1.57-7.04, P = .002) or steroids (OR 4.04, 95%CI 1.41-11.59, P = .01) than with ASMs and a greater odds of electroencephalography improvement after steroids (OR 3.36, 95% CI 1.09-10.33, P = .03) than after ASMs. CONCLUSIONS: Benzodiazepines and ASMs are the most frequent initial therapy prescribed for CSWS in the US. Our data suggests that ASMs are inferior to benzodiazepines and steroids and support earlier use of these therapies. Multicenter prospective studies that rigorously assess treatment protocols and outcomes are needed.

Diagnosing and managing childhood absence epilepsy by telemedicine.

The diagnosis of childhood absence epilepsy (CAE) is typically based on history and description of spells, supported by an office-based positive hyperventilation test and confirmed by routine electroencephalography (EEG). In the current coronavirus disease 2019 (COVID-19) pandemic, many pediatric neurologists have switched to telemedicine visits for nonemergent outpatient evaluations. We present a series of children diagnosed as having CAE on the basis of a positive hyperventilation test performed during remote televisits. Several of these children were begun on treatment for CAE prior to obtaining an EEG, with significant seizure reduction. Our series documents the feasibility of CAE diagnosis and management by telemedicine.

The onset of pediatric refractory status epilepticus is not distributed uniformly during the day.

PURPOSE: To evaluate whether the onset of pediatric refractory status epilepticus (rSE) is related to time of day. METHOD: We analyzed the time of day for the onset of rSE in this prospective observational study performed from June 2011 to May 2019 in pediatric patients (1 month to 21 years of age). We evaluated the temporal distribution of pediatric rSE utilizing a cosinor analysis. We calculated the midline estimating statistic of rhythm (MESOR) and amplitude. MESOR is the estimated mean number of rSE episodes per hour if they were evenly distributed. Amplitude is the difference between MESOR and maximum rSE episodes/hour, or between MESOR and minimum rSE episodes/hour. We also evaluated the temporal distribution of time to treatment. RESULTS: We analyzed 368 patients (58% males) with a median (p25 - p75) age of 4.2 (1.3-9.7) years. The MESOR was 15.3 (95% CI: 13.9-16.8) and the amplitude was 3.2 (95% CI: 1.1-5.3), p = 0.0024, demonstrating that the distribution is not uniform, but better described as varying throughout the day with a peak in the morning (11am-12 pm) and trough at night (11 pm-12 am). The duration from rSE onset to application of the first non-benzodiazepine antiseizure medication peaked during the early morning (2am-3 am) with a minimum during the afternoon (2 pm-3 pm) (p = 0.0179). CONCLUSIONS: The distribution of rSE onset is not uniform during the day. rSE onset shows a 24-h distribution with a peak in the mid-morning (11am-12 pm) and a trough at night (11 pm-12am).

Characterization of the Basal Ganglia Using Diffusion Tensor Imaging in Children with Self-Injurious Behavior and Tuberous Sclerosis Complex.

BACKGROUND AND PURPOSE: Tuberous sclerosis complex (TSC) is a rare, genetic disease that is associated with multiple manifestations including epilepsy and autism. Self-injurious behaviors (SIBs) also occur in a subset of patients. This study used diffusion tensor imaging (DTI) in children with TSC for quantitative and volumetric analysis of brain regions that have been associated with SIB in other genetic conditions. METHODS: We used DTI to compare 6 children with TSC-associated SIB and 10 children with TSC without SIB. Atlas-based analysis of DTI data and calculation of number of voxels; fractional anisotropy (FA); and mean, axial, and radial diffusivity were performed for multiple regions; DTI measures were summarized using medians and interquartile ranges and were compared using Wilcoxon rank sum tests and false discovery rates (FDRs). RESULTS: Analysis showed that children with TSC and SIB had reduced numbers of voxels (median) in the bilateral globus pallidus (right: 218 vs. 260, P = .008, FDR = .18; left: 222 vs. 274, P = .002, FDR = .12) and caudate nucleus (right: 712 vs. 896, P = .01, FDR = .26; left: 702 vs. 921, P = .03, FDR = .44) and reduced FA in the bilateral globus pallidus (right: .233 vs. .272, P = .003, FDR = .12; left: .223 vs. .247, P = .004, FDR = .12) and left caudate nucleus (.162 vs. .186, P = .03, FDR = .39) versus children without SIB. No other statistically significant differences were found. CONCLUSIONS: These data support a correlation between lower volumes of the globus pallidus and caudate with SIB in children with TSC.

Child Life Services in an Epilepsy Monitoring Unit.

The goal of this study was to determine the value of a certified child life specialist (CCLS) on the patient and staff experiences in an epilepsy monitoring unit (EMU). We integrated a CCLS into the EMU for all children as well as adults with intellectual disability. We surveyed families to determine the impact of child life services on their stay. EMU staff completed questionnaires to determine perceived impact to their job performance from the integration of the CCLS. All of the families (pediatric and adult patients) who responded to the survey reported the presence of the CCLS improved their hospital experience. Staff reported that the CCLS improved their daily work by allowing them to focus on their assigned medical duties. This preliminary pilot study suggests that CCLS can have a strong impact on the experience of patients and staff in an EMU.

Bottom-of-sulcus focal cortical dysplasia presenting as epilepsia partialis continua multimodality characterization including 7T MRI.

INTRODUCTION: Bottom-of-sulcus focal cortical dysplasias are an under recognized, surgically treatable cause of focal epilepsy. Resection can dramatically reduce the seizure burden for children with refractory epilepsy, or eliminate seizures altogether. MATERIAL AND METHODS: We report the case and present the results of multimodality evaluation of a 15-year-old young man who presented with long-standing partial epilepsy affecting his right leg, which over the years became refractory to therapy. RESULTS: High-resolution 3T MRI images acquired as a dedicated epilepsyprotocol were initially interpreted as unremarkable. On further review by an experienced specialist aware of clinical and electroencephalographic findings, a subtle focal cortical dysplasia was identified at the bottom of a sulcus near the medial aspect of the left precentral gyrus. After confirmation of the extent of the lesion with PET and ultra-high field 7T MRI, the patient underwent cortical mapping and focal resection and remains free of seizures. COCLUSIONS: This case emphasizes the need for a multidisciplinary approach to the evaluation of refractory focal epilepsy in children and highlights the potential role of ultra-high field 7T MRI in identifying the often subtle causative anatomic abnormalities.

Comorbidity of migraine in children presenting with epilepsy to a tertiary care center.

OBJECTIVES: Migraine and epilepsy are 2 of the most common neurologic disorders in children. In this cross-sectional study we investigated a population of children with epilepsy to determine if children with a greater seizure burden or certain epilepsy syndromes had a higher risk of migraines. We also examined how often migraine is addressed and treated in a pediatric epilepsy cohort. METHODS: Between January 2010 and March 2011 we distributed questionnaires regarding headache symptoms and treatment to consecutive children with epilepsy seen in clinic at Johns Hopkins Hospital (400 children were studied). Records were subsequently reviewed for seizure type, age at onset, and treatment. RESULTS: The prevalence of migraine in our pediatric epilepsy population was 25%, which is greater than reported for children without epilepsy (3%-23%). Migraine was more prevalent in children ≥10 years (p = 0.0009), children with benign epilepsy with centrotemporal spikes (BECTS) (p = 0.003), and children with juvenile myoclonic epilepsy (JME) (p = 0.008). Migraine onset was more likely to have occurred after epilepsy was diagnosed (p = 0.0002), but was not more prevalent in those with intractable epilepsy. Only 50% of patients with weekly or greater migraines had documented discussions regarding headaches with their neurologist. CONCLUSION: Migraine was comorbid in one-quarter of children with epilepsy in a tertiary care center. Children who were older or who had BECTS or JME were more likely to have migraines. Migraines were infrequently addressed within the neurology clinic. It is imperative to address comorbid migraine in treating children with epilepsy.

Metabolic treatments for intractable epilepsy.

When a child on anticonvulsant medications continues to have seizures, what other options should be considered? Over the past 100 years, dietary therapies for the treatment of intractable epilepsy have become more widely recognized, and their use has continued to expand throughout the world. An increasing number of studies has shown efficacy of these metabolic treatments in improving seizure control. Currently, 4 types of dietary therapy are available in the clinic: the classic long chain fatty acid "ketogenic" diet, the medium chain triglyceride diet, the modified Atkins diet, and the low glycemic index treatment. These therapies should be considered earlier in the treatment of intractable epilepsy because they offer a different approach to treatment that has proven efficacious, tolerable, and cost-effective.

Doose syndrome (myoclonic-astatic epilepsy): 40 years of progress.

Doose syndrome, otherwise traditionally known as myoclonic-astatic epilepsy, was first described as a unique epilepsy syndrome by Dr Hermann Doose in 1970. In 1989, the International League Against Epilepsy classified it formally as a symptomatic generalized epilepsy, and 20 years later it was renamed 'epilepsy with myoclonic-atonic seizures'. In this review, we discuss the components of this unique disorder including its incidence, clinical features, and electroencephalographic findings. Recent evidence has suggested possible genetic links to the GEFS+ (generalized epilepsy with febrile seizures plus) family, and, additionally, some children with structural brain lesions can mimic the Doose syndrome phenotype. Treatment strategies such as corticosteroids, ethosuximide, and valproate have been described as only partially effective, but newer anticonvulsants, such as levetiracetam and zonisamide, may provide additional seizure control. The most effective treatment reported to date appears to be the ketogenic diet. Prognosis is quite varied in this disorder; however, many children can have a remarkably normal neurodevelopmental outcome.