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Brain Dev. 2016 Jan;38(1):128-31. doi: 10.1016/j.braindev.2015.07.002. Epub 2015 Jul 23.

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

Author information

1
Unit of Clinical Neurophysiology, Department of Neuroscience and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Electronic address: robertino.dilena@policlinico.mi.it.
2
Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Institute "G. Gaslini", University of Genova, Genoa, Italy.
3
Pediatric Neurology and Muscular Diseases Unit, Laboratory of Neurogenetics, Institute "G. Gaslini", Genoa, Italy.
4
Pediatric Neurology Unit and Epilepsy Center, Department of Neuroscience, "Fatebenefratelli e Oftalmico" Hospital, Milan, Italy.
5
Neonatal Intensive Care Unit, Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
6
Unit of Clinical Neurophysiology, Department of Neuroscience and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Abstract

BACKGROUND:

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.

KEYWORDS:

Antiepileptic drugs; Early onset epileptic encephalopathy; Levetiracetam; Pharmacogenetics; STXBP1 mutation

PMID:
26212315
DOI:
10.1016/j.braindev.2015.07.002
[Indexed for MEDLINE]

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