Optimizing Dravet syndrome diagnosis and management

Wirrell EC, Laux L, Donner E, Jette N, Knupp K, Meskis MA, Miller I, Sullivan J, Welborn M, Berg AT. Optimizing the Diagnosis and Management of Dravet Syndrome: Recommendations From a North American Consensus Panel. Pediatr Neurol. 2017 Mar;68:18-34.e3.

Abstract

OBJECTIVES:

To 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.

METHODS:

An 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.

RESULTS:

The 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.

CONCLUSIONS:

We 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.
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From the article

There was strong consensus that genetic testing should be pursued for all patients with a clinical

picture suggestive of Dravet syndrome and on the specific types of genetic testing to order.
Moderate to strong consensus was reached regarding the specific clinical scenarios that should /should not mandate genetic testing for Dravet syndrome, with one noted exception. There was no consensus regarding the need for genetic testing for a child <12 months of age, with normal early development, a normal MRI and no known seizure etiology who presents with >2 prolonged (>15 minute) generalized febrile seizures (72.2% strongly agreed/agreed/somewhat agreed that testing should be done, 5.6% indicated they did not know and 22.2% strongly disagreed/disagreed/somewhat disagreed)...

Twelve of 18 (67%) panelists had experience with the use of medical marijuana in Dravet
syndrome and 9 had adequate experience to comment on perceived efficacy. While these individuals felt that medical marijuana was moderately efficacious, no consensus could be reached regarding which concentration of cannabidiol (CBD)/tetrahydrocannabinol (THC) should be used…

 There was consensus that benzodiazepines should be administered first line for in-hospital management of status epilepticus. There was little consensus regarding the next best option if benzodiazepines were ineffective. Only valproic acid was recommended as a preferred next option. No consensus could be reached on the use of fosphenytoin or phenytoin for the treatment of convulsive status epilepticus, with these agents rated as preferred choices by 7/13 physicians and 1/5 parents and as non-preferred choices by 4/13 physicians and 4/5 parents. The remainder of respondents indicated they were unsure or neutral about their use. Levetiracetam was considered a preferred option by 9/13 physicians, and 1/5 parents, with the remainder of parents indicating that they were unsure or neutral regarding its use...

 While the group acknowledged that sleep problems, dysautonomia, constipation and dysmotility

may be seen in Dravet syndrome, the exact prevalence of these symptoms is not known, and referral is only indicated if there are clinical concerns…

Although the group acknowledged that seizure detection devices may help reduce the risk of
SUDEP, rigorous scientific evidence for such a claim is lacking. Consensus was reached for the use of baby monitors, as well as benefits and drawbacks of seizure detection devices.