Faculty Bibliography

PURPOSE: Status epilepticus (SE) is a life-threatening condition that can be refractory to initial treatment. Randomized controlled studies to guide treatment choices, especially beyond first-line drugs, are not available. This report summarizes the evidence that guides the management of refractory convulsive SE (RCSE) in children, defines gaps in our clinical knowledge and describes the development and works of the 'pediatric Status Epilepticus Research Group' (pSERG). METHODS: A literature review was performed to evaluate current gaps in the pediatric SE and RCSE literature. In person and online meetings helped to develop and expand the pSERG network. RESULTS: The care of pediatric RCSE is largely based on extrapolations of limited evidence derived from adult literature and supplemented with case reports and case series in children. No comparative effectiveness trials have been performed in the pediatric population. Gaps in knowledge include risk factors for SE, biomarkers of SE and RCSE, second- and third-line treatment options, and long-term outcome. CONCLUSION: The care of children with RCSE is based on limited evidence. In order to address these knowledge gaps, the multicenter pSERG was established to facilitate prospective collection, analysis, and sharing of de-identified data and biological specimens from children with RCSE. These data will allow identification of treatment strategies associated with better outcomes and delineate evidence-based interventions to improve the care of children with SE.

BACKGROUND: As part of the development of the Neurocritical Care Society (NCS) Status Epilepticus (SE) Guidelines, the NCS SE Writing Committee conducted an international survey of SE experts. METHODS: The survey consisted of three patient vignettes (case 1, an adult; case 2, an adolescent; case 3, a child) and questions regarding treatment. The questions for each case focused on initial and sequential therapy as well as when to use continuous intravenous (cIV) therapy and for what duration. Responses were obtained from 60/120 (50%) of those surveyed. RESULTS: This survey reveals that there is expert consensus for using intravenous lorazepam for the emergent (first-line) therapy of SE in children and adults. For urgent (second-line) therapy, the most common agents chosen were phenytoin/fosphenytoin, valproate sodium, and levetiracetam; these choices varied by the patient age in the case scenarios. Physicians who care for adult patients chose cIV therapy for RSE, especially midazolam and propofol, rather than a standard AED sooner than those who care for children; and in children, there is a reluctance to choose propofol. Pentobarbital was chosen later in the therapy for all ages. CONCLUSION: There is close agreement between the recently published NCS guideline for SE and this survey of experts in the treatment of SE.

SUMMARY:: Continuous EEG monitoring has become an essential modality for monitoring the central nervous system in the critically ill and has expanded beyond seizure detection. The massive amount of data generated and the associated logistical problems have limited the timely interpretation of these data. Digital trending analysis is a complimentary tool that creates a graphic display of the EEG data that may be visualized and interpreted at the bedside. This article reviews the use of digital trending analysis for pediatric and neonatal continuous EEG monitoring and its limitations.

PURPOSE:: To describe current continuous EEG monitoring (cEEG) utilization in critically ill children. METHODS:: An online survey of pediatric neurologists from 50 US and 11 Canadian institutions was conducted in August 2011. RESULTS:: Responses were received from 58 of 61 (95%) surveyed institutions. Common cEEG indications are altered mental status after a seizure or status epilepticus (97%), altered mental status of unknown etiology (88%), or altered mental status with an acute primary neurologic condition (88%). The median number of patients undergoing cEEG per month per center increased from August 2010 to August 2011 (6 to 10 per month in the United States; 2 to 3 per month in Canada). Few institutions have clinical pathways addressing cEEG use (31%). Physicians most commonly review cEEG twice per day (37%). There is variability regarding which services can order cEEG, the degree of neurology involvement, technologist availability, and whether technologists perform cEEG screening. CONCLUSIONS:: Among the surveyed institutions, which included primarily large academic centers, cEEG use in pediatric intensive care units is increasing and is often considered indicated for children with altered mental status at risk for nonconvulsive seizures. However, there remains substantial variability in cEEG access and utilization among institutions.

Rationale: 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. Methods: 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) nonconvulsive status epilepticus and infrequent myoclonic jerks. Results: 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 yi!

The study objective was to compare qualitatively the clinical features of patients with electrical status epilepticus in sleep with focal versus generalized sleep potentiated epileptiform activity. We enrolled patients 2 to 20 years of age, studied between 2001 and 2009, and with sleep potentiated epileptiform activity defined as an increase of epileptiform activity of 50% or more during non-rapid eye movement sleep compared with wakefulness. Eighty-five patients met the inclusion criteria, median age was 7.3 years, and 54 (63.5%) were boys. Sixty-seven (78.8%) patients had focal sleep potentiated epileptiform activity, whereas 18 (21.2%) had generalized sleep potentiated epileptiform activity. The 2 groups did not differ with respect to sex, age, presence of a structural brain abnormality, epilepsy, or other qualitative cognitive, motor, or behavioral problems. Our data suggest that there are no qualitative differences in the clinical features of patients with focal versus generalized sleep potentiated epileptiform activity.

Sturge-Weber syndrome (SWS) is a neurocutaneous disorder comprised typically of a facial nevus, leptomeningeal angioma with calcifications, and seizures. SWS without a port-wine stain is a rare variant with only 30 cases reported in the literature. Here, a case of an 8-year-old girl with no cutaneous abnormalities presenting with medically intractable epilepsy and MRI and CT findings consistent with SWS is described. The patient underwent multistage surgery with subdural electrode monitoring before and after resection of the epileptogenic focus, with complete excision of the lesion and postoperative resolution of her seizures. This is the first reported case of three-stage surgery for localized resection of the seizure focus for SWS. (c) 2014 S. Karger AG, Basel.

Purpose:A number of genes in the 9q34.11 region may be haploinsufficient. However, studies analyzing genotype-phenotype correlations of deletions encompassing multiple dosage-sensitive genes in the region are lacking.Methods:We mapped breakpoints of 10 patients with 9q34.11 deletions using high-resolution 9q34-specific array comparative genomic hybridization (CGH) to determine deletion size and gene content.Results:The 9q34.11 deletions range in size from 67 kb to 2.8 Mb. Six patients exhibit intellectual disability and share a common deleted region including STXBP1; four manifest variable epilepsy. In five subjects, deletions include SPTAN1, previously associated with early infantile epileptic encephalopathy, infantile spasms, intellectual disability, and hypomyelination. In four patients, the deletion includes endoglin (ENG), causative of hereditary hemorrhagic telangiectasia. Finally, in four patients, deletions involve TOR1A, of which molecular defects lead to early-onset primary dystonia. Ninety-four other RefSeq genes also map to the genomic intervals investigated.Conclusion:STXBP1 haploinsufficiency results in progressive encephalopathy characterized by intellectual disability and may be accompanied by epilepsy, movement disorders, and autism. We propose that 9q34.11 genomic deletions involving ENG, TOR1A, STXBP1, and SPTAN1 are responsible for multisystemic vascular dysplasia, early-onset primary dystonia, epilepsy, and intellectual disability, therefore revealing cis-genetic effects leading to complex phenotypes.Genet Med 2012:14(10):868-876.

OBJECTIVE: To compare the prevalence and type of early developmental lesions in patients with a clinical presentation consistent with electrical status epilepticus in sleep either with or without prominent sleep-potentiated epileptiform activity (PSPEA). METHODS: We performed a case-control study and enrolled patients with 1) clinical features consistent with electrical status epilepticus in sleep, 2) >/=1 brain MRI scan, and 3) >/=1 overnight EEG recording. We quantified epileptiform activity using spike percentage, the percentage of 1-second bins in the EEG tracing containing at least 1 spike. PSPEA was present when spike percentage during non-REM sleep was >/=50% than spike percentage during wakefulness. RESULTS: One hundred patients with PSPEA (cases) and 47 patients without PSPEA (controls) met the inclusion criteria during a 14-year period. Both groups were comparable in terms of clinical and epidemiologic features. Early developmental lesions were more frequent in cases (48% vs 19.2%, p = 0.002). Thalamic lesions were more frequent in cases (14% vs 2.1%, p = 0.037). The main types of early developmental lesions found in cases were vascular lesions (14%), periventricular leukomalacia (9%), and malformation of cortical development (5%). Vascular lesions were the only type of early developmental lesions that were more frequent in cases (14% vs 0%, p = 0.005). CONCLUSIONS: Patients with PSPEA have a higher frequency of early developmental lesions and thalamic lesions than a comparable population of patients without PSPEA. Vascular lesions were the type of early developmental lesions most related to PSPEA.