Optimizing the Diagnosis and Management of Dravet Syndrome: Recommendations From a North American Consensus Panel
Publication date: March 2017 Source:Pediatric Neurology, Volume 68 Author(s): Elaine C. Wirrell, Linda Laux, Elizabeth Donner, Nathalie Jette, Kelly Knupp, Mary Anne Meskis, Ian Miller, Joseph Sullivan, Michelle Welborn, Anne T. Berg ObjectivesTo establish standards for early, cost-effective, and accurate diagnosis; optimal therapies for seizures; and recommendations for evaluation and management of comorbidities for children and adults with Dravet syndrome, using a modified Delphi process.MethodsAn expert panel was convened comprising epileptologists with nationally recognized expertise in Dravet syndrome and parents of children with Dravet syndrome, whose experience and understanding was enhanced by their active roles in Dravet syndrome associations. Panelists were asked to base their responses to questions both on their clinical expertise and results of a literature review that was forwarded to each panelist. Three rounds of online questionnaires were conducted to identify areas of consensus and strength of that consensus, as well as areas of contention.ResultsThe panel consisted of 13 physicians and five family members. Strong consensus was reached regarding typical clinical presentation of Dravet syndrome, range of electroencephalography and magnetic resonance imaging findings, need for genetic testing, critical information that should be conveyed to families at diagnosis, priorities for seizure control and typical degree of control, seizure triggers and recommendations for avoidance, first- and second-line therapies for seizures, requirement and indications for rescue therapy, specific recommendations for comorbidity screening, and need for family support. Consensus was not as strong regarding later therapies, including vagus nerve stimulation and callosotomy, and for specific therapies of associated comorbidities. Beyond the initial treatment with benzodiazepines and use of valproate, there was no consensus on the optimal in-hospital management of convulsive status epilepticus.ConclusionsWe were able to identify areas where there was strong consensus that we hope will (1) inform health care providers on optimal diagnosis and management of patients with Dravet syndrome, (2) support reimbursement from insurance companies for genetic testing and Dravet syndrome–specific therapies, and (3) improve quality of life for patients with Dravet syndrome and their families by avoidance of unnecessary testing and provision of an early accurate diagnosis allowing optimal selection of therapeutic strategies.
Publication date: April 2017 Source:Pediatric Neurology, Volume 69 Author(s): Sarah Lee, David M. Mirsky, Lauren A. Beslow, Catherine Amlie-Lefond, Amy R. Danehy, Laura Lehman, Nicholas V. Stence, Arastoo Vossough, Max Wintermark, Michael J. Rivkin PurposeTo provide consensus-based, suggested imaging protocols to facilitate the accurate and timely diagnosis of a neonate with symptoms concerning for stroke.MethodsThe Writing Group, an international collaboration of pediatric neurologists and neuroradiologists with expertise in perinatal and childhood stroke, participated in a series of pediatric stroke neuroimaging symposia. These discussions, in conjunction with extensive literature review, led to a consensus for imaging protocols to guide practitioners in the diagnosis of neonatal stroke subtypes as defined by the National Institute of Neurological Disorders and Stroke Common Data Elements. The epidemiology, clinical presentation, and associated risk factors for arterial ischemic stroke, cerebral sinovenous thrombosis, and hemorrhagic stroke are reviewed, with a focused discussion regarding the role of neuroimaging for each subtype.ResultsIn a neonate with suspected stroke, magnetic resonance imaging is the preferred modality, given the lack of X-irradiation, superior anatomic resolution, and sensitivity for acute ischemia. Core recommended sequences include diffusion-weighted imaging and apparent diffusion coefficient mapping to diagnose acute ischemia, gradient-recalled echo or susceptibility-weighted imaging to detect intracranial blood and its breakdown products, and T1- and T2-weighted imaging to assess for myelination, extra-axial blood, and edema. Magnetic resonance angiography of the brain may be useful to detect vascular abnormalities, with venography if venous sinus thrombosis is suspected. The application of more novel sequences, as well as the utility of follow up-imaging, is also discussed.
The Potential for Advanced Magnetic Resonance Neuroimaging Techniques in Pediatric Stroke Research
Publication date: April 2017 Source:Pediatric Neurology, Volume 69 Author(s): Trish Domi, Arastoo Vossough, Nicholas V. Stence, Ryan J. Felling, Jackie Leung, Pradeep Krishnan, Christopher G. Watson, P. Ellen Grant, Andrea Kassner BackgroundThis article was written to provide clinicians and researchers with an overview of a number of advanced neuroimaging techniques in an effort to promote increased utility and the design of future studies using advanced neuroimaging in childhood stroke. The current capabilities of advanced magnetic resonance imaging techniques provide the opportunity to build on our knowledge of the consequences of stroke on the developing brain. These capabilities include providing information about the physiology, metabolism, structure, and function of the brain that are not routinely evaluated in the clinical setting.MethodsDuring the Proceedings of the Stroke Imaging Laboratory for Children Workshop in Toronto in June 2015, a subgroup of clinicians and imaging researchers discussed how the application of advanced neuroimaging techniques could further our understanding of the mechanisms of stroke injury and repair in the pediatric population. This subgroup was established based on their interest and commitment to design collaborative, advanced neuroimaging studies in the pediatric stroke population.ResultsIn working toward this goal, we first sought to describe here the magnetic resonance imaging techniques that are currently available for use, and how they have been applied in other stroke populations (e.g., adult and perinatal stroke).ConclusionsWith the continued improvement in advanced neuroimaging techniques, including shorter acquisition times, there is an opportunity to apply these techniques to their full potential in the research setting and learn more about the effects of stroke in the developing brain.
Cannabidiol Treatment for Refractory Seizures in Sturge-Weber syndrome
Publication date: Available online 22 February 2017 Source:Pediatric Neurology Author(s): Emma H. Kaplan, Elizabeth A. Offermann, Jacqueline W. Sievers, Anne M. Comi BackgroundSturge-Weber syndrome (SWS) results in leptomeningeal vascular malformations, medically-refractory epilepsy, stroke(s), and cognitive impairments. Cannabidiol (CBD), a cannabinoid without psychoactive properties, has been demonstrated in preclinical models to possibly have anticonvulsant, anti-oxidant, and neuroprotective actions.MethodsFive subjects with SWS brain involvement and treatment-resistant epilepsy were enrolled. Motor seizure frequency, quality of life (QoL), and adverse events were recorded from the 8 week pre-treatment period, 8 weeks after starting maintenance dose (Week 14), and most recent visit.ResultsFour subjects had data through Week 14; one of whom initially withdrew for lack of efficacy, but because of other benefits re-enrolled with a lower dose. Two subjects at Week 14 and three bilaterally brain involved subjects at last visit had greater than 50% seizure reduction, reported improved quality of life, and remain on CBD 63 to 80 weeks after starting drug. Three subjects reported mild side effects considered related to CBD.ConclusionThis study suggests that CBD may be well-tolerated as adjunctive medication for seizure management and provides initial data supporting further study of CBD in SWS patients.