Febrile Seizures: Evaluation and Treatment

By the second year, other seizure types including myoclonic, atypical absence, clonic, and tonic seizures arise. The EEG frequently begins to show generalized spike wave and polyspike wave discharges. Seizures continue occurring frequently during early childhood, often resulting in status epilepticus. Cognitive development begins to stagnate between the ages of 1 and 4 years with emergence of autistic traits and hyperactivity [44]. Development may stabilize between the ages of 5 and 16 years, but fails to demonstrate much improvement [44]. Higher frequency of seizures may correlate with increase in cognitive impairment and behavior problems, supporting the need for rapid diagnosis and appropriate therapy [44].

Over the years, several cases of atypical or borderline Dravet syndrome have been described, most highlighting the absence of myoclonic seizures [45]. Others may present with primarily clonic or tonic-clonic type seizures only [46]. Despite these differences, all cases share a similar drug resistance and cognitive delay and are categorized as Dravet syndrome.

In 2001, Claus et al discovered the genetic alteration in SCN1A responsible for 70% of Dravet syndrome cases [47]. The disorder is inherited in an autosomal dominant fashion, though 40% to 80% of mutations resulting in Dravet syndrome are de novo [48]. Mutations can be present in other family members, as this syndrome is part of the spectrum of GEFS+, though parental phenotypes are often much less severe. Approximately 50% of mutations resulting in Dravet syndrome are truncating, while the other 50% are missense mutations involving splice site or pore forming regions leading to loss of function [49]. Finally, small and large chromosome rearrangements make up 2% to 3% of cases [50]. Other genes reported to result in Dravet syndrome include SCN1B and GABRG2 mutations. In addition, PCDH19 can produce a phenotype similar to Dravet syndrome in females and is discussed in more detail below.

With the emergence of more rapid and cheaper forms of genetic testing, molecular diagnosis can now be made earlier in life before all the typical clinical features of Dravet syndrome arise. As a result, one might hope to alter treatment strategy and gear therapy towards the most effective medications. While drug resistance is the norm for the condition, certain drugs such as benzodiazepines, valproate, and stiripentol may be most effective [43]. Topiramate and levetiracetam have been reported as effi-cacious in small series, as has the ketogenic diet [51–55]. Varieties of medications which target sodium channels are known to exacerbate seizures in Dravet syndrome and should be avoided, including lamotrigine, carbamazepine, oxcarbazepine, and phenytoin [56]. In addition to maintenance therapy, it is important to provide patients with a rescue plan for acute seizures in an effort to avoid status epilepticus. In addition, measures to avoid overheating may provide additional benefit.

Case 3 Continued

After a careful history, the physician discovers that the child also has frequent myoclonic seizures described as brief jerks of the extremities or sudden forward falls. The family notes they have seen these seizures more frequently since antiepileptic therapy was started. The physician recognize that this child may have Dravet syndrome and suspect her medication may be resulting in aggravation of seizures.