North American Consensus
Presentation & Treatment for Physicians
Thanks to an educational grant from Greenwich™ Biosciences, DSF funded a North American Consensus Panel Study in 2016. A panel of 13 epileptologists with expertise in Dravet syndrome and five parent caregivers answered a series of in-depth questionnaires about the diagnosis and management of Dravet syndrome. After reading a thorough literature review and drawing on their experience with patients, strong consensus was reached regarding clinical presentation, EEG and MRI findings, genetic testing, first and second-line treatments for seizures, and other aspects of treatment, outlined below. The full text of this paper is available at this link.
Initial presentation of Dravet syndrome includes:
- Typical seizure onset between 1-18 months
- Recurrent generalized tonic-clonic or hemiconvulsive seizures which are mandatory for diagnosis. These are often prolonged, but may be shorter
- Myoclonic seizures are typically seen by age 2 years. Obtundation status, focal dyscognitive seizures and atypical absences are also typical but usually occur after age 2 years. Typical absences and epileptic spasms are atypical
- Hyperthermia, which may be associated with vaccination or illness, triggers seizures in the majority of patients; other triggers may include flashing lights, visual patterns, bathing, eating and overexertion
- Normal development and neurological examination at onset
- Normal MRI and nonspecific EEG findings at onset
Presentation in older children and adults: In the absence of the early, characteristic history, the following features are characteristics of Dravet syndrome at any age
- Persisting seizures, which include focal and/or generalized convulsive seizures, and, in many cases, myoclonic, focal, atypical absence and tonic seizures. Recurrent status epilepticus and obtundation status become less frequent with time, and may not be seen in adolescence and young adulthood
- Hyperthermia as a seizure trigger may become less problematic in adolescence and adulthood
- Seizure exacerbation with the use of sodium channel agents
- Intellectual disability which is typically evident by 18-60 months of age
- Abnormalities on neurological examination which are typically evident by age 3-4 years and include crouched gait, hypotonia, incoordination and impaired dexterity
- An MRI which is typically normal, but may show mild generalized atrophy and/or hippocampal sclerosis
SCN1A mutations are found in as many as 85% of patients clinically diagnosed with Dravet syndrome. However, SCN1A mutations are also found in less severe epilepsy types, such as generalized epilepsy with febrile seizures plus (GEFS+), and more severe forms of epilepsy such as migrating focal seizures, therefore careful clinical correlations are needed. The experts strongly agreed that genetic testing should be considered for all patients who meet any one of these criteria assuming the child’s early development is normal, there are no causal lesions, and the seizure etiology remains unknown:
- Clinical picture suggestive of DS
- ≥ 2 prolonged (>15 min) focal or generalized febrile seizures in the first 12 months of life
- ≥ 1 prolonged (>15 min) febrile seizure before age 18 months and myoclonic or atypical absence seizures refractory to one or more antiepileptic drug
- Teen or adult with pharmacoresistant focal and/or generalized seizures without congenital dysmorphism in whom an early-life history is not available.
While simple SCN1A sequencing is appropriate when all clinical criteria are met, an epilepsy gene panel may be preferable for infants, when clinical history is less distinct, or when atypical features are present.
Although there is no literature to support the benefits of early diagnosis, based on their clinical experience, the experts reached moderate consensus that earlier diagnosis improves long-term outcome for patients overall, with improved cognition and seizure control.
Treatment (Note this study was conducted prior to the US FDA’s approval of Diacomit (stiripentol), Epidiolex and Fintepla for the treatment of Dravet syndrome.)
*Ketogenic diet is not suitable for all patients; its use is not required before moving to third-line therapies. aAgreed upon by moderate consensus. Agreed upon by strong consensus. cStiripentol not approved for use in all jurisdictions. sz, seizures.
Consensus was not as strong for other treatments including corpus callosotomy and specific therapies addressing comorbidities. Half of the panel had experience with medical marijuana and agreed it was moderately effective for Dravet syndrome. The remaining half had insufficient experience to comment on efficacy.
The experts agreed an at-home emergency medication such as rectal diazepam or buccal/nasal midazolam should be administered within 3-5 minutes of seizure onset unless there is a recent history of prolonged convulsive seizures, in which case medication should be given at seizure onset. A second dose should be given 5-10 minutes after the initial dose if the seizure has not stopped.
Benzodiazepines and valproate should be included in initial treatment at the hospital for convulsive status epilepticus, but there was no consensus on subsequent treatment. Phenytoin and fosphenytoin, often used in treating status epilepticus, are of debated usefulness due to their undesired effect on sodium ion channels.
On October 1, 2020 (FY2021), three distinct ICD-10 codes were approved for Dravet syndrome, thanks to the work of DSF and their Medical Advisors.
- G40.834 Dravet syndrome, intractable, without status epilepticus