Dramatic effect of levetiracetam in early-onset epileptic encephalopathy due to STXBP1 mutation

详细信息    查看全文

• 作者：Robertino Dilena^a ; ^{robertino.dilena@policlinico.mi.it" class="auth_mail" title="E-mail the corresponding author} ; Pasquale Striano^b ; Monica Traverso^c ; Maurizio Viri^d ; Gloria Cristofori^e ; Laura Tadini^a ; Sergio Barbieri^a ; Antonino Romeo^d ; Federico Zara^c
• 关键词：STXBP1 mutation ; Early onset epileptic encephalopathy ; Levetiracetam ; Antiepileptic drugs ; Pharmacogenetics
• 刊名：Brain and Development
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：38
• 期：1
• 页码：128-131
• 全文大小：1693 K

文摘

Syntaxin Binding Protein 1 (STXBP1) mutations determine a central neurotransmission dysfunction through impairment of the synaptic vesicle release, thus causing a spectrum of phenotypes varying from syndromic and non-syndromic epilepsy to intellectual disability of variable degree. Among the antiepileptic drugs, levetiracetam has a unique mechanism of action binding SV2A, a glycoprotein of the synaptic vesicle release machinery.

Patient description

We report a 1-month-old boy manifesting an epileptic encephalopathy with clonic seizures refractory to phenobarbital, pyridoxine and phenytoin that presented a dramatic response to levetiracetam with full epilepsy control and EEG normalization. Genetic analysis identified a novel de novo heterozygous mutation (c.[922A > T]p.[Lys308^∗]) in the STXBP1 gene that severely affects the protein.

Conclusions

The observation of a dramatic efficacy of levetiracetam in a case of STXBP1 epileptic encephalopathy refractory to other antiepileptic drugs and considerations regarding the specific mechanism of action of levetiracetam modulating the same system affected by STXBP1 mutations support the hypothesis that this drug may be able to reverse specifically the disease epileptogenic abnormalities. Further clinical observations and laboratory studies are needed to confirm this hypothesis and eventually lead to consider levetiracetam as the first choice treatment of patients with suspected or confirmed STXBP1-related epilepsies.